On November 1, 2018 Quanterix Corporation (NASDAQ:QTRX), a company digitizing biomarker analysis to advance the science of precision health, reported financial results for the three months and nine months ended September 30, 2018 (Press release, Quanterix, NOV 1, 2018, View Source [SID1234530628]).

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"This third quarter has been an incredibly productive one for our company, as we continue to achieve strong momentum and hit important milestones, including gaining back unrestricted rights to our Simoa technology for the in vitro diagnostics (IVD) markets," said Kevin Hrusovsky, Chief Executive Officer, President and Chairman. "Our Simoa technology is at the bleeding edge of the biomarker revolution, which has gained considerable traction recently as biomarkers are increasingly being recognized for their abilities to transform treatment options by accelerating development of more effective and safer drugs for all disease categories, and then longer-term, enabling and empowering individuals to take control of their lives and prevent disease."

Third Quarter 2018 Financial Highlights

Key financial results for the third quarter are shown below:

· Q3 revenue of $10.6M versus prior year Q3 of $5.7M, an increase of 85%.

· Q3 product revenue was $6.0M versus prior year Q3 of $3.3M, an increase of 82%.

· Q3 Service and Other revenue totaled $3.0M versus prior year Q3 of $2.2M, an increase of 36%.

Q3 2018 revenue includes a one-time item of $1.3M related to termination of a licensing agreement with bioMérieux for the Simoa technology. Revenue growth would have been 61% excluding this item.

YTD 2018 Financial Highlights

Key financial results for 2018 YTD are shown below:

· YTD revenue of $26.8M versus prior year $16.3M, an increase of 64%.

· YTD product revenue of $15.9M versus prior year $10.1M, an increase of 57%.

·YTD Service and Other revenue of $8.7M versus prior year $5.4M, an increase of 61%.

Excluding the $1.3M one-time item, total YTD revenue growth would have been 56%.

Third Quarter 2018 Business Highlights

· Gained unrestricted rights back for its Simoa technology in IVD markets with the termination of a license agreement with bioMérieux.

· Cadence of publications continued to increase with more than 40 new publications featuring Simoa technology in Q3 alone, bringing the total to approximately 300.

· Major presence at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress with a record number of posters/presentations mentioning the use of Quanterix’ serum neurofilament light (NfL) assay for a wide range of clinical studies in multiple sclerosis (MS) disease progression and monitoring.

· Led webinar alongside world-renowned researchers on how Simoa technology is enabling advances in drug development through the use of digital biomarkers; presented at MedCity

CONVERGE describing the power of predictive biomarkers for the diagnosis of cancer; delivered presentations at several leading investor conferences and garnered additional analyst coverage; featured in leading publications, including Forbes, Bloomberg and Digital Biotech.

Conference Call

In conjunction with this announcement, Quanterix Corporation will host a conference call on November 1, 2018, at 4:30 p.m. EDT to discuss the Company’s financial results and business outlook. To access this call, dial (833) 686-9351 for domestic callers, or (612) 979-9890 for international callers. Please reference the following conference ID: 2573579.

On November 1, 2018 Geron Corporation (Nasdaq: GERN) reported recent company events and reported financial results for the three and nine months ended September 30, 2018 (Press release, Geron, NOV 1, 2018, View Source [SID1234530644]). The Company ended the third quarter of 2018 with $184.8 million in cash and marketable securities and expects to utilize these financial resources to advance the clinical development of imetelstat, the Company’s first-in-class telomerase inhibitor.

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"We are very excited to have 100% ownership of imetelstat, a Phase 3 ready asset with Phase 2 data from both IMerge and IMbark that have been selected for oral presentations at the ASH (Free ASH Whitepaper) meeting in December," said John A. Scarlett, M.D., Geron’s President and Chief Executive Officer. "We are in the process of transitioning imetelstat back to Geron and have the cash to support our key near-term objective of commencing enrollment for the Phase 3 portion of IMerge by mid-year 2019."

Recent Company Events

Geron regained the global rights to develop and commercialize imetelstat upon the termination of a collaboration and license agreement with Janssen Biotech, Inc. (Janssen). The transition of the entire imetelstat program back to Geron is expected to occur over approximately 12 months, through September 2019, with operational support from Janssen. Patients currently enrolled in the ongoing imetelstat clinical trials in myelofibrosis (IMbark) and myelodysplastic syndromes (IMerge) will continue to be supported through the respective trial protocols, including treatment and follow-up. Previously, Geron and Janssen shared both the IMerge and IMbark clinical development costs 50/50. While Geron is now solely accountable for imetelstat development costs, each company will be responsible for their own respective transition costs as the imetelstat program transfers back to Geron.

After sponsorship of the imetelstat Investigational New Drug (IND) application has been transferred from Janssen, Geron plans to initiate the Phase 3 portion of IMerge in lower risk myelodysplastic syndromes (MDS) and is targeting mid-year 2019 for patient screening and enrollment. In addition, Geron intends to discuss the results of the IMbark primary analysis, including the assessment of overall survival as it compares to historical data, with experts in myelofibrosis (MF), as well as regulatory authorities. The Company believes feedback from these discussions will provide important information on the feasibility, scope and design of any potential future clinical trials for imetelstat in Intermediate-2 or High-risk MF patients who have relapsed after or are refractory to prior treatment with a JAK inhibitor.

Third Quarter and Year to Date 2018 Results

For the third quarter of 2018, the Company reported a net loss of $5.6 million, or $0.03 per share, compared to $6.9 million, or $0.04 per share, for the comparable 2017 period. Net loss for the first nine months of 2018 was $19.7 million, or $0.11 per share, compared to $20.5 million, or $0.13 per share, for the comparable 2017 period.

Revenues for the three and nine months ended September 30, 2018 were $165,000 and $691,000, respectively, compared to $163,000 and $874,000 for the comparable 2017 periods. Revenues for the three and nine months ended September 30, 2018 and 2017 included royalty and license fee revenues under various non-imetelstat license agreements. The Company adopted the new revenue recognition accounting standard as of January 1, 2018 using the modified retrospective transition method. Financial results for the three and nine months ended September 30, 2018 are presented under the new accounting standard, but prior period amounts have not been adjusted and continue to be reported under accounting standards used historically. Therefore, there is a lack of comparability to the prior periods presented. As a result, the decrease in revenues for the nine months ended September 30, 2018, compared to the same period in 2017, reflects not only a reduction in the number of active non-imetelstat license agreements, but also a change in the accounting method. However, the Company does not expect the adoption of the new revenue recognition accounting standard to have a material impact to its financial statements on an ongoing basis.

Total operating expenses for the three and nine months ended September 30, 2018 were $7.0 million and $22.2 million, respectively, compared to $7.4 million and $22.3 million for the comparable 2017 periods.

Research and development expenses for the three and nine months ended September 30, 2018 were $2.7 million and $8.4 million, respectively, compared to $2.6 million and $8.5 million for the comparable 2017 periods. The changes in research and development expenses for the three and nine months ended September 30, 2018, compared to the same periods in 2017, primarily reflect the net result of higher personnel related expenses, partially offset by lower costs for our proportionate share of clinical development expenses under the former imetelstat collaboration with Janssen. Geron expects research and development expenses to increase in the future as Geron’s share of imetelstat development costs increases from 50% previously to 100% as of the termination date of the collaboration agreement and as it adds personnel, consultants and a global contract research organization (CRO) to support the further development of imetelstat.

General and administrative expenses for the three and nine months ended September 30, 2018 were $4.3 million and $13.8 million, respectively, compared to $4.8 million and $13.8 million for the comparable 2017 periods. The decrease in general and administrative expenses for the three months ended September 30, 2018, compared to the same period in 2017, primarily reflects the net result of reduced personnel related expenses, including lower stock-based compensation expense, partially offset by higher consulting expenses. Geron expects general and administrative expenses to increase in the future with the elimination of cost-sharing with Janssen as of the termination date of the collaboration agreement for imetelstat patent prosecution expenses and as it adds additional personnel to support the expansion of internal research and development functions.

Interest and other income for the three and nine months ended September 30, 2018 was $1.1 million and $2.2 million, respectively, compared to $363,000 and $1.0 million for the comparable 2017 periods. The increase in interest and other income for the three and nine months ended September 30, 2018, compared to the same periods in 2017, primarily reflects higher yields on the Company’s increased marketable securities portfolio.

Conference Call and Webcast

Geron will host a conference call to discuss third quarter financial results and recent events at 4:30 p.m. ET on Thursday, November 1, 2018.

Participants may access the conference call live via telephone by dialing domestically +1 (877) 303-9139 or internationally +1 (760) 536-5195. The passcode is 7133129. A live, listen-only webcast will also be available on the Company’s website at www.geron.com/investors/events. If you are unable to listen to the live call, an archived webcast will be available on the Company’s website for 30 days.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat include a Phase 2/3 trial called IMerge in lower risk myelodysplastic syndromes (MDS) and a Phase 2 trial called IMbark in Intermediate-2 to High-risk myelofibrosis. Imetelstat received Fast Track designation from the United States Food and Drug Administration for the treatment of patients with transfusion-dependent anemia due to lower risk MDS who are non-del(5q) and refractory or resistant to an erythroid stimulating agent.

On November 1, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported that the European Commission (EC) has approved the type-II variation application for VENCLYXTO (venetoclax) in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) who have received at least one prior therapy (Press release, AbbVie, NOV 1, 2018, View Source [SID1234530458]). This approval allows more patients to receive VENCLYXTO in the second-line setting and gives healthcare providers the ability to prescribe this medicine to a broader population of patients with R/R CLL than the previously approved indication for VENCLYXTO as monotherapy in the European Union (EU). The approval is valid in all 28 member states of the EU, as well as Iceland, Liechtenstein and Norway.

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The EC approval is based on results from the MURANO Phase 3 randomized clinical trial, which evaluated the efficacy and safety of VENCLYXTO in combination with rituximab compared to bendamustine in combination with rituximab, an established standard of care chemoimmunotherapy regimen for patients with R/R CLL.1 At the time of the primary analysis, the trial demonstrated a statistically significant improvement in investigator-assessed progression-free survival (PFS; the time on treatment without disease progression or death2) in patients who received VENCLYXTO plus rituximab, resulting in an 83 percent reduction in the risk of disease progression or death (hazard ratio [HR]:0.17; 95% confidence interval [CI]: 0.11-0.25; P<0.0001) and prolonged overall survival (OS) compared to the standard of care chemoimmunotherapy (HR: 0.48; 95% CI: 0.25-0.90; overall survival data are not yet mature).1

In the MURANO Phase 3 clinical trial, undetectable minimal residual disease (uMRD) was a secondary endpoint assessed at the end of combination therapy (nine-month assessment1,3). The majority of patients in the trial who received VENCLYXTO plus rituximab achieved uMRD in the peripheral blood, with 62.4 percent of patients achieving uMRD versus 13.3 percent with bendamustine in combination with rituximab.1 uMRD is an objective measure defined as the presence of less than one CLL cell in 10,000 white blood cells remaining in the blood or bone marrow following treatment.2 Earlier prospective clinical trials have provided evidence that achieving uMRD in CLL patients is associated with improved clinical outcomes.2

"Chronic lymphocytic leukemia can relapse and become refractory to first-line treatment, and there is a need for better therapies to treat these patients who otherwise have limited options," said Prof. John Seymour, MBBS, Ph.D., lead investigator of the MURANO trial and Director of Cancer Medicine at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia. "The venetoclax plus rituximab combination provides these patients with an alternative treatment option that is superior to a type of chemoimmunotherapy and can achieve deep responses, as shown by MRD negativity rates in the peripheral blood and bone marrow, allowing for a fixed duration of treatment without the need for chemoimmunotherapy."

CLL is a slow-growing form of leukemia, or blood cancer, in which too many immature lymphocytes (a type of white blood cell) are found predominantly in the blood and bone marrow.4 CLL accounts for approximately one third of new leukemia diagnoses.5

In September 2018, AbbVie announced the European Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for the Marketing Authorization Application for VENCLYXTO plus rituximab for the treatment of patients with R/R CLL.

"The approval of VENCLYXTO in combination with rituximab is an important step forward in providing patients with relapsed/refractory chronic lymphocytic leukemia a strong chance to live longer without their disease progressing," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "We look forward to bringing VENCLYXTO to more patients with chronic lymphocytic leukemia, while continuing to further the research and development of therapies with the potential to transform the standards of care in blood cancers."

VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

About the MURANO Trial
A total of 389 patients with R/R CLL who had received at least one prior therapy were enrolled in the international, multicenter, open-label, randomized Phase 3 MURANO trial. The trial was designed to evaluate the efficacy and safety of VENCLYXTO in combination with rituximab (N=194) compared with bendamustine in combination with rituximab (N=195). The median age of patients in the trial was 65 years (range: 22-85).1

The primary efficacy endpoint was investigator (INV)-assessed PFS. Median PFS with VENCLYXTO in combination with rituximab was not reached compared with 17.0 months for bendamustine in combination with rituximab (HR: 0.17; 95% CI: 0.11-0.25; P<0.0001). The median follow-up was 23.8 months (range: 0.0 to 37.4). Additional efficacy endpoints included independent review committee (IRC)-assessed PFS, INV- and IRC-assessed overall response rate (defined as complete response + complete response with incomplete marrow recovery + partial response + nodular partial response), overall survival and rates of uMRD.1

The safety profile of the combination of VENCLYXTO plus rituximab is consistent with the known safety profile of each of the medicines alone. The most common adverse reactions (ARs; ≥20 percent) of any grade for VENCLYXTO in combination with rituximab were neutropenia, diarrhea and upper respiratory tract infection. In the VENCLYXTO in combination with rituximab arm due to any AR, discontinuation occurred in 16 percent of patients, dose reduction in 15 percent, and dose interruption in 71 percent. In the VENCLYXTO in combination with rituximab arm, neutropenia led to dose interruption of VENCLYXTO in 43 percent of patients and discontinuation in 3 percent. The most serious ARs (≥2 percent) for VENCLYXTO in combination with rituximab or VENCLYXTO monotherapy were pneumonia, febrile neutropenia and tumor lysis syndrome.1

About VENCLYXTO (venetoclax)
VENCLEXTA (VENCLYXTO in the EU) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other cancerous tumors, BCL-2 builds up and prevents cancer cells from undergoing their natural death or self-destruction process, which is called apoptosis. VENCLEXTA/VENCLYXTO targets the BCL-2 protein and works to restore the process of apoptosis.

VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers.

VENCLEXTA/VENCLYXTO is approved in more than 50 countries, including the U.S. AbbVie and Roche are currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

Important VENCLYXTO (venetoclax) EU Safety Information3

Contraindications
Hypersensitivity to the active substance or to any of the excipients is contraindicated. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumor lysis syndrome (TLS). Concomitant use of preparations containing St. John’s wort as VENCLYXTO efficacy may be reduced.

Special Warnings & Precautions for Use
Tumor lysis syndrome (TLS), including fatal events, has occurred in patients with previously treated CLL with high tumor burden when treated with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial 5-week dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS.

Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period. Serious infections including events of sepsis with fatal outcome have been reported. Supportive measures including antimicrobials for any signs of infection should be considered.

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. At initiation and dose-titration phase: Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: If moderate or strong CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations.

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose-titration phase.

CYP3A4 inducers may decrease VENCLYXTO plasma concentrations. Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions
The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in the combination study with rituximab were neutropenia, diarrhea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhea, nausea, anemia, fatigue, and upper respiratory tract infection.

The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with rituximab or as monotherapy were pneumonia, febrile neutropenia and TLS.

Discontinuation due to adverse reactions occurred in 16% of patients receiving venetoclax plus rituximab and 9% receiving venetoclax monotherapy. Dosage adjustments due to adverse reactions occurred in 15% of patients receiving venetoclax plus rituximab and 2% receiving venetoclax monotherapy. Dose interruptions occurred in 71% of patients treated with the combination of venetoclax and rituximab.

Specific Populations
Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS. Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined. VENCLYXTO should be administered to patients with severe renal impairment only if the benefit outweighs the risk and patients should be monitored closely for signs of toxicity due to increased risk of TLS.

VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.

On November 1, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that updated data from its isocitrate dehydrogenase (IDH) programs and pyruvate kinase (PK) deficiency program will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 1 – 4, 2018 in San Diego (Press release, Agios Pharmaceuticals, NOV 1, 2018, View Source [SID1234530488]).

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In total, five abstracts led by Agios describing updated data from the company’s IDH programs and PKD program have been accepted for presentation at ASH (Free ASH Whitepaper).

The accepted abstracts are listed below and are available online on the ASH (Free ASH Whitepaper) conference website: View Source

Oral presentations by Agios:

Title: Ivosidenib (AG-120) Induced Durable Remissions and Transfusion Independence in Patients with IDH1-Mutant Untreated AML: Results from a Phase 1 Dose Escalation and Expansion Study
Date & Time: Monday December 3, 2018 at 7:30 a.m. PST
Oral Abstract Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy
Abstract: 561
Location: Manchester Grand Hyatt San Diego, Seaport Ballroom F
Presenter: Gail J. Roboz, M.D., Weill Cornell Medical College

Title: Ivosidenib or Enasidenib Combined with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML with an IDH1 or IDH2 Mutation is Safe, Effective, and Leads to MRD-Negative Complete Remissions
Date & Time: Monday December 3, 2018 at 7:15 a.m. PST
Oral Abstract Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Targeted Therapy
Abstract: 560
Location: Manchester Grand Hyatt San Diego, Seaport Ballroom F
Presenter: Eytan Stein, M.D., Memorial Sloan Kettering Cancer Center

Poster presentations by Agios:

Title: Ivosidenib (AG-120) Induced Durable Remissions and Transfusion Independence in Patients with IDH1-Mutant Relapsed or Refractory Myelodysplastic Syndrome: Results from a Phase 1 Dose Escalation and Expansion Study
Poster Session Date & Time: Saturday December 1, 2018 from 6:15-8:15 p.m. PST
Poster Session: 637. Myelodysplastic Syndromes—Clinical Studies: Poster I
Abstract: 1812
Poster Location: San Diego Convention Center, Hall GH
Author: Courtney Denton DiNardo, M.D., University of Texas MD Anderson Cancer Center

Title: Population Pharmacokinetics of Ivosidenib (AG-120) in Patients with IDH1-Mutant Advanced Hematologic Malignancies
Poster Session Date & Time: Saturday December 1, 2018 from 6:15-8:15 p.m. PST
Poster Session: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I
Abstract: 1394
Poster Location: San Diego Convention Center, Hall GH
Author: Kha Le, Ph.D., Agios Pharmaceuticals

Title: Genotype-Response Correlation in DRIVE PK, a Phase 2 Study of AG-348 in Patients with Pyruvate Kinase Deficiency
Poster Session Date & Time: Monday December 3, 2018 from 6:00-8:00 p.m. PST
Poster Session: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron: Poster III
Abstract: 3621
Poster Location: San Diego Convention Center, Hall GH
Author: Charles Kung, Ph.D., Agios Pharmaceuticals

On November 1, 2018 Celgene Corporation (NASDAQ:CELG) reported that data from more than 100 abstracts, including a study being featured as a plenary presentation and more than 40 selected for oral presentations, evaluating Celgene investigational agents and investigational uses of marketed products will be presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting between Dec. 1-4 in San Diego, CA (Press release, Celgene, NOV 1, 2018, View Source [SID1234530504]).

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"Celgene is deeply committed to furthering our understanding of blood cancers and encouraged by the promise of new innovations to improve or extend the lives of patients living with these intractable diseases," said Dr. Alise Reicin, President, Global Clinical Development for Celgene. "Importantly, this year’s ASH (Free ASH Whitepaper) data highlight the advancement of Celgene’s pipeline including first-in-class compounds with the potential to transform treatment across multiple blood cancers."

Presentations will include data from Celgene investigational agents in company-sponsored or investigator-initiated clinical studies across the company’s approved and investigational portfolio. Abstracts highlight some of the first results of key pivotal data for the company’s pipeline assets, illustrating the breadth and potential of the hematology portfolio. Of note, a first look at the results from the MEDALIST trial in patients with myelodysplastic syndrome (MDS) will be presented during the Plenary Scientific Session, which honors the top six research papers submitted for presentation at the meeting. Experts will also share results from key approved therapies and investigational CAR T cell therapies in non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, beta thalassemia and multiple myeloma.

Key presentations include:

First data of the pivotal, Phase 3, MEDALIST trial featured in the Plenary Scientific Sessions, highlighting the potential of luspatercept to address a significant unmet need in patients with MDS;
First data of the pivotal, Phase 3, BELIEVE trial highlighting the potential for luspatercept to address a significant unmet need in adult patients with beta thalassemia;
Data from the phase 1/2 TRANSCEND CLL-004 trial evaluating liso-cel (JCAR017) in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL);
Initial results from a phase 1 trial of bb21217, a next-generation anti-BCMA CAR T therapy, in patients with relapsed and/or refractory multiple myeloma (RRMM);
Data from the phase 1/2 EVOLVE trial evaluating JCARH125 in patients with RRMM; and
First data from the Phase 3, AUGMENT trial, a chemotherapy-free regimen of REVLIMIDplus rituximab (R2) in patients with relapsed and/or refractory indolent non-Hodgkin’s lymphoma.
Selected abstracts include*:

Plenary Session

Abstract #1: Plenary; Sunday, Dec. 2, 2:00 p.m., Hall AB, The MEDALIST Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Randomized Study of Luspatercept to Treat Anemia in Patients with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts (RS) Who Require Red Blood Cell (RBC) Transfusions (List)

Beta Thalassemia

Abstract #163; Oral; Saturday, Dec. 1, 2:00 p.m., Room 30D, The BELIEVE Trial: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled, Study of Luspatercept in Adult Beta-Thalassemia Patients Who Require Regular Red Blood Cell (RBC) Transfusions (Cappellini)

Myeloid Diseases

New data findings evaluate Celgene in-line and investigational therapies in myeloid diseases.

Abstract #835; Oral; Monday, Dec. 3, 2:45 p.m., Room 25B, Real-World Treatment Patterns and Comparative Effectiveness Among a Population of Elderly Patients with Acute Myeloid Leukemia (AML) (Medeiros)

Abstract #4731; Poster; Monday, Dec. 3, 6:00 p.m., Hall GH, Factors Associated with Early Therapy Initiation in Patients (Pts) with Myelodysplastic Syndromes (MDS) in the Connect MDS/AML Disease Registry (Cogle)

Chimeric Antigen Receptor T-cell therapy (CAR T)

New data highlight growing base of research in cellular immunotherapy across multiple blood cancers.

Abstract #319; Oral; Sunday, Dec. 2, 7:30 a.m., Room 25B, Estimation of the Resource Utilization and Costs of Cytokine Release Syndrome Observed in the TRANSCEND-NHL Clinical Trial: A Micro-Costing Study (Siddiqi)

Abstract #300; Oral; Sunday, Dec. 2, 8:45 a.m., Marriott Marquis San Diego Marina, Pacific Ballroom 20, Rapid MRD-negative Responses in Patients with Relapsed/Refractory CLL Treated with Liso-cel, a CD-19-directed CAR T-cell Product: Preliminary Results from TRANSCEND CLL 004, a Phase 1/2 Study Including Patients with High-Risk Disease Previously Treated with Ibrutinib (Siddiqi)

Abstract #488; Oral; Sunday, Dec. 2, 4:45 p.m., Room 6B, Initial results from a phase 1 clinical study of bb21217, a next-generation anti-BCMA CAR T therapy (Shah)

Abstract #957; Oral; Monday, Dec. 3, 5:00 p.m., Ballroom 20A, JCARH125, Anti-BCMA CAR T-cell Therapy for Relapsed/Refractory Multiple Myeloma: Initial Proof of Concept Results from a Phase 1/2 Multicenter Study (EVOLVE) (Mailankody)

Lymphoma/Chronic Lymphocytic Leukemia (CLL)

Multiple studies evaluate novel chemotherapy-free combinations in lymphoma and chronic lymphocytic leukemia.

Abstract #445; Oral; Sunday, Dec. 2, 4:30 p.m., Hall AB, AUGMENT: A Phase III Randomized Study of Lenalidomide Plus Rituximab (R2) vs. Rituximab/Placebo in Patients with Relapsed/Refractory Indolent Non-Hodgkin’s Lymphoma (Leonard)

Abstract #446; Oral; Sunday, Dec. 2, 4:45 p.m., Hall AB, A Phase II LYSA Study of Obinutuzumab Combined with Lenalidomide for Advanced Front-Line Follicular B-Cell Lymphoma in Need of Systemic Therapy (Morschhauser)

Abstract #999; Oral; Monday, Dec. 3, 6:45 p.m., Room 6F, Lenalidomide in Combination with CHOP in Patients with Angioimmunoblastic T Cell Lymphoma (AITL): Final Analysis of Clinical and Molecular Data of a Phase 2 LYSA Study (Lemonnier)

Multiple Myeloma

New multiple myeloma data reinforces IMiD therapies as a foundation of myeloma research.

Abstract #112; Oral; Saturday, Dec 1, 10:15 a.m., Marriott Marquis San Diego Marina, Grand Ballroom 7, Clinical Significance and Transcriptional Profiling of Persistent Minimal Residual Disease (MRD) in Multiple Myeloma (MM) Patients With Standard-Risk (SR) and High-Risk (HR) Cytogenetics (Goicoechea)

Abstract #243; Oral; Saturday, Dec. 1, 4:30 p.m., Marriott Marquis San Diego Marina, Grand Ballroom 7, Deep immunoprofiling of the bone marrow microenvironment changes underlying the multistep progression of multiple myeloma (Young)

Abstract #121; Oral; Sunday, Dec 2, 8:30 a.m., Marriott Marquis San Diego Marina, Grand Ballroom 7, Efficacy and Feasibility of Dose/Schedule-Adjusted Rd-R vs. Continuous Rd in Elderly and Intermediate-Fit Newly Diagnosed Multiple Myeloma (NDMM) Patients: RV-MM-PI-0752 Phase III Randomized Study (Larocca)

Abstract #474; Oral; Sunday, Dec 2, 5:45 p.m., Marriott Marquis San Diego Marina, Grand Ballroom 7, Immunofixation (IF) in Urine is Really Necessary to Define Complete Remission in Multiple Myeloma (MM): A Subanalysis from the PETHEMA/GEM2012MENOS65 Phase III Clinical Trial (Ubieto)

Abstract #716; Oral; Monday, Dec. 3, 10:45 a.m., Room 25B, The Impact of Lenalidomide, Bortezomib, and Dexamethasone Treatment on Health-Related Quality of Life in Transplant-Eligible Patients with Newly-Diagnosed Multiple Myeloma: Results from the IFM/DFCI 2009 Trial (Roussel)

Abstract #1960; Poster; Saturday, Dec. 1, 6:00 p.m., Hall GH, Health-Related Quality of Life among Patients with Relapsed or Refractory Multiple Myeloma who Received Pomalidomide, Bortezomib, and Low-Dose Dexamethasone Versus Bortezomib and Low-Dose Dexamethasone – Results from the Phase 3 OPTIMISMM Study (Weisel)

Abstract #2012; Poster; Saturday, Dec. 1, 6:15 p.m., Hall GH, Immune Profiling of Relapsed or Refractory Multiple Myeloma Patients Treated With Pomalidomide and Low-Dose Dexamethasone in Combination With Daratumumab (Pierceall)

Abstract #2243; Poster; Saturday, Dec. 1, 6:15 p.m., Hall GH, Real-World Outcomes for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma (NDMM) Treated With Lenalidomide, Bortezomib, and Dexamethasone (RVd) or Vd: An Enhanced Electronic Health Records (EHR) Database Analysis (Chari)

Abstract #3271; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH, Pomalidomide + Low-Dose Dexamethasone + Daratumumab in Relapsed and/or Refractory Multiple Myeloma after Lenalidomide-Based Treatment Failure (Siegel)

Abstract #3278; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH, Pomalidomide + Bortezomib + Low-Dose Dexamethasone vs Bortezomib + Low-Dose Dexamethasone as Second-Line Treatment in Patients with Lenalidomide-Pretreated Multiple Myeloma: A Subgroup Analysis of the Phase 3 OPTIMISMM Trial (Dimopoulos)

Abstract #3445; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH, The Impact of RVD or VCD Induction on Response 3 Months after First Line Autologous Transplant in Multiple Myeloma. A single-center Retrospective Analysis (Moksnes)

Abstract #3232; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH Treatment Choices and Outcomes for Patients with Multiple Myeloma (MM) After Relapse on Lenalidomide (LEN) Maintenance Therapy (mt): Results from the Connect MM Registry (Jagannath)

Abstract # 3245; Poster; Sunday, Dec. 2, 6:00 p.m., Hall GH, Integrated Analysis of Randomized Controlled Trials Evaluating Bortezomib + Lenalidomide + Dexamethasone or Bortezomib + Thalidomide + Dexamethasone Induction in Transplant-Eligible Newly Diagnosed Multiple Myeloma (Rosinol)

Abstract #4744; Poster; Monday, Dec. 3, 6:00 p.m., Hall GH, Relative Efficacy of Treatment Options in Newly Diagnosed Multiple Myeloma (NDMM): Results from a Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) (Ramasamy)

Abstract #4737; Poster; Monday, Dec. 3, 6:00 p.m., Hall GH, Survival Analysis from the CALGB Study of Lenalidomide Maintenance Therapy in Newly Diagnosed Multiple Myeloma Post-Autologous Stem Cell Transplantation Adjusted for Crossover (McCarthy)

The safety and efficacy of investigational agents and/or investigational uses of approved marketed products have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

A complete listing of abstracts can be found on the ASH (Free ASH Whitepaper) Web site at View Source

*All times Pacific Standard Time

ABOUT REVLIMID

REVLIMID (lenalidomide) in combination with dexamethasone (dex) is indicated for the treatment of patients with multiple myeloma (MM)

REVLIMID is indicated as maintenance therapy in patients with MM following autologous hematopoietic stem cell transplantation (auto-HSCT)

REVLIMID is indicated for the treatment of patients with transfusion-dependent anemia due to low-or intermediate-1–risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities

REVLIMID is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid embryo-fetal exposure to lenalidomide, REVLIMID is only available through a restricted distribution program, the REVLIMID REMS program.

Information about the REVLIMID REMS program is available at www.celgeneriskmanagement.com or by calling the manufacturer’s toll-free number 1-888-423-5436.

Hematologic Toxicity (Neutropenia and Thrombocytopenia)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. Thirty-four percent of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

Venous and Arterial Thromboembolism

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient’s underlying risks.

CONTRAINDICATIONS

Pregnancy: REVLIMID can cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus

Severe Hypersensitivity Reactions: REVLIMID is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity: See Boxed WARNINGS

Females of Reproductive Potential: See Boxed WARNINGS
Males: Lenalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking REVLIMID and for up to 4 weeks after discontinuing REVLIMID, even if they have undergone a successful vasectomy. Male patients taking REVLIMID must not donate sperm
Blood Donation: Patients must not donate blood during treatment with REVLIMID and for 4 weeks following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to REVLIMID
REVLIMID REMS Program: See Boxed WARNINGS: Prescribers and pharmacies must be certified with the REVLIMID REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements

Hematologic Toxicity: REVLIMID can cause significant neutropenia and thrombocytopenia.Monitor patients with neutropenia for signs of infection. Advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may increase risk of bleeding. MM: Patients taking REVLIMID/dex or REVLIMID as maintenance therapy should have their complete blood counts (CBC) assessed every 7 days for the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days thereafter. MDS: Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or dose reduction. Please see the Black Box WARNINGS for further information. MCL: Patients taking REVLIMID for MCL should have their CBCs monitored weekly for the first cycle (28 days), every 2 weeks during cycles 2-4, and then monthly thereafter. Patients may require dose interruption and/or dose reduction

Venous and Arterial Thromboembolism: See Boxed WARNINGS: Venous thromboembolic events (DVT and PE) and arterial thromboses (MI and CVA) are increased in patients treated with REVLIMID. Patients with known risk factors, including prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended and the regimen should be based on patient’s underlying risks. ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision

Increased Mortality in Patients with CLL: In a clinical trial in the first-line treatment of patients with CLL, single agent REVLIMID therapy increased the risk of death as compared to single agent chlorambucil. Serious adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction, and cardiac failure, occurred more frequently in the REVLIMID arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials

Second Primary Malignancies (SPM): In clinical trials in patients with MM receiving REVLIMID, an increase of hematologic plus solid tumor SPM, notably AML and MDS, have been observed. Monitor patients for the development of SPM. Take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment

Increased Mortality with Pembrolizumab: In clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID/dex. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered

Severe Cutaneous Reactions Including Hypersensitivity Reactions: Angioedema and severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash, or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS, TEN, or DRESS is suspected and should not be resumed following discontinuation for these reactions

Tumor Lysis Syndrome (TLS): Fatal instances of TLS have been reported during treatment with lenalidomide. The patients at risk of TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction (TFR): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma. Monitoring and evaluation for TFR is recommended in patients with MCL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with REVLIMID until TFR resolves to ≤Grade 1. REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physician’s discretion

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment (>4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection

Thyroid Disorders: Both hypothyroidism and hyperthyroidism have been reported. Measure thyroid function before start of REVLIMID treatment and during therapy

Early Mortality in Patients with MCL: In another MCL study, there was an increase in early deaths (within 20 weeks), 12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk factors for early deaths include high tumor burden, MIPI score at diagnosis, and high WBC at baseline (≥10 x 109/L)

ADVERSE REACTIONS

Multiple Myeloma

In newly diagnosed: The most frequently reported Grade 3 or 4 reactions included neutropenia, anemia, thrombocytopenia, pneumonia, asthenia, fatigue, back pain, hypokalemia, rash, cataract, lymphopenia, dyspnea, DVT, hyperglycemia, and leukopenia. The highest frequency of infections occurred in Arm Rd Continuous (75%) compared to Arm MPT (56%). There were more Grade 3 and 4 and serious adverse reactions of infection in Arm Rd Continuous than either Arm MPT or Rd18
The most common adverse reactions reported in ≥20% (Arm Rd Continuous): diarrhea (46%), anemia (44%), neutropenia (35%), fatigue (33%), back pain (32%), asthenia (28%), insomnia (28%), rash (26%), decreased appetite (23%), cough (23%), dyspnea (22%), pyrexia (21%), abdominal pain (21%), muscle spasms (20%), and thrombocytopenia (20%)
Maintenance Therapy Post Auto-HSCT: The most frequently reported Grade 3 or 4 reactions in ≥20% (REVLIMID arm) included neutropenia, thrombocytopenia, and leukopenia. The serious adverse reactions of lung infection and neutropenia (more than 4.5%) occurred in the REVLIMID arm
The most frequently reported adverse reactions in ≥20% (REVLIMID arm) across both maintenance studies (Study 1, Study 2) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%)
After at least one prior therapy: The most common adverse reactions reported in ≥20% (REVLIMID/dex vs dex/placebo): fatigue (44% vs 42%), neutropenia (42% vs 6%), constipation (41% vs 21%), diarrhea (39% vs 27%), muscle cramp (33% vs 21%), anemia (31% vs 24%), pyrexia (28% vs 23%), peripheral edema (26% vs 21%), nausea (26% vs 21%), back pain (26% vs 19%), upper respiratory tract infection (25% vs 16%), dyspnea (24% vs 17%), dizziness (23% vs 17%), thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor (21% vs 7%), and weight decreased (20% vs 15%)
Myelodysplastic Syndromes

Grade 3 and 4 adverse events reported in ≥ 5% of patients with del 5q MDS were neutropenia (53%), thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%), leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain (5%)
Adverse events reported in ≥15% of del 5q MDS patients (REVLIMID): thrombocytopenia (61.5%), neutropenia (58.8%), diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral edema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea (17%), pharyngitis (16%), epistaxis (15%), asthenia (15%), upper respiratory tract infection (15%)
Mantle Cell Lymphoma

Grade 3 and 4 adverse events reported in ≥5% of patients treated with REVLIMID in the MCL trial (N=134) included neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (9%), leukopenia (7%), fatigue (7%), diarrhea (6%), dyspnea (6%), and febrile neutropenia (6%)
Adverse events reported in ≥15% of patients treated with REVLIMID in the MCL trial included neutropenia (49%), thrombocytopenia (36%), fatigue (34%), anemia (31%), diarrhea (31%), nausea (30%), cough (28%), pyrexia (23%), rash (22%), dyspnea (18%), pruritus (17%), peripheral edema (16%), constipation (16%), and leukopenia (15%)
DRUG INTERACTIONS

Periodic monitoring of digoxin plasma levels is recommended due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thrombosis. It is not known whether there is an interaction between dex and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin

USE IN SPECIFIC POPULATIONS

PREGNANCY: See Boxed WARNINGS: If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a REVLIMID pregnancy exposure registry that monitors pregnancy outcomes in females exposed to REVLIMID during pregnancy as well as female partners of male patients who are exposed to REVLIMID. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to REVLIMID to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436
LACTATION: There is no information regarding the presence of lenalidomide in human milk, the effects of REVLIMID on the breastfed infant, or the effects of REVLIMID on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from REVLIMID, advise female patients not to breastfeed during treatment with REVLIMID
PEDIATRIC USE: Safety and effectiveness have not been established in pediatric patients
RENAL IMPAIRMENT: Adjust the starting dose of REVLIMID based on the creatinine clearance value and in patients on dialysis
Please see full Prescribing Information , including Boxed WARNINGS.

About POMALYST/IMNOVID

POMALYST (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment.
Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.
POMALYST is only available through a restricted distribution program called POMALYST REMS .

Venous and Arterial Thromboembolism

Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.

CONTRAINDICATIONS

Pregnancy : POMALYST can cause fetal harm and is contraindicated in females who are pregnant. If POMALYST is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.
WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS
Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm.
Blood Donation: Patients must not donate blood during treatment with POMALYST and for 4 weeks following discontinuation of POMALYST therapy because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST.
POMALYST REMS Program: See Boxed WARNINGS
Prescribers and pharmacies must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive POMALYST. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements.
Further information about the POMALYST REMS program is available at www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436.
Venous and Arterial Thromboembolism: See Boxed WARNINGS. Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.
Increased Mortality with Pembrolizumab : In clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.
Hematologic Toxicity : Neutropenia (46%) was the most frequently reported Grade 3/4 adverse reaction in patients taking POMALYST in clinical trials, followed by anemia and thrombocytopenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.
Hepatotoxicity : Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.
Severe Cutaneous Reactions Including Hypersensitivity Reactions : Angioedema and severe cutaneous reactions including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe cutaneous reactions such as SJS, TEN or DRESS, and do not resume therapy.
Dizziness and Confusional State : In patients taking POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.
Neuropathy : In patients taking POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.
Second Primary Malignancies : Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
Tumor Lysis Syndrome (TLS) : TLS may occur in patients treated with POMALYST. Patients at risk are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.
ADVERSE REACTIONS

The most common adverse reactions for POMALYST (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia.

In the phase III trial, nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). Adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥2% higher than control) included neutropenia (51.3%), fatigue and asthenia (46.7%), upper respiratory tract infection (31%), thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%), back pain (19.7%), cough (20%), pneumonia (19.3%), bone pain (18%), edema peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms (15.3%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15% in the POMALYST + low-dose dex arm and ≥1% higher than control) included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

DRUG INTERACTIONS

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative treatments. If a strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50%.

USE IN SPECIFIC POPULATIONS

Pregnancy: See Boxed WARNINGS. If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a POMALYST pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.
Lactation : There is no information regarding the presence of pomalidomide in human milk, the effects of POMALYST on the breastfed child, or the effects of POMALYST on milk production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in a breastfed child from POMALYST, advise women not to breastfeed during treatment with POMALYST.
Pediatric Use : Safety and effectiveness have not been established in pediatric patients.
Geriatric Use : No dosage adjustment is required for POMALYST based on age. Patients >65 years of age were more likely than patients ≤65 years of age to experience pneumonia.
Renal Impairment : Reduce POMALYST dose by 25% in patients with severe renal impairment requiring dialysis. Take dose of POMALYST following hemodialysis on hemodialysis days.
Hepatic Impairment : Reduce POMALYST dose by 25% in patients with mild to moderate hepatic impairment and 50% in patients with severe hepatic impairment.
Smoking Tobacco : Advise patients that smoking may reduce the efficacy of POMALYST. Cigarette smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.
Please see full Prescribing Information , including Boxed WARNINGS.

About IDHIFA

IDHIFA (enasidenib) is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation as detected by an FDA-approved test.

Important Safety Information

WARNING: DIFFERENTIATION SYNDROME

Patients treated with IDHIFA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, lymphadenopathy, bone pain, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 14% of patients treated with IDHIFA experienced differentiation syndrome, which may be life-threatening or fatal if not treated. Differentiation syndrome has been observed with and without concomitant hyperleukocytosis, as early as 10 days and at up to 5 months after IDHIFA initiation. Symptoms in patients treated with IDHIFA included acute respiratory distress represented by dyspnea and/or hypoxia and need for supplemental oxygen; pulmonary infiltrates and pleural effusion; renal impairment; fever; lymphadenopathy; bone pain; peripheral edema with rapid weight gain; and pericardial effusion. Hepatic, renal, and multi-organ dysfunction have also been observed. If differentiation syndrome is suspected, initiate systemic corticosteroids and hemodynamic monitoring until improvement. Taper corticosteroids only after resolution of symptoms. Differentiation syndrome symptoms may recur with premature discontinuation of corticosteroids. If severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after initiation of corticosteroids, interrupt IDHIFA until signs and symptoms are no longer severe. Hospitalization for close observation and monitoring of patients with pulmonary and/or renal manifestation is recommended.

Embryo-Fetal Toxicity:Based on animal embryo-fetal toxicity studies, IDHIFA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with IDHIFA and for at least 1 month after the last dose. Pregnant women, patients becoming pregnant while receiving IDHIFA, or male patients with pregnant female partners should be apprised of the potential risk to the fetus.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) included total bilirubin increased (81%), calcium decreased (74%), nausea (50%), diarrhea (43%), potassium decreased (41%), vomiting (34%), decreased appetite (34%), and phosphorus decreased (27%)
The most frequently reported ≥Grade 3 adverse reactions (≥5%) included total bilirubin increased (15%), potassium decreased (15%), phosphorus decreased (8%), calcium decreased (8%), diarrhea (8%), differentiation syndrome (7%), non-infectious leukocytosis (6%), tumor lysis syndrome (6%), and nausea (5%)
Serious adverse reactions were reported in 77.1% of patients. The most frequent serious adverse reactions (≥2%) were leukocytosis (10%), diarrhea (6%), nausea (5%), vomiting (3%), decreased appetite (3%), tumor lysis syndrome (5%), and differentiation syndrome (8%). Differentiation syndrome events characterized as serious included pyrexia, renal failure acute, hypoxia, respiratory failure, and multi-organ failure
LACTATION

Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants, advise women not to breastfeed during treatment with IDHIFA and for at least 1 month after the last dose.