On November 22, 2016 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical company developing innovative targeted therapies for cancers lacking effective treatment options, reported that it has issued a letter to shareholders highlighting the Company’s accomplishments in 2016 and anticipated milestones for 2017 (Press release, Actinium Pharmaceuticals, NOV 22, 2016, View Source [SID1234516763]).

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Key Accomplishments To-Date in 2016

Iomab-B Pivotal Phase 3 Trial Initiated, Significant and Growing Support from Major Transplant Hospitals, Orphan Drug Protection Awarded and Process for EU Access Started

The Phase 3 pivotal trial dubbed the SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory AML) trial for Iomab-B was initiated in 1H:2016, as forecasted, representing a major step forward for this program given the manufacturing issues that were a key focus in 2015.
Significant enthusiasm for Iomab-B and the SIERRA trial was seen at our Investigator Meeting in July with continued participation interest post-meeting from most of the leading bone marrow transplant (BMT) centers.
Orphan Drug Designation awarded for Iomab-B in the US and the EU with potential regulatory, financial and marketing incentives.
Initiated pursuit of Scientific Advice for Iomab-B from the European Medicines Agency (EMA) to explore regulatory pathway in the EU and awarded preferential Small and Medium-Sized Enterprise (SME) status providing enhanced support from regulators.
Expected prominent position in major peer reviewed scientific publication and outreach program at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting will continue to drive interest for Iomab-B and the SIERRA trial.
Promising Phase 1 Trial Results for Actimab-A Sets Stage for Ongoing Phase 2 Clinical Trial to Yield Potentially Best in CD33 Class Results

Results from an analysis of the two Actimab-A Phase I trials in our HuM195-Alpha program showed that Actimab-A was well tolerated amongst patients who have few treatment options due to the toxicity of chemotherapy and also had promising efficacy.
A key discovery made while analyzing these trials was that patients with high levels of immature white blood cells or Peripheral Blasts (PBs) had lower treatment response rates than those with lower PB’s. This finding gave rise to the PB Burden Hypothesis which postulates that PB levels are predictive of, and inversely correlated with patient responses to Actimab-A.
The ongoing Phase 2 trial stipulates low PB burden below a key threshold as an inclusion criteria with use of hydroxyurea mandated to lower PB burden where necessary in order to maximize the addressable patient population.
Importantly, the Phase 2 PB burden threshold corresponds to a response rate of fifty percent at equivalent dose levels in the Phase I trials. If these results are replicated in the ongoing Phase 2 they will imply that Actimab-A with its benign safety profile and relatively simple regimen and route of administration is a best in class treatment compared to other CD33 programs.
Regulatory and intellectual property related activity, strategic hiring sets stage for international expansion and growth

Activity related to strengthening the intellectual property remains robust with key patents being filed and notices of allowance being received this year for Iomab-B, Actimab-A and the platform.
Orphan drug designation for Iomab-B in the U.S. and EU was achieved this year as mentioned earlier. Pursuit of orphan designation in the EU for Actimab-A is expected imminently.
An independent analysis indicates the EU market for Iomab-B is larger than the U.S. market with a favorable reimbursement outlook and the company has begun exploring regulatory approval strategies.
Key managerial hires were made in the supply chain, quality control and clinical development areas to support the expanded clinical development and pipeline expansion activity expected going forward.
Positive Outlook for 2017 and Beyond

Efficiently execute on the pivotal Phase 3 SIERRA trial to reach the first independent Data Monitoring Committee (DMC) report at 25% of enrollment by 1H:2017, 50% and 75% in 2H:2017 and maintain the pace of enrollment to enable topline results the following year.
Report interim data from Phase 2 trial for Actimab-A by mid-2017 and explore the regulatory pathway for a pivotal trial based on this data.
Complete enrollment of the Phase 2 trial by end of 2017 and report top line data results.
Actively explore strategic partnership, licensing and collaborations as appropriate.
Continue to expand our clinical development, regulatory and supply chain teams to support our continued growth and begin to explore early commercial efforts.
Initiate additional clinical programs with the first trial expected to begin in 2017 and the second trial expected to begin in 2018.
The full letter to shareholders can be viewed and downloaded through the following link:
View Source

Sandesh Seth, Executive Chairman of Actinium said, "2016 has been a key transitional year for the Company as Iomab-B began the pivotal Phase 3 SIERRA trial and Actimab-A began a Phase 2 trial underpinned by promising Phase 1 results. In addition, we focused on building a foundation for the future with key hires, expansion of our intellectual property portfolio, execution of key regulatory pathways and by bolstering our balance sheet. We look ahead to 2017 with great excitement as we expect to have data for both of our clinical trials which we believe will validate their potential and serve to unlock value."

On November 22, 2016 BioLineRx Ltd. (NASDAQ: BLRX; TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported its financial results for the third quarter ended September 30, 2016 (Press release, BioLineRx, NOV 22, 2016, View Source;p=RssLanding&cat=news&id=2225224 [SID1234516761]).

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Highlights and achievements during third quarter of 2016 and to date:

Signing of significant immuno-oncology collaboration with Genentech, a member of the Roche Group, for several Phase 1b studies for BL-8040 in combination with Genentech’s Atezolizumab, in multiple solid tumor indications and AML
Steady progress in existing immuno-oncology collaboration with MSD (known as Merck in the US and Canada), with initiation of a Phase 2a study in pancreatic cancer for BL-8040 in combination with Merck’s KEYTRUDA
Signing of immuno-oncology collaboration with MD Anderson Cancer Center for additional Phase 2a combination study in pancreatic cancer, as part of strategic clinical research immunotherapy collaboration between MSD and MD Anderson Cancer Center
In-licensing of three new projects under strategic collaboration with Novartis, including two novel liver fibrosis/failure projects, and a novel anti-inflammatory treatment for dry eye syndrome
Presentation of growing body of clinical evidence surrounding BL-8040 at leading medical and scientific conferences, including an oral presentation at the upcoming ASH (Free ASH Whitepaper) 2016
Expanded geographic reach with new joint venture in China for development of novel drug candidates
Expected upcoming significant milestones for 2017:

Partial results from Phase 2 study for BL-8040 in stem-cell mobilization for allogeneic transplantation expected by Q1 2017
Partial results in immuno-oncology Phase 2a study for pancreatic cancer for BL-8040 in combination with Merck’s KEYTRUDA expected by H2 2017
Phase 1b immuno-oncology studies for BL-8040 in combination with Genentech’s Atezolizumab, in multiple solid tumor indications and AML, expected to commence during 2017
Philip A. Serlin, Chief Executive Officer of BioLineRx, remarked, "The third quarter of 2016 demonstrated our continued ability to leverage our leading BL-8040 oncology platform, as well as our access to cutting edge technologies. In particular, our immunotherapy collaboration efforts continued to bear fruit, with the signing of a significant agreement with Genentech to carry out multiple clinical trials in a variety of oncology indications, as well as a collaboration agreement with MD Anderson Cancer Center. Meanwhile, our immunotherapy collaboration with Merck, announced earlier in the year, steadily progressed, with our Phase 2a clinical trial in pancreatic cancer now in active enrollment. Further, following extensive due diligence, we are now pleased to roll out three programs under our Novartis collaboration, including two in the exciting field of liver fibrosis. We expect a number of additional novel assets to enter our pipeline in 2017, including several within the framework of the Novartis collaboration. Finally, we continue to highlight growing clinical evidence supporting our lead oncology program, BL-8040, which is regularly featured at leading medical and scientific conferences."

"We are excited about our prospects ahead and are focused on achieving our expected milestones for 2017 and beyond. With $39 million of cash on hand, we remain well positioned to carry out our operational plans for the next few years," Mr. Serlin concluded.

Financial Results for the Third Quarter Ended September 30, 2016

Research and development expenses for the three months ended September 30, 2016 were $3.0 million, an increase of $0.4 million, or 14.7%, compared to $2.6 million for the comparable period in 2015. The increase resulted primarily from spending on new projects and from increased spending on BL-8040 in the 2016 period. Research and development expenses for the nine months ended September 30, 2016 were $8.2 million, a decrease of $0.4 million, or 5.1%, compared to $8.7 million for the comparable period in 2015. The decrease resulted primarily from lower expenditures for BL-7010 during the 2016 period and conclusion of one of the clinical trials for BL-8040 in 2015, partially offset by increased spending on a new project.

Sales and marketing expenses for the three months ended September 30, 2016 were $0.41 million, an increase of $0.14 million, or 54.3%, compared to $0.27 million for the comparable period in 2015. The increase resulted primarily from consultancy and legal expenses related to increased business development activity in the 2016 period. Sales and marketing expenses for the nine months ended September 30, 2016 were $0.9 million, an increase of $0.1 million, or 12.6%, compared to $0.8 million for the nine months ended September 30, 2015. The reason for the increase is similar to the one discussed above in the three-month comparison.

General and administrative expenses for the three months ended September 30, 2016 were $1.1 million, an increase of $0.4 million, or 47.6%, compared to $0.8 million for the comparable period in 2015. The increase resulted primarily from an increase in non-cash share-based compensation. General and administrative expenses for the nine months ended September 30, 2016 were $3.0 million, an increase of $0.4 million, or 14.4%, compared to $2.6 million for the nine months ended September 30, 2015. The reason for the increase is similar to the one discussed above in the three-month comparison.

The Company’s operating loss for the three months ended September 30, 2016 amounted to $4.5 million, compared with an operating loss of $3.6 million for the corresponding 2015 period. The Company’s operating loss for the nine months ended September 30, 2016 amounted to $12.1 million, similar to the comparable period in 2015.

Non-operating income (expenses) for the three and nine months ended September 30, 2016 and 2015 primarily relate to fair-value adjustments of warrant liabilities on the Company’s balance sheet. These fair-value adjustments, which were material in the 2015 periods, but not material in the 2016 periods, are highly influenced by the Company’s share price at each period end (revaluation date).

Net financial income (expenses) for the three and nine months ended September 30, 2016 and 2015 primarily relate to investment income earned on bank deposits, as well as banking fees.

The Company’s net loss for the three months ended September 30, 2016 amounted to $4.3 million, compared with a net loss of $1.6 million for the corresponding 2015 period. The Company’s net loss for the nine months ended September 30, 2016 amounted to $11.6 million, compared with a net loss of $10.7 million for the corresponding 2015 period.

The Company held $38.9 million in cash, cash equivalents and short-term bank deposits as of September 30, 2016.

Net cash used in operating activities was $10.4 million for the nine months ended September 30, 2016, compared with net cash used in operating activities of $11.0 million for the comparable period in 2015. The $0.6 million decrease in net cash used was primarily the result of an increase in other receivables.

Net cash provided by investing activities for the nine months ended September 30, 2016 was $7.3 million, compared to net cash used in investing activities of $18.7 million for the comparable period in 2015. The changes in cash flows from investing activities relate primarily to investments in, and maturities of, short-term bank deposits and other investments during the respective periods.

Net cash provided by financing activities for the nine months ended September 30, 2016 was $1.5 million, compared to net cash provided by financing activities of $29.3 million for the comparable period in 2015. The decrease in cash flows from financing activities reflects the underwritten public offering which was completed in March 2015.

On November 22, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that new data regarding the investigational use of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, in patients with a range of blood cancers including classical Hodgkin lymphoma and primary mediastinal large B-cell lymphoma, will be presented at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, Dec. 3-6 (Press release, Merck & Co, NOV 22, 2016, View Source [SID1234516757]).

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"There is an urgent need for new treatment approaches in blood cancers, especially for those patients who have relapsed or not responded to current therapies," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "We hope to learn that PD-1-directed immunotherapy may be used to help patients suffering from these difficult to treat malignancies."

The KEYTRUDA clinical development program includes more than 30 tumor types in more than 360 clinical trials, including over 200 trials that combine KEYTRUDA with other cancer treatments. For hematologic malignancies specifically, Merck is conducting broad immuno-oncology research assessing the role of monotherapy and combination regimens with KEYTRUDA. The program includes nearly 40 ongoing studies – several of which are registration-enabling trials – across more than 20 hematologic disease subtypes, including leukemia, lymphomas, and myeloma.

Below is a select list of KEYTRUDA data to be featured in oral presentations (all at the San Diego Convention Center):

(Abstract #1107) Pembrolizumab in Relapsed/Refractory Classical Hodgkin Lymphoma: Primary End Point Analysis of the Phase 2 Keynote-087 Study. C. Moskowitz. Monday, Dec. 5, 5 p.m. PST (session: 4:30-6 p.m. PST). Location: Room 6B.
(Abstract #1108) Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Long-Term Efficacy from the Phase 1b Keynote-013 Study. P. Armand. Monday, Dec. 5, 5:15 p.m. PST (session: 4:30-6 p.m. PST). Location: Room 6B.
(Abstract #619) Phase 1b Study of Pembrolizumab in Patients with Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Results from the Ongoing Keynote-013 Trial. P. Zinzani. Monday, Dec. 5, 7 a.m. PST (session: 7-8:30 a.m. PST). Location: Room 6B.
Additional meeting information and full abstracts are available on the ASH (Free ASH Whitepaper) meeting website.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA (pembrolizumab) is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA (pembrolizumab) can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA (pembrolizumab) and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The most common adverse reactions with KEYTRUDA (pembrolizumab) vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 360 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On November 22, 2016 Celgene Corporation (NASDAQ:CELG) reported that data from nearly 350 abstracts, including more than 150 oral presentations, evaluating Celgene investigational agents and investigational uses of marketed products will be presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting between Dec. 3-6 in San Diego, California (Press release, Celgene, NOV 22, 2016, View Source [SID1234516753]).

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Relevant presentations will include investigational data from Celgene agents in company-sponsored and investigator-initiated studies.

"Once again we look forward to an impactful collection of clinical and scientific data at ASH (Free ASH Whitepaper) providing new insights into a broad range of hematologic malignancies," said Michael Pehl, President, Hematology and Oncology for Celgene. "The studies being shared this year underscore our continuing commitment to delivering innovative therapies to patients with serious blood cancers around the world."

Selected abstracts include*:

Multiple Myeloma

Clinical Data on Lenalidomide in Myeloma:

Abstract #241; Oral; Saturday, Dec. 3, 4 p.m., Seaport Ballroom ABCD (Manchester Grand Hyatt) Final Analysis of Overall Survival from the FIRST Trial (Facon)

Abstract #537; Oral; Sunday, Dec. 4, 5 p.m., Room 29 Health related Quality of Life in Patients with Newly Diagnosed Multiple Myeloma Receiving Any or Lenalidomide Maintenance after Autologous Stem Cell Transplant in the Connect MM Disease Registry (Abonour)

Abstract #673; Oral; Monday, Dec. 5, 7 a.m., Seaport Ballroom DE (Manchester Grand Hyatt) Intensification Therapy with Bortezomib-Melphalan-Prednisone Versus Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma: An Intergroup, Multicenter, Phase III Study of the European Myeloma Network (EMN02/HO95 MM Trial) (Cavo)

Abstract #1143; Oral; Monday, Dec. 5, 5 p.m., Seaport Ballroom ABCD (Manchester Grand Hyatt) Lenalidomide is a Highly-Effective Maintenance Therapy in Myeloma Patients of All Ages; results of the Phase III Myeloma XI Study (Jackson)

Abstract #4497; Poster; Monday, Dec. 5, 6 p.m., Hall GH Pomalidomide + Low-Dose Dexamethasone Following Second-Line Lenalidomide-Based Therapy in Relapsed or Refractory Multiple Myeloma: A Phase 2 Study Investigating Efficacy and Safety (Siegel)

Clinical Data on Pomalidomide in Relapsed/Refractory Myeloma:

Abstract #2119; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH Pembrolizumab in Combination with Pomalidomide and Dexamethasone (PEMBRO/POM/DEX) for Pomalidomide Exposed Relapsed or Refractory Multiple Myeloma (Wilson)

Abstract #3316; Poster; Sunday, Dec. 4, 6 p.m., Hall GH A Phase I/II Trial of Ixazomib (Ix), Pomalidomide (POM) and Dexamethasone (DEX), in Relapsed/Refractory (R/R) Multiple Myeloma (MM) Patients; Responses in Double Refractory and High Risk Disease (Krishnan)

Abstract #3307; Poster; Sunday, Dec. 4, 6 p.m., Hall GH Selective HDAC6 Inhibitor ACY-241, an Oral Tablet, Combined with Pomalidomide and Dexamethasone: Safety and Efficacy of Escalation and Expansion Cohorts in Patients with Relapsed or Relapsed-and-Refractory Multiple Myeloma (ACE-MM-200 Study) (Niesvizky)

Abstract #1145; Oral; Monday, Dec. 5, 5:30 p.m., Seaport Ballroom BC (Manchester Grand Hyatt) A Multicenter, Open Label Phase I/II Study of Carfilzomib, Pomalidomide and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma (MM) Patients (Bringhen)

Abstract #1151; Oral; Monday, Dec. 5, 5:30 p.m., Hall AB Efficacy of Daratumumab, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma Patients with 1 to 3 Prior Lines of Therapy: Updated Analysis of Pollux (Usmani)

Early Development Initiatives in Myeloma:

Abstract #1591; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH CC-220 is a Potent Cereblon Modulating Agent that Displays Anti-proliferative, Pro-Apoptotic and Immunomodulatory Activity on Sensitive and Resistant Multiple Myeloma Cell Lines (Bjorklund)

Abstract #1592; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH CC-122 is a Cereblon Modulating Agent that is Active in Lenalidomide-Resistant and Lenalidomide/Dexamethasone-Double-Resistant Multiple Myeloma Pre-clinical Models (Bjorklund)

Abstract #196; Oral; Saturday, Dec. 3, 2:45 p.m., Grand Hall D (Manchester Grand Hyatt) The Multiple Myeloma Genome Project: Development of a Molecular Segmentation Strategy for the Clinical Classification of Multiple Myeloma (Walker)

Lymphomas/CLL

Lenalidomide Maintenance Data:

Abstract #229; Oral; Saturday, Dec. 3, 4 p.m., Room 5AB Lenalidomide Maintenance after Front Line Therapy Substantially Prolongs Progression Free Survival in High Risk CLL: Interim Results of a Phase 3 Study (CLL M1 study of the German CLL Study Group) (Fink)

Abstract #230; Oral; Saturday, Dec. 3, 4:15 p.m., Room 5AB Results of the Phase III Study of Lenalidomide Versus Placebo as Maintenance Therapy Following Second-Line Treatment for Patients with B-Cell Chronic Lymphocytic Leukemia (the CONTINUUM Trial) (Foa)

Abstract #471; Oral; Sunday, Dec. 4, 5 p.m., Room 6B Final Analysis of an International Double-Blind randomized Phase III Study of Lenalidomide Maintenance in Elderly Patients with DLBCL Treated with R-CHOP in First Line, the REMARC Study from LYSA (Thieblemont)

Lenalidomide Combination Data:

Abstract #1798; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH MAGNIFY: Phase IIIb Randomized Study of Lenalidomide Plus Rituximab (R2) Followed by Lenalidomide vs. Rituximab Maintenance in Subjects with Relapsed/Refractory Follicular, Marginal Zone, or Mantle Cell Lymphoma (Andorsky)

Abstract #473; Oral; Sunday, Dec. 4, 5:30 p.m., Room 6B A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Combination with Lenalidomide and Rituximab in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (Goy)

Abstract #1099; Oral; Monday, Dec. 5, 4:30 p.m., Ballroom 20A Rituximab Plus Lenalidomide Versus Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. First Analysis of Survival Endpoints of the Randomized Phase II Trial SAKK 35/10 (Kimby)

Abstract #4199; Poster; Monday, Dec. 5, 6 p.m., Hall GH A Phase 1B Study of CC 122 in Combination with Obinutuzumab (GA101) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Indolent Non-Hodgkin Lymphoma (Michot)

Lenalidomide Data in Mantle Cell Lymphoma:

Abstract #1786; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH Effectiveness of Lenalidomide in Mantle Cell Lymphoma Patients who Relapsed/Progressed After or were Refractory/Intolerant to Ibrutinib: The MCL-004 Study (Wang)

Abstract #4188; Poster; Monday, Dec. 5, 6 p.m., Hall GH CC-122 Exhibits Greater Preclinical Activity in Mantle Cell Lymphoma Than Lenalidomide Through A Combination of Direct Cell-autonomous and Increased Antibody Dependent Cell-mediated Cytotoxicity (Hagner)

Surrogate Outcomes Data:

Abstract #3027; Poster; Sunday, Dec. 4, 6 p.m., Hall GH Utility of Progression-Free Survival at 24 months (PFS24) to Predict Subsequent Outcome for Patients with Diffuse Large B-cell Lymphoma (DLBCL) Enrolled on Randomized Clinical Trials: Findings from a Surrogate Endpoint in Aggressive Lymphoma (SEAL) Analysis of Individual Patient Data (Maurer)

Abstract #1102; Oral; Monday, Dec. 5, 5:15 p.m., Ballroom 20A Outcomes for Elderly Patients with Follicular Lymphoma (FL) Using Individual Patient Data (IPD) from 5922 Patients in 18 Randomized Controlled Trials (RCTs): A FL Analysis of Surrogate Hypothesis (FLASH) Group Study (Flowers)

Abstract #4196; Poster; Monday, Dec. 5, 6 p.m., Hall GH Evaluation of Progression-free Survival (PFS) as a Surrogate Endpoint for Overall Survival (OS) in First-Line Therapy for Diffuse Large B-Cell Lymphoma (DLBCL): Findings from the Surrogate Endpoint in Aggressive Lymphoma (SEAL) Analysis of Individual Patient Data from 7507 Patients (Shi)

MDS/AML/Beta-Thalassemia

Emerging Clinical Data from Investigational cc486, ag221 (enasidenib) and Luspatercept Studies:

Abstract #905; Oral; Monday, Dec. 5, 3:45 p.m., San Diego Ballroom AB (Marriott Marquis San Diego Marina) CC-486 (Oral Azacitidine) in Patients with Hematological Malignancies Who Had Received Prior Treatment with Injectable Hypomethylating Agents (HMAs): Results from Phase 1/2 CC-486 Studies (Garcia-Manero)

Abstract #343; Oral; Sunday, Dec. 4, 9:30 a.m., Grand Hall C (Manchester Grand Hyatt) Enasidenib (AG-221), a Potent Oral Inhibitor of Mutant Isocitrate Dehydrogenase 2 (IDH2) Enzyme, Induces Hematologic Responses in Patients with Myelodysplastic Syndromes (MDS) (Stein)

Abstract #851; Oral; Monday, Dec. 5, 3:45 p.m., Room 7 AB Luspatercept Increases Hemoglobin, Decreases Transfusion Burden and Improves Iron Overload in Adults with Beta-Thalassemia (Piga)

Abstract #3168; Poster; Sunday, Dec. 4, 6 p.m., Hall GH Luspatercept Increases Hemoglobin and Reduces Transfusion Burden in Patients with Low-Intermediate Risk Myelodysplastic Syndromes (MDS): Long-Term results from Phase II PACE-MDS Study (Platzbecker)

The safety and efficacy of the agents and/or uses under investigation 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 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 (formerly known as the "RevAssist" 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 hazard to the fetus

Allergic Reactions: REVLIMID is contraindicated in patients who have demonstrated 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 28 days 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 1 month 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 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 regimen is based on patients 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 invasive SPM notably AML and MDS have been observed. Monitor patients for the development of SPMs. Take into account both the potential benefit of REVLIMID and risk of SPMs when considering treatment

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

Allergic Reactions: Angioedema and serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. 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 or TEN is suspected and should not be resumed following discontinuation for these reactions. REVLIMID capsules contain lactose; risk-benefit of treatment should be evaluated in patients with lactose intolerance

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 of 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

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%)
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 MM patients taking concomitant warfarin

NURSING MOTHERS

Discontinue drug or nursing taking into consideration the importance of the drug to the mother

PEDIATRIC USE

Safety and effectiveness in patients below the age of 18 have not been established

RENAL IMPAIRMENT

REVLIMID is primarily excreted unchanged by the kidneys; adjustments to the starting dose are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment and in patients on dialysis

Please see full Prescribing Information, including Boxed WARNINGS.

About POMALYST/IMNOVID

Indication

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 1 month 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.
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.
Hypersensitivity Reactions: Angioedema and severe dermatologic reactions have been reported. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe dermatologic reactions, 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

Nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). The most common adverse reactions 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 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 infant, 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 breastfed infants from POMALYST, advise a nursing woman to discontinue breastfeeding 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.