On December 5, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported updated results from an ongoing Phase 1 first-in-human dose escalation study (NCT03145181) of teclistamab (JNJ-64007957) for the treatment of relapsed or refractory multiple myeloma (MM) (Press release, Janssen Pharmaceuticals, DEC 5, 2020, View Source [SID1234572251]). In heavily pretreated patients, the overall response rate (ORR) with teclistamab was 73 percent (16/22) at the recommended SC Phase 2 dose (RP2D).1 These results for the SC formulation support the recommended dose for the pivotal Phase 2 registration trial, which has started. In addition, updated results for the intravenous (IV) formulation demonstrate the durability of responses.1

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"The data presented today for the subcutaneous formulation build on promising results presented earlier this year for the intravenous regimen," said Alfred Garfall, M.D.,* Assistant Professor of Medicine, Perelman School of Medicine, University of Pennsylvania, and presenting author. "The preliminary efficacy, including durability of responses, combined with the initial safety profile in this highly pretreated population is encouraging and supports further studies of teclistamab in patients with relapsed or refractory multiple myeloma who are in need of additional treatment options."

The study is conducted in two parts: dose escalation (part 1) and dose expansion (part 2), and enrolled patients with MM who had relapsed or were refractory to established therapies and had previously been treated with a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD).1 Patients had received a median of six prior lines of treatment (range, 2-14); 96 percent were triple-class exposed, 81 percent were triple-class refractory, 91 percent were refractory to the last line of therapy, and 39 percent were penta-drug refractory (to two or more immunomodulatory agents, two or more PIs, and an anti-CD38 therapy).1 Prognosis is poor for patients with refractory MM as treatment options are limited.1

The RP2D was identified as 1500 µg/kg SC, and the maximum tolerated dose has not been identified. Fifty-five percent of patients achieved a very good partial response or better (12/22), and 23 percent of patients (5/22) achieved a complete response (CR) or better with RP2D SC dosing.1 After median follow-up of 3.9 months (range of 1.7–7.4 months), 94 percent (15/16) of responders treated with the SC RP2D were alive and progression-free.1 Responses appeared durable and deepened over time at the RP2D.1

Of the 11 patients who achieved CR and were evaluable for minimal residual disease (MRD) analysis across all IV and SC doses, eight patients attained MRD-negative CR at a threshold of 10-6 and one at a 10-5 threshold. Sustained MRD-negativity was confirmed for all five evaluable patients across the IV and SC cohorts.1

At the SC RP2D, 64 percent of patients experienced cytokine release syndrome (CRS) events, all of which were Grade 1 or 2 and generally confined to step-up, or a gradual increase in dosing, and first full doses.1 No patients discontinued treatment due to CRS. Of 33 treated patients at the RP2D, only one neurotoxicity event, which was reversible, was observed.1 Selection of the 1500ug/kg SC RP2D is supported by promising safety, efficacy, pharmacokinetics and pharmacodynamics. The SC formulation may provide an opportunity for less frequent dosing for patients than the IV formulation, although this has not been explored in the current study.1

The most common adverse events (AEs) (all grade ≥20 percent) for the RP2D in the SC cohort were CRS (64 percent); neutropenia (52 percent); anaemia (39 percent); thrombocytopenia (33 percent); leukopenia (33 percent); and fatigue (24 percent).1 In patients who experienced Grade 3 and above AEs (≥20 percent), the most common at the RP2D SC dose were neutropenia (33 percent); and anaemia (21 percent).1 One Grade 5 treatment related AE (pneumonia) was reported at the 80 µg/kg IV dose, but none at the RP2D.1

"We are committed to exploring treatment options that use promising modalities in multiple myeloma, including bispecific antibodies like teclistamab, that increase treatment responses through antigen targeting," said Yusri Elsayed, M.D., M.HSc., Ph.D., Vice President, Global Head, Hematologic Malignancies, Janssen Research & Development, LLC. "Our research in multiple myeloma is broad, exploring multiple targets through a variety of approaches. We continue to identify new treatment options, particularly for patients who have relapsed or become refractory to existing therapies."

"These initial results demonstrate the early promise of bispecific antibodies for people living with multiple myeloma and may, in the future, provide healthcare professionals with another tool in their arsenal to treat this devastating disease." said Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "Their development builds on our rich heritage in multiple myeloma, where we have continually sought to investigate new treatment strategies that have the potential to address remaining unmet needs."

Additional pharmacokinetic and ex vivo data for teclistamab will be highlighted in a poster on Monday, December 7 from 4:00pm to 12:30am CET (Abstract #3194).2 This study evaluated the ability of teclistamab to induce cytotoxicity and T-cell activation.2

*Alfred Garfall is lead investigator of the NCT03145181 study and was not compensated for any media work

#ENDS#

About Teclistamab
Teclistamab is an investigational bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3. BCMA is expressed at high levels on multiple myeloma cells.3,4,5,6,7 Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce cytotoxicity of the targeted cells.5,6 Results from preclinical studies demonstrate that teclistamab kills myeloma cell lines and bone marrow-derived myeloma cells from heavily pretreated patients.6

Teclistamab is currently being evaluated in a Phase 2 clinical study for the treatment of relapsed or refractory multiple myeloma (NCT04557098) and is also being explored in combination studies (NCT04586426, NCT04108195). The production and development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for use of its DuoBody technology platform.** In October and November 2020, the European Commission and the U.S. Food and Drug Administration (FDA), respectively, granted teclistamab orphan designation for the treatment of multiple myeloma.8,9

**DuoBody is a registered trademark of Genmab A/S.

About Multiple Myeloma
Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.10 In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.11 Around 50 percent of newly diagnosed patients do not reach five-year survival,12,13 and almost 29 percent of patients with multiple myeloma will die within one year of diagnosis.14

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.15 Relapsed and refractory myeloma is defined as disease that is nonresponsive while on salvage therapy, or progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better at some point previously before then progressing in their disease course.16 While some patients with MM have no symptoms at all, others are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.17 Patients who relapse after treatment with standard therapies, including proteasome inhibitors and immunomodulatory agents, have poor prognoses and require new therapies for continued disease control.18

On December 5, 2020 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that new safety and efficacy findings from the expansion phase of the Phase 1/2 study of IMGN632 in patients with relapsed/refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN) were presented during an oral session at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, ImmunoGen, DEC 5, 2020, View Source [SID1234572250]).

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"Comprising the largest prospective study with a single agent in patients with relapsed/refractory BPDCN, the results presented at ASH (Free ASH Whitepaper) build on the previous data reported for IMGN632 and reinforce the potential of this CD123-targeting ADC as a best-in-class treatment option for BPDCN," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "Given IMGN632’s favorable safety profile, demonstrated anti-tumor activity, and ease of administration via short infusion in an outpatient setting, we continue to enroll both frontline and relapsed/refractory BPDCN patients in this trial. In addition, the preclinical data presented by our partners at MD Anderson Cancer Center in relapsed/refractory AML further support the combination of IMGN632 with azacitidine and venetoclax, which we are actively enrolling in a Phase 1b/2 clinical trial."

"BPDCN is a rare, aggressive hematologic malignancy that is characterized by historically low overall survival rates," said Naveen Pemmaraju, MD, Associate Professor in the Department of Leukemia at MD Anderson Cancer Center. "Despite currently available therapies, outcomes for relapsed/refractory patients remain poor and there is an urgent need to develop better-tolerated treatment options in the frontline setting. These updated safety and efficacy findings for IMGN632 in patients with relapsed/refractory BPDCN are encouraging, and I look forward to advancing IMGN632 into pivotal development."

IMGN632 MONOTHERAPY DATA IN BPDCN

Title: "Clinical Profile of IMGN632, a Novel CD123-Targeting Antibody-Drug Conjugate, in Patients with Relapsed/Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm" (Abstract #167)

Oral Presentation Session: 616
Date: Saturday, December 5, 2020
Time: 12:30pm PT/3:30pm ET
Updated key findings include:

Safety

IMGN632 demonstrated a favorable safety profile in 29 patients who received 0.045 mg/kg once every 3 weeks via a short (under 30 minutes) intravenous infusion, with limited grade ≥3 treatment-related adverse events (AEs) and no treatment-related deaths.
The most common grade ≥3 AEs were febrile neutropenia, hyperglycemia, and thrombocytopenia (10% each).
Grade ≥3 liver function test elevations were seen in one patient (3%).
No capillary leak syndrome was reported.
Efficacy

In all relapsed/refractory BPDCN patients, the overall response rate (ORR) was 29% (8/28) with a composite complete remission (CCR) rate of 18% (5/28).
In patients with prior SL-401 exposure (tagraxofusp-erzs), the ORR was 31% (4/13) with a CCR of 15% (2/13).
Among patients with bone marrow response assessment, 60% (9/15) achieved a bone marrow complete response (blasts <5%).
Durable responses were seen in multiple patients, up to 9.2 months without hematopoietic stem cell transplant.
Two patients have been successfully bridged to hematopoietic stem cell transplant.
TRIAL IN PROGRESS POSTER

Title: "A Phase 1b/2 Study of IMGN632, a CD123-Targeting Antibody-Drug Conjugate, As Monotherapy or in Combination with Venetoclax and/or Azacitidine for Patients with CD123-Positive Acute Myeloid Leukemia" (Abstract 1047)
Poster Session: 616
Date: Saturday, December 5, 2020
Time: 7:00am – 3:30pm PT/10:00am – 6:30pm ET

PRECLINICAL POSTER

In addition, our partners at MD Anderson Cancer Center will present preclinical data from their study combining IMGN632, venetoclax, and azacitidine in in vitro and in vivo AML models.

Title: "Combining IMGN632, a Novel CD123-Targeting Antibody Drug Conjugate with Azacitidine and Venetoclax Facilitates Apoptosis in Vitro and Prolongs Survival In Vivo in AML Models" (Abstract 2886)
Poster Session: 617
Date: Monday, December 7, 2020
Time: 7:00am – 3:30pm PT/10:00am – 6:30pm ET

Additional information can be found at www.hematology.org, including abstracts.

CONFERENCE CALL INFORMATION

ImmunoGen will hold a conference call on Monday, December 7 at 8:00 a.m. ET to discuss the data presented at ASH (Free ASH Whitepaper), the pathway to FDA approval in BPDCN, and an AML program progress update; Dr. Naveen Pemmaraju, Associate Professor in the Department of Leukemia at MD Anderson Cancer Center, will join the call to review the BPDCN data presented at ASH (Free ASH Whitepaper). To access the live call by phone, dial (877) 621-5803; the conference ID is 1795760. The call, along with associated slides, may also be accessed through the Investors and Media section of immunogen.com. Following the call, a replay will be available at the same location.

ABOUT IMGN632

IMGN632 is a CD123-targeting ADC in clinical development for hematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and acute lymphocytic leukemia (ALL). IMGN632 is currently being evaluated in multiple cohorts, including monotherapy for patients with BPDCN and minimal residual disease positive (MRD+) AML following frontline induction therapy and in combinations with Vidaza (azacitidine) and Venclexta (venetoclax) for patients with relapsed/refractory AML. IMGN632 uses one of ImmunoGen’s novel indolinobenzodiazepine (IGN) payloads, which alkylate DNA without crosslinking. IGNs have been designed to have high potency against tumor cells, while demonstrating less toxicity to normal marrow progenitors than other DNA-targeting payloads. FDA has granted IMGN632 Breakthrough Therapy Designation in relapsed/refractory BPDCN.

ABOUT BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN)

BPDCN is a rare form of blood cancer that has features of both leukemia and lymphoma, with characteristic skin lesions, lymph node involvement, and frequent spread to the bone marrow. This aggressive cancer requires intense treatment often followed by stem cell transplant. Despite the approval of a CD123-targeting therapy, the unmet need remains high for patients, both in the frontline and in the relapsed/refractory setting.

ABOUT ACUTE MYELOID LEUKEMIA (AML)

AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems, and anemia. It is estimated that, in the U.S. alone, 21,380 patients will be diagnosed with AML this year and 10,590 patients will die from the disease.

ABOUT CD123

CD123, the interleukin-3 alpha chain, is expressed on multiple myeloid and lymphoid cancers including AML, BPDCN, ALL, chronic myeloid leukemia, and myeloproliferative neoplasms. With limited expression on normal hematopoietic cells, rapid internalization, and expression on AML leukemia stem cells, CD123 is a validated therapeutic target, with the approval of a CD123-targeting therapy for BPDCN.

On December 5, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reportedlonger-term results from the combined Phase 1b/2 CARTITUDE-1 study (NCT03548207) evaluating the efficacy and safety of ciltacabtagene autoleucel (cilta-cel), an investigational B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients with relapsed and/or refractory multiple myeloma (Press release, Janssen Pharmaceuticals, DEC 5, 2020, View Source [SID1234572249]). These data, presented as an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting (Abstract #177), continued to demonstrate a very high overall response rate of 97 percent, which deepened over time with 67 percent of patients achieving a stringent complete response.1 With a median follow-up of 12.4 months, median duration of response and progression-free survival (PFS) were not reached.1

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"Unfortunately, for patients with multiple myeloma for whom at least three established treatment regimens have stopped working, the prognosis is often not good," said Deepu Madduri,* M.D., Assistant Professor of Medicine, Hematology and Medical Oncology, The Tisch Cancer Institute at Mount Sinai, New York, and principal study investigator. "In the CARTITUDE-1 study, heavily pretreated patients, including those who were triple-class refractory, achieved an impressive response following a single infusion of ciltacabtagene autoleucel."

Median time to first response was one month (range, 0.9-8.5), with responses observed at a low dose of CAR-T cells (median administered dose 0.71×106 CAR+ viable T cells/kg) and were ongoing in 72 percent (n=70) of patients. Additionally, 93 percent of evaluable patients (n=53) achieved minimal residual disease (MRD) negative disease status at 10-5.1 The trial included heavily pretreated patients, with evaluated patients having received a median of six prior treatment regimens (range, 3-18); 88 percent (n=85) were triple-refractory, 42 percent (n=41) were penta-refractory, and 99 percent (n=96) were refractory to the last line of therapy.1 The 12-month PFS rate was 77 percent (95 percent confidence interval [CI], 66-84).1 The 12-month overall survival (OS) rate was 89 percent (95 percent CI, 80-94) and manufacturing of cilta-cel was successful for all patients.1

"The combined Phase 1b/2 data from the CARTITUDE-1 study include a larger patient population than previously reported in the initial Phase 1b results, and we are encouraged that patients treated with cilta-cel continued to achieve impressive, deep responses," said Sen Zhuang, M.D., Ph.D., Vice President, Clinical Research Development, Janssen Research & Development, LLC. "The responses also appeared to be durable as indicated by the estimate that 89 percent of patients remained alive and 77 percent of patients remained progression-free after one year of follow up."

"We are committed to applying the best science and disease insights to bring transformational therapies for people living with blood cancers," adds Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "We are excited to see these latest results reinforce the early promising data previously presented and hope that one day cilta-cel can offer a viable treatment option for multiple myeloma patients who have limited therapeutic options."

In these combined results, the most common haematologic adverse events (AEs) observed in the CARTITUDE-1 study were neutropenia (96 percent); anemia (81 percent); thrombocytopenia (79 percent); leukopenia (62 percent); and lymphopenia (53 percent).1 Cytokine release syndrome (CRS) of any grade was observed in 95 percent of patients, with a median duration of four days (range, 1-97), and 99 percent of which were resolved within 14 days of onset.1 Of the 92 patients with CRS, 95 percent (n=87) were Grade 1/2, three percent (n=3) were Grade 3, one percent (n=1) was Grade 4 and one percent (n=1) was Grade 5.1 The median onset of CRS was at seven days (range, 1-12) post-infusion, with 89 percent (n=82) of patients experiencing CRS onset at day four or later.1

Neurotoxicity of any grade was observed in 21 percent (n=20) of patients, with Grade 3 or higher neurotoxicity observed in 10 percent (n=10) of patients.1 Of these, Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) was observed in 16 patients; other neurotoxicities were observed in 12 patients and generally occurred after resolution of CRS and/or ICANS.1 ICANS events were resolved in all patients with a median time to recovery of four days (range, 1-12).1 Other neurotoxicities were resolved in six patients with a median time of 75 days (range, 2-160) and were not resolved in six patients (one with ongoing toxicity, one died from neurotoxicity and four died due to other causes).1 Fourteen deaths were reported during the study: five due to disease progression, three due to adverse events unrelated to treatment (acute myelogenous leukemia (n=2), pneumonia (n=1)) and six due to adverse events related to treatment (sepsis and/or septic shock (n=2), CRS/ hemophagocytic lymphohistiocytosis (n=1), lung abscess (n=1), respiratory failure (n=1) and neurotoxicity (n=1)).1

*Deepu Madduri is the lead investigator of the CARTITUDE-1 study. She was compensated for media work during the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting

#ENDS#

About CARTITUDE-1
CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, multicentre study evaluating the safety and efficacy of cilta-cel in adults with relapsed and/or refractory multiple myeloma, 99 percent of whom were refractory to the last line of treatment; 88 percent of whom were triple-class refractory, meaning their cancer did not, or no longer responds to an immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 antibody.1,2

The primary objective of the Phase 1b portion of the study, involving 29 patients, was to characterise the safety and confirm the dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2).2 Based on the safety profile observed in this portion of the study.1 The Phase 2 portion of the study, is evaluating the efficacy of cilta-cel with overall response as the primary endpoint.1

About Ciltacabtagene Autoleucel (cilta-cel)
Cilta-cel is an investigational chimeric antigen receptor T cell (CAR-T) therapy for the treatment of patients with multiple myeloma. The design comprises a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies.1 CAR-T cells are an innovative approach to eradicating cancer cells by harnessing the power of a patient’s own immune system.3 BCMA is a protein that is highly expressed on myeloma cells.4

In December 2017, Janssen entered into an exclusive worldwide license and collaboration agreement with Legend Biotech to develop and commercialise cilta-cel.5 In May 2018, Janssen initiated a Phase 1b/2 CARTITUDE-1 trial (NCT03548207) to evaluate the efficacy and safety of cilta-cel in adults with relapsed and/or refractory multiple myeloma, informed by the LEGEND-2 study results.2

In April 2019, cilta-cel was granted PRIME (PRIority MEdicines) designation by the European Medicines Agency (EMA).6 PRIME offers enhanced interaction and early dialogue to optimise drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.7 In February 2020, the European Commission granted orphan designation for cilta-cel.8

About Multiple Myeloma
Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.9 In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.10 Around 50 percent of newly diagnosed patients do not reach five-year survival,11,12 and almost 29 percent of patients with multiple myeloma will die within one year of diagnosis.13

Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.14 Refractory MM is when a patient’s disease progresses within 60 days of their last therapy.15 Relapsed cancer is when the disease has returned after a period of initial, partial or complete remission.15 While some patients with MM have no symptoms at all, others are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.16 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and require new therapies for continued disease control.17

On December 5, 2020 Legend Biotech Corporation (NASDAQ: LEGN) ("Legend Biotech"), a global clinical-stage biopharmaceutical company engaged in the discovery and development of novel cell therapies for oncology and other indications, reported the latest data results from the combined Phase 1b/2 CARTITUDE-1 study (NCT03548207) of ciltacabtagene autoleucel (cilta-cel), an investigational B-cell maturation antigen (BCMA) directed chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients with relapsed or refractory multiple myeloma (RRMM), sponsored by Janssen Research & Development, LLC (Press release, Legend Biotech, DEC 5, 2020, View Source [SID1234572248]). The data continued to show a very high overall response rate (ORR) that deepened over time, with 97 percent of patients achieving a response and 67 percent of patients achieving a stringent complete response (sCR) at a median follow-up of 12.4 months.1 The data were presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract #177) as an oral presentation.

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"A 97 percent response rate is extraordinary when you consider the patient population who, prior to cilta-cel, have generally experienced low response rates," said Deepu Madduri, M.D., Assistant Professor of Medicine, Hematology and Medical Oncology, Tisch Cancer Institute at Mount Sinai, New York, and principal CARTITUDE-1 study investigator. "Considering the early, deep and durable responses that we’ve seen at low-dose infusion of cilta-cel and its manageable safety profile, we look forward to further studying outpatient administration of cilta-cel in patients with multiple myeloma in earlier settings."

The trial included 97 patients treated with cilta-cel who received a median of six (range, 3-18) prior lines of therapy; 88 percent (n=85) were triple-refractory, 42 percent (n=41) were penta-refractory and 99 percent (n=96) were refractory to the last line of therapy.1 The median administered dose was 0.71×106 CAR+ viable T cells/kg and manufacturing of cilta-cel was successful for all patients. ORR per independent review was 97 percent, which included a sCR rate of 67 percent, very good partial response rate (VGPR) of 26 percent (VGPR or better, 93 percent) and partial response rate of 4 percent. Median time to first response was 1 month (range, 0.9-8.5) and responses were ongoing in 72 percent (n=70) of patients. Of 57 minimal residual disease (MRD) evaluable patients, 93 percent (n=53) were MRD negative at 10-5.1 Median progression-free survival (PFS) was not reached at median follow-up of 12.4 months (range, 1.5-24.9). The 12-month PFS rate was 77 percent (95 percent confidence interval [CI], 66-84) and the 12-month OS rate was 89 percent (95 percent CI, 80-94).1

The study also demonstrated a manageable safety profile for cilta-cel at the recommended Phase 2 dose.1 In the combined results, the most common hematologic adverse events (AEs) observed in the CARTITUDE-1 study were neutropenia (96 percent); anemia (81 percent); thrombocytopenia (79 percent); leukopenia (62 percent); and lymphopenia (53 percent).1 Cytokine release syndrome (CRS) of any grade was observed in 95 percent of patients, with a median duration of four days (range, 1-97), and 99 percent of which resolved within 14 days of onset. Of the 92 patients with CRS, most were Grade 1/2 (95 percent, n=87), 3 percent were Grade 3 (n=3), 1 percent was Grade 4 (n=1) and 1 percent was Grade 5 (n=1).1 The median onset of CRS was seven days (range, 1-12) post-infusion, with 89 percent (n=82) of patients experiencing CRS onset at day four or later, which is supportive of potential outpatient administration for cilta-cel. Total CAR-T cell neurotoxicity of any grade was observed in 21 percent (n=20) of patients, with Grade ≥3 neurotoxicity observed in 10 percent (n=10) of patients.1 Of these, Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) was observed in 16 patients and generally occurred concurrently with CRS; other neurotoxicities were observed in 12 patients and generally occurred after resolution of CRS and/or ICANS (eight patients experienced both ICANS and other neurotoxicities).1 ICANS events were resolved in all patients with a median time to recovery of four days (range, 1-12).1 Other neurotoxicities were resolved in six patients at a median time of 75 days (range, 2-160) and were not resolved in six patients (one with ongoing toxicity, one died from neurotoxicity and four died due to other causes).1 Fourteen deaths were reported during the study: five due to disease progression, three due to adverse events unrelated to treatment (acute myelogenous leukemia [n=2], pneumonia [n=1]) and six due to adverse events related to treatment (sepsis and/or septic shock [n=2], CRS/HLH [n=1], neurotoxicity [n=1], respiratory failure [n=1], and lung abscess [n=1]).1

"We are encouraged by the see strong results from the CARTITUDE-1 study showing the potential of our lead product candidate cilta-cel to be a transformative treatment option for patients living with relapsed or refractory multiple myeloma," said Dr. Ying Huang, Chief Executive Officer and Chief Financial Officer of Legend Biotech. "We look forward to advancing this potentially life-saving treatment approach for patients in need."

About CARTITUDE-1

CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of ciltacabtagene autoleucel in adults with relapsed or refractory multiple myeloma, 99 percent of whom were refractory to the last line of treatment; 88 percent of whom were triple-class refractory(to at least 1 immunomodulatory drug [IMiD], 1 proteasome inhibitor [PI] and 1 anti-CD38 antibody).

The primary objective of the Phase 1b portion of the study, involving 29 patients, was to characterize the safety and confirm the dose of ciltacabtagene autoleucel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The Phase 2 portion of the study, involving 68 additional patients, is evaluating the efficacy of ciltacabtagene autoleucel with overall response rate as the primary endpoint.

About Cilta-cel

Cilta-cel is an investigational chimeric antigen receptor T (CAR-T) cell therapy, formerly identified as JNJ-4528 outside of China and LCAR-B38M CAR-T cells in China, that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and in earlier lines of treatment. The design consists of a structurally differentiated CAR-T with two BCMA-targeting single domain antibodies. In December 2017, Legend Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel. In addition to a Breakthrough Therapy Designation (BTD) granted in the U.S. in December 2019, cilta-cel received a PRIority MEdicines (PRiME) designation from the European Commission in April 2019 and BTD in China in August 2020. In addition, Orphan Drug Designation was granted for cilta-cel by the U.S. FDA in February 2019, and by the European Commission in February 2020.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.2 Although treatment may result in remission, unfortunately, patients will most likely relapse. 3 Relapsed myeloma is when the disease has returned after a period of initial, partial or complete remission and does not meet the definition of being refractory.4 Refractory multiple myeloma is when a patient’s disease is non-responsive or progresses within 60 days of their last therapy.5,6 While some patients with multiple myeloma have no symptoms until later stages of the disease, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.7 Patients who relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents, have poor prognoses and few treatment options.8

On December 5, 2020 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that new data from the pivotal Phase III MURANO and CLL14 studies support the efficacy of fixed-duration, chemotherapy-free Venclexta (venetoclax)-based combinations in certain people with chronic lymphocytic leukemia (CLL) and provide more evidence on the potential value of minimal residual disease (MRD) (Press release, Genentech, DEC 5, 2020, View Source [SID1234572246]). Data were presented at the all-virtual 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on Saturday, December 5, 2020.

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"These results reinforce the long-term value of fixed-duration, chemotherapy-free Venclexta-based combinations in CLL, potentially offering patients a significant period of time without treatment following initial therapy," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "These data also reflect our ongoing commitment to accelerating clinical advancements for patients by exploring the novel endpoint minimal residual disease as a potential predictor of patient outcomes."

Five-year data from the pivotal Phase III MURANO trial continue to show sustained investigator-assessed progression-free survival (PFS) with Venclexta plus Rituxan (rituximab). Data, presented in an oral session, showed:

Venclexta plus Rituxan reduced the risk of disease progression or death by 81% (HR=0.19; 95% CI: 0.15, 0.26; p<0.0001) compared to bendamustine plus Rituxan (BR) in people with relapsed or refractory (R/R) CLL.
At the time of analysis, median overall survival (OS) had not been reached in either arm (HR=0.40; 95% CI: 0.26, 0.62), however, five-year OS was 82.1% in the Venclexta plus Rituxan arm, compared to 62.2% in the BR arm.
In the Venclexta arm, among the 130 patients who completed two years of treatment without progressive disease, 63.8% (n=83/130) had undetectable MRD (uMRD) levels at the end of treatment. In an analysis of this patient subgroup, uMRD was associated with improved progression-free survival. Undetectable MRD, sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes.
No new safety events were reported in the study.
Data from the Phase III CLL14 study contributes to growing evidence regarding the potential of MRD measurements to predict future outcomes for certain people with previously untreated CLL who were treated with fixed-duration Venclexta plus Gazyva (obinutuzumab):

Patients with uMRD and a partial response (PR) had longer PFS than patients with detectable MRD and a complete response (CR).
In collaboration with Adaptive Biotechnologies, clonal growth rate, a measure for how quickly cancer cells grow, was analyzed using the next-generation sequencing Adaptive clonoSEQ Assay and insights were used to better understand the potential role of MRD in predicting outcomes. In this analysis, after treatment with fixed-duration Venclexta plus Gazyva, the estimated clonal growth rate was slower and lower, suggesting more effective MRD eradication in these patients compared to those treated with Gazyva plus chlorambucil. Early data suggest a correlation between MRD responses and PFS, which will be further evaluated by the study authors.
Exploring novel endpoints, such as MRD, is an important area of development for Genentech, which continues to investigate Venclexta in a robust clinical development program. This includes the Phase III CRISTALLO trial in previously untreated CLL, which uses MRD as a primary endpoint.

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States.

*Minimal residual disease (MRD) is a measure of the number of remaining cancer cells. Undetectable MRD (uMRD), sometimes referred to as MRD-negativity, means that no cancer cells could be detected using a specific and highly sensitive test, and is defined as less than one cancer cell in 10,000 leukocytes.

About the MURANO Study

MURANO [NCT02005471] is a Phase III open-label, international, multicenter, randomized study evaluating the efficacy and safety of fixed-duration Venclexta (venetoclax) in combination with Rituxan (rituximab) compared to bendamustine in combination with Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta, patients on the Venclexta plus Rituxan arm received six cycles of Venclexta plus Rituxan followed by Venclexta monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukemia, with or without 17p deletion, who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan or BR. The primary endpoint of the study was progression-free survival. Secondary endpoints included overall survival, overall response rate and complete response rate (with or without complete blood count recovery).

About the CLL14 Study

CLL14 [NCT02242942] is a randomized Phase III study evaluating the combination of fixed-duration Venclexta (venetoclax) plus Gazyva (obinutuzumab) compared to Gazyva plus chlorambucil in adult patients with previously untreated chronic lymphocytic leukemia (CLL) and co-existing medical conditions. 432 patients with previously untreated CLL were randomly assigned to receive either a 12-month duration of Venclexta alongside six-month duration of Gazyva (Arm A) or six-month duration of Gazyva alongside 12-month duration of chlorambucil (Arm B). Arm A started with an initial dosing of Gazyva followed by a five-week Venclexta dose ramp-up to help reduce the risk of tumor burden. The primary endpoint of the study is investigator-assessed progression-free survival (PFS). Secondary endpoints include PFS assessed by independent review committee, minimal residual disease (MRD) status, overall response rate, complete response rate (with or without complete blood count recovery), overall survival, duration of response, event-free survival, time to next CLL treatment, and safety. MRD-negativity, or undetectable MRD, means no cancer can be detected using a specific and highly sensitive test, and was defined as less than one cancer cell in 10,000 leukocytes. The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne.

About CLL

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. In the United States, it is estimated that more than 20,000 new cases of CLL will be diagnosed in 2020. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.

About Venclexta

Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the United States and commercialized by AbbVie outside of the United States. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood and other cancers.

In the United States, Venclexta has been granted five Breakthrough Therapy Designations by the U.S. Food and Drug Administration (FDA): one for previously untreated CLL, two for relapsed or refractory CLL and two for previously untreated acute myeloid leukemia.

Venclexta Indications

Venclexta is a prescription medicine used:

to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
‒ are 75 years of age or older, or
‒ have other medical conditions that prevent the use of standard chemotherapy.

It is not known if Venclexta is safe and effective in children.

Important Safety Information

What is the most important information patients should know about Venclexta?

Venclexta can cause serious side effects, including:

Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids into their vein.

The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should tell their doctor right away if they have any symptoms of TLS during treatment with Venclexta, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Patients should drink plenty of water during treatment with Venclexta to help reduce the risk of getting TLS.

Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before the first dose on the day of the first dose of Venclexta, and each time a dose is increased.

The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects. When restarting Venclexta after stopping for 1 week or longer, the patient’s doctor may again check for the risk of TLS and change the patient’s dose.

What patients should not take Venclexta?

Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased TLS.

Patients should tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other causing serious side effects.
Patients must not start new medicines during treatment with Venclexta without first talking with their doctor.
Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:

Have kidney or liver problems.
Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium.
Have a history of high uric acid levels in the blood or gout.
Are scheduled to receive a vaccine. Patients should not receive a "live vaccine" before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their doctor. These vaccines may not be safe or may not work as well during treatment with Venclexta.
Are pregnant or plan to become pregnant. Venclexta may harm an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away.
Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients are instructed to not breastfeed during treatment with Venclexta and for 1 week after the last dose.
What to avoid while taking Venclexta:

Patients should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood.

What are the possible side effects of Venclexta?

Venclexta can cause serious side effects, including:

Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta and may pause dosing.
Infections. Death and serious infections such as pneumonia and blood infection (sepsis) have happened during treatment with Venclexta. The patient’s doctor will closely monitor and treat the patient right away if they have a fever or any signs of infection during treatment with Venclexta.
Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta.

The most common side effects of Venclexta when used in combination with obinutuzumab or rituximab or alone in people with CLL or SLL include low white blood cell count; low platelet count; low red blood cell count; diarrhea; nausea; upper respiratory tract infection; cough; muscle and joint pain; tiredness; and swelling of arms, legs, hands, and feet.

The most common side effects of Venclexta in combination with azacitidine or decitabine or low-dose cytarabine in people with AML include nausea; diarrhea; low platelet count; constipation; low white blood cell count; fever with low white blood cell count; tiredness; vomiting; swelling of arms, legs, hands, or feet; fever; infection in lungs; shortness of breath; bleeding; low red blood cell count; rash; stomach (abdominal) pain; infection in your blood; muscle and joint pain; dizziness; cough; sore throat; and low blood pressure.

Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility.

These are not all the possible side effects of Venclexta. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

Please see the Venclexta full Prescribing Information, including the Medication Guide, for additional Important Safety Information.

Rituxan Indications

Rituxan (rituximab) is a prescription medicine used to treat adults with:

Non-Hodgkin’s lymphoma (NHL): alone or with other chemotherapy medicines
Chronic lymphocytic leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide.
Important Safety Information:

Rituxan can cause serious side effects that can lead to death, including:

Infusion-Related Reactions: Infusion-related reactions are very common side effects of Rituxan treatment. Serious infusion-related reactions can happen during the patient’s infusion or within 24 hours after the patient’s infusion of Rituxan. The patient’s doctor should give the patient medicines before infusion of Rituxan to decrease the chance of having a severe infusion-related reaction.

Patients must tell their doctor or get medical help right away about any of these symptoms during or after an infusion of Rituxan:
Hives (red itchy welts) or rash
Itching
Swelling of the lips, tongue, throat, or face
Sudden cough
Shortness of breath, difficulty breathing, or wheezing
Weakness
Dizziness or feel faint
Palpitations (feel like the heart is racing or fluttering)
Chest pain
Severe Skin and Mouth Reactions: Patients must tell their doctor or get medical help right away about any of these symptoms at any time during treatment with Rituxan:
Painful sores or ulcers on the skin, lips, or in the mouth
Blisters
Peeling skin
Rash
Pustules
Hepatitis B Virus (HBV) Reactivation: Before receiving Rituxan treatment, the patient’s doctor will do blood tests to check for HBV infection. If the patient has had hepatitis B or is a carrier of hepatitis B virus, receiving Rituxan could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems, including liver failure, and death. The patient’s doctor will monitor for hepatitis B infection during and for several months after the patient stops receiving Rituxan.

Patients must tell their doctor right away about worsening tiredness, or yellowing of the skin or white part of the eyes during treatment with Rituxan.
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare, serious brain infection caused by a virus that can happen in people who receive Rituxan. People with weakened immune systems can get PML. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML.

Patients must tell their doctor right away about new or worsening symptoms or if anyone close to the patient notices these symptoms:
Confusion
Dizziness or loss of balance
Difficulty walking or talking
Decreased strength or weakness on one side of the body
Vision problems, such as blurred vision or loss of vision
What should patients tell their doctor before receiving Rituxan?

Before receiving Rituxan, patients should tell their doctor if they:

Have had a severe reaction to Rituxan or a rituximab product
Have a history of heart problems, irregular heartbeat, or chest pain
Have lung or kidney problems
Have had an infection, currently have an infection, or have a weakened immune system
Have or have had any severe infections including:
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Cytomegalovirus (CMV)
Herpes simplex virus (HSV)
Parvovirus B19
Varicella zoster virus (chickenpox or shingles)
West Nile Virus
Have had a recent vaccination or are scheduled to receive vaccinations. Patients should not receive certain vaccines before or during treatment with Rituxan
Have any other medical conditions
Are pregnant or plan to become pregnant. Patients must talk to their doctor about the risks to the patient’s unborn baby if receiving Rituxan during pregnancy. Females who are able to become pregnant should use effective birth control (contraception) during treatment with Rituxan and for 12 months after the last dose of Rituxan. Patients should talk to their doctor about effective birth control. Patients should tell their doctor right away if they become pregnant or think that they are pregnant during treatment with Rituxan
Are breastfeeding or plan to breastfeed. It is not known if Rituxan passes into the breast milk. Do not breastfeed during treatment and for at least 6 months after the last dose of Rituxan
Are taking any medications, including prescription and over-the-counter medicines, vitamins, and herbal supplements
What are the possible side effects of Rituxan?

Rituxan can cause serious side effects, including:

Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of cancer cells. TLS can cause the patient to have:
Kidney failure and the need for dialysis treatment
Abnormal heart rhythm
TLS can happen within 12 to 24 hours after an infusion of Rituxan. The patient’s doctor may do blood tests to check for TLS. The patient’s doctor may give medicine to help prevent TLS. Patients must tell their doctor right away if they have any of the following signs or symptoms of TLS:

Nausea
Vomiting
Diarrhea
Lack of energy
Serious Infections: Serious infections can happen during and after treatment with Rituxan, and can lead to death. Rituxan can increase the patient’s risk of getting infections and can lower the ability of the patient’s immune system to fight infections. Types of serious infections that can happen with Rituxan include bacterial, fungal, and viral infections. After receiving Rituxan, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months). Some of these patients with low antibody levels developed infections. People with serious infections should not receive Rituxan. Patients must tell their doctor right away if they have any symptoms of infection:
Fever
Cold symptoms, such as runny nose or sore throat that do not go away
Flu symptoms, such as cough, tiredness, and body aches
Earache or headache
Pain during urination
Cold sores in the mouth or throat
Cuts, scrapes, or incisions that are red, warm, swollen, or painful
Heart Problems: Rituxan may cause chest pain, irregular heartbeats, and heart attack. The patient’s doctor may monitor the patient’s heart during and after treatment with Rituxan if they have symptoms of heart problems or have a history of heart problems. Patients must tell their doctor right away if they have chest pain or irregular heartbeats during treatment with Rituxan.
Kidney Problems: especially if the patient is receiving Rituxan for NHL. Rituxan can cause severe kidney problems that lead to death. The patient’s doctor should do blood tests to check how well their kidneys are working.
Stomach and Serious Bowel Problems That Can Sometimes Lead to Death: Bowel problems, including blockage or tears in the bowel can happen if the patient receives Rituxan with chemotherapy medicines. Patients must tell their doctor right away if they have any stomach-area (abdomen) pain or repeated vomiting during treatment with Rituxan.
The patient’s doctor will stop treatment with Rituxan if they have severe, serious, or life-threatening side effects.

What are the most common side effects during treatment with Rituxan?

Infusion-related reactions
Infections (may include fever, chills)
Body aches
Tiredness
Nausea
Other side effects include:

Aching joints during or within hours of receiving an infusion
More frequent upper respiratory tract infections
These are not all of the possible side effects with Rituxan.

Please see the Rituxan full Prescribing Information, including the Medication Guide, for additional Important Safety Information at View Source

Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Gazyva Indications

Gazyva (obinutuzumab) is a prescription medicine used:

With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment.
With the chemotherapy drug, bendamustine, followed by Gazyva alone for follicular lymphoma (FL) in adults who did not respond to a rituximab-containing regimen, or whose FL returned after such treatment.
With chemotherapy, followed by Gazyva alone in those who responded, to treat stage II bulky, III, or IV FL in adults who have not had previous FL treatment.
Important Safety Information

The most important safety information patients should know about Gazyva

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that can become serious or life threatening, including:

Hepatitis B Virus (HBV): Hepatitis B can cause liver failure and death. If the patient has a history of hepatitis B infection, Gazyva could cause it to return. Patients should not receive Gazyva if they have active hepatitis B liver disease. The patient’s doctor or healthcare team will need to screen them for hepatitis B before, and monitor the patient for hepatitis during and after, their treatment with Gazyva. Sometimes this will require treatment for hepatitis B. Symptoms of hepatitis include: worsening of fatigue and yellow discoloration of skin or eyes.
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare and serious brain infection caused by a virus. PML can be fatal. The patient’s weakened immune system could put them at risk. The patient’s doctor will watch for symptoms. Symptoms of PML include: confusion, difficulty talking or walking, dizziness or loss of balance, and vision problems.
Who should not receive Gazyva:

Patients should NOT receive Gazyva if they have had an allergic reaction (e.g., anaphylaxis or serum sickness) to Gazyva. Patients must tell their healthcare provider if they have had an allergic reaction to obinutuzumab or any other ingredients in Gazyva in the past.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effect they experience. Gazyva can cause side effects that may become severe or life threatening, including:

Infusion Reactions: These side effects may occur during or within 24 hours of any Gazyva infusion. Some infusion reactions can be serious, including, but not limited to, severe allergic reactions (anaphylaxis), acute life-threatening breathing problems, or other life-threatening infusion reactions. If the patient has a reaction, the infusion is either slowed or stopped until their symptoms are resolved. Most patients are able to complete infusions and receive medication again. However, if the infusion reaction is life threatening, the infusion of Gazyva will be permanently stopped. The patient’s healthcare team will take steps to help lessen any side effects the patient may have to the infusion process. The patient may be given medicines to take before each Gazyva treatment. Symptoms of infusion reactions may include: fast heartbeat, tiredness, dizziness, headache, redness of the face, nausea, chills, fever, vomiting, diarrhea, rash, high blood pressure, low blood pressure, difficulty breathing, and chest discomfort.
Hypersensitivity Reactions Including Serum Sickness: Some patients receiving Gazyva may have severe or life-threatening allergic reactions. This reaction may be severe, may happen during or after an infusion, and may affect many areas of the body. If an allergic reaction occurs, the patient’s doctor will stop the infusion and permanently discontinue Gazyva.
Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including fatal cases, has been reported in patients receiving Gazyva. Gazyva works to break down cancer cells quickly. As cancer cells break apart, their contents are released into the blood. These contents may cause damage to organs and the heart, and may lead to kidney failure requiring the need for dialysis treatment. The patient’s doctor may prescribe medication to help prevent TLS. The patient’s doctor will also conduct regular blood tests to check for TLS. Symptoms of TLS may include nausea, vomiting, diarrhea, and tiredness.
Infections: While the patient is taking Gazyva, they may develop infections. Some of these infections may be fatal and severe, so the patient should be sure to talk to their doctor if they think they have an infection. Patients administered Gazyva in combination with chemotherapy, followed by Gazyva alone are at a high risk of infections during and after treatment. Patients with a history of recurring or chronic infections may be at an increased risk of infection. Patients with an active infection should not be treated with Gazyva. Patients taking Gazyva plus bendamustine may be at higher risk for fatal or severe infections compared to patients taking Gazyva plus CHOP or CVP.
Low White Blood Cell Count: When the patient has an abnormally low count of infection-fighting white blood cells, it is called neutropenia. While the patient is taking Gazyva, their doctor will do blood work to check their white blood cell count. Severe and life-threatening neutropenia can develop during or after treatment with Gazyva. Some cases of neutropenia can last for more than one month. If the patient’s white blood cell count is low, their doctor may prescribe medication to help prevent infections.
Low Platelet Count: Platelets help stop bleeding or blood loss. Gazyva may reduce the number of platelets the patient has in their blood; having low platelet count is called thrombocytopenia. This may affect the clotting process. While the patient is taking Gazyva, their doctor will do blood work to check their platelet count. Severe and life-threatening thrombocytopenia can develop during treatment with Gazyva. Fatal bleeding events have occurred in patients treated with Gazyva. If the patient’s platelet count gets too low, their treatment may be delayed or reduced.
The most common side effects of Gazyva in CLL were infusion reactions, low white blood cell counts, low platelet counts, low red blood cell counts, fever, cough, nausea, and diarrhea.

The safety of Gazyva was evaluated based on 392 patients with relapsed or refractory NHL, including FL (81 percent), small lymphocytic lymphoma (SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is not indicated), who did not respond to or progressed within 6 months of treatment with rituximab product or a rituximab product-containing regimen. In patients with follicular lymphoma, the profile of side effects that were seen were consistent with the overall population who had NHL. The most common side effects of Gazyva were infusion reactions, low white blood cell counts, nausea, fatigue, cough, diarrhea, constipation, fever, low platelet counts, vomiting, upper respiratory tract infection, decreased appetite, joint or muscle pain, sinusitis, low red blood cell counts, general weakness, and urinary tract infection.

A randomized, open-label multicenter trial (GALLIUM) evaluated the safety of Gazyva as compared to rituximab product in 1,385 patients with previously untreated follicular lymphoma (86 percent) or marginal zone lymphoma (14 percent). The most common side effects of Gazyva were infusion reactions, low white blood cell count, upper respiratory tract infection, cough, constipation and diarrhea.

Before receiving Gazyva, patients should talk to their doctor about:

Immunizations: Before receiving Gazyva therapy, the patient should tell their healthcare provider if they have recently received or are scheduled to receive a vaccine. Patients who are treated with Gazyva should not receive live vaccines.
Pregnancy: The patient should tell their doctor if they are pregnant, think that they might be pregnant, plan to become pregnant, or are breastfeeding. Gazyva may harm their unborn baby. The patient should speak to their doctor about using Gazyva while they are pregnant. The patient should talk to their doctor or their child’s doctor about the safety and timing of live virus vaccinations to their infant if they received Gazyva during pregnancy. It is not known if Gazyva may pass into the patient’s breast milk. The patient should speak to their doctor about using Gazyva if they are breastfeeding.
Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or View Source Report side effects to Genentech at (888) 835-2555.

Please visit View Source for the Gazyva full Prescribing Information, including BOXED WARNINGS, for additional Important Safety Information.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit View Source