On December 5, 2020 Bristol Myers Squibb (NYSE: BMY) reported the presentation of research across its hematology portfolio at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, which will take place virtually from December 5 to 8, 2020 (Press release, Bristol-Myers Squibb, DEC 5, 2020, View Source [SID1234572240]). Data from nearly 100 company-sponsored studies will be featured, reinforcing the depth and diversity of the company’s development program and commitment to discovering potential new options to treat patients with blood cancers and other serious hematologic diseases.

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Key data being presented by Bristol Myers Squibb and its partners at the 62nd ASH (Free ASH Whitepaper) Annual Meeting and Exposition include:

Multiple analyses of CD19-targeted CAR T cell therapy liso-cel, highlighting studies of the treatment in additional hematologic malignancies, including results from the Phase 1 TRANSCEND NHL 001 study in patients with heavily pretreated, relapsed or refractory (R/R) mantle cell lymphoma and results from the Phase 1 TRANSCEND CLL 004 study in patients with R/R chronic lymphocytic leukemia. Moreover, a matching-adjusted indirect comparison of liso-cel vs. axicabtagene ciloleucel and tisagenlecleucel, and an analysis of outcomes in the outpatient setting will highlight new insights in treating R/R large B-cell lymphoma.
Reinforcing the company’s commitment to patients with multiple myeloma, presentations evaluating BCMA-targeted CAR T cell therapies in collaboration with bluebird bio, including: an analysis for ide-cel from the pivotal KarMMA study evaluating quality of life outcomes in R/R multiple myeloma. Additional safety, patient subgroup and correlative analyses from the KarMMa study highlighting the impact of prior therapies and features associated with CAR T expansion. In addition, updated results from the Phase 1 CRB-401 trial evaluating safety and responses in heavily pretreated patients with longer follow-up will be reported. Finally, updated results from the Phase 1 CRB-402 study of early-stage CAR T cell therapy bb21217 will also be presented.
The first efficacy and safety results from a triplet combination study including iberdomide, a cereblon E3 ligase modulator (CELMoD) agent, with daratumumab or bortezomib and dexamethasone in patients with heavily pretreated R/R multiple myeloma.
More than 40 abstracts highlighting Bristol Myers Squibb’s recent treatment advances for hard-to-treat myeloid diseases, with multiple quality of life analyses including data on reduced hospitalizations and associated estimated costs with Onureg (azacitidine tablets) in patients with acute myeloid leukemia in first remission from the Phase 3 QUAZAR AML-001 study. New health-related quality of life outcomes from the Phase 3 BELIEVE and MEDALIST studies of Reblozyl (luspatercept-aamt), in beta thalassemia and lower-risk myelodysplastic syndromes, will also be presented.
"Our purpose continues to be translating groundbreaking research across many hard-to-treat diseases and the nearly 100 studies being presented at this meeting illustrate our continued focus, with new modalities and different targets in our pipeline supporting the next waves of innovation in hematology," said Samit Hirawat, M.D., executive vice president, chief medical officer, global drug development, Bristol Myers Squibb. "This year’s ASH (Free ASH Whitepaper) represents an opportunity to highlight new data supporting our recently approved therapies, as well as other important advances across our pipeline. As we mark one year in growing a combined organization, we look forward to ASH (Free ASH Whitepaper) as an exchange that underscores our commitment to delivering potentially beneficial survival outcomes and quality of life improvements for patients."

Summary of Presentations:
Selected Bristol Myers Squibb studies at the 62nd ASH (Free ASH Whitepaper) Annual Meeting and Exposition include:

Acute Myeloid Leukemia

Escalated Dosing Schedules of CC-486 are Effective and Well Tolerated for Patients Experiencing First Acute Myeloid Leukemia (AML) Relapse: Results from the Phase III QUAZAR AML-001 Maintenance Trial
Presenter: H. Doehner
Presentation: #111
Date/Time: Saturday, December 5, 9:30 am EST
Health-related Quality of Life with CC-486 in Patients with Acute Myeloid Leukemia in First Remission Following Induction Chemotherapy: Results from the Phase III QUAZAR AML-001 Maintenance Trial
Presenter: G. Roboz
Presentation: #214
Date/Time: Saturday, December 5, 12:15 pm EST
CC-486 Reduces Hospitalization and Associated Estimated Costs in Patients with Acute Myeloid Leukemia in First Remission After Intensive Chemotherapy: Results of the QUAZAR AML-001 Maintenance Trial
Presenter: E. Olivia
Presentation: #621
Date/Time: Monday, December 7, 9:15 am EST
CC-486 Prolongs Survival for Patients with Acute Myeloid Leukemia in Remission after Intensive Chemotherapy Independent of Presence of Measurable Residual Disease at Study Entry: Results from the QUAZAR-AML-001 Maintenance Trial
Presenter: G. Roboz
Presentation: #692
Date/Time: Monday, December 7, 2:30 pm EST
CC-486 Improves Overall Survival and Relapse-free Survival for Patients with Acute Myeloid Leukemia in First Remission after Intensive Chemotherapy, Regardless of Amount of Consolidation Received: Results from the Phase III QUAZAR AML-001 Maintenance Trial
Presenter: A. Wei
Poster: #1036
Date: Saturday, December 5
Gastrointestinal Events and Management Strategies for Patients with Acute Myeloid Leukemia (AML) in First Remission Receiving CC-486 in the Randomized, Placebo-controlled, Phase III QUAZAR AML-001 Maintenance Trial ​
Presenter: F. Ravandi
Poster: #1917
Date: Sunday, December 6
Real-World Use of Enasidenib in Relapsed or Refractory (RR) Acute Myeloid Leukemia (AML) Is Associated with Reduced Risk of Disease Progression and Death
Presenter: A. Klink
Poster: #1912
Date: Sunday, December 6
Beta Thalassemia

Health-Related Quality of Life Outcomes for Patients with Transfusion-Dependent Beta-Thalassemia Treated With Luspatercept in the BELIEVE Trial
Presenter: M. Cappellini
Presentation: #364
Date/Time: Sunday, December 6, 9:30 am EST
Longitudinal Effect of Luspatercept Treatment on Iron Overload and Iron Chelation Therapy in Adult Patients with β-Thalassemia in the BELIEVE Trial
Presenter: O. Hermine
Poster: #1697
Date: Sunday, December 6
Sustained Reductions in Red Blood Cell (RBC) Transfusion Burden and Events in β-Thalassemia With Luspatercept: Longitudinal Results of the BELIEVE Trial
Presenter: A. Taher
Poster: #1695
Date: Sunday, December 6
Lymphoma and Chronic Lymphocytic Leukemia

Safety and Preliminary Efficacy in Patients with Relapsed/Refractory Mantle Cell Lymphoma Receiving Lisocabtagene Maraleucel in TRANSCEND NHL 001
Presenter: M. Palomba
Presentation: #118
Date/Time: Saturday, December 5, 9:45 am EST
Subgroup Analyses of Elderly Patients Aged ≥ 70 years in MAGNIFY: A Phase IIIb Interim Analysis of Induction R2 Followed by Maintenance in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
Presenter: F. Lansigan
Presentation: #340
Date/Time: Sunday, December 6, 10:30 am EST
Frontline Brentuximab Vedotin as Monotherapy or in Combination for Older Hodgkin Lymphoma Patients ​
Presenter: C. Yasenchak
Presentation: #471​
Date/Time: Sunday, December 6​, 2:15 pm​ EST
TRANSCEND CLL 004: Phase 1 Cohort of Lisocabtagene Maraleucel (liso-cel) in Combination With Ibrutinib for Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Presenter: W. Wierda
Presentation: #544
Date/Time: Monday, December 7, 7:30 am EST
Updated Follow-up of Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Treated with Lisocabtagene Maraleucel in the Phase 1 Monotherapy Cohort of TRANSCEND CLL 004, Including High-Risk and Ibrutinib-Treated Patients
Presenter: T. Siddiqi
Presentation: #546
Date/Time: Monday, December 7, 8:00 am EST
Outcomes of Treatment With the Chimeric Antigen Receptor (CAR) T Cell Therapy Lisocabtagene Maraleucel (liso-cel) in the Nonuniversity Setting: Initial Results from the OUTREACH Study
Presenter: J. Godwin
Poster: #1196
Date: Saturday, December 5
Patients With Relapsed/Refractory Marginal Zone Lymphoma in the MAGNIFY Phase IIIb Interim Analysis of Induction R2 Followed by Maintenance
Presenter: M. Coleman
Poster: #1123
Date: Saturday, December 5
Costs of Postinfusion Monitoring by Site of Care for Patients with Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL) Who Received Third-Line or Later Treatment with Lisocabtagene Maraleucel (liso-cel) in the TRANSCEND NHL 001 and OUTREACH Trials
Presenter: M. Palomba
Poster: #2514
Date: Sunday, December 6
Matching-Adjusted Indirect Comparison (MAIC) of Lisocabtagene Maraleucel (Liso-cel) vs Axicabtagene Ciloleucel (Axi-cel) and Tisagenlecleucel in Relapsed/Refractory (R/R) Large B‐Cell Lymphoma (LBCL)
Presenter: D. Maloney
Poster: #2116
Date: Sunday, December 6
Nivolumab Combined with Brentuximab Vedotin (BV) for Relapsed/Refractory Mediastinal Gray Zone Lymphoma (R/R MGZL): Primary Efficacy and Safety Analysis of Phase 2 CheckMate 436 Study
Presenter: A. Santoro
Poster: #2045
Date: Sunday, December 6
Qualitative Analysis of the Treatment Experience and Well-Being of Patients with Relapsed/Refractory Large B-Cell Lymphoma Enrolled in 2 Trials of Lisocabtagene Maraleucel (liso-cel) during the Initial Stages of Therapy
Presenter: T. Siddiqi
Poster: #2565
Date: Sunday, December 6
Long-Term Results from a Phase 1b Study of Avadomide in Combination with Obinutuzumab in Patients with Relapsed and/or Refractory B-Cell Non-Hodgkin Lymphoma
Presenter: J. Michot
Poster: #2939
Date: Monday, December 7
Multiple Myeloma

Updated results from the Phase I CRB-402 study of anti-BCMA CAR-T cell therapy bb21217 in patients with relapsed and refractory multiple myeloma: correlation of expansion and duration of response with T cell phenotype
Presenter: M. Alsina
Presentation: #130
Date/Time: Saturday, December 5, 9:45 am EST
Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy, in Patients with Relapsed and Refractory Multiple Myeloma: Updated Results from Phase 1 CRB-401 Study
Presenter: Y. Lin
Presentation: #131
Date/Time: Saturday, December 5, 10:00 am EST
Secondary Quality of Life Domains in Patients with Relapsed and Refractory Multiple Myeloma treated with the BCMA Directed CAR T cell therapy Idecabtagene Vicleucel (ide-cel, bb2121): results from the KarMMa Clinical Trial
Presenter: N. Shah
Presentation: #437
Date/Time: Sunday, December 6, 12:15 pm EST
First results of Iberdomide (IBER; CC-220) in Combination With Dexamethasone (DEX) and Daratumumab (DARA) or Bortezomib (BORT) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM)
Presenter: N. Van de Donk
Presentation: #724
Date/Time: Monday, December 7, 1:30 pm EST
Characterization of Cytokine Release Syndrome in the KarMMa Study of Idecabtagene Vicleucel (ide-cel, bb2121) for Relapsed and Refractory Multiple Myeloma
Presenter: A. Kansagra
Poster: #1378
Date: Saturday, December 5
Efficacy and Safety of Idecabtagene Vicleucel (ide-cel, bb2121) in Elderly Patients With Relapsed and Refractory Multiple Myeloma: KarMMa Subgroup Analysis
Presenter: J. Berdeja
Poster: #1367
Date: Saturday, December 5
Molecular and Phenotypic Profiling of Drug Product and Post-Infusion Samples from CRB-402, an Ongoing: Phase I Clinical Study of bb21217 a BCMA Directed CAR T Cell Therapy
Presenter: O. Finnery
Poster: #1401
Date: Saturday, December 5
Association of Baseline and Postinfusion Biomarkers with Safety and Efficacy Endpoints in Patients Treated with Orvacabtagene Autoleucel (orva-cel; JCARH125) in the Phase 1/2 EVOLVE Study
Presenter: P. McCarthy
Poster #2350
Date: Sunday, December 6
Dose- and Schedule-Dependent Immunomodulatory Effects of the Novel CELMoD Agent CC-92480 in Patients with Relapsed/Refractory Multiple Myeloma
Presenter: L. Wong
Poster: #2295
Date: Sunday, December 6
Orvacabtagene Autoleucel (orva-cel; JCARH125): A Fully Human BCMA-Targeted Second-Generation CAR T Cell Product Characterized by a Predominant Central Memory Phenotype with High In Vitro and In Vivo Proliferative Potential and Sustained In Vivo Persistence
Presenter: L. Colonna
Poster: #2350
Date: Sunday, December 6
Pomalidomide, Dexamethasone, and Daratumumab after Lenalidomide Treatment in Relapsed Refractory Multiple Myeloma: Updated Results from an Open-Label, Multicenter, Phase 2 Trial
Presenter: N. Bahlis
Poster: #2314
Date: Sunday, December 6
Idecabtagene Vicleucel (ide-cel, bb2121) in Relapsed and Refractory Multiple Myeloma: Analyses of High-Risk Subgroups in the KarMMa Study
Presenter: N. Raje
Poster: #3234
Date: Monday, December 7
Myelodysplastic Syndromes

Health-Related Quality of Life Outcomes in Patients with Myelodysplastic Syndromes with Ring Sideroblasts Treated with Luspatercept in the MEDALIST Study
Presenter: E. Olivia
Poster: #1611
Date: Saturday, December 5
Efficacy and Safety of Luspatercept Treatment in Patients with Myelodysplastic Syndrome/ Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T): A Retrospective Analysis from the MEDALIST Study
Presenter: R. Komrokji
Poster: #3111
Date: Monday, December 7
Physicians’ Experience in Blood Supply Shortages and the Top Factors That Impact the Clinical, Economic, and Humanistic Outcomes of Myelodysplastic Syndrome (MDS) Patients in Five European Countries
Presenter: J.Tang
Poster: #3492
Date: Monday, December 7
Myelofibrosis

Long-Term Safety of Fedratinib in Patients with Intermediate- or High-Risk Myelofibrosis
Presenter: A. Pardanani
Poster: #3006
Date: Monday, December 7
Preclinical Presentations

FEIBA and NovoSeven Neutralize the Anticoagulant Effects of a Novel Small Molecule FXIa Inhibitor BMS-986177/JNJ-70033093 in Human Plasma and Whole Blood In Vitro
Presenter: M. Bunce
Poster: #1809
Date: Sunday, December 6
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision—transforming people’s lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

On December 5, 2020 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported new data highlighting progress on its AUTO1 program, the company’s CAR T cell therapy being investigated in the ongoing ALLCAR Phase 1 study in relapsed / refractory adult B-Acute Lymphocytic Leukemia (ALL), during the American Society of Hematology (ASH) (Free ASH Whitepaper) All-Virtual Annual Meeting, held between December 5-8, 2020 (Press release, Autolus, DEC 5, 2020, View Source [SID1234572235]).

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As of the November 12, 2020 data cut-off date, 20 patients with r/r ALL had received AUTO1. AUTO1 was well tolerated, with no patients experiencing ≥ Grade 3 cytokine release syndrome (CRS). Three patients (15%), all of whom had high leukemia burden (>50% blasts), experienced Grade 3 neurotoxicity (NT) that resolved swiftly with steroids.

Of the 19 patients evaluable for efficacy, 16 (84%) patients achieved minimum residual disease (MRD)-negative complete response (CR) at one month. Most notably, the durability of remissions is highly encouraging. Across all treated patients, event free survival (EFS) at six and 12 months is 69% and 52% respectively. Median EFS and overall survival (OS) has not been reached at a median follow up of 16.9 months (range up to 30.5 months).

"The high level of sustained CRs observed with AUTO1 in adult ALL, achieved without subsequent stem cell transplant, point to a potentially transformational treatment for adult ALL," said Dr. Claire Roddie, Consultant Hematologist, UCL Cancer Institute and University College London Hospital. "Despite high disease burden and despite this being a heavily pre-treated patient population on study, AUTO1 remains well tolerated. It’s encouraging to also observe promising early activity and safety in indolent NHL."

"Adult ALL is a disease with high unmet need, whereby approximately 60% of patients relapse or are refractory to first line therapy," said Dr. Elias Jabbour, Professor of Leukemia at The University of Texas MD Anderson Cancer Center. "AUTO1 is a novel CD19 CAR T candidate with an impressive clinical profile. This profile has the potential to change standard of care as a curative therapy for r/r ALL."

Dr. Christian Itin, chairman and chief executive officer of Autolus, added "We are excited about the long-term remissions observed without a need for an additional stem cell transplant. Remarkably, this outstanding result was achieved with a well-tolerated safety profile in this fragile adult ALL population. We believe the unique characteristics of AUTO1, seen in the ALLCAR study, point to the potential for AUTO1 as a standalone and transformational therapy in r/r ALL. Our Phase 1b/2 pivotal study is under way, however, with the escalating COVID-19 pandemic, enrolment projections have had to be adjusted. We now expect to enroll patients throughout 2021 with a full data set in 2022."

In addition to adult ALL, the ALLCAR study was extended to patients with indolent B cell Non-Hodgkin Lymphoma (NHL) (Cohort 1), high grade B-NHL (Cohort 2) and chronic lymphocytic leukemia (CLL) (Cohort 3). As of the data cut-off date of November 12, 2020, four patients in Cohort 1 had been infused with AUTO1. AUTO1 was well tolerated, with no patients experiencing ≥ Grade 2 CRS and no patients experiencing NT of any grade. All four patients achieved a Complete Metabolic Response (CMR).

Investor call on Monday December 7, 2020
Management will host a conference call and webcast on Monday, December 7, 2020 at 4:00 pm ET/9:00 pm GMT to discuss the ASH (Free ASH Whitepaper) data. To listen to the webcast and view the accompanying slide presentation, please go to: View Source

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 9188389. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 9188389.

About Autolus Therapeutics plc
Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information please visit www.autolus.com.

About AUTO1
AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety – while maintaining similar levels of efficacy – compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the ability of the programmed T cells to engage in serial killing of target cancer cells. AUTO1 is currently being evaluated in two Phase 1 studies, one in pediatric ALL and one in adult ALL. The company has also now progressed the program to a potential pivotal study, AUTO1-AL1.

About AUTO1-AL1 pivotal study
The AUTO1-AL1 study will enroll patients with relapsed / refractory ALL. The study will have a short Phase1b component prior to proceeding to a single arm Phase 2 study. The primary end point is overall response rate and the key secondary end points include duration of response, MRD negative CR rate and safety. The study will enroll approximately 100 patients across 30 of the leading academic and non-academic centers in the US, UK and Europe.

On December 5, 2020 Kite, a Gilead Company (Nasdaq: GILD), reported results from the primary analysis of ZUMA-5, a global, multicenter, single-arm, open-label Phase 2 study evaluating Yescarta (axicabtagene ciloleucel) in adult patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL) after at least two prior lines of therapy (Press release, Kite Pharma, DEC 5, 2020, View Source [SID1234572234]). After a single infusion of Yescarta, 92 percent of iNHL patients (n=104 evaluable for efficacy) responded, including 76 percent of patients achieving a complete response (CR) at a median follow-up of 17.5 months. The data are being presented in an oral session during the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract #700). The presentation is also being considered for Best of ASH (Free ASH Whitepaper) and has been selected for inclusion in the ASH (Free ASH Whitepaper) Annual Meeting Press Program.

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Based on these data, the U.S. Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application (sBLA) and granted Priority Review designation for Yescarta for the treatment of relapsed or refractory follicular lymphoma (FL) and marginal zone lymphoma (MZL) after two or more prior lines of systemic therapy, with a target action date under the Prescription Drug User Fee Act (PDUFA) of March 5, 2021. Yescarta has previously been granted a Breakthrough Therapy Designation (BTD) by the FDA for these indications. If approved, Yescarta would become the first chimeric antigen receptor (CAR) T therapy approved for the treatment of relapsed or refractory indolent NHLs.

"It is encouraging to see this level of response to CAR T-cell therapy in a heavily pretreated and multiply relapsed patient population, in whom response duration to other available therapies is expected to be short," said Caron A. Jacobson, MD, MMSc, Medical Director, Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute and Assistant Professor of Medicine, Harvard Medical School. "Our goal with treatment is to prolong overall survival, and the impressive durability following a one-time treatment of axicabtagene ciloleucel is incredibly promising for relapsed/refractory patients, who are often at a higher risk for early progression."

Ninety-four percent of patients with relapsed or refractory FL (n=84) responded to Yescarta, including 80 percent of patients achieving a CR and 64 percent of patients in an ongoing response at a median follow-up of 17.5 months. Of patients with relapsed or refractory MZL (n=20), 85 percent responded to Yescarta, with 60 percent achieving a CR. Median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were not reached.

In the safety analysis (n=146), Grade 3 or higher cytokine release syndrome (CRS) and neurologic events (NEs) occurred in 7 percent and 19 percent of patients, respectively. Lower incidence of Grade 3 or higher NEs was observed in patients with FL (15 percent) compared to MZL (41 percent), and CRS rates were comparable between the two groups. There were three Grade 5 adverse events, including one patient with multisystem organ failure in the context of CRS related to treatment with Yescarta, one with aortic dissection unrelated to Yescarta treatment, and one with coccidioidomycosis infection unrelated to Yescarta treatment.

"As we continue to advance Kite’s cell therapy franchise, this analysis further demonstrates the practice-changing potential of Yescarta in additional hematologic malignancies," said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. "We’re excited about the potential role of Yescarta in indolent NHL and look forward to continuing to work with the FDA to bring it to these patients as soon as possible."

Kite has presented four-year survival data for Yescarta in the ZUMA-1 study of patients with refractory large B-cell lymphoma. Based on these data and other data presented at ASH (Free ASH Whitepaper), Kite believes that Yescarta could bring the hope of survival to patients with a number of other hematological malignancies.

Yescarta has not been approved by any regulatory agency for the treatment of indolent NHL, including FL or MZL. Its safety and efficacy have not been established in these lymphomas.

Yescarta was the first CAR T-cell therapy to be approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), and high grade B-cell lymphoma and DLBCL arising from FL. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities, and Yescarta is approved with a risk evaluation and mitigation strategy (REMS) due to these risks; see below for Important Safety Information.

About Indolent Non-Hodgkin Lymphoma

Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are both forms of indolent non-Hodgkin lymphoma (NHL) in which malignant tumors slowly grow but can become more aggressive over time.

FL is the most common form of indolent lymphoma and the second most common type of lymphoma globally. It accounts for approximately 22 percent of all lymphomas diagnosed worldwide. MZL is the third most common lymphoma, accounting for 8 to 12 percent of all B-cell NHLs.

Despite advances in management and substantial improvements in long-term survival, patients living with FL have varied outcomes. Currently, there are limited options for the treatment of relapsed or refractory FL and MZL after two or more lines of therapy.

About ZUMA-5

ZUMA-5 is a single-arm, multicenter, open-label Phase 2 study that aims to enroll patients (≥18 years old) with relapsed or refractory iNHL of either follicular lymphoma (FL) or marginal zone lymphoma (MZL) subtypes, who received at least two prior lines of systemic therapy, including an anti-CD20 monoclonal antibody combined with an alkylating agent. The objectives of the study are to evaluate the efficacy and safety of a single infusion of Yescarta in this patient population. The primary endpoint of the trial is objective response rate (ORR) as assessed by an independent review committee per the 2014 Lugano Classification. Secondary endpoints include CR rate, DOR, PFS, OS, safety and CAR T cell and cytokines levels. The study is ongoing.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.
CYTOKINE RELEASE SYNDROME (CRS) occurred in 94% of patients, with 13% ≥ Grade 3. Among patients who died after receiving Yescarta, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to Yescarta infusion. Following infusion, monitor patients for signs and symptoms of CRS at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES occurred in 87% of patients, 98% of which occurred within the first 8 weeks with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade ≥3 occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%), and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures, as well as fatal and serious cases of cerebral edema have occurred. Following Yescarta infusion, monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly.

REMS: Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program called the Yescarta and Tecartus REMS Program which requires that: Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Yescarta are trained about the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS: Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of Yescarta.

SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients. Grade ≥3 infections occurred in 23% of patients; those due to an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. Grade ≥3 cytopenias not resolved by Day 30 following Yescarta infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA and B-cell aplasia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES may develop. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS: The most common (incidence ≥20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

On December 5, 2020 Kite, a Gilead Company (Nasdaq: GILD), reported follow-up results from the pivotal ZUMA-2 trial of Tecartus (brexucabtagene autoleucel, formerly KTE-X19) in adult patients with relapsed or refractory mantle cell lymphoma (MCL) (Press release, Kite Pharma, DEC 5, 2020, View Source [SID1234572233]). At a median follow-up of 17.5 months (n=60 evaluable for efficacy), 92 percent of patients had achieved a response, including 67 percent with a complete response (CR). Secondary endpoints of median duration of response, progression-free survival (PFS) and overall survival (OS) all were not yet reached. These data were presented at the 62nd ASH (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract #1120).

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"Patients with mantle cell lymphoma face a disease that often becomes more aggressive over time and nearly always relapses after initial therapy," said Michael Wang, MD, Puddin Clarke Endowed Professor, Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. "Many patients with relapsed or refractory MCL will have high-risk disease that is more likely to keep progressing after treatment, so our goal with any therapy is to provide durable remission. With more than half of the patients in the ZUMA-2 trial still alive at nearly one and a half years after infusion, these results reinforce brexucabtagene autoleucel’s potential to address the gap in existing treatment."

Among all efficacy-evaluable patients (n=60), 48 percent had ongoing responses at data cut-off. Estimates for PFS and OS at 15 months were 59 percent and 76 percent, respectively. The first 28 patients treated had a median follow-up of 32.3 months, and 39 percent of these patients remain in remission with no further therapy.

Among all patients (n=68), Grade 3 or higher cytokine release syndrome (CRS) and neurologic events (NE) occurred in 15 percent and 31 percent of patients, respectively. No new Grade 5 events occurred with additional follow-up.

"These Tecartus data build on the significant response rates seen previously with an impressive durability, which continues to show that we have a potentially transformative treatment option for patients with relapsed or refractory MCL," said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. "As we continue to observe longer-term results with Tecartus, as well as with the most recent four-year results for Yescarta, our first CAR T-cell therapy, we are encouraged by the unparalleled long-term survival benefits that may be possible with these cell therapies."

In July, Tecartus became the first CAR T-cell therapy to receive accelerated approval from the FDA for the treatment of relapsed or refractory mantle cell lymphoma, based on overall response rate and durability of response. Continued approval for this indication may be contingent upon additional data from a confirmatory trial. The Tecartus U.S. Prescribing Information has a Boxed Warning in its product label regarding the risks of CRS and neurologic toxicities, and Tecartus is approved with a risk evaluation and mitigation strategy (REMS) due to these risks; see below for Indication and Important Safety Information.

About Mantle Cell Lymphoma

MCL is a rare form of non-Hodgkin lymphoma (NHL) that arises from cells originating in the "mantle zone" of the lymph node and predominantly affects men over the age of 60. MCL is highly aggressive following relapse, with many patients progressing following therapy.

About ZUMA-2

ZUMA-2 is an ongoing, single arm, open-label trial that enrolled 74 adult patients with relapsed or refractory MCL who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib). The primary endpoint is objective response rate (ORR) per the Lugano Classification (2014), defined as the combined rate of CR and partial responses as assessed by an Independent Radiologic Review Committee (IRRC).

About Tecartus

Tecartus is an autologous, anti-CD19 CAR T cell therapy. Tecartus uses the XLP manufacturing process that includes T cell enrichment, a necessary step in certain B-cell malignancies in which circulating lymphoblasts are a common feature. In addition to MCL, Tecartus is also currently in Phase 1/2 trials in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). The use of Tecartus in ALL and CLL is investigational, and its safety and efficacy have not been established in these cancer types.

Tecartus Indication

Tecartus is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred in patients receiving Tecartus. Do not administer Tecartus to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including life-threatening reactions, occurred in patients receiving Tecartus, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Tecartus. Provide supportive care and/or corticosteroids as needed.
Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.
Cytokine Release Syndrome (CRS), including life-threatening reactions, occurred following treatment with Tecartus. In ZUMA-2, CRS occurred in 91% (75/82) of patients receiving Tecartus, including ≥ Grade 3 CRS in 18% of patients. Among the patients who died after receiving Tecartus, one had a fatal CRS event. The median time to onset of CRS was three days (range: 1 to 13 days) and the median duration of CRS was ten days (range: 1 to 50 days). Among patients with CRS, key manifestations (>10%) included fever (99%), hypotension (60%), hypoxia (37%), chills (33%), tachycardia (37%), headache (24%), fatigue (19%), nausea (13%), alanine aminotransferase increased (13%), aspartate aminotransferase increased (12%), and diarrhea (11%). Serious events associated with CRS included hypotension, fever, hypoxia, acute kidney injury, and tachycardia.

Ensure that a minimum of two doses of tocilizumab are available for each patient prior to infusion of Tecartus. Following infusion, monitor patients for signs and symptoms of CRS daily for at least seven days at the certified healthcare facility, and for four weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

Neurologic Toxicities, including those that were life-threatening, occurred following treatment with Tecartus. In ZUMA-2, neurologic events occurred in 81% of patients, 37% of whom experienced Grade ≥3 adverse reactions. The median time to onset for neurologic events was six days (range: 1 to 32 days). Neurologic events resolved for 52 out of 66 (79%) patients with a median duration of 21 days (range: 2 to 454 days). Three patients had ongoing neurologic events at the time of death, including one patient with serious encephalopathy. The remaining unresolved neurologic events were either Grade 1 or Grade 2. Fifty-four (66%) patients experienced CRS by the onset of neurological events. Five (6%) patients did not experience CRS with neurologic events and eight patients (10%) developed neurological events after the resolution of CRS. 85% of all treated patients experienced the first CRS or neurological event within the first seven days after Tecartus infusion.

The most common neurologic events (>10%) included encephalopathy (51%), headache (35%), tremor (38%), aphasia (23%), and delirium (16%). Serious events including encephalopathy, aphasia, and seizures occurred.

Monitor patients daily for at least seven days at the certified healthcare facility and for four weeks following infusion for signs and symptoms of neurologic toxicities and treat promptly.

REMS Program: Because of the risk of CRS and neurologic toxicities, Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program which requires that:

Healthcare facilities that dispense and administer Tecartus must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of two doses of tocilizumab are available for each patient for infusion within two hours after Tecartus infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Tecartus are trained in the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).
Hypersensitivity Reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) or residual gentamicin in Tecartus.

Severe Infections: Severe or life-threatening infections occurred in patients after Tecartus infusion. In ZUMA-2, infections (all grades) occurred in 56% of patients. Grade 3 or higher infections, including bacterial, viral, and fungal infections, occurred in 30% of patients. Tecartus should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 6% of patients after Tecartus infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

Viral Reactivation

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Tecartus infusion. In ZUMA-2, Grade ≥3 cytopenias not resolved by Day 30 following Tecartus infusion occurred in 55% of patients and included thrombocytopenia (38%), neutropenia (37%), and anemia (17%). Monitor blood counts after infusion.

Hypogammaglobulinemia and B-cell aplasia can occur in patients receiving treatment with Tecartus. In ZUMA-2, hypogammaglobulinemia occurred in 16% of patients. Monitor immunoglobulin levels after treatment with Tecartus and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Tecartus treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least six weeks prior to the start of lymphodepleting chemotherapy, during treatment, and until immune recovery following treatment with Tecartus.

Secondary Malignancies may develop. Monitor life-long for secondary malignancies. In the event that it occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Tecartus infusion. Advise patients to refrain from driving and engaging in hazardous activities, such as operating heavy or potentially dangerous machinery, during this period.

Adverse Reactions: The most common adverse reactions (incidence ≥ 20%) were pyrexia, CRS, hypotension, encephalopathy, fatigue, tachycardia, arrhythmia, infection – pathogen unspecified, chills, hypoxia, cough, tremor, musculoskeletal pain, headache, nausea, edema, motor dysfunction, constipation, diarrhea, decreased appetite, dyspnea, rash, insomnia, pleural effusion, and aphasia. Serious adverse reactions occurred in 66% of patients. The most common serious adverse reactions (> 2%) were encephalopathy, pyrexia, infection – pathogen unspecified, CRS, hypoxia, aphasia, renal insufficiency, pleural effusion, respiratory failure, bacterial infections, dyspnea, fatigue, arrhythmia, tachycardia, and viral infections.

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.

About Yescarta

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Limitation of Use: Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.
CYTOKINE RELEASE SYNDROME (CRS) occurred in 94% of patients, with 13% ≥ Grade 3. Among patients who died after receiving Yescarta, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to Yescarta infusion. Following infusion, monitor patients for signs and symptoms of CRS at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES occurred in 87% of patients, 98% of which occurred within the first 8 weeks with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade ≥3 occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%), and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures, as well as fatal and serious cases of cerebral edema have occurred. Following Yescarta infusion, monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly.

REMS: Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program called the Yescarta and Tecartus REMS Program which requires that: Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Yescarta are trained about the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS: Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of Yescarta.

SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients. Grade ≥3 infections occurred in 23% of patients; those due to an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. Grade ≥3 cytopenias not resolved by Day 30 following Yescarta infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA and B-cell aplasia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES may develop. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS: The most common (incidence ≥20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

On December 5, 2020 Kite, a Gilead Company (Nasdaq: GILD), reported four-year follow-up data from the pivotal ZUMA-1 trial of Yescarta (axicabtagene ciloleucel) in adult patients with refractory large B-cell lymphoma (LBCL) (Press release, Kite Pharma, DEC 5, 2020, View Source [SID1234572232]). Among Yescarta-treated patients (modified intent to-treat analysis, n=101) with a minimum follow-up of four years after a single infusion of Yescarta (median follow-up of 51.1 months), the Kaplan-Meier estimate of the four-year overall survival (OS) rate was 44 percent. The data were presented today at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Abstract #1187).

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Of 111 patients enrolled in the ZUMA-1 Phase 2 cohorts, Yescarta was administered to 101 patients with refractory LBCL, and the median time from leukapheresis to complete response (CR) was less than two months. There have been no Yescarta-related secondary malignancies reported.

"With close to half of patients still alive after a single infusion of axicabtagene ciloleucel, we are transforming the way relapsed or refractory large B-cell lymphoma can be treated," said Frederick L. Locke, MD, ZUMA-1 Co-Lead Investigator and Vice Chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center in Tampa, Florida. "As a practicing oncologist I continue to see these patients in the clinic, and this overall survival data confirms the durability of CAR T-cell therapy in a patient population that previously exhausted all viable treatment options."

Blood sample analyses provided by 21 patients who were treated with Yescarta and showed an ongoing response at a minimum of three years follow-up also demonstrated that 67 percent (n=14/21) had detectable CAR gene-marked cells and polyclonal B cells in blood. Additionally, normal B-cells were present in 91 percent (n=21/23) of evaluable patients. These results suggest that persistence of functional CAR T cells is not necessary for durable remissions in patients with refractory LBCL and may support long-term safety of the therapy.

"With these first-ever four-year data from a pivotal CAR T clinical trial in lymphoma, we continue to show the potential long-term survival of Yescarta in relapsed/refractory large B-cell lymphoma and push the boundaries of what is possible with this CAR T treatment," said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. "And equally importantly, we are encouraged by similar trends in long-term survival with real-world experience, with thousands of patients treated since Yescarta first became available."

Kite has presented four-year survival data for Yescarta in the ZUMA-1 study of patients with refractory large B-cell lymphoma. Based on these data and other data presented at ASH (Free ASH Whitepaper), Kite believes that Yescarta could bring the hope of survival to patients with a number of other hematological malignancies.

Yescarta was the first CAR T-cell therapy to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, and high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of cytokine release syndrome (CRS) and neurologic toxicities, and Yescarta is approved with a risk evaluation and mitigation strategy (REMS) due to these risks; see below for Important Safety Information.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.
CYTOKINE RELEASE SYNDROME (CRS) occurred in 94% of patients, with 13% ≥ Grade 3. Among patients who died after receiving Yescarta, 4 had ongoing CRS at death. The median time to onset was 2 days (range: 1-12 days) and median duration was 7 days (range: 2-58 days). Key manifestations include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome. Ensure that 2 doses of tocilizumab are available prior to Yescarta infusion. Following infusion, monitor patients for signs and symptoms of CRS at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES occurred in 87% of patients, 98% of which occurred within the first 8 weeks with a median time to onset of 4 days (range: 1-43 days) and a median duration of 17 days. Grade ≥3 occurred in 31% of patients. The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%), and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures, as well as fatal and serious cases of cerebral edema have occurred. Following Yescarta infusion, monitor patients for signs and symptoms of neurologic toxicities at least daily for 7 days at the certified healthcare facility, and for 4 weeks thereafter, and treat promptly.

REMS: Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program called the Yescarta and Tecartus REMS Program which requires that: Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer Yescarta are trained about the management of CRS and neurologic toxicities. Further information is available at www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).

HYPERSENSITIVITY REACTIONS: Allergic reactions, including serious hypersensitivity reactions or anaphylaxis, may occur with the infusion of Yescarta.

SERIOUS INFECTIONS: Severe or life-threatening infections occurred. Infections (all grades) occurred in 38% of patients. Grade ≥3 infections occurred in 23% of patients; those due to an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines. Febrile neutropenia was observed in 36% of patients and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. Grade ≥3 cytopenias not resolved by Day 30 following Yescarta infusion occurred in 28% of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA and B-cell aplasia can occur. Hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement. The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES may develop. Monitor life-long for secondary malignancies. In the event that one occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status or seizures, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

ADVERSE REACTIONS: The most common (incidence ≥20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.