On November 2, 2023 Gilead Sciences, Inc. (Nasdaq: GILD) and Kite, a Gilead Company, reported that it will share 29 presentations, including 10 oral presentations, during the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (December 9-12) (Press release, Gilead Sciences, NOV 2, 2023, View Source [SID1234636838]).
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Key presentations for Yescarta (axicabtagene ciloeleucel) in relapsed/refractory (R/R) large B-cell lymphoma (R/R LBCL) across lines of therapy include: three-year results from ZUMA-12 investigating CAR T-cell therapy as part of first-line treatment; ZUMA-7 overall survival sub-group analysis in patients aged 65+; and post-hoc analyses showing the curative intent of Yescarta using six-year follow-up data from ZUMA-1. Additional Yescarta research will focus on new four-year follow-up results from ZUMA-5 evaluating Yescarta in R/R indolent non-Hodgkin lymphoma, including follicular lymphoma and marginal zone lymphoma.
"We’re pleased to present new data that continue to support the long-term survival and durability of response of our CAR T-cell therapies in blood cancers, across lines of therapy and age groups," said Frank Neumann, MD, PhD, Senior Vice President, Global Head of Clinical Development, Kite. "Data from our ZUMA-7 sub-analysis will show that Yescarta can help older adults with relapsed/refractory large B-cell lymphoma live longer, underscoring that age is not a barrier to adult patients being treated with CAR T."
The largest real-world evidence dataset for Tecartus (brexucabtagene autoleucel) in adult relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and relapsed/refractory mantle cell lymphoma (R/R MCL) will also be presented. Additionally, four-year overall survival data from ZUMA-2 and a ZUMA-18 primary analysis of expanded access in R/R MCL will be highlighted in an oral presentation.
New data from the Phase 1 study of CART-dd BCMA will be presented from our multiple myeloma partner, Arcellx. CART-ddBCMA is Arcellx’s BCMA-specific CAR-modified T-cell therapy with a novel D-Domain BCMA binder that may improve CAR T-cell binding and killing of multiple myeloma cells.
Dates and times* for accepted abstracts and presentations of note are as follows:
*Times listed are in PT
Oral Presentations
Abstract Details
Titles
Large B-cell Lymphoma
Abstract #103
Saturday, December 9, 2023
9:30 AM
Room 6A
Real-World Evidence in the United States (US) of the Impact of Bridging Therapy Prior to Axicabtagene Ciloleucel (Axi-cel) for the Treatment of Relapsed or Refractory Large B-cell Lymphoma (R/R LBCL)
Abstract #223
Saturday, December 9, 2023
2:00 PM
Room 6CF
Baseline Immune State and T-cell Clonal Kinetics are Associated with Response to CAR-T Therapy in Large B-cell Lymphoma*
*In collaboration with Dana Farber Cancer Institute
Abstract #226
Saturday, December 9, 2023
2:45 PM
Room 6CF
Pre- and Post-treatment Immune Contexture Correlates with Long Term Response in Large B-cell Lymphoma Patients Treated with Axicabtagene Ciloleucel (Axi-cel)*
*In collaboration with Veracyte
Abstract #894
Monday, December 11, 2023
4:00 PM
Room 6A
3-Year Analysis of ZUMA-12: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-cel) as First-Line Therapy in Patients with High-Risk Large B-cell Lymphoma (LBCL)
Abstract #224
Saturday, December 9, 2023
2:15 PM
Room 6CF
An Inflammatory Biomarker Signature Reproducibly Predicts CAR T Treatment Failure in Patients with Aggressive Lymphoma Across the ZUMA Trial Cohorts*
*In collaboration with Memorial Sloan Kettering Cancer Center
Mantle Cell, Follicular and Other Indolent B-Cell Lymphomas
Abstract #106
Saturday, December 9, 2023
10:15 AM
Room 6A
Outcomes of Patients with Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Treated with Brexucabtagene Autoleucel (Brexu-cel) in ZUMA-2 and ZUMA-18, an Expanded Access Study
Abstract #107
Saturday, December 9, 2023
10:30 AM
Room 6A
Real-world Outcomes of Brexucabtagene Autoleucel (Brexu-cel) for Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL): A CIBMTR Subgroup Analysis of High-Risk Characteristics
Abstract #224
Saturday, December 9, 2023
2:45 PM
Room 30
Advancing CAR-T Therapy in Acute Lymphoblastic Leukemia: Multi-Omic Analyses of CD19-Directed CAR-T Cells Enabled by an Ex Vivo Co-Culture Platform*
*In collaboration with Lynx Biosciences, Inc.
Abstract #1029
Monday, December 11, 2023
5:00 PM
Room 6CF
Real-world Outcomes of Brexucabtagene Autoleucel (Brexu-cel) for Relapsed or Refractory (R/R) Adult B-cell Acute Lymphoblastic Leukemia (B-cell ALL): Evidence from the CIBMTR Registry
Multiple Myeloma
Abstract #1023
Monday, December 11, 2023
5:00 PM
Room 6A
Phase 1 Study of CART-ddBCMA for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Results from at Least 1-year Follow-up in All Patients*
*Led by Kite partner Arcellx
Poster Presentations
Large B-cell Lymphoma
Abstract #1761
Saturday, December 9, 2023
5:30 – 7:30 PM
Halls G-H
Improved Overall Survival with Axicabtagene Ciloleucel vs. Standard of Care in Second-Line Large B-cell Lymphoma Among the Elderly: A Subgroup Analysis of ZUMA-7
Abstract #1638
Saturday, December 9, 2023
5:30 – 7:30 PM
Halls G-H
Personal and Shared Tumor-Antigen Prioritization in Diffuse Large B-cell Lymphoma Patients Undergoing CD19 CAR T-cell Treatment*
*In collaboration with Beth Deaconess Israel Medical Center
Abstract #2336
Saturday, December 9, 2023
5:30 – 7:30 PM
Halls G-H
Economic Burden Associated with ASCT in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma: A Nationwide Health Insurance Claims Database Study in Japan During 2012-2022
Abstract #4864
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
Curative Potential of Axicabtagene Ciloleucel (Axi-cel): An Exploratory Long-Term Survival Assessment in Patients with Refractory Large B-cell Lymphoma from ZUMA-1
Mantle Cell, Follicular and Other Indolent B-Cell Lymphomas
Abstract #2121
Saturday, December 9, 2023
5:30 – 7:30 PM
Halls G-H
Comparative Effectiveness of Axicabtagene Ciloleucel vs Historical Standard-of-Care in Patients with Relapsed or Refractory Follicular Lymphoma: An Analysis of CIBMTR and SCHOLAR-5 Data
Abstract #4868
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
Axicabtagene Ciloleucel (Axi-cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL): 4-Year Follow-up from the Phase 2 ZUMA-5 Trial
Abstract #4424
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
Physician Treatment Preferences in Relapsed/Refractory Follicular Lymphoma: A Discrete Choice Experiment
Abstract #5082
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
Cost-effectiveness of Axicabtagene Ciloleucel Versus Mosunetuzumab in Relapsed/Refractory Follicular Lymphoma in the US
Abstract #4869
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
An Updated Comparison of Clinical Outcomes from 4-year Follow-up of ZUMA-5 (Axicabtagene Ciloleucel) and the International SCHOLAR-5 External Control Cohort in Relapsed/Refractory Follicular Lymphoma
Abstract #4865
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
A Retrospective Intra-Patient Analysis from ZUMA-5: Axicabtagene Ciloleucel (Axi-cel) Compared with Prior Standard-of-Care (SOC) Therapy in Patients with Relapsed/Refractory Follicular Lymphoma
Abstract #5136
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
Matching-Adjusted Indirect Comparison (MAIC) of Brexucabtagene Autoleucel (Brexu-cel) and Pirtobrutinib in Patients with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor (cBTKi)
Abstract #2120
Saturday, December 9, 2023
5:30 – 7:00 PM
Halls G-H
Assessment of Early Intervention Strategies for Management of Cytokine Release Syndrome and Neurologic Events after Brexucabtagene Autoleucel (Brexu-cel) Treatment in Patients with Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL) in ZUMA-2
TBD
A Propensity Score-Matched Analysis on the Outcomes of Brexucabtagene Autoleucel from ZUMA-2 Study and Allogeneic Stem Cell Transplantation from the EBMT Database in Relapsed and Refractory Post-BTKi Mantle Cell Lymphoma*
*In collaboration with EBMT
Higher-Risk Myelodysplastic Syndromes
Abstract #2434
Saturday, December 9, 2023
5:30 – 7:30 PM
Halls G-H
Evaluation of Disparities in Higher-Risk Myelodysplastic Syndromes (HR-
MDS) Patient Treatment Patterns in a Large US Health System
Abstract #5101
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
A Patient-Centered Programmatic Approach for Higher-Risk Myelodysplastic Syndromes
(HR-MDS) in the US Community Oncology Setting
Abstract #5100
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
Machine Learning Approach to Understand Real-World Treatment in Patients with Higher-Risk Myelodysplastic Syndromes
Abstract #5178
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
Patient, Caregiver, and Physician Perspectives on Communication in Diagnosing and
Treating Higher-Risk Myelodysplastic Syndromes: A Qualitative Study
Multiple Myeloma
Abstract #3383
Sunday, December 10, 2023
6:00 – 8:00 PM
Halls G-H
Safety and Tolerability of Magrolimab Combinations in Patients with Relapsed/Refractory Multiple
Myeloma (RRMM): Safety Run-in Results from a Phase 2 Study
Independently Led and Sponsored**
Abstract #4884
Monday, December 11, 2023
6:00 – 8:00 PM
Halls G-H
Cladribine and Cyclophosphamide Lymphodepletion Prior to Axicabtagene Ciloleucel in Relapsed or Refractory Large B-cell Lymphoma
Abstract #6126
Radiomic Features Prognosticates Treatment Response in CAR T-cell Therapy
Real World Data of Axicabtagene Ciloleucel as Second Line Therapy for Patients with Large B-cell Lymphoma: First Results of a LYSA Study from the French DESCAR-T Registry
Efficacy and Tolerance of Brexucabtagene Autoleucel in Adults with Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia – A GRAALL Study from the DESCAR-T Registry
Publication Only
Abstract #6899
Statistical Challenges from Trials of Potentially Curative Treatments: Validation of Cure Assumptions When Analyzing ZUMA-7 Follow-up Data of Axi-cel and Standard of Care Therapy
For more information, including a complete list of abstract titles at the meeting, please visit: View Source
**Presentations independently led and sponsored feature Kite CAR T-cell therapies, but are not included in Kite accepted abstracts.
About Yescarta
Please see full Prescribing Information, including BOXED WARNING and Medication Guide.
YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
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, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.
Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
U.S. IMPORTANT SAFETY INFORMATION
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)
CRS, including fatal or life-threatening reactions, occurred. CRS occurred in 90% (379/422) of patients with non- Hodgkin lymphoma (NHL), including ≥ Grade 3 in 9%. CRS occurred in 93% (56/2) of patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 in 9%. Among patients with LBCL who died after receiving YESCARTA, 4 had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1-12 days) and the median duration was 7 days (range: 2-58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1-10 days) and the median duration was 7 days (range: 2-43 days). CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA- 5, including ≥ Grade 3 in 8%. Among patients with iNHL who died after receiving YESCARTA, 1 patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1-20 days) and median duration was 6 days (range: 1-27 days) for patients with iNHL.
Key manifestations of CRS (≥ 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome.
The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events, CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1-8 days) and the median duration of CRS was 7 days (range: 2-16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS and were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing ≥ Grade 3 CRS. The median time to onset of CRS was 5 days (range: 1-15 days) and the median duration of CRS was 4 days (range: 1-10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities.
Ensure that 2 doses of tocilizumab are available prior to YESCARTA 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
Neurologic toxicities (including immune effector cell-associated neurotoxicity syndrome) that were fatal or life- threatening occurred. Neurologic toxicities occurred in 78% (330/422) of all patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%. Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range:1- 133 days) and median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including ≥ Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion for 87% of affected patients with LBCL and 74% of affected patients with iNHL.
The most common neurologic toxicities (≥ 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred.
The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41) and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities, 8% (3/39) developed Grade 3, and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset and decrease the duration of CRS.
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 45% of patients with NHL. Grade 3 or higher infections occurred in 17% of patients, including ≥ Grade 3 or higher infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. 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 antimicrobials according to local guidelines.
Febrile neutropenia was observed in 36% of all patients with NHL 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.
In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed. 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, including YESCARTA. 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 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion.
HYPOGAMMAGLOBULINEMIA
B-cell aplasia and hypogammaglobulinemia can occur. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. 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
Secondary malignancies may develop. Monitor life-long 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 non-laboratory adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting.
The most common adverse reactions (incidence ≥ 20%) in patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.
The most common non-laboratory adverse reactions (incidence ≥ 20%) in patients with iNHL in ZUMA-5 included fever, CRS, hypotension, encephalopathy, fatigue, headache, infections with pathogen unspecified, tachycardia, febrile neutropenia, musculoskeletal pain, nausea, tremor, chills, diarrhea, constipation, decreased appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness.
About Tecartus
Please see full FDA Prescribing Information, including BOXED WARNING and Medication Guide.
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.
Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
U.S. 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. CRS occurred in 92% (72/78) of patients with ALL, including ≥ Grade 3 (Lee grading system) CRS in 26% of patients. Three patients with ALL had ongoing CRS events at the time of death. The median time to onset of CRS was five days (range: 1 to 12 days) and the median duration of CRS was eight days (range: 2 to 63 days) for patients with ALL.
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 Events, including those that were fatal or life-threatening, occurred following treatment with Tecartus. Neurologic events occurred in 87% (68/78) of patients with ALL, including ≥ Grade 3 in 35% of patients. The median time to onset for neurologic events was seven days (range: 1 to 51 days) with a median duration of 15 days (range: 1 to 397 days) in patients with ALL. For patients with MCL, 54 (66%) patients experienced CRS before 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. Neurologic events resolved for 119 out of 134 (89%) patients treated with Tecartus. Nine patients (three patients with MCL and six patients with ALL) had ongoing neurologic events at the time of death. For patients with ALL, neurologic events occurred before, during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients; respectively. Three patients (4%) had neurologic events without CRS. The onset of neurologic events can be concurrent with CRS, following resolution of CRS or in the absence of CRS.
The most common neurologic events (>10%) were similar in MCL and ALL and included encephalopathy (57%), headache (37%), tremor (34%), confusional state (26%), aphasia (23%), delirium (17%), dizziness (15%), anxiety (14%), and agitation (12%). Serious events including encephalopathy, aphasia, confusional state, and seizures occurred after treatment with Tecartus.
Monitor patients daily for at least seven days for patients with MCL and at least 14 days for patients with ALL 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. Infections (all grades) occurred in 56% (46/82) of patients with MCL and 44% (34/78) of patients with ALL. Grade 3 or higher infections, including bacterial, viral, and fungal infections, occurred in 30% of patients with ALL and MCL. Tecartus should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Tecartus infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.
Febrile neutropenia was observed in 6% of patients with MCL and 35% of patients with ALL after Tecartus infusion and may be concurrent with CRS. The febrile neutropenia in 27 (35%) of patients with ALL includes events of "febrile neutropenia" (11 (14%)) plus the concurrent events of "fever" and "neutropenia" (16 (21%)). In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.
In immunosuppressed patients, life-threatening and fatal opportunistic infections have been reported. The possibility of rare infectious etiologies (e.g., fungal and viral infections such as HHV-6 and progressive multifocal leukoencephalopathy) should be considered in patients with neurologic events and appropriate diagnostic evaluations should be performed.
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 patients with MCL, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 55% (45/82) of patients and included thrombocytopenia (38%), neutropenia (37%), and anemia (17%). In patients with ALL who were responders to Tecartus treatment, Grade 3 or higher cytopenias not resolved by Day 30 following Tecartus infusion occurred in 20% (7/35) of the patients and included neutropenia (12%) and thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved by Day 60 following Tecartus infusion occurred in 11% (4/35) of the patients and included neutropenia (9%) and thrombocytopenia (6%). Monitor blood counts after Tecartus infusion.
Hypogammaglobulinemia: B cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Tecartus. Hypogammaglobulinemia was reported in 16% (13/82) of patients with MCL and 9% (7/78) of patients with ALL. 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 Tecartus treatment, and until immune recovery following treatment with Tecartus.
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 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 non-laboratory adverse reactions (≥ 20%) were fever, cytokine release syndrome, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting. The most common serious adverse reactions (≥ 2%) were cytokine release syndrome, febrile neutropenia, hypotension, encephalopathy, fever, infection with pathogen unspecified, hypoxia, tachycardia, bacterial infections, respiratory failure, seizure, diarrhea, dyspnea, fungal infections, viral infections, coagulopathy, delirium, fatigue, hemophagocytic lymphohistiocytosis, musculoskeletal pain, edema, and paraparesis.
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