SANTA MONICA, Calif.--(
BUSINESS WIRE
)--Kite, a Gilead Company (Nasdaq: GILD), will share 18 presentations, including six oral presentations, demonstrating the strength of its CAR T-cell therapy portfolio across a spectrum of blood cancers during the 66th American Society of Hematology (ASH) Annual Meeting and Exposition (December 7-10).
“
Our data underscore our commitment to helping people with blood cancers live longer and demonstrate the benefit of CAR T-cell therapy as a mainstay of blood cancer treatment,” said Dominique Tonelli, M.D., VP, Global Head of Medical Affairs, Kite. “
Notably for this year, along with our partner Arcellx, we are excited to share clinically meaningful data from the Phase 1 study and the iMMagine-1 Phase 2 registrational study of anito-cel for the treatment of relapsed/refractory multiple myeloma.”
Anito-cel Data from Partner, Arcellx
Key presentations for anitocabtagene autoleucel (anito-cel) include data from the Phase 1 study that demonstrate a 30.2-month median progression-free survival (PFS) with a median follow-up of 38.1 months and the median overall survival not yet reached; and preliminary results from 58 patients in the Phase 2 iMMagine-1 study that demonstrate a 95% objective response rate (ORR) and a 62% complete response / stringent complete response (CR/sCR) at a median follow-up of 10.3 months. Additional patients with a more recent data cut for the Phase 2 iMMagine-1 study will be presented in an oral presentation.
Both the Phase 1 and Phase 2 iMMagine-1 studies highlight durable responses in patients with relapsed or refractory (R/R) multiple myeloma (MM) and show no delayed neurotoxicities have been observed to date, including no parkinsonism, no cranial nerve palsies, and no Guillain Barre syndrome.
Positive Survival Outcomes with Yescarta
®
and Tecartus
®
Key presentations for Yescarta
®
(axicabtagene ciloleucel) include a five-year follow-up analysis from ZUMA-5 evaluating response rate and long-term survival in patients with R/R indolent non-Hodgkin lymphoma (iNHL), including follicular lymphoma and marginal zone lymphoma. Additionally, Yescarta is the only treatment to have demonstrated superior overall survival versus standard therapy for patients with early R/R large B-cell lymphoma (LBCL), and this continues to be seen in the largest real-world analysis of patients with R/R LBCL who received second-line Yescarta. Additional research will focus on improvements in Yescarta manufacturing for patients with R/R LBCL.
Key presentations for Tecartus
®
(brexucabtagene autoleucel) include five-year outcomes from ZUMA-2 cohorts 1 and 2 and a primary analysis of ZUMA-2 cohort 3, both highlighting durable responses in adult patients with R/R mantle cell lymphoma (MCL) and showing that Tecartus continues to deliver unprecedented efficacy in R/R MCL three years after its approval. Also to be presented are real-world outcomes in adults with R/R B-cell precursor acute lymphoblastic leukemia (B-ALL) treated with Tecartus, highlighting the CAR T-cell therapy’s high effectiveness in a broader R/R B-ALL patient population.
Advancements in Kite’s pipeline will also be highlighted, including data presented on Kite’s next generation CAR T-cell therapy KITE-753, an autologous anti-CD19/CD20 CAR T-cell therapy for the treatment of B-cell malignancies.
Kite is also collaborating with independent investigators and respected institutions including The Lymphoma Study Association, Sarah Cannon Transplant and Cellular Therapy Network, and Dana-Farber Cancer Institute to share additional insights on Kite’s CAR T-cell therapies.
Dates and times* for accepted abstracts and presentations of note are as follows:
*Times listed are in PT
Oral Presentations
Abstract Details
Titles
Axicabtagene ciloleucel
Abstract #526
Sunday, December 8, 2024
10:15 AM
Marriott Marquis San Diego Marina, Pacific Ballroom Salons 24-26
Real-World Early Outcomes of Second-Line Axicabtagene Ciloleucel (Axi-Cel) Therapy in Patients (Pts) With Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Abstract #527
Sunday, December 8, 2024
10:30 AM
Marriott Marquis San Diego Marina, Pacific Ballroom Salons 24-26
Real-world Trends of Cytokine Release Syndrome and Neurologic Events, and Pattern of Their Management among Patients Receiving Axicabtagene Ciloleucel for Relapsed or Refractory (r/r) Large B-cell Lymphoma (LBCL) in the US: a CIBMTR Report
Abstract #609
Sunday, December 8, 2024
12:30 PM
Marriott Marquis San Diego Marina, Marriott Grand Ballroom 2-4
Predictors of Early Safety Outcomes with Axicabtagene Ciloleucel (axi-cel) in Patients with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Abstract #864
Monday, December 9, 2024
4:00 PM
Marriott Marquis San Diego Marina, Marriott Grand Ballroom 11-13
5-Year Follow-Up Analysis From ZUMA-5: a Phase 2 Trial of Axicabtagene Ciloleucel (Axi-Cel) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
Brexucabtagene autoleucel
Abstract #748
Monday, December 9, 2024
11:15 AM
Marriott Marquis San Diego Marina, Marriott Grand Ballroom 8-9
Primary Analysis of ZUMA-2 Cohort 3: Brexucabtagene Autoleucel (Brexu-Cel) in Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Who Were Naive to Bruton Tyrosine Kinase Inhibitors (BTKi)
Anitocabtagene autoleucel
Abstract #1031
Monday, December 9, 2024
5:30 PM
Marriott Marquis San Diego Marina, Pacific Ballroom 24-26
Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of Patients With Relapsed and/or Refractory Multiple Myeloma: Preliminary Results From the iMMagine-1 Trial
*Led by Arcellx
Poster Presentations
Axicabtagene ciloleucel
Abstract #2367
Saturday, December 7, 2024
5:30 PM - 7:30 PM
San Diego Convention Center, Halls G-H
Treatment Patterns and Predictors of Survival after First Line Therapy in Large B-Cell Lymphoma in a Real-World US Cohort
Abstract #3347
Sunday, December 8, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Improvements in Axicabtagene Ciloleucel Manufacturing Result in High Delivery Success and More Predictable Turnaround Time for Patients With Relapsed/Refractory Large B-Cell Lymphoma
Abstract #4368
Monday, December 9, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Impact of Inflammation, Tumor and Product Attributes on Clinical Outcomes in Patients with Relapsed/Refractory Follicular Lymphoma Treated with Axicabtagene Ciloleucel
Abstract #5037
Monday, December 9, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Estimating the Impact on Survival of Not Receiving CAR T Therapy Despite Being Eligible in Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) Patients in Germany
Brexucabtagene autoleucel
Abstract #4388
Monday, December 9, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Five-Year Outcomes of Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Treated With Brexucabtagene Autoleucel (Brexu-cel) in ZUMA-2 Cohorts 1 and 2
Abstract #5092
Monday, December 9, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Real-World (RW) Outcomes for Brexucabtagene Autoleucel (Brexu-Cel) Treatment in Patients (Pts) With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) by High-Risk Features and Prior Treatments: Updated Evidence From the CIBMTR® Registry
Abstract #4193
Monday, December 9, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Impact of disease burden, CAR-T expansion, and mononuclear cell recovery on overall response and duration of response in ZUMA-3 pivotal study
Anitocabtagene autoleucel
Abstract #4825
Monday, December 9, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Phase 1 Study of Anitocabtagene Autoleucel for the Treatment of Patients With Relapsed and/or Refractory Multiple Myeloma (RRMM): Efficacy and Safety With 34-Month Median Follow-up
*Led by Arcellx
Kite next generation CAR T-cell therapies
Abstract #3481
Sunday, December 8, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
KITE-753: An Autologous Rapid Manufactured Anti-CD19/CD20 CAR-T Product for the Treatment of B-cell Malignancies
Investigator-Sponsored / Collaboration**
Abstract #4505
Sunday, December 8, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Health-related quality of life after Axi-cel as a second-line therapy in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation: results of the ALYCANTE phase II trial
*Led by The Lymphoma Study Association
Abstract #4721
Monday, December 9, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Health Related Quality of Life (HRQoL) in Relapsed/Refractory Multiple Myeloma (RRMM): A Systematic Literature Review (SLR) and Meta-Analysis
*Investigator led
Abstract #3734
Sunday, December 8, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
The Patient Journey and Treatment Outcomes Comparing Inpatient Versus Outpatient Axicabtagene Ciloleucel in Non-Hodgkin’s Lymphoma (NHL) - a Large, Multicenter Study
*In collaboration with Sarah Cannon Transplant and Cellular Therapy Network
Abstract #3124
Sunday, December 8, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
CAR T-cells for relapsed/refractory B-cell lymphoma in people living with HIV (PLWH): a LYSA study from the DESCAR-T registry
*Led by The Lymphoma Study Association
Abstract #2031
Saturday, December 7, 2024
6:00 PM - 8:00 PM
San Diego Convention Center, Halls G-H
Early MRD detection after CAR-T Associated with Poor Outcome in LBCL
*In collaboration with Dana-Farber Cancer Institute
Abstract #239
Saturday, December 7, 2024
3:00 PM
Session: 623 (2:00 - 3:30 PM)
Marriot Grand Ballroom 11-13
Outcome of patients with Mantle cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T Study By Lysa Group
*Led by The Lymphoma Study Association
Abstract #
Date TBD
Time TBD
Room TBD
A Real-World Weighted Comparison of Tisagenlecleucel and Axicabtagene Ciloleucel CAR T Cells in Relapsed or Refractory Diffuse Large B Cell Lymphoma Aged 75 Years and Older: A Lysa Study from the Descar-T Registry
*Led by The Lymphoma Study Association
Publication Only
Abstract #7775
Real-World Interim PET/CT Scan Use During Frontline (1L) Therapy and Subsequent Treatment Characteristics in Patients with Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Abstract #7607
Short-term Costs Associated With Outpatient Use of Axicabtagene Ciloleucel in Second-line Relapsed/Refractory Large B-cell Lymphoma Based on ZUMA-24 Clinical Trial
Abstract #7592
A United States (US) Cost-Effectiveness Analysis of Axicabtagene Ciloleucel Compared to Odronextamab in Third Line or Later (3L+) Diffuse Large B-Cell Lymphoma
Abstract #6962
Treatment Patterns and Outcomes in Triple-Class Exposed Patients with Relapsed and Refractory Multiple Myeloma: Findings from the Flatiron Database
Abstract #7159
In Vitro and In Vivo Characterization of Axicabtagene Ciloleucel Identifies Features Associated with Treatment Resistance in Patients, Including a Dysfunctional CD8+ T Cell State Characterized by Overexpression of GATA3 Transcript
For more information, including a complete list of abstract titles at the meeting, please visit:
https://ash.confex.com/ash/2024/webprogram/start.html
**Presentations independently led and sponsored feature Kite CAR T-cell therapies but are not included in total number of 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, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES
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.
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA.
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 following treatment with YESCARTA. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL) receiving YESCARTA, including ≥ Grade 3 (Lee grading system1) CRS in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 CRS in 9%. Among patients with LBCL who died after receiving YESCARTA, four 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 to 12 days) and the median duration of CRS was 7 days (range: 2 to 58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1 to 10 days) and the median duration was 7 days (range: 2 to 43 days).
CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 CRS in 8%. Among patients with iNHL who died after receiving YESCARTA, one patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1 to 20 days) and the median duration was 6 days (range: 1 to 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 (HLH/MAS)
.
The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in two 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 to 8 days) and the median duration of CRS was 7 days (range: 2 to 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 at which point the patients were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing Grade 3 or higher CRS. The median time to onset of CRS was 5 days (range: 1 to 15 days) and the median duration of CRS was 4 days (range: 1 to 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 infusion of YESCARTA. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. 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
Patients treated with YESCARTA may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes.
Monitor life-long for secondary malignancies. In the event that a secondary malignancy 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, NEUROLOGIC TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES
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.
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies
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. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. 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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About Kite
Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on cell therapy to treat and cure cancer. As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company. Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial supply and commercial product manufacturing. For more information on Kite, please visit
www.kitepharma.com
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About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. Gilead acquired Kite in 2017.
About Arcellx and Kite Collaboration
Arcellx and Kite, a Gilead Company, formed a global strategic collaboration and license agreement to co-develop and co-commercialize anito-cel for patients with relapsed or refractory multiple myeloma, RRMM. Anito-cel is currently being developed in a Phase 2 registrational pivotal study and a Phase 3 randomized controlled study for RRMM. Kite and Arcellx will jointly commercialize the anito-cel asset in the United States, and Kite will commercialize the product outside the United States.
About Anitocabtagene autoleucel (anito-cel)
Anitocabtagene autoleucel (anito-cel, previously CART-ddBCMA) is the first BCMA-directed CAR T-cell therapy to be investigated in multiple myeloma that utilizes Arcellx’s novel and compact binder known as the D-Domain. Anito-cel has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.
About iMMagine-3 Global Phase 3 Randomized Controlled Clinical Study
iMMagine-3 is a global Phase 3, randomized controlled study designed to compare the efficacy and safety of anitocabtagene autoleucel (anito-cel) with standard of care (SOC) in patients with relapsed and/or refractory multiple myeloma (RRMM) who have received one to three prior lines of therapy, including an immunomodulatory drug (lMiD) and an anti-CD38 monoclonal antibody.
iMMagine-3 will enroll approximately 450 adult patients. Prior to randomization, investigator’s choice of SOC regimens include: pomalidomide, bortezomib, and dexamethasone (PVd); daratumumab, pomalidomide, and dexamethasone (DPd); carfilzomib, daratumumab and dexamethasone (KDd); or carfilzomib and dexamethasone (Kd). Patients in the anito-cel arm will undergo leukapheresis and optional bridging therapy (with the SOC regimen selected by the investigator prior to randomization) followed by lymphodepleting chemotherapy (fludarabine 30 mg/m2/d and cyclophosphamide 300 mg/m2/d for 3 days) and one infusion of anito-cel (115×106 CAR+ T cells) on Day 1.
The primary endpoint is progression free survival (PFS) per blinded independent review according to the 2016 IMWG uniform response criteria for MM with the hypothesis that anito-cel will prolong PFS compared to SOC. Key secondary endpoints include complete response rate (CR/sCR), minimal residual disease negativity, overall survival, and safety.
The iMMagine-3 study initiated in the second half of 2024 at approximately 130 study sites across North America, Europe, and rest of world.
Forward-Looking Statements
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical studies, including those involving Tecartus, Yescarta anito-cel and KITE-753 (such as iMMagine-1, ZUMA-2, ZUMA-3 and ZUMA-5); uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for indications currently under evaluation; the possibility that Gilead and Kite may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and other factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements.
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For more information on Kite, please visit the company’s website at
www.kitepharma.com
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