Ying Huang, PhD, CEO of Legend Biotech, discusses updated results from the CARTITUDE-1 study and data from two cohorts in the CARTITUDE-2 study. Both of these studies are evaluating cilta-cel in patients with relapsed/refractory multiple myeloma. These data were recently presented at the American Society of Hematology Meeting & Exposition (ASH 2022).

Multiple myeloma is a blood cancer associated with uncontrolled growth of plasma cells. Symptoms of multiple myeloma may include: bone pain (particularly in the chest and spine), frequent infections, weakness or numbness in the legs, fatigue, confusion, excessive thirst, and constipation. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.

As Dr. Huang explains, the CARTITUDE-1 study is an ongoing Phase 1b/2, open-label, multi-center study evaluating the safety and efficacy of cilta-cel in adults with relapsed and/or refractory multiple myeloma who have received ≥3 prior therapies or were refractory to a proteasome inhibitor (PI) and a immunomodulatory drug (IMiD) and had received a PI, IMiD, and an anti-CD38 antibody. In this study, cilta-cel demonstrated deep and durable responses in this patient group. The overall response rate was 97.9%, and at a median follow-up of 28 months the duration of response was not reached. 

The first abstract presented at ASH 2022 details an analysis from the CARTITUDE-1 study assessing patients with sustained minimal residual disease (MRD) negativity (≥6 months, and ≥12 months). Of the 97 patients reported on in the study, 61 were evaluable for minimal residual disease (MRD) negativity, with 56 (91.8%) of these 61 patients achieving MRD negativity (10-5) at any point. MRD negativity was assessed on bone marrow samples at baseline, day 28, and 6, 12, 18, and 24 months using next-generation sequencing, regardless of disease status. An additional sample was collected and assessed at the time of suspected complete response and every 12 months until progressive disease for patients who remained on the study. Patients who did not achieve MRD negativity at any time point were considered to be MRD positive.

MRD negativity was sustained for 6 or more months in 68% (34 of 50 with at least 6 months follow-up without progression after initial MRD-negativity) and 12 or more  months in 55% (24 of 44 with at least 12 months follow-up without progression after initial MRD-negativity. 

Dr. Huang also discussed data presented on two cohorts from the CARTITUDE-2 study. In cohort B of the study, the efficacy and safety of cilta-cel was evaluated in patients with multiple myeloma who had early relapse (≤12 months after autologous stem cell transplant [ASCT] or ≤12 months after start of initial treatment with anti-myeloma therapy). As of June 1, 2022, 19 patients (16% high-risk cytogenetics, 63.2% standard risk, 21.1% unknown) received cilta-cel and 16 remained on study. Median follow-up was 17.8 months. Overall response rate was excellent, with 100% achieving very good partial response or better, and 90% achieving complete response or better. . The most common treatment-emergent AEs were hematologic (grade 3/4: neutropenia, 90%; lymphopenia, 42%; thrombocytopenia, 26%; leukopenia, 26%). Median time from cilta-cel infusion to onset of cytokine release syndrome (CRS) was 8 days and occurred in 16 (84.2%) patients (grade 4, n=1). CRS resolved in all patients. Immune effector cell-associated neurotoxicity syndrome (ICANS; grade 1) occurred in 1 patient and movement and neurocognitive TEAEs/parkinsonism (grade 3) occurred in 1 patient. Three patients died post cilta-cel at days 158, 417, and 451 due to progressive disease. 

Finally, Dr. Huang discusses an abstract presented efficacy and safety data on Cohort C from the CARTITUDE-2 trial. Twenty patients in Cohort C had progressive multiple myeloma after treatment with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and non-cellular BCMA-targeting agent. A single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg) was administered 5-7 days post-lymphodepletion. The primary endpoint was minimal residual disease (MRD) negativity at 10-5

At a median follow-up of 18.0 months, 7/10 evaluable patients (70%) were MRD-negative at 10-5. Median duration of response was 12.8 months and median progression-free survival was 9.1 months. The most common AEs were hematologic. There were 12 deaths: 8 due to progressive disease, 2 due to COVID-19 pneumonia (not treatment-related), and 1 each due to subarachnoid hemorrhage (not treatment-related) and C. difficile colitis (treatment-related). Overall, this data demonstrates that heavily pretreated multiple myeloma patients with previous exposure to a non-cellular anti-BCMA therapy had favorable responses following cilta-cel.

To learn more about multiple myeloma and other rare cancers, visit checkrare.com/diseases/cancers/