Idecabtagene vicleucel elicited a median overall survival of 24.8 months with a 51% event-free rate at 24 months in patients with heavily pretreated, relapsed/refractory multiple myeloma.
Idecabtagene vicleucel (Abecma) elicited a median overall survival (OS) of 24.8 months with a 51% event-free rate at 24 months in patients with relapsed/refractory multiple myeloma that had been treated with 3 different classes of therapies prior to study entry, according to long-term findings released by developers Bristol Myers Squibb (BMS) and bluebird bio ahead of the ASCO 2021 Virtual Annual Meeting.
The updated findings come from the phase 2 KarMMA study, which were instrumental in the FDA approval of idecabtagene vicleucel in March 2021. The long-term results represent more than 24 months of follow-up, which is the longest for a CAR T-cell therapy in multiple myeloma. At this analysis, the overall response rate was 73%, with a complete response or better rate of 33%. Many of these responses were ongoing at the analysis.
“With these updated data from the KarMMa study, we are seeing the longest follow-up from a global clinical trial for an anti-BCMA CAR T cell therapy in multiple myeloma, which continues to reinforce that idecabtagene vicleucel provides deep and durable responses with the potential for long-term disease control and survival in patients with triple-class exposed relapsed or refractory multiple myeloma,” lead author of the ASCO study Larry D. Anderson Jr, MD, PhD, associate professor, Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, said in a statement.
Idecabtagene vicleucel consists of autologous T cells collected by leukapheresis, which are modified ex vivo with a lentiviral vector to express a second-generation chimeric antigen receptor (CAR). This CAR incorporates an anti-BCMA single-chain variable fragment with a 4-1BB costimulatory domain, and a CD3-zeta signaling domain for T-cell activation. Prior to administration of the modified T cells, patients undergo lymphodepletion with a combination of fludarabine and cyclophosphamide for 3 consecutive days followed by 2 days of rest.
Overall, the study treated 128 patients with relapsed or refractory multiple myeloma who had received at least 3 prior treatment regimens, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. The dose levels of idecabtagene vicleucel ranged from 150 x 10^6 to 450 x 10^6 CAR-positive T cells. Prior to entering the study, patients had received a median of 6 prior regimens (range, 3-16), with the majority (84%) refractory to all 3 classes of therapy, representing a heavily pretreated population.
Responses to idecabtagene vicleucel were experienced regardless of the number of prior lines of therapy received. This included for patients who were triple-refractory and penta-refractory. At the ASCO analysis, the median duration of response was 10.9 months. When looking specifically at those who experienced a CR or better, the median duration of response was 21.5 months.
In addition to the strong median and 24-month OS data, at 18 months 65% of patients had not yet experienced an OS event and the data continue to mature. The median progression-free survival (PFS) with idecabtagene vicleucel was 8.6 months (95% CI, 5.6-11.6), which matched previously reported numbers. This increased based on the level of response achieved, with those having a CR or better experiencing a PFS of 20.2 months.
The most common adverse events of any grade were cytopenias (97%) and cytokine release syndrome (CRS; 84%). Most incidences of CRS were grade 1/2 in severity (78%), with grade 3 CRS occurring in 5 patients and grade 4 CRS in 1 patient. Neurotoxicity (NT) of any grade was reported in 18% of patients, with 4 being grade 3. There were no grade 4/5 events.
“The benefit-risk profile of idecabtagene vicleucel is further reinforced by the updated data with low rates of severe CRS and our separate analysis showing low rates of mostly low-grade neurotoxicity in the KarMMa study, confirming that idecabtagene vicleucel represents an important treatment option for patients who have been exposed to many prior therapies,” said Anderson.
Full findings from the long-term analysis will be presented at the ASCO meeting on June 4. The March 2021 approval for idecabtagene vicleucel was specifically for adult patients with relapsed or refractory multiple myeloma after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The approval came with a boxed warning for CRS, NT, prolonged cytopenias, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome.