Idecabtagene vicleucel (ide-cel; Abecma) demonstrated an efficacy and safety profile in real-world patients with relapsed or refractory multiple myeloma (RRMM), which was 75%, but comparable to that observed in the phase 2 KarMMa trial (NCT03601078). was possible. The majority of patients would not have met the trial criteria. The results of the study were published in a retrospective analysis Journal of Clinical Oncology.1
Of the 196 patients, 159 received ide-cel at the time of data cutoff. In this group, 82% (n = 131) and 3% (n = 5) had any grade or grade 3 or higher cytokine release syndrome (CRS). Neurotoxicity of any grade was observed in 18% (n = 29) of patients and grade 3 or higher in 6% (n = 9).
The best response rate was 84%, complete response (CR) or better at 42%. In addition, median progression-free survival (PFS) was 8.5 months (95% CI, 6.5 not reached) with a median follow-up of 6.1 months after infusion. [NR]), median survival was 12.5 months (95% CI, 11.3-NR).
Multivariate analysis revealed that the following baseline characteristics were associated with inferior PFS: use of prior B-cell maturation antigen-targeted therapy (BCMA-TT; HR, 2.81; 95% CI, 1.44–5.51; P = .003), high-risk cytogenetics (HR, 2.31; 95% CI, 1.34–3.97; P = .003), 2-4 ECOG performance status during lymphadenopathy (HR, 0.97; 95% CI, 0.95-1.00; P = .043), younger age (HR, 2.19; 95% CI, 1.16-4.14; P = .016).
“Overall, we observed comparable efficacy and toxicity to ide-cel in the KarMMa trial, but 75% of our patients did not meet KarMMa criteria,” wrote Dr. Doris K. Hansen of the Department of Blood Marrow Transplantation. Moffitt Cancer Center’s Cellular Immunotherapy and co-investigators in the study. “The most common reasons for failure to pass the test include inadequate organ function, prior exposure to BCMA-TT, cytopenias, and poor performance.”
Furthermore, they noted that 90% of eligible patients used ide-cel in the real-world setting, which is comparable to the 91% administration rate in the KarMMa trial.
“Our data demonstrate that CAR T is feasible, safe, and effective in the real world, even in patients with comorbidities,” the study authors wrote.
The phase 2 KarMMa trial supported the 2021 approval of ide-cel in patients with RRMM after 4 or more prior therapies including immunomodulators, proteasome inhibitors, and anti-CD38 monoclonal antibodies.2
In KarMMa, the overall response rate (ORR), CR rate, and minimal residual disease (MRD) adverse rate were 73%, 33%, and 26%, respectively.3 However, the KarMMa trial criteria do not best represent patients for whom ide-cel is the standard of care, especially since most patients with comorbidities were not eligible for the trial.1 Therefore, the purpose of this retrospective analysis was to see how the ide-cel profile translated to a real-world patient population.
Researchers retrospectively evaluated data collected from patients with RRMM who underwent leukapheresis at 11 different institutions to receive commercial ide-cel. American Society for Transplantation and Cell Therapy guidelines were used to categorize and manage relevant toxicities according to each institution’s policy. Patient response was categorized according to the International Myeloma Task Force response criteria.
All patients included in this analysis received at least 4 cycles of leukapheresis between April 1, 2021, and February 28, 2022. After leukapheresis, patients may receive optional adjuvant therapy in the form of chemotherapy and/or radiation. of the attending physician. Lymphodepressant chemotherapy was administered once daily on days -5, -4, and -3 until CAR T-cell infusion.
A total of 196 patients were treated with leukapheresis, with the aim of receiving commercial ide-cel. At the time of data cutoff, 17 patients did not receive CAR T, 5 due to manufacturing failure, and 12 due to disease progression or death. Twenty patients were awaiting infusion.
A key component of CAR T-cell therapy is the successful and timely production of the product, the study authors say. In a real-time analysis, production failure occurred in 6% (n = 12 of 196) of first-time apheresis patients, which was higher than the production failure rate observed in the KarMMA trial (n = 1 of 140). They hypothesize that poor bone marrow reserve may be a contributing factor, and further efforts should consider factors associated with poor CAR T cell production to allow for optimal patient selection. Seven (58%) of those with production failure had successful repeat apheresis.
The median number of hospital days was 9 (range, 5–69 days). The percentages of patients who received tocilizumab (Actemra), anakinra, or glucocorticoids for CRS, neurotoxicity, or both were 71%, 5%, and 26%, respectively.
Neutropenia of any grade, anemia, and thrombocytopenia were 97%, 95%, and 95%, respectively. The percentages of patients who experienced these adverse events (AEs) were grade 3 or worse, 88%, 51%, and 68%, respectively.
30 days after infusion, 60% of patients had neutropenia, 38% had anemia, and 59% had thrombocytopenia. Additionally, 74% of patients received granulocyte colony-stimulating factor, 15% thrombopoietin agonist, and 5% autologous stem cell augmentation. The infection rate was 34% (n = 52), including 31 bacterial (20%), 24 viral (16%), and 2 fungal infections (1%).
At last follow-up, 19% (n = 31) of patients receiving commercial ide-cel died, including 20 deaths due to disease progression, 8 non-relapse deaths, and 2 deaths of unknown cause. Non-relapse causes of death included grade 5 CRS, hemophagocytic lymphoid histiocytosis, grade 5 CRS, neurotoxicity, COVID-19 disease, and cardiomyopathy.
A total of 159 patients were evaluated at day 30 and had a best response; 149 patients had a 90-day response, as 10 patients in active surveillance did not reach this time.
Best ORR rate and r84% and 42% achieved CR or better after commercial ide-cel, respectively. 72% of patients with CR or strong complete response achieved MRD-negative status.
30-day ORR rate 78%, 90-day ORR 72%; the corresponding CR rates were 30% and 38%, respectively. The median duration of both overall response and CR or greater was 30 days. Median time to response was 8.6 months (95% CI, 6.6-NR).
According to the researchers, limitations of the study include retrospective design, limited follow-up, and heterogeneity of institutional standards for toxicity management across different centers.
“Our real-world safety profile of ide-cel was comparable to that of the KarMMa trial, with similar levels of CRS. [neurotoxicity], infection, persistent cytopenia, “said the authors of the study. “It can be managed as ide-cel [standard of care]higher response rates, lower incidence of severe CRS and [neurotoxicity]Although persistent cytopenia remains a persistent problem.”
Reference
- Hansen DK, Sidana S, Peres LC, et al. Idecabtagen vicleusel in relapsed/refractory multiple myeloma: real-world experience from the myeloma CAR T consortium. J Clin Oncol. Published online January 9, 2023. doi:10.1200/JCO.22.01365
- Abekma. Prescription Information. Bristol-Myers Squibb Company; 2022. Accessed 1 February 2023. https://bit.ly/3kZ0pWu
- Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene viclecel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi: 10.1056/NEJMoa2024850
