Idecabtagene vicleucel (ide-cel; Abecma) showed an efficacy and safety profile in real-world patients with relapsed or refractory multiple myeloma (RRMM) that was comparable to what was observed in the phase 2 KarMMa trial (NCT03601078), even if 75% of patients would not have satisfied the trial eligibility criteria. Findings were published in a retrospective analysis in the Journal of Clinical Oncology.1
Of 196 patients, 159 received ide-cel before the data cut-off time. In this group, the rate of any grade or grade 3 or higher cytokine release syndrome (CRS) was 82% (n = 131), and 3% (n = 5), respectively. Neurotoxicity of any grade was observed in 18% of patients (n = 29) and grade 3 or higher events were reported among 6% (n = 9).
The best overall response rate was 84% ​​with a complete response (CR) or better rate of 42%. In addition, at a median follow-up of 6.1 months from infusion, the median progression-free survival (PFS) was 8.5 months (95% CI, 6.5-not reached). [NR]), and the median overall survival was 12.5 months (95% CI, 11.3-NR).
Of note, multivariate analysis identified that the following baseline characteristics were associated with inferior PFS: previous B-cell maturation antigen-targeted therapy use (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), ECOG performance status of 2 to 4 at time of lymph depletion (HR, 0.97; 95% CI, 0.95–1.00; p = .043), and younger age (HR, 2.19; 95% CI, 1.16–4.14; p = .016).
“Overall, we observed comparable efficacy and toxicity to ide-cel as reported in the KarMMa trial even though 75% of our patients would not have met KarMMa eligibility criteria,” wrote Doris K. Hansen, MD, of the Department of Blood Marrow Transplantation and Cellular Immunotherapy at Moffitt Cancer Center, and co-investigators, in the study. “The most common reasons for trial ineligibility included inadequate organ function, prior exposure to BCMA-TT, cytopenias, and poor performance status.”
Further, they noted that 90% of eligible patients were managed ide-cel in the real world, which is comparable to the 91% management rate in the KarMMa trial.
“Our data indicate that the administration of CAR T in the real world is feasible, safe and effective, even among patients with diseases,” study authors said.
The phase 2 KarMMa trial supported the 2021 approval of ide-cel for patients with RRMM, after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.2
In KarMMa, the overall response rate (ORR), CR rate, and minimal residual disease (MRD) negative rates were 73%, 33%, and 26%, respectively.3 However, the KarMMa trial eligibility criteria are unlikely to best represent patients for whom ide-cel is a standard of care, especially since most patients with comorbidities would not have been able to participate in the trial.1 The aim of this retrospective analysis, therefore, was to see how the ideal-target profile translated to a population of real patients.
Investigators evaluated data retrospectively collected from patients with RRMM who underwent leukapheresis across 11 different institutions to receive commercial ide-cel. American Society of Transplantation and Cell Therapy guidelines were used to grade and manage relevant toxicities, according to each institution’s policies. Patient responses were graded according to the response criteria of the International Myeloma Working Group.
All patients included in this analysis received at least 4 prior lines of therapy and underwent leukapheresis between April 1, 2021 and February 28, 2022. After leukapheresis, patients could receive bridging therapy in the form of chemotherapy and/or radiation at discretion. by the treating physician. Lymphodepleting chemotherapy was administered once daily on days -5, -4-, and -3 leading up to CAR T-cell infusion.
A total of 196 patients completed leukapheresis with intent to produce and receive commercial ide-cel. At data cutoff, 17 patients could not receive CAR T, 5 due to manufacturing failure and 12 due to disease progression or death. Twenty patients were waiting for an infusion.
Study authors noted that a key component of managing CAR T-cell therapy is the successful and timely manufacture of the product. In the real-world analysis, fabrication error occurred in 6% (n = 12 of 196) of patients undergoing first apheresis, which was higher than the fabrication failure rate seen in the KarMMA trial (n = 1 of 140). They speculated that poor bone marrow reserves could contribute to this, and they argue that future efforts should consider factors associated with poor CAR T cell production to allow for optimal patient selection. Seven of those who had production failure (58%) were able to successfully repeat apheresis.
The median number of days spent in the hospital was 9 (range, 5–69 days). The percentage of patients who received tocilizumab (Actemra), anakinra, or glucocorticoids for CRS, neurologic toxicity, or both were 71%, 5%, and 26%, respectively.
The rates of any grade neutropenia, anemia, and thrombocytopenia were 97%, 95%, and 95%, respectively. The percentage of patients who experienced these adverse events (AEs) of grade 3 or worse severity were 88%, 51% and 68%.
Thirty days after infusion, there was evidence of neutropenia in 60% of patients, anemia in 38%, and thrombocytopenia in 59%. Additionally, 74% of patients received granulocyte colony-stimulating factor, 15% received a thrombopoietin agonist, and 5% received an autologous stem cell boost. The rate of infection was 34% (n = 52), this included 31 bacterial (20%), 24 viral (16%), and 2 fungal infections (1%).
At last follow-up, 19% (n = 31) patients who received commercial ide-cel had died, this included 20 deaths related to disease progression, 8 non-relapse-related deaths, and 2 deaths for which the cause was unknown. Non-relapse-related causes of death included grade 5 CRS, hemophagocytic lymphohistiocytosis along with concurrent grade 5 CRS, neurologic toxicity, COVID-19 disease, and cardiomyopathy.
A total of 159 patients were evaluable at day 30 and best overall responses; 149 patients were evaluable for 90-day responses because 10 patients who were in active follow-up did not reach this time.
The best ORR rate and rate of CR or better after commercial ide-cel was 84% ​​and 42%, respectively. In patients who achieved a CR or strict complete response, 72% achieved MRD-negative status.
The 30-day ORR rate was 78% and the 90-day ORR was 72%; the corresponding CR rates were 30% and 38%, respectively. The median time for both overall response and the rate of CR or better was 30 days. The median duration of response was 8.6 months (95% CI, 6.6-NR).
Limitations of the study include the retrospective design, limited follow-up and heterogeneity in institutional standard for toxicity management across different centers, according to the researchers.
“The safety profile of ide-cel in our real-world cohort was comparable to those in the KarMMa trial, with similar rates of CRS, [neurotoxicity]infections, and persistent cytopenias,” study authors concluded. “It is feasible to administer ide- [standard of care]with high response rates and a low incidence of severe CRS and [neurotoxicity]although persistent cytopenias remain an ongoing problem.”
References
- Hansen DK, Sidana S, Peres LC, et al. Idecabtagene vicleucel for 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
- Abecma Prescribing information. Bristol-Myers Squibb Company; 2022. Accessed February 1, 2023. https://bit.ly/3kZ0pWu
- Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850
