Real-World Data Confirm Ide-cel Safety and Efficacy for Patients With Multiple Myeloma

Doris K. Hansen, MD

Idecabtagene vicleucel (ide-cel; Abecma) demonstrated 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 though 75% of patients would not have met the trial eligibility criteria. Findings were published in a retrospective analysis in the Journal of Clinical Oncology.¹

Out of 196 patients, 159 received ide-cel by the time of data cutoff. 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. Any-grade neurotoxicity was observed in 18% of patients (n = 29) and grade 3 or higher events were reported among 6% (n = 9).

The rate of best overall response was 84% with a complete response (CR) or better rate of 42%. Moreover, 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, a multivariable analysis identified that the following baseline characteristics were linked 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), an ECOG performance status of 2 to 4 at time of lymphodepletion (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 with ide-cel as reported in the KarMMa trial although 75% of our patients would not have met KarMMa eligibility criteria,” wrote Doris K. Hansen, MD, of the Department of Blood Marrow Transplant 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 administered ide-cel in the real-world setting, which is comparable with the 91% administration rate in the KarMMa trial.

“Our data indicate that CAR T administration in the real world is feasible, safe, and effective, even among patients with comorbidities,” 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 not believed to best represent patients for whom ide-cel is a standard of care, particularly because most patients with comorbidities would not have been able to participate in the trial.¹ The goal of this retrospective analysis, therefore, was to see how the profile of ide-cel translated to a population of real-world patients.

Investigators assessed data retrospectively collected from patients with RRMM who underwent leukapheresis across 11 different institutions in order to receive commercial ide-cel. The American Society of Transplantation and Cellular Therapy guidelines were used to both grade and manage corresponding toxicities, according to each institution’s policies. Patient responses were graded in accordance with the International Myeloma Working Group response criteria.

All patients included in this analysis had received at least 4 prior lines of therapy and underwent leukapheresis between April 1, 2021, and February 28, 2022. Following leukapheresis, patients could receive bridging therapy in the form of chemotherapy and/or radiation at the discretion of 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 manufacture and receive commercial ide-cel. At data cutoff, 17 patients were unable to receive CAR T, 5 because of manufacturing failure and 12 because of a disease progression or death. Twenty patients were pending infusion.

Study authors noted that a key component of administering CAR T-cell therapy is the successful and timely manufacturing of the product. In the real-world analysis, manufacturing error occurred in 6% (n = 12 of 196) of patients undergoing first apheresis, which was higher than the rate of manufacturing failure seen in the KarMMA trial (n = 1 out 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 manufacturing to allow for optimal patient selection. Seven of those who had manufacturing 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, neurological toxicity, or both was 71%, 5%, and 26%, respectively.

The rates of any-grade neutropenia, anemia, and thrombocytopenia was 97%, 95%, and 95%, respectively. The percentage of patients who experienced these adverse events (AEs) at a grade 3 or worse severity was 88%, 51%, and 68%.

Thirty days postinfusion, there was evidence of neutropenia in 60% of patients, anemia in 38%, and thrombocytopenia in 59%. Moreover, 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 the last follow-up, 19% (n = 31) patients who received commercial ide-cel had died, this included 20 deaths related to disease progression, 8 nonrelapse-related deaths, and 2 deaths for which the cause was unknown. Nonrelapse related mortality causes included grade 5 CRS, hemophagocytic lymph histiocytosis along with concomitant grade 5 CRS, neurological 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 since 10 patients who were in active follow-up had not reached this time point.

The best ORR rate and rate of CR or better after commercial ide-cel were 84% and 42%, respectively. In patients who received CR or a stringent complete response, 72% reached 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 investigators.

“The safety profile of ide-cel in our real-world cohort was comparable with those in the KarMMa trial, with similar rates of CRS, [neurotoxicity], infections, and persistent cytopenias,” study authors concluded. “It is feasible to administer ide-cel as [standard of care], with high response rates and low incidence of severe CRS and [neurotoxicity], although persistent cytopenias remain an ongoing issue.”

References

1. 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
2. Abecma. Prescribing information. Bristol-Myers Squibb Company; 2022. Accessed February 1, 2023. https://bit.ly/3kZ0pWu
3. 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