Doris K. Hansen, MD, discussed results of an efficacy analysis examining the BCMA-directed CAR T-cell therapy idecabtagene vicleucel in real-world treatment of patients with relapsed/refractory multiple myeloma.
The B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (Abecma) demonstrated clinical benefits in a real-world standard-of-care setting akin to those observed in the registrational phase 2 KarMMa-1 trial (NCT03361748), according to results from an analysis presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1
“Delivery of idecabtagene vicleucel appears to be safe and feasible in real-world settings, and patients don’t need to meet clinical trial criteria to benefit from this treatment,” Doris K. Hansen, MD, assistant member in the Moffitt Cancer Center Department of Blood and Marrow Transplant and Cellular Immunotherapy as well as chief investigator of this study, said in an interview with CancerNetwork®.
This multicenter retrospective study of real-world outcomes demonstrated comparable efficacy and toxicity in patients commercially treated with idecabtagene vicleucel vs those treated with the same therapy in the KarMMa-1 trial, even though 77% would have been ineligible for inclusion in the trial. After a median follow-up of 5.3 months, the overall response rate (ORR) was 86% in this study population vs 73% at 24.8 months in the KarMMa-1 trial population. Investigators concluded that the use of idecabtagene vicleucel is feasible in real-world settings.
Hansen: Idecabtagene vicleucel was approved by the FDA in March 2021 based on the pivotal phase 2 KarMMa-1 clinical trial.2,3 The last median follow-up was at 24.8 months, [at which time] the ORR was found to be 73%, with 33% of patients achieving a complete response or better. Moreover, the MRD-negative rate was 79%, the median progression free survival [PFS] was roughly 8.6 months, and the duration of response was roughly 10.9 months.
Our study was a multicenter observational analysis of patients treated with standard-of-care idecabtagene vicleucel at 11 medical centers in the United States. We leukapheresed a total of 196 patients, out of which 159 were infused. It’s important to note that 77% [n = 150] of this patient population would have been ineligible for participation in the KarMMA-1 trial, most commonly due to prior exposure to BCMA-targeted therapy, organ dysfunctions like renal insufficiency, poor performance status, and cytopenias.
Notably, the fact that 77% of our patients would have been ineligible did not appear to impact efficacy. Our median follow up was approximately 5.3 months and the best ORR was 86%. Additionally, 42% of patients achieved a complete response or better. The MRD-negative rate was 78% and the projected median PFS was 8.9 months. [These all] resembled the results from KarMMa-1.
The safety profiles were also consonant—[we saw similar rates of] cytokine release syndrome, neurotoxicity, and hematologic toxicity. We identified on a multivariable model that patients previously exposed to BCMA-targeted therapy experienced inferior outcomes, which impacted rates of complete response and PFS. Patients with high-risk cytogenetics also showed inferior PFS.
Yes, certainly. An area of active investigation within the United States Multiple Myeloma Cellular Therapy Consortium is the question of prior BCMA exposure. We have done a very small analysis thus far. Roughly 43 patients [22%] in our study had received prior BCMA-targeted therapy and 33 were infused. Of that number, 25 had received prior treatment with belantamab mafodotin [Blenrep], 4 had received other BCMA-targeted therapies on trials, and 4 had received prior BCMA-targeted CAR T-cell therapies, of whom 3 received [Allogene’s investigational CAR T-cell therapy].
There was certainly a difference in outcomes. Median PFS in patients who had received any prior BCMA-targeted therapy was 5.8 months as compared with 8.9 months in the total study population. Patients who had received some other BCMA CAR T-cell therapy on trial, such as [treatment with] bispecific antibodies, showed a median PFS of 2.7 months.
We need more information, more granularity, in this BCMA-targeted therapy story. We need more analysis of the timing, duration of response, and mechanism of action in patients receiving prior BCMA-targeted therapy. Hopefully we will present those data soon.
There are also sub-analyses trying to identify the appropriate dosage of fludarabine for patients with renal insufficiency. We’re also analyzing outcomes by ethnicity and we have several ongoing collaborations with Bristol Meyers Squibb to generate predictive models of toxicity and efficacy.
Idecabtagene vicleucel has been a tremendous new therapy option for patients, especially those who have taken multiple lines of therapy. The median PFS is longer [with this treatment], and so it provides patients with another good treatment option. [Our study shows] that delivery of idecabtagene vicleucel is feasible in a real-world standard-of-care setting and that patients need not meet the KarMMa-1 trial criteria to benefit from this treatment.
As we discussed, 77% of our patients didn’t meet the eligibility criteria for KarMMa-1 and yet efficacy was not impacted. Moreover, prior exposure to BCMA-targeted therapy and high-risk cytogenetics appear to be independent predictors of inferior outcomes. Further investigation is needed into the granularity of BCMA-targeted therapy.