Doris K. Hansen, MD, Analyzes Real-World Experiences With Idecabtagene Vicleucel in Relapsed/Refractory Multiple Myeloma

Doris K. Hansen, MD
Assistant Member, Department of Blood and Marrow Transplant and Cellular Immunotherapy
Moffitt Cancer Center
Tampa, FL

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.

CancerNetwork^®: What clinical outcomes were seen with idecabtagene vicleucel in this patient population?

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.

Were there any notable differences between the clinical outcomes in KarMMA-1 and the real-world outcomes examined in your study?

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.

Are there any future analyses of this research planned?

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.

How do you think this new CAR T-cell therapy idecabtagene vicleucel impacted the treatment landscape?

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.

What do you hope your colleagues take away from this research?

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.

References

1. Hansen DK, Sidana S, Peres L, et al. Idecabtagene vicleucel (Ide-cel) chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory multiple myeloma (RRMM): Real-world experience. J Clin Oncol. 2022;40(16):8042. doi:10.1200/JCO.2022.40.16_suppl.8042
2. 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
3. FDA approves idecabtagene vicleucel for multiple myeloma. News release. FDA. March 29, 2021. Accessed September 15, 2022. https://bit.ly/3eI693Q