Dr Patel on Safety Data and Biomarker Outcomes With Ide-Cel in High-Risk R/R Multiple Myeloma

Krina K. Patel, MD, MSc, associate professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the safety profile of idecabtagene vicleucel (ide-cel, Abecma) in a subgroup of patients with high-risk, relapsed/refractory multiple myeloma, as well as findings with soluble BCMA levels from the phase 3 KarMMa-3 trial (NCT03651128).

KarMMa-3 investigated the efficacy and safety of ide-cel vs standard of care (SOC) in patients with relapsed/refractory multiple myeloma who had received 2 to 4 prior therapies. In high-risk patient subgroups, treatment with ide-cel did not lead to an increased safety risk compared with SOC, even when administered in earlier lines of therapy, Patel says. The investigators hypothesized that patients who had received few prior lines of therapy would experience more adverse effects than more heavily pretreated patients, as shown in trials with checkpoint inhibitors in patients with multiple myeloma, Patel notes. However, in KarMMa-3, on average, patients experienced a lower incidence of cytokine release syndrome (CRS), few had high-grade CRS, and the investigators reported no Parkinsonism.

Although these data indicate that ide-cel is safe in the high-risk multiple myeloma population, long-term data are needed to confirm the safety of this agent in all patient subgroups, especially those with standard-risk disease for whom other potentially safer treatment options are available, Patel explains.

In addition, patient-reported outcomes from KarMMa-3 demonstrate that patients who received ide-cel experienced improved quality of life (QOL) compared with those who continued SOC. Therefore, patients receiving SOC may in the future switch to ide-cel, since this agent can improve both disease outcomes and QOL, Patel emphasizes.

Furthermore, an analysis of soluble BCMA levels in the high-risk population evaluated for safety showed that although both the ide-cel and SOC arms had similar soluble BCMA levels at screening, across all subgroups, the patients who received ide-cel achieved deeper tumor clearance compared with those who received SOC. Additionally, in the ide-cel arm, although BCMA levels slowly rose during disease progression, they remained lower compared with the BCMA levels in patients who progressed in the SOC arm, according to Patel. These findings show that ide-cel may change the multiple myeloma disease biology to a less aggressive form, Patel says. Decreased soluble BCMA levels are associated with decreased tumor burdens and may be a biomarker to use with novel therapies, such as ide-cel, in the future, Patel concludes.