Sequential T-Cell Redirection Therapies Yield Deep, Durable Responses in R/R Multiple Myeloma

Sequential use of different T cell redirection therapies, including chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies (BiAb) led to deep and durable responses in patients with relapsed/refractory multiple myeloma following relapse after BiAb therapy.¹

“As the clinical use and advancement of T-cell redirection therapies continue to grow, effective strategies are needed to manage outcomes for patients who relapse or are unresponsive to this initial treatment,” senior author Samir Parekh, MD, Director, Translational Research in Myeloma, and co-leader, Cancer Clinical Investigation program, The Tisch Cancer Institute, and member, Icahn Genomics Institute, Icahn School of Medicine, Mount Sinai, said in a statement.²

Parekh and colleagues assessed 58 evaluable patients that had relapsed after participating in a phase 1 or phase 2 BiAb trial at Mount Sinai’s Tisch Cancer Institute. These patients had a median age of 7 years (range, 41-83) at the time of their first salvage therapy (FST), had a median of prior lines of therapy (range, 3-17), and around half (52%) were male. FST was administered after a median of 82 months (range, 15-212) after the previous trial. Most (83%) had received at least one autologous stem cell transplant, 6 patients had previous anti-BCMA therapy, including antibody-drug conjugate and CAR T-cell therapy,and 40% had extramedullary disease after the previous trial. All patients were triple-class exposed, with 88% being triple-class refractory and 43% penta-drug refractory at enrollment.

Participants in the trial received a median of 2 lines of salvage therapy (range, 1-9), including a second BiAb(n = 10) and BCMA-directed CAR T-cell therapy (n = 9). Nineteen patients received chemotherapy. 32 received combination chemotherapy regimens and 3 received a BCMA antibody-drug conjugate. Most patients received a second salvage therapy (SST; n = 37). More patients that received T-cell redirection therapies as FST (n = 11; 58%) continued to have a response compared to those who received non-T cell redirection therapy as FST (n = 3; 8%).

READ MORE: Achieving Deep Responses With CART-ddBCMA in Relapsed/Refractory Multiple Myeloma

“The clinical outcomes of RRMM patients progressing after clinical trials of BiAbs are still unknown and whether patients could be salvaged with other BiAbs or CAR-Ts remains an important clinical question,” Parekh and colleagues wrote in their paper, published in Blood Advances.¹

Overall response rate was 60%: 13 patients had complete responses (CR), 4 had very good partial responses (VGPR), 18 had partial responses (PR), 2 had minimal residual disease (MRD), 9 had stable disease (SD), and 12 had disease progression. ORR was 84% in patients that received a T-cell redirection therapy as FST compared to 49% in those who did not (P <.01). Similarly, these patients had a progression free survival (PFS) after FST of 28.9 months (95% CI, 18.7-not estimable [NE]) compared to 2.6 months (95% CI, 1.9-4.1).

Specifically, patients that received BiAb FST had a median PFS of 18.7 months (95% CI, 2.3-18.7) while patients that received CAR T-cell therapy did not reach median PFS (95% CI, 28.9-NE; ^P = .1054). Median PFS after SST was 30.9 months (95% CI, 1.3-37.3) in patients that received T-cell redirection therapy compared to 5.7 months (95% CI, 3.7-7.7) in patients that received other SSTs and median OS was not reached (95% CI, 21.4-NE) in the T-cell SST group compared to 12.1 months (95% CI, 8.6-30.5) in the other therapies group.

Median OS was not reached in patients with CAR T-cell therapy as FST compared to 21.4 months (95% CI, 21.3-NE; P = .1730). Altogether, the 28 patients who received T-cell redirection therapy as FST or SST did not reach a median OS (95% CI, 24.0-NE) and was 62% (95% CI, 44%-88%) at 2 years, compared to a median OS of 9.6 months (95% CI, 5.5-22.5) and 24% (95% CI, 11%- 49%) at 2 years for the other 30 patients.

“This study shows patients relapsing after initial bispecific antibodies therapy can benefit from a second bispecific antibody or CAR-T cell therapy,” Parekh added to the statement.²

REFERENCES

1. Mouhieddine TH, Oekelen OV, Melnekoff DT, et al. Sequencing T-cell redirection therapies leads to deep and durable responses in relapsed/refractory myeloma patients. Blood Adv. Published online August 2, 2022. doi: 10.1182/bloodadvances.2022007923
2. Mount Sinai researchers report encouraging immunotherapy option for relapsed myeloma patients. News release. Mount Sinai. September 1, 2022. https://www.mountsinai.org/about/newsroom/2022/mount-sinai-researchers-report-encouraging-immunotherapy-option-for-relapsed-myeloma-patients