Researchers found that the addition of lenalidomide before apheresis improved pharmacodynamics in patients with multiple myeloma undergoing autologous hematopoietic cell transplantation.
The study was presented by Debashree Basudhar, of Bristol Myers Squibb, at the 67th ASH Annual Meeting and Exposition.
AHCT can result in T-cell dysfunction and impact the effectiveness of subsequent lines of therapy in this patient population.
This analysis assessed two cohorts from the KarMMa-2 study:
- Cohort 2C included newly diagnosed MM patients with a best overall response of less than very-good partial response after frontline AHCT. This cohort had an overall response rate (ORR) of 87.1% and a complete response rate (CRR) of 80.6% with idecabtagene vicleucel treatment. Median time from AHCT was 5.8 months.
- Cohort 3 included newly diagnosed MM patients who had less than a complete response after AHCT. Median time from AHCT was 4.2 months. This cohort received lenalidomide pre-apheresis.
Baseline soluble BCMA (sBCMA) was lower in both cohorts compared with a relapsed/refractory MM population, but cohort 2C showed higher sBCMA than cohort 3 (27 vs 14.5 ng/mL). Cohort 3 had improved T-cell fitness, with greater CD8 TEM, fewer CD8 TEMRA cells, and reduced expression of CD57, PD-1, and CD38 across CD4 and CD8 subsets. Cohort 3 patients also exhibited lower Ki67 and CTLA4 on CD4 T cells and higher CD27 expression on CD4 TCM and TEM, “suggesting a less differentiated and potentially more effective drug product phenotype,” the authors noted.
Cohort 3 had increased levels of IL2, IL7, and perforin, which the authors said may support enhanced chimeric antigen receptor (CAR)-T cytotoxic activity, while lower levels of IFNγ indicated a more favorable immune microenvironment.
At day 15 post-infusion, cohort 3 had higher abundance of TEM and lower abundance of TCM subtypes in both CD4 and CD8 CAR T cells. CAR T-cell expansion was comparable between the two cohorts, and cellular kinetics were similar to those with relapsed/refractory MM from the KarMMa-3 trial.
Cohort 3 also had “superior” clearance of sBCMA compared with cohort 2C (93.3%; n=28/30 vs 77.4%; n=24/31), “indicating enhanced [pharmacodynamic] activity,” according to the researchers.
Reference
Tang H, Thompson E, Descalzi-Montoya D, et al. Impact of lenalidomide pre-apheresis on markers of T cell fitness and pharmacodynamic biomarkers in newly diagnosed multiple myeloma patients with suboptimal response to autologous stem cell transplantation. Abstract #9163. Presented at the 67th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2025; Orlando, Florida.
