Ide-Cel Yields Consistent Outcomes for Relapsed/Refractory Myeloma Across Subgroups Stratified by Baseline BMI

­A correlation between total dose of cyclophosphamide and fludarabine as lymphodepletion prior to idecabtagene vicleucel (ide-cel; Abecma) and body mass index (BMI) was reported in a small retrospective analysis by the Moffitt Cancer Center.

Those who were overweight received a higher median total dose of both cyclophosphamide (P = .0001) and fludarabine (P = .0001), as stratified by BMI. However, there was no correlation between response outcomes, cytokine release syndrome (CRS)/neurotoxicity (NT) or infections, renal function, or lymphodepletion effect and BMI.

“This retrospective review did not find an association of BMI with early response or toxicities following commercial ide-cel, therefore suggesting therapy can be safely offered to overweight/obese patients,” the study authors who were led by Doris K. Hansen, MD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, wrote. “Obesity was associated with higher absolute dose of LD chemotherapy and increased baseline and peak CRP levels post CAR-T infusion.”

As obesity in patients with hematologic malignancies have varying effects, such as worse outcomes following CAR T-cell therapy in lymphoma and better outcomes in patients with multiple myeloma treated with immunotherapy, investigators set out to determine if baseline BMI had bearing on the efficacy of ide-cel.

Forty patients who received ide-cel with cyclophosphamide and fludarabine lymphodepletion who were 30 or more days from ide-cel infusion were included in the analysis. Overweight or obese status was at 25 kg/m² or above. The primary outcome measures were response at 30- and 90-day timepoints overall and by BMI. Secondary outcomes were toxicities at 30 and 90 days overall and by BMI.

There were 11 patients in the BMI below 25 kg/m² cohortand 29 in the group with BMI of 25 kg/m² or higher. Median patient age was 66.0 years (range, 43.0-78.0), 50% of patients were men, and most (82%) had an ECOG performance status of 0 or 1. Most patients (70%) had Revised International Staging System II status, extramedullary disease (57%), low tumor burden (65%), and double-refractory status (92%). A majority (82%) had previously received autologous hematopoietic stem cell transplant and the median number of prior lines of therapy was 6 (range, 4-13). Around two-thirds (72%) of patients were administered bridging therapy and the median CAR T-cell therapy dose was 416.1 × 10⁶ cells (126.0-456.4).

The objective response rate (ORR) at 30 days in patients with a BMI of 25 kg/m² or higher was 86%, comprised of 11 complete responses (CRs; 39.1%), 3 very good partial responses (VGPRs; 11%), and 10 PRs (36%); 6 of the patients who achieved CR had a negative minimal residual disease (MRD) response. The 30-day ORR in patients with a BMI lower than 25 kg/m² was 73%, comprised of 3 CRs (27.1%), 2 VGPRs (18%), and 3 PRs (27%); 2 of the patients who achieved CR had a negative MRD response. No statistically significant difference was noted between groups for either 30-day ORR (P = .4).

At 90 days, ORR in patients with a BMI of 25 kg/m² or above was 88%, comprised of 11 CRs (45%), of which 8 were MRD-negative responses, and 9 PRs (38%). At the same timepoint, ORR in those with a BMI lower than 25 kg/m² was 82%, comprised of 4 CRs (36%), all of which were MRD-negative responses, and 4 PRs (36%). No statistically significant difference was noted between groups in terms of 90-day ORR (P < .6).

There were greater baseline levels of C-reactive protein (CRP) at 0.8 μg/dL (range, 0.0-9.0) for those with high BMI vs 0.2 μg/dL (range, 0.0-3.0) with low BMI (P = .049). Median maximum CRP was higher in the 25 kg/m2 or above group (5.6 μg/dL vs 1.5 μg/dL; P = .001).

Between the BMI of 25 kg/m² or above and below 25 kg/m² groups, any-grade CRS (83% vs 82%; P >.9), time to CRS onset (1.0 days each; P = .9), duration of CRS (2.0 days vs 1.0 days; P = .3), and any-grade NT (21% vs 27%; P = .7) were similar. Additionally, use of steroids (P = .7) or tocilizumab (P >.9) to manage these toxicities were consistent, regardless of BMI.

“Longer follow-up, larger number of patients, and correlative studies on CAR-T kinetics are required to establish significance of obesity on CAR-T outcomes,” concluded the authors. These results were presented in a poster as part of the 2022 Tandem Meeting.

Reference

Hansen DK, Shrewsbury AM, Peres L, et al. Impact of obesity on lymphodepletion and outcomes following idecabtagene vicleucel. Presented at: 2022 Tandem Meeting; April 23-26, 2022; Salt Lake City, UT. Abstract 243.