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

Those who were overweight received a higher median total dose of cyclophosphamide (P = 0.0001) and fludarabine (P = 0.0001), as stratified by BMI. However, there was no correlation between the results of response, 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 after commercial ide-cel, therefore suggesting that the 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 a higher absolute dose of LD chemotherapy and an increase in baseline and peak CRP levels after CAR-T infusion.”

Since obesity in patients with hematological malignancies has variable effects, such as poorer outcomes after CAR T-cell therapy in lymphoma and better outcomes in patients with multiple myeloma treated with immunotherapy, the researchers sought to determine whether baseline BMI affects the effectiveness of ide-cel.

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

There were 11 patients whose BMI was less than 25 kg/m² cohort and 29 in the group with a BMI of 25 kg/m² or more. The median patient age was 66.0 years (range, 43.0-78.0), 50% of patients were male, 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 state (92%). A majority (82%) had previously received autologous hematopoietic stem cell transplantation and the median number of prior lines of treatment was 6 (range, 4-13). Approximately two-thirds (72%) of patients received bridging therapy, and the median dose of CAR T-cell therapy 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 more was 86%, consisting of 11 complete responses (CR; 39.1%), 3 very good partial responses (VGPR; 11%) and 10 PR (36%); 6 of the patients who achieved CR had a negative minimal residual disease (MRD) response. ORR at 30 days in patients with a BMI less than 25 kg/m² was 73%, composed of 3 CR (27.1%), 2 VGPR (18%) and 3 PR (27%); 2 of the patients who achieved a CR had a negative MRD response. No statistically significant difference was noted between groups for ORR at 30 days (P = .4).

At 90 days, ORR in patients with a BMI of 25 kg/m² or more was 88%, comprising 11 CRs (45%), of which 8 were negative MRD responses and 9 PRs (38%). At the same time, ORR in people with a BMI of less than 25 kg/m² was 82%, consisting of 4 CRs (36%), all of which were negative MRD responses, and 4 PRs (36%). There was no statistically significant difference between the groups in terms of ORR at 90 days (P

There were higher baseline C-reactive protein (CRP) levels at 0.8 μg/dL (range, 0.0-9.0) for those with high BMI compared to 0.2 μg/ dL (range, 0.0-3.0) with low BMI (P = 0.049). Median peak CRP was higher in the 25 kg/m2 or greater group (5.6 μg/dL vs 1.5 μg/dL; P = 0.001).

Between BMI of 25 kg/m² or above and below 25 kg/m² groups, CRS all grades (83% vs 82%; P >0.9), time to onset of CRS (1.0 day each; P = 0.9), duration of CRS (2.0 days versus 1.0 day; P = 0.3) and NT of any grade (21% versus 27%; P = 0.7) were similar. Additionally, the use of steroids (P = .7) or tocilizumab (P >.9) to manage these toxicities were consistent regardless of BMI.

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

Reference

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