Comparison of Fludarabine/Cyclophosphamide Vs Bendamustine As Lymphodepleting Regimen for CAR-T: A Safety and Efficacy Analysis in Patients with Relapsed/ Refractory Multiple Myeloma

Background

Two commercially available anti-BCMA chimeric antigen receptor T-cell therapies (CAR-T) are

approved by FDA for use in patients with relapsed multiple myeloma (RRMM). Lymphodepletion

(LD) with fludarabine in combination with cyclophosphamide (Flu/Cy) is used as a standard

regimen sequentially prior to CAR-T. Due to a national shortage with regards to availability of

fludarabine, bendamustine (B) has emerged as a possible alternative regimen for LD.

We evaluated the impact of bendamustine as an alternative lymphodepleting regimen to Flu/Cy

on safety and efficacy profile of CAR-T therapy in patients with relapsed multiple myeloma.

Patients and methods

We conducted a single center, retrospective, IRB-approved study for patients with RRMM who

received LD with B and FC at Hackensack University Medical Center (HUMC). Efficacy

outcomes included overall response rates (ORR), Progression free survival (PFS) and Overall

survival (OS). Response to CAR-T was assessed by the treating physician per International

Myeloma Working Group (IMWG) criteria. Safety outcomes included the incidence and severity

of adverse events (AEs). AEs were graded using National Cancer Institute Common

Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0). Cytokine release

syndrome (CRS) and immune effector associated neurotoxicity syndrome (ICANS) were graded

as per the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

Results

We identified 53 patients with RRMM who received anti-BCMA CAR-T therapy between 6/2021

and 6/2023, who had a follow-up of at least 30 days following infusion. Due to shortage of

fludarabine, the majority of pts (67.9%) received LD with B. Baseline characteristics are

described in table 1. The median age of the entire cohort was 69.6 years, not significantly

different between the B vs FC group. There were no statistically significant differences between

the two groups with respect to the baseline characteristics except more pts were male in the B

group (66.7% vs 32.1%, p=0.03) and the type of CAR-T product received. No significant

differences were found with regards to the safety profile; however, the ORR were found to be

higher in the FC group compared to the B group (88.2% vs 69.4%) although not statistically

significant (p=0.1). Median PFS (mPFS) was shorted in the B group compared with the FC

group (7.7 months vs 13.1 months) respectively (p=0.0047). Median OS (mOS) was not

reached in the FC group, whereas it was 12.4 months in the B group, p=0.5.

Conclusions

LD with B was not found to have any significant impact on the CRS or ICANS, however a lower

ORR (although not statistically significant) was found. mPFS was shorter for the B group

compared to the FC group which was a statistically significant finding. Although the follow-up is

short, our experience suggests that the use of B as LD may have a negative impact on

outcomes of pts receiving CAR-T therapy for RRMM.