Real World Outcomes of Multiple Myeloma Patients Who Underwent Apheresis for Planned Chimeric Antigen Receptor (CAR) T Cell Therapy: A Single Center Experience
Authors: Bangolo Ayrton I , Gill Sarvarinder Kaur , Amoozgar Behzad , Dey Shraboni , Slotky Ronit , Siegel David S. , Parmar Harsh , Biran Noa , Vesole David H. , Phull Pooja 
Published: December 2024

Background: Despite the promising outcomes demonstrated by Chimeric Antigen Receptor T-cell (CAR-T) therapy in heavily pretreated Relapsed/Refractory Multiple Myeloma (RRMM), the manufacturing time for CAR-T presents significant challenges in treating, primarily due to the lengthy and complex process of harvesting, modifying, and expanding the patient's T-cells, which can take several weeks. This delay is critical for patients with rapidly progressing disease, who may experience substantial health decline during this period. Furthermore, the variability in T-cell quality and manufacturing success can impact the efficacy and safety of the therapy, with some patients facing manufacturing failures or delays.

Our study aimed to review the outcomes of RRMM patients who underwent T-cell collection for CAR-T therapy but did not receive the infusion, focusing on the reasons for this. Additionally, we evaluated progression-free survival (PFS) and overall survival (OS) in patients who received CAR-T therapy. We specifically sought to evaluate the PFS and OS for patients receiving these therapies when calculated from the date of apheresis for CAR-T.

Methods: Following institutional review board approval at Hackensack University Medical Center, we included all patients with RRMM who underwent T-cell apheresis for CAR-T therapy. Demographic characteristics, molecular studies, treatment and response information were recorded and included in the study. PFS and OS were calculated from the time of cell collection for all patients. Survival analysis was carried out using the Kaplan-Meier method and the log-rank test was used to compare survival curves.

Results: Our study found that 12 (12%) of patients who underwent apheresis for CAR-T cell therapy did not ultimately receive their manufactured CAR-T product (the no CAR-T patients). In our comparative analysis between patients who received CAR-T treatment (n=87) and those who underwent apheresis without CAR-T treatment (n=12), the median age was similar (67.7 vs. 70.2 years, p=0.415). There were no significant differences in the presence of plasma cell leukemia (3.45% vs. 8.33%, p=0.420) or high-risk cytogenetics (34.1% vs. 36.4%, p=0.883). Forty-two (42) percent of patients that underwent apheresis but did not receive CAR-T infusion received bridging therapy after apheresis. The median number of prior therapy lines was the same for both groups (5, p=0.431). However, disease progression and patient mortality were significantly higher in the no CAR-T treatment group (100% vs. 39.08%, p&lt;0.005; 83.3% vs. 19.54%, p&lt;0.005). The lymphodepleting regimens were evenly split between Fludarabine/Cyclophosphamide and Bendamustine, and CAR-T products were almost equally divided between ciltacabtagene autoleucel and idecabtagene vicleucel. Notably, the majority (58%) of patients in the no CAR-T group did not receive CAR-T treatment due to disease progression and/or death. The remaining patients did not receive CAR-T due to infection, death from other cause, or manufacturing failure. The median PFS for the CAR-T group was 17.5 months (1.46 years, p&lt;0.0001) and 1.5 months (1.3 years, p&lt;0.0001) for the non CAR-T group. The OS was not reached in the CAR-T group, whereas the median OS for the non CAR-T group was 1.9 months (0.16 years, p&lt;0.0001).

Conclusion: Our study highlights a critical period between apheresis and CAR-T cell infusion during which up to 12% of patients may experience significant morbidity and mortality related primarily to disease progression. While CAR-T therapy significantly improves survival outcomes for patients with RRMM, the manufacturing period poses a substantial risk for all patients regardless of disease aggressiveness, and reflects the urgent need for expeditious manufacturing processes and effective bridging therapies to stabilize patients during the waiting period. Addressing this issue through expedited production techniques and effective interim treatments is crucial to maximize the benefits of CAR-T therapy for all eligible patients. In addition, it is important to counsel eligible patients about this critical window of time, and we propose that studies evaluating CAR-T cell therapies should calculate outcomes including PFS and OS from date of apheresis rather than date of CAR-T cell infusion to reflect the experience of all patients receiving this therapeutic modality.