Introduction: Plasma cell leukemia (PCL) is unique in the spectrum of malignant monoclonal gammopathies and characterized by a poor prognosis. Despite significant improvement over recent years, the use of immunomodulatory drugs, proteasome inhibitors and either autologous or allogeneic stem cell transplantation cannot overcome the poor prognosis in this disease. Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary treatment for multiple myeloma, but its role in PCL is unclear.
Methods: This is the first comprehensive international study on current CAR T-cell therapy for patients with PCL. We aimed to describe patient characteristics and efficacy and safety of CAR T-cell therapy in this challenging patient population. Furthermore, detailed description of post-relapse treatments and outcomes will be reported.
Results: Patient characteristics. The total cohort included 22 patients with PCL with a median age of 59 years at time of CAR T infusion (range, 28-76 years), of whom more patients (59%) were male. The majority was of white/caucasian background (86%), while 9% were black and 5% Hispanic. ECOG performance status was 0 (35%), 1 (47%), 2 (12%), and 3 (6%). Extramedullary disease (EMD) was present in 36%. High-risk cytogenetics (including del(17p), t(4;14), t(14;16), and gain/amp chromosome 1) was present in 73%, and 36% had two or more high-risk aberrations.
Treatment characteristics. Refractory status before CAR T was triple-class refractory in 36% and penta-refractory in 14%, and 94% of patients had received autologous or allogeneic transplant before CAR T. Median number of prior lines of therapy was 5 (range, 1-11). In terms of CAR T product: 11 (50%) received ide-cel, 3 (14%) received cilta-cel, and 8 (36%) received academic CAR T. Median time to CAR T from diagnosis was 3 years.
Safety. The incidence of CRS was 45% (n=10), occurring within a median of 1 day after infusion and lasting a median of 3 days (range, 1-8 days). Only 1 case of grade 3 CRS occurred. The incidence of ICANS was 5% (n=1), which was of grade 1, occurring 4 days after infusion and lasting 3 days. One patient developed severe HLH and eventually died.
Efficacy. The median follow-up from CAR T infusion was 16 months, and 1 patient (5%) died between apheresis and infusion due to progressive disease. Overall response in 21 evaluable patients was 81%, with 29% complete response. The 1-year overall survival estimate in the intention-to-treat cohort of all 22 patients was 58% and the 1-year progression-free survival was 42%. Concurrent EMD was associated with worse progression-free survival (P=0.04).
Conclusions: This first comprehensive report on CAR T-cell therapy for PCL with long follow-up indicates feasibility with promising survival outcomes in this challenging and heavily pretreated patients.