PA-355: Real-World Impact of Anti-CD38 Monoclonal Antibodies and Hematopoietic Stem Cell Transplant in Primary Plasma Cell Leukemia (2021 IMWG Criteria): A Single-Center Analysis

Primary plasma cell leukemia (pPCL) is a rare and aggressive disease with dismal outcomes. Hematopoietic stem cell transplantation (HSCT), whether autologous or allogeneic, is key in achieving durable remissions after front-line therapy. In multiple myeloma, novel agents have improved outcomes, with anti-CD38 monoclonal antibodies (mAb) markedly improving survival. However, real-world reports on the impact of HSCT and especially anti-CD38 mAb therapy in pPCL are scarce.

Methods:

This single-center study explored the impact of front-line therapies on survival in pPCL patients between 2002 and 2024 at our institution. We defined PCL according to the 2021 diagnostic criteria by the International Myeloma Working Group (IMWG), applied retrospectively to patients diagnosed before 2021. We evaluated overall survival (OS) and progression-free survival (PFS) from start of front-line therapy in the entire cohort, as well as by anti-CD38 mAb exposure and by HSCT status.

Results:

Fifty patients were identified. Median age was 69 years (range 41-95), with 50% being male. The median follow-up duration was 18.1 months (IQR 9.6-46.5), and 56% of patients were staged as ISS III. Cytogenetic risk profiles were available for 25 patients, of whom 21 were high-risk (84% of available). The median OS (mOS) for the entire population was 25.3 months (95%CI: 12.7-53.2), and median PFS (mPFS) was 11.2 months (95%CI: 8.0-25.1).

Among anti-CD38 mAb exposed (n=18), mOS was 35.4 months (95%CI: 17.4-NA) and mPFS was 27.9 months (95%CI: 8.5-NA). Patients not exposed (n=32) had a mOS of 16.4 months (95%CI: 10.9-49.8) and mPFS of 10.9 (6.4-14.7). Patients who underwent HSCT (n=19) had a mOS of 56.7 months (95%CI: 30.8-NA) and mPFS 27.3 months (95%CI: 14.5-NA). In contrast, patients not undergoing HSCT (n=31) had a mOS and mPFS of 15.0 months (95%CI: 10.4-35.4) and 6.4 months (95%CI: 4.7-13.5), respectively. In patients who underwent allogeneic HSCT (n=7), mOS was not reached (95%CI: 10.3-NA) and mPFS 27.3 months (95%CI: 10.3-NA).

Further, we analyzed the impact of front-line treatment regimens, where the overall response rate was 86%. Patients receiving doublet had a mOS of 17.4 months (95%CI: 8.8-NA) and mPFS of 7.7 months (95%CI: 1.0-NA). Patients receiving triplet had a mOS 16.2 months (95%CI: 11.9-50.1) and mPFS of 10.9 months (95%CI: 5.0-25.1). In patients receiving quadruplet, mOS was not reached (95%CI: 35.4-NA) and mPFS was 27.3 months (10.3-NA).

Univariate analysis indicates diagnosis year after 2018, HSCT, anti-CD38 mAb, IMiD and quadruplet regimen as prognostic factors for PFS (p< 0.05). Multivariate modeling suggests IMiD and anti-CD38 mAb as independent predictors.

Conclusions:

Our findings indicate that patients with pPCL exposed to anti-CD38 mAb, and patients who underwent HSCT have superior outcomes in terms of OS and PFS. In particular, allogeneic HSCT is associated with vastly improved outcomes. It is crucial to note the small cohort size, where further studies are needed to confirm our results.