The evolving landscape of chimeric antigen receptor (CAR) T-cell therapy for plasma cell leukemia: A systematic review of early outcomes.

Abstract

e19508 Background: Plasma cell leukemia (PCL) is an aggressive and rare manifestation of multiple myeloma with limited therapeutic options and poor survival despite treatment with novel agents and transplantation. Chimeric antigen receptor T-cell (CAR-T) therapy has achieved durable remissions in relapsed myeloma, but its role in PCL remains undefined due to disease rarity and manufacturing challenges associated with leukemic plasma burden. Methods: A systematic search of PubMed, ClinicalTrials.gov, and conferences (Jan 2019–Nov 2025) was conducted in accordance with PRISMA principles. Two reviewers independently screened records and extracted data; discrepancies were resolved by a third reviewer. Studies reporting CAR-T outcomes in plasma cell leukemia were included (bispecific antibodies excluded), and risk of bias was assessed using Joanna Briggs Institute checklists. Cumulative efficacy and safety outcomes were summarized using sample-size–weighted descriptive analyses. Results: Five studies were identified—four early academic series and one multicenter retrospective analysis—comprising 42 PCL patients, all treated with BCMA-directed CAR-T cells (ide-cel, cilta-cel, or academic constructs). Pooled overall response rate (ORR) was approximately 91% with a complete response (CR) of approximately 60%. Median progression-free survival (PFS) across available studies ranged from 5 to 16 months, and median overall survival (OS) was approximately 13 months. Toxicity profiles were similar to CAR-T in relapsed myeloma; grade ≥3 cytokine-release syndrome occurred infrequently (reported up to ~15%), and neurotoxicity was uncommon. Both primary and secondary PCL cases achieved CAR-T infusion, with durable responses observed in select patients. Given that the majority of pooled data derive from a single multicenter cohort, the findings may be disproportionately weighted by that experience and should be interpreted accordingly. Conclusions: CAR-T therapy demonstrates notable activity and manageable safety in plasma cell leukemia, representing a highly promising approach for this ultra-high-risk plasma-cell disorder. Despite encouraging early outcomes, evidence remains limited to small heterogeneous cohorts. Prospective, multi-center trials specifically enrolling PCL patients are urgently needed to define long-term efficacy, optimize antigen targeting, and establish CAR-T sequencing strategies. Summary of included studies and clinical outcomes. Study Year Target PCL Patients (n) ORR (%) CR (%) Median PFS (months) Median OS (months) Li et al. 2020 BCMA CAR-T 1 100 100 — — Li et al. 2021 BCMA CAR-T 2 90 43 5.2 14 Deng et al. 2022 BCMA CAR-T 1 100 100 16 — Zhang et al. (S103) 2025 BCMA dual nanobody CAR-T 4 96 59 — — Fortuna et al. 2025 BCMA CAR-T (ide-cel / cilta-cel) 34 90 59 9 13 Totals / Weighted — — 42 — — — — Abbreviation: BCMA = B-cell maturation antigen.