Efficacy and Safety of BCMA-CAR-T Cell Therapy in Relapsed/Refractory Extramedullary Plasmacytoma: Exploring the Role of Consolidation Therapy

Background:

Extramedullary plasmacytoma (EMD) is a rare type of plasma cell tumor where plasma cells escape the bone marrow environment and invade other organs, leading to extramedullary disease. EMD is closely associated with poor prognosis in patients with relapsed/refractory multiple myeloma (R/RMM). In recent years, many new treatments for R/RMM have significantly improved patient outcomes, particularly chimeric antigen receptor (CAR) T-cell therapy targeting BCMA, which has shown promising efficacy in R/RMM patients. However, data on anti-BCMA CAR T-cell therapy in EMD patients is currently very limited, and further exploration is needed to determine whether consolidation therapy post-CAR T-cell therapy can improve efficacy and survival in these patients.

Aims:

Investigate the effectiveness and safety of CAR-T cell immunotherapy in patients with relapsed/refractory extramedullary plasmacytoma; and explore the necessity of consolidation therapy following CAR-T cell immunotherapy.

Methods:

This study is a single-center retrospective analysis, investigating 24 patients with extramedullary plasmacytoma who underwent BCMA-CAR-T therapy at Beijing Gobroad Hospital from March 2019 to June 2024. Among them, 12/24 (50%) were male, with a median age of 56.5 years (range 34-78 years). 13/24 (54.2%) were identified with ≥1 high-risk genetic factors (including: 1q21+, t(4;14), t(14;16), t(14;20), 17p-, p53). 12/24(50%) had an ECOG score>2. All patients had received more than 3 lines of prior therapy, being resistant to proteasome inhibitors and immunomodulatory agents; 19 /24 (79.2%) were resistant to CD38 monoclonal antibodies.14/24 (58.3%) had undergone autologous transplantation previously, and 9/24 (37.5%) had received prior local radiotherapy. Prior to BCMA-CAR-T cell therapy, 20/24 (83.3%) underwent cytoreductive chemotherapy primarily with the DECP regimen and local radiotherapy. Following BCMA-CAR-T cell therapy, 9/24 (37.5%) received consolidation therapy, which included allogeneic transplantation, maintenance with targeted drugs, and local radiotherapy.

Results:

20 out of 24 patients (83.3%) received cytoreductive chemotherapy with the DECP regimen or local radiotherapy before BCMA-CAR-T cell therapy. Fifteen evaluable patients showed an overall response rate (ORR) of 40% (6/15), including 1 VGPR and 5 PR. The median CAR-T cell infusion dose was 0.53710^6/kg (range 0.011-6), and the median peak expansion was 8.59*10^6/L (range 0.129-884), occurring around day 13.5 post-CAR-T cell therapy (range 7-30). CRS occurred in 83.3% of patients (20/24), with 3 patients (12.5%) experiencing grade ≥3 CRS, and ICANS occurred in 3 patients (12.5%), with 3 patients (12.5%) experiencing grade ≥3 ICANS.Following BCMA-CAR-T cell therapy, the best ORR among the 24 patients was 70.8%, with a complete response rate (CRR) of 25%. Median follow-up was 16.044 months (range 13.440-18.647).Median overall survival (OS) was 12.427 months (range 1.376-23.478), and median progression-free survival (PFS) was 4.603 months (range 4.037-5.169).Among all patients, 9 (37.5%) received consolidation therapy after BCMA-CAR-T cell therapy, with prior efficacy assessment showing 4 PR, 3 VGPR, and 2 CR. Subgroup analysis indicated significantly longer median OS in the consolidation therapy group (28.734 months) compared to the non-consolidation therapy group (4.997 months, p=0.0014), as well as longer median PFS (12.066 vs 3.058 months, p=0.0011).

Summary/Conclusion:

BCMA-CAR-T therapy demonstrates efficacy and good safety in relapsed/refractory extramedullary plasmacytoma, though long-term survival remains suboptimal, with some patients experiencing relapse and progression post-treatment. This retrospective study highlights that patients who received consolidation therapy after BCMA-CAR-T treatment showed superior short-term efficacy and long-term survival compared to those who did not. These findings underscore the need for achieving deep remission in extramedullary plasmacytoma, and future research should focus on optimizing CAR-T cell immunotherapy and consolidation strategies.