Clinical Efficacy Observation of Humanized BCMA-CAR-T in the Treatment of Relapsed/Refractory Multiple Myeloma Complicated with Extramedullary Lesions

Introduction Multiple Myeloma (MM) is an incurable malignant hematological disease. Even though treated with systematic therapies, most patients reoccurred and developed into relapsed/refractory MM. The progression of MM has various manifestations, of which secondary plasma cell leukemia and extramedullary infiltration belong to late stage manifestations, with the worst clinical prognosis. Previous studies have shown that CAR-T therapy targeting BCMA can effectively improve the clinical prognosis of most R/R MM, but there is limited research on the clinical efficacy of CAR-T on R/R MM with extramedullary lesions.

Objective To observe the adverse reactions, clinical efficacy, and duration of efficacy of humanized BCMA-CAR-T in R/R MM treatment with extramedullary lesions.

Methods We retrospectively analyzed the data of R/R MM patients with extramedullary lesions who received autologous BCMA-CAR-T therapy in Shaanxi Provincial People's Hospital from March 2021 to May 2022 (Registration NO. CHiCTR2100043093), including the adverse reactions, efficacy of CAR-T therapy, and the duration of improvement. Follow-up analysis was up to July 25, 2022, or the date of patient death.

Results We evaluated the therapy in a large cohort of 37 R/R MM patients with extramedullary invasion that comprised both males (n = 21) and females (n = 16), aged between 41 and 68 years old (median age = 58). The types of immunoglobulin included light chain 21.3% (8/37), IgG 37.8% (14/37), IgA 24.3% (9/37), and IgD 13.5% (5/37). Patients with ECOG score more than 2 accounted for 70.2% (26/37), of which 16.2% (6/37) of them were paraplegia with extramedullary infiltration. Patients with extramedullary involvement in a single site accounted for 51.3% (19/37), while 48.7% (18/37) of them involved ≥ 2 sites. The median number of previous treatment lines was 3 (2-7), with 54.1% (20/37) of patients received autologous hematopoietic stem transplantation, and 21.6% (8/37) received CAR-T infusion in the past. Cytokine Release Syndrome (CRS) occurred at the 4^th hour after infusion and lasted for 4h to 16d (median time = 5d). The occurrence of CRS was 94.5% (34/37), with CRS ≤2 91.8% (34/37), CRS = 3 2.7%, and CRES = 1 8.1% (3/37). All the patients were treated for more than 1 month, with 70.2% (25/37) treated for more than 3 months and 27.0% (12/37) treated for more than 6 months. After 1 month of treatment, the Overall Response Rate (ORR) was up to 97.3% (36/37), including Complete Remission (CR), Very Good Partial Remission (VGPR), and Partial Remission (PR). Among them, CR was 18.9% and VGPR was 43.2%. After 3 months of treatment, ORR was 56% (14/25), CR was 20% (5/25), VGPR was 32% (8/25), while 8.0% (2/25) died due to serious infection (paraplegia with lung infection). After 6 months, ORR was 66.7% (8/12), with 58.3% CR (7/12). However, 33.3% (4/12) showed Disease Progression (PD), of which 16.7% (2/12) died.

Conclusion Our study shows autologous humanized BCMA-CAR-T treatment of MM with extramedullary lesions is effective, but the duration of improvement is short. The long-term efficacy needs to be demonstrated by more clinical studies.

No relevant conflicts of interest to declare.