A novel two-step administration of XPO-1 inhibitor may enhance the effect of anti-BCMA CAR-T in relapsed/refractory extramedullary multiple myeloma.

BACKGROUND: Extramedullary disease usually implies a dismal outcome in relapsed/refractory multiple myeloma patients, and requires novel treatment approaches. We designed a trial using Selinexor, a nuclear export protein 1 inhibitor, together with anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell product CT103A to treat these patients, and describe the first two cases in this report. METHODS: Selinexor was administered with a novel two-step schedule in bridging therapy and in maintenance. The clinical responses and adverse events were recorded after CAR-T infusion and Selinexor administration. In vitro analysis of the influence of Selinexor on CAR-T cell function was performed using myeloma cell lines. RESULTS: After infusion, both patients achieved stringent complete remission (sCR), and were maintained in sCR at data-cutoff, with survival over 13 and 10 months, respectively. Neither immune effector cell-associated neurotoxicity syndrome nor over grade 2 cytokine release syndrome was observed. Meanwhile, the patients showed good tolerance to the combination. In addition, we demonstrated that low dose of Selinexor could upregulate the expression of BCMA on plasma cell lines and subsequently enhance the function of CAR-T cell in vitro. CONCLUSIONS: The combination of Selinexor and CT103A exerts preliminary synergistic effect, and can be developed as a promising strategy for relapsed/refractory extramedullary myeloma.

Patients' experience with chimeric antigen receptor T-cell therapy for DLBCL in China: a qualitative study.

PURPOSE: The experiences of patients with diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor (CAR) T-cell therapy have received little attention. This study aimed to explore the treatment experiences of patients with relapsed or refractory (R/R) B-cell lymphoma during CAR T-cell therapy in China. METHODS: This descriptive qualitative study was conducted using face-to-face semi-structured interviews with 21 DLBCL patients 0-2 years after CAR-T infusion. Two researchers independently coded the interviews in MAXQDA 2022, and the original data were analyzed by conventional content analysis. RESULTS: Four themes emerged from the transcripts: (1) physiological distress, (2) functional impacts, (3) psychological experience, and (4) support requirement. Participants expressed 29 short-term or long-term symptoms related to their disease and treatment, influencing their daily life and function in a social setting. The participants expressed different negative emotions, polarized expectations about efficacy, and over-reliance on authoritative medical care. Their major concerns and hopes were achieving life goals, being treated with respect, obtaining more information about CAR T-cell therapy, and receiving government financial sponsorship. CONCLUSIONS: The patients experienced short-term and long-term symptoms of physical distress. Patients who have experienced failure in CAR T-cell therapy also experience strong negative emotions, such as dependency and guilt. They also require authentic spiritual and financial information that is authentic. Our study may guide the development of standardized and comprehensive nursing care for R/R DLBCL patients undergoing CAR T-cell therapy in China.