BCMA CAR-T cell therapy(Chongqing Precision Biotechnology Co., Ltd.)

There is no currently available standard of care for triple‐class exposed, relapsed refractory myeloma (RRMM) patients in Australia. CARTITUDE‐1 (CART‐1) was a single‐arm, phase 1b/2 study of 97 triple‐class exposed RRMM patients, who received BCMA‐CAR‐T cell therapy with ciltacabtagene autocel. Overall response rate (ORR) was 98%. Median progression free survival (PFS) and overall survival (OS) had not been reached at a median follow‐up of 28 months.

We performed a retrospective analysis on a cohort of CART‐1 comparable RRMM patients participating in the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR), to compare outcomes in triple‐class exposed MM patients treated with currently available therapies, in a real‐world context. The CE‐MRDR cohort (n = 28) fulfilled CARTITUDE‐1 eligibility (CE) criteria: ≥3 lines of therapy (LOT) including an immunomodulatory agent, proteasome inhibitor and CD38‐directed monoclonal antibody (CD38mAb) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0–2 at diagnosis. The modified‐CE‐MRDR (n = 132) received ≥3 LOT but may not have received a CD38mAb with an ECOG PS score of 3 (0–3).

Responses to the first subsequent therapy after eligibility were poor – ORR was 23% and 0% with progressive disease (PD) reported in 61% and 36%, CE‐MRDR and m‐CE‐MRDR respectively. Responses to the second subsequent therapy after eligibility were worse, ORR 0% and 31%, CE‐MRDR and m‐CE‐MRDR respectively, with high rates of PD, particularly in CE‐MRDR. Median OS was 5.4 versus 9.5 months, CE‐MRDR versus m‐CE‐MRDR.

This retrospective analysis confirms uniformly poor outcomes for Australian RRMM patients. There remains a critical need for greater accessibility to novel treatments, such as CAR‐T, outside clinical trials.

Objective: To investigate the characteristics of cytopenia and its impact on prognosis in patients with relapsed and refractory multiple myeloma (RRMM) after B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) immunotherapy therapy. Methods: Clinical data of 36 RRMM patients received BCMA CAR-T therapy at the First Affiliated Hospital of Nanjing Medical University from April 2017 to March 2023 were retrospectively collected. Among them, there were 17 males and 19 females, with an age [M (Q₁, Q₃)] of 62 (53, 67) years. The follow-up deadline was August 31, 2023, and the follow-up time [M (Q₁, Q₃)] was 33 (10, 30) months. The characteristics of cytopenia at different time points before lymphodepleting chemotherapy and after CAR-T cell infusion in all patients were analyzed. Kaplan-Meier method was used to compare the differences in progression-free survival (PFS) and overall survival (OS) in patients with different clinical characteristics. Single-cell sequencing analysis was used to analyze the changes in hematopoietic stem cells in three patients after CAR-T cell therapy. Results: The incidence of cytopenia after BCMA CAR-T cell therapy in 36 RRMM patients reached 100%. The incidence of neutropenia peaked on the 7th and 28th day after cell infusion with a biphasic pattern of change.Patients with all grade neutropenia reached 61.1% (22/36) and grade 3 or higher reached 33.3% (12/36) on the 7th day, while patients with all grade neutropenia reached 67.9% (19/28) and grade 3 or higher reached 28.6% (8/28) on the 28th day (P<0.001),respectively. The occurrence rate of lymphopenia reached a peak on the day of CAR-T cell infusion [97.2% (35/36) patients showed lymphopenia, while 80.6% (29/36) patients showed grade 3 or higher lymphopenia] (P<0.001).The incidence of all grade of thrombocytopenia and severe thrombocytopenia (grade 3 or higher) peaked on the 14th day after cell infusion, with the rates of 69.4% (25/36) and 30.6% (11/36) respectively, which had a prolonged duration(P<0.001). Even after 12 months, 40% (8/20) of patients still experienced thrombocytopenia.The incidence of anemia peaked on the 7th and 14th day after cell infusion, with a rate of 100% (36/36) (P<0.001). 50% (10/20) of patients still had anemia even 12 months after cell infusion. Kaplan-Meier survival analysis showed that patients with thrombocytopenia < grade 3 had undefined OS, while patients with thrombocytopenia ≥grade 3 had shorter OS [17 (95%CI: 2-32) months, χ²=4.154, P=0.042], indicating a poorer prognosis. However, there was no statistically significant difference in the relationship between other cytopenia and survival (all P>0.05). Single-cell sequencing analysis of bone marrow cells revealed decreased proliferation, increased apoptosis, and cell cycle arrest of hematopoietic stem cells after CAR-T cell infusion. Conclusions: All patients experienced varying degrees of cytopenia after receiving BCMA CAR-T cell infusion, and patients with thrombocytopenia ≥grade 3 had shorter OS and poorer prognosis.