Equecabtagene Autoleucel Demonstrates 82.4% Stringent Complete Response Rate in CAR-T-Naïve Relapsed/Refractory Multiple Myeloma Patients: Updated Long-Term Follow-Up Data from the FUMANBA-1 Trial

(1) Abstract Title: Latest Long-term Follow-up Results of the Phase 1b/2 Study (FUMANBA-1) of Ixazomib Injection in the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM)

Conference Theme: Treatment of Relapsed/Refractory Multiple Myeloma

Abstract Number：P-290

Report Time: 12:30 PM - 1:30 PM, September 28, 2023 (Local time in Athens, Greece)

This report updates the safety and efficacy data of the phase 1/2 registrational clinical study (FUMANBA-1) on the treatment of relapsed/refractory multiple myeloma (hereinafter referred to as "RRMM") with Ixazomib injection at 14 clinical research centers in China.

This study (CTR20192510, NCT05066646) required the enrollment of RRMM patients who had previously undergone at least three lines of therapy or more (including chemotherapy regimens based on proteasome inhibitors and immunomodulatory agents) and had progressed on their last line of treatment. As of December 31, 2022, a total of 105 subjects receiving Icaritin Cell Injection were enrolled, with a reinfusion dose of 1.0×10.⁶CAR-T cells/kg, with a median follow-up time of 18.07 (IQR 12.6-21.8) months, and a median number of prior treatment lines of 4 (3-23) lines.

Among the 105 subjects who received the infusion of Idecabtagene Vicleucel, 69.5% (73/105) had high-risk cytogenetic abnormalities according to the mSMART3.0 criteria, 13.3% (14/105) had extramedullary plasmacytoma, and 11.4% (12/105) had previously received non-fully human BCMA CAR-T therapy.

In terms of effectiveness: Among the 103 evaluable subjects, the overall response rate (ORR) was 96.1% (99/103), with 91.3% (94/103) of subjects achieving very good partial response or better (≥VGPR). The rate of stringent complete response/complete response (sCR/CR) was 77.7% (80/103). Among the 91 subjects without a history of prior CAR-T therapy,ORR reached 98.9% (90/91), with sCR/CR rate reaching 82.4% (75/91), and the 12-month progression-free survival (PFS) rate was 85.5% (95% CI: 75.75, 91.51).。

Among the 103 evaluable subjects, the median time to response was 16 (11, 179) days, and the 12-month PFS rate was 80.0% (95% CI: 70.33, 86.76). 94.2% (97/103) of the subjects achieved minimal residual disease (MRD) negativity, with all sCR/CR subjects achieving MRD negativity. Additionally, 80.8% (95% CI: 69.59, 88.24) of the subjects maintained MRD negativity for over 12 months.

Idecabtagene vicleucel injection also demonstrated good efficacy in multiple myeloma (hereinafter referred to as "MM") subjects who had previously received CAR-T therapy. Among 12 MM subjects who had previously received CAR-T therapy, 9 achieved remission, and 5 achieved stringent complete remission.

In terms of safety: Among 105 subjects, 93.3% (98/105) experienced cytokine release syndrome (CRS), the vast majority being grade 1-2 CRS, with only one subject experiencing grade 3 or higher CRS. The median time to onset of CRS was day 6.0 (range: 1-13) post-infusion, and the median duration of CRS was 5.0 (range: 2-30) days. Only 1.9% (2/105) of subjects developed immune effector cell-associated neurotoxicity syndrome (ICANS), including one case each of grade 1 and grade 2; no cases of ICANS ≥ grade 3 occurred. All subjects' CRS and ICANS were resolved.

Amplification and Persistence:The median peak time of CAR copy numbers in peripheral blood was 12 days after infusion, with a median peak level of 88,001.13 copies/microgram DNA. Among subjects followed up to 12 months and 24 months post-infusion, 50% (32/64) and 40% (4/10), respectively, still showed detectable CAR-T cell persistence. Only 19.2% (20/104) of the subjects tested positive for anti-drug antibodies (ADA) after infusion.

(2) Abstract Title: Risk Model Analysis for Predicting Prolonged Thrombocytopenia Recovery Time in Patients with Relapsed/Refractory Multiple Myeloma After Anti-BCMA CAR-T Therapy

Conference ThemeTreatment of Relapsed/Refractory Multiple Myeloma

Abstract Number：P-288

Report Time: 12:30 PM - 1:30 PM, September 28, 2023 (Local time in Athens, Greece)

The most common adverse reaction in RRMM patients after BCMA CAR-T cell therapy is hematological toxicity, particularly persistent thrombocytopenia. This report also presents a model for distinguishing the clinical risk levels of long-term thrombocytopenia. After analyzing the baseline characteristics of the subjects, the final platelet count, hemoglobin, C-reactive protein, ferritin, and the proportion of plasma cells in the bone marrow were identified as being associated with the recovery from thrombocytopenia and were used to establish the model. Patients with a model score of 5 or higher are at greater risk of developing persistent thrombocytopenia post-infusion.

The principal investigators of this clinical study, Professor Luogui Qiu from the Blood Disease Hospital of the Chinese Academy of Medical Sciences and Professor Chunrong Li from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.Stated: "Multiple myeloma is a common and highly prevalent malignant tumor in the blood system, and recurrence and drug resistance are almost inevitable during treatment. There is an urgent clinical need for treatments with good tolerability and deep, durable responses. Idecabtagene vicleucel injection is a fully human BCMA-targeted CAR-T product that can more precisely kill tumor cells and has longer persistence in vivo. Compared to the follow-up data presented at the 2023 ASCO Annual Meeting, the updated data presented at this IMS conference showed that subjects who had not previously received CAR-T therapy maintained an ORR of 98.9%, with significant improvements in sCR/CR rates and 12-month PFS rates. This indicates that after including more subjects and longer follow-up periods, idecabtagene vicleucel injection continues to demonstrate encouraging efficacy and safety, with the potential to change the treatment landscape for RRMM and offer hope of a cure to patients."