In 2023, there were an estimated 36,000 cases of multiple myeloma in the US and ~22,000 in China. In clinical practice, transplant eligibility is determined by several factors, including age, comorbidities, and other clinical considerations. Data suggests that roughly 50% to 60% of newly diagnosed multiple myeloma patients are ineligible for transplant and around a third of eligible patients end up not receiving the transplant.

In July 2023, the National Medical Products Administration (NMPA) approved the New Drug Application (NDA) for FUCASO (Equecabtagene Autoleucel, developed by IASO Bio and Innovent, co-commercialized by IASO Bio), for the treatment of relapsed and/or refractory multiple myeloma (RRMM) patients who have received ≥3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent. In 2023, the FDA granted fast-track and regenerative medicine advanced therapy designations to equecabtagene autoleucel (CT103A) for treating patients with relapsed or refractory multiple myeloma. Previously, in February 2022, the FDA awarded orphan drug designation to equecabtagene autoleucel for the management of RRMM. The product's robust design and prolonged persistence in patients are supported by stringent screening, selection criteria, and ongoing improvements in its manufacturing process and optimization platform.

According to the data from the FUMANBA-2 study presented in EHA 2024, as of January 25th, 2024, 16 subjects received Eque-cel therapy. High-risk cytogenetics were detected in all subjects, including 62.5% double-hit and 12.5% triple-hit. 25% of subjects had extramedullary disease. 37.5% of subjects had R-ISS stage III disease, among whom 6.3% with double-hit and 6.3% with triple-hit.

Following infusion of Eque-cel, patients had a median follow-up of 7.46 months (2.8–18.1). Median progression-free survival (PFS) was not reached, with a 12-month PFS rate of 84.4% (95% CI: 49.31–96.00). All patients achieved minimal residual disease (MRD) negativity, with 71.4% (95% CI: 25.8-92.0) maintaining MRD negativity for more than 12 months. The overall response rate (ORR) was 100%, with 93.8% achieving stringent complete response (sCR).

Post-infusion, grade 1-2 cytokine release syndrome (CRS) occurred in 68.8% of patients, with no instances of grade 3 or above CRS or immune effector cell-related neurotoxicity syndrome (ICANS) observed. CRS typically occurred on the 7th day post-infusion (range: 2-9 days), lasting a median of 3 days (range: 1-8 days). The most common grade 3 or above drug-related adverse event was blood cell count reduction, and grade 3 or above infectious disease adverse events occurred in 25.0% of patients.

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The median peak time for CAR copy number in peripheral blood was 10 days post-infusion (range: 7–21 days), with a median peak level of 79,681.299 copies/μg DNA. Clearance of free B-cell maturation antigen (sBCMA) was achieved within one month post-infusion by 81.25% of patients. Median peak times for cytokine IL-6 and CRP detection post-infusion were the 7th and 10th days, respectively, while serum ferritin levels did not show significant changes.

KOL insights

“High-risk newly diagnosed multiple myeloma patients have a poor prognosis in standard first-line treatment. For high-risk NDMM patients who do not meet the conditions for ASCT, Eque-cel has shown superior efficacy and safety, achieving deep and sustained remission, with all patients achieving MRD negativity.  This opens up a new approach to reverse the poor prognosis of high-risk myeloma patients.” – MD, China.

"Eque-cel, as a novel fully human BCMA CAR-T therapy, has shown encouraging efficacy and safety in high-risk patients with newly diagnosed multiple myeloma who are ineligible for transplantation. This is the world’s first report on CAR-T therapy being used as a first-line treatment in this specific patient population. For NDMM patients who are not suitable for transplantation, the application of CAR-T therapy as a first-line treatment is expected to further improve the remission rate, extend survival, and improve patient prognosis compared to traditional chemotherapy and other targeted drug treatments. This allows us to see the application potential of Eque-cel in the front-line treatment of MM. Advancing CAR-T therapy to the first line will provide patients with more diverse and promising treatment options. With further research and the continuous improvement of treatment strategies, we look forward to CAR-T therapy benefiting more patients in the future."– MD, China.

Conclusion 

The results from the use of Eque-cel in high-risk NDMM patients who are ineligible for autologous stem cell transplantation (ASCT) represent a significant breakthrough. These patients typically face a poor prognosis with standard first-line treatments, but Eque-cel has demonstrated superior efficacy and safety, achieving deep and sustained remissions characterized by 100% ORR and 93.8% sCR. Importantly, all patients achieved MRD negativity, with a substantial proportion maintaining this status for more than 12 months.

Moving forward, further investigation with longer-term follow-up is crucial to fully understand the durability and sustained benefits of Eque-cel in this patient group. The potential application of CAR-T therapy as a front-line treatment option for NDMM patients not suitable for transplantation holds promise for significantly improving remission rates, extending survival, and enhancing overall prognosis compared to conventional chemotherapy and targeted therapies.

If and when approved, Eque-cel stands poised to offer direct competition to other CAR-T therapies and bispecific antibodies such as CARVYKTI and ELREXFIO, currently under evaluation in the similar settings.