Background:Although the overall survival of multiple myeloma (MM) has improved significantly, patients with ultra-high-risk features (UHR-MM) had dismal outcomes. New therapies to address this unmet medical need are warranted. Equecabtagene autoleucel (eque-cel) has been approved for patients who have received at least three previous lines of therapy by the Chinese National Medical Products Administration. With good efficacy and safety profile in these patients, eque-cel is being explored in early relapse or newly diagnosed UHR-MM patients, Hereby, we report the primary real world data of eque-cel followed ASCT in UHR-MM patients.

Methods:We conducted a retrospective chart review on UHR-MM patients who received eque-cel followed ASCT. UHR-MM are defined as: 1) Genetic ultra-high risk: del(17p)≥60%; or ≥2 high-risk cytogenetic abnormalities including TP53 mutation, del(17p)/P53 deletion, t(4;14), t(14;16), t(14;20), 1q21 gain/ amplification; 2) Primary refractory: <MR after 2 cycles or <PR after 4 cycles standard first-line therapy; 3) Early relapse: disease progression within 6 months from the standard first-line therapy; 4) primary plasma cell leukemia (PCL) history. Standard first-line therapy should be standard triplet-based regimen including at least one PI, one IMIDs, and glucocorticoid. Patients undergo conditioning (melphalan 140mg/m2 based) followed by ASCT on Day 0 and eque-cel single intravenous infusion on Day 2-4. IMIDs based maintenance is allowed after 3 months post ASCT.

Results:From August 2023 to April 2025, 12 UHR-MM patients completed ASCT followed by eque-cel infusion. Six patients received melphalan, five received bendamustine combining melphalan and one patient received fludarabine combining melphalan conditioning. Peripheral stem cell was administrated at (2.3-5.5) × 106 cells/kg, and eque-cel was administrated at 1 × 106 cells/kg for all 12 patients.

The median age was 53 years (range: 36-67) and 11 (91.7%) were male. Eight patients (72.7%) had genetic ultra-high risk features, one patients (8.3%) were early progression, and two patients (16.7%) had primary PCL history. Two (16.7%) patients had extramedullary disease. With median 2 (range: 1-4) previous line of therapy, the median disease course is 10.5 months before ASCT. Eleven (91.7%) patients had received daratumumab based triplet or quadruplet therapy. All patients received bridging and 11 received maintenance therapy. Two patients, who had received eque-cel infusion within the preceding 6 months but did not achieve a complete response (CR), subsequently underwent consolidation therapy with eque-cel followed ASCT.

With a median follow-up of 196 days (from ASCT date), seven patients (58.3%) experienced grade 1 and three patients (25.0%) experienced grade 2 CRS and fully recovered. Four patients were treated with glucocorticoids. No ICANS event was reported. As expected, AEs are dominated by hematological toxicities. All 12 patients achieved hematopoietic reconstitution within 1 months after ASCT, with a median time of 15 days for ANC reconstitution (≥0.5×109/L) and 11.5 days for PLT reconstitution (≥20×109/L) post ASCT.

By July 1st, 2025, the ORR was 100%, with all 12 patients reached CR. All patients are MRD negative. Two patients received first eque-cel 3 month before ASCT, which achieved both VGPR. After ASCT and second eque-cel infusion, achieved sCR and MRD negative status on day 23 and day 190 post-ASCT, respectively. The early progression patient relapsed at 55 days post ASCT, all the other patients are keeping their response and under follow-up. The median DOR, PFS and OS were not reached by cutoff date.

Robust CAR T-cell expansion was observed, with a median Tmax of 11 days (range 7~21). The median Cmax was 665.04 cells/μL. The pharmacokinetic profile is similar to that of eque-cel in R/RMM patients.

Conclusion:Eque-cel followed ASCT demonstrated promising deep and durable response and was well tolerated in UHR-MM patients. CRS events are slight, hematopoietic reconstruction rate was 100%. We are looking forward to more patients gaining long-term benefit from this new treatment.

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2025
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