Promising Safety and Efficacy of Eque-Cel Followed ASCT in Ultra High-Risk Multiple Myeloma (UHR-MM) Patients: Primary Real World Data from a Single Center

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 1^st, 2023 to July 10^th, 2024, 6 UHR-MM patients completed ASCT followed by eque-cel infusion. 5 patients received melphalan and 1 received bendamustine combining melphalan conditioning. Peripheral stem cell was administrated at (2.64-5.5) × 10⁶ cells/kg, and eque-cel was administrated at 1 × 10⁶ cells/kg for all 6 patients.

The median age was 63 years (range: 59-67) and 4 (66.7%) were male. Four patients (66.7%) had genetic ultra-high risk features, one patients (16.7%) were primary refractory, and one patients (16.7%) had primary PCL history. Two (33.3%) patients had extramedullary disease. With median 1 (range: 1-3) previous line of therapy, the median disease course is 7 months before ASCT. All patients had received daratumumab based triplet or quadruplettherapy. All patients received bridging and 5 received maintenance therapy.

With a median follow-up of 4 (1-11) months (from ASCT date), Five patients (83.3%) had experienced grade 1 CRS and fully recovered. Two patients were treated with DXM. No ICANS event was reported. As expected, AEs are dominated by hematological toxicities. All 6 patients achieved hematopoietic reconstitution within 1 months after ASCT, with a median time of 16 days for ANC reconstitution (≥0.5×10⁹/L) and 13 days for PLT reconstitution (≥20×10⁹/L) post ASCT.

By July 31th, the ORR was 100%, with 5 patients reached sCR (83.3%), 1 PR (16.7%). All sCR patients are MRD negative. The primary refractory patient relapsed at 2 months 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 T_max of 12 days (range 7~14). The median C_max was 1078/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.

No relevant conflicts of interest to declare.

eque-cel is approved to treat RRMM patients with more than 3 lines.