Phase 2 study of aponermin +kt-decp in patients(pts) with Relapsed/Refractory multiple myeloma and extramedullary disease

Abstract Background and Aims： The survival of Relapsed/refractory multiple myeloma (RRMM) with extramedullary Disease (EMD) was still poor (3-year OS: 58%). Aponermin (Apo), the first approved DR4/DR5 agonist, triggers the extrinsic apoptotic pathway through caspase cascade activation. This study was to evaluate the efficacy and safety of Apo+KT-DECP* regimen in pts of RRMM and EMD. Methods: This multicenter, single-arm, phase 2 study (NCT05013190) aimed to enroll 31 pts with EMD-confirmed RRMM according to IMWG criteria. Patients received Apo-KT-DECP regimen*at least 4-6 cycles; and add radiotherapy when efficacy less than complete remission (CR). The primary endpoint was overall response rate (ORR) after two cycles treatment. Key secondary endpoints including CR, very good partial remission (VGPR), Time to response (TOR) and safety. Results: 23 pts have been enrolled in this study, median age was 62 years, male was 47.8%, median prior lines of therapy was 3(range:1–9), 43.5% of pts with EMD≥3(1-7), 60.9% of pts with bone-independent and paraskeletal mass together, 30.4% of pts with big EMD(diameter≥5cm), high-risk cytogenetics was 37.5%, EMD of 4 pts with anaplastic or blast-type plasma cell, 2 pts with malignant pleural effusion, 3 triple-class refractory (TCR) was 56.5%, and no BCMA exposure pts. By the data cutoff, all enrolled pts had received a median of 4 cycle of regimen (range: 1.5–7). Median follow-up of 7.5 months, median PFS were not reached, 5-month PFS rate was 77.0%. ORR of 2-cycle was 90.0% (18/20), the best response included 30.0% of pts achieving ≥VGPR (25.0% achieving ≥CR, 2 pts with radiotherapy); medium TOR was 0.5 month (0.5-3). In this study, 78.3% (18/23) of patients had any grade adverse events (AE). In which, the most frequent AEs were infection (34.8%), thrombocytopenia (65.2%), granulocytopenia (56.5%), tumor lysis syndrome (8.7%). Most common grade 3/4 AEs were thrombocytopenia (13.0%), granulocytopenia (17.4%), pneumonia (17.4%). Conclusion： Our study demonstrate that Apo-KT-DECP regimen are quickly effective with RRMM and EMD, with deeper response and less toxicity. *Apo-KT-DECP: Apo 10 mg/kg, days 1–3 and 15–18; carfilzomib: 27 mg/m², days 1–2, 8–9, 15–16; thalidomide: 100 mg, days 1–10 and 15–24; cisplatin, etoposide, cyclophosphamide, and dexamethasone at protocol-specified doses.