Abstract
Introduction: Carfilzomib (CFZ) and pomalidomide maintain clinical efficacy in relapsed/refractory multiple myeloma (RRMM). The phase 2 SELECT trial demonstrated once-weekly KPd (CFZ 56 mg/m²) as an effective and well-tolerated regimen for lenalidomide-refractory RRMM (Perrot, Aurore et al. Leukemia & lymphoma 2024), distinct from historical twice-weekly KPd (CFZ 27-36 mg/m²) data. Prospective real-world evidence for once-weekly K56Pd in first-relapse MM remains limited. We therefore conducted a multicenter prospective study evaluating once-weekly K56Pd in this population to generate critical real-world evidence.
Methods:
Eligible participants were adults aged ≥18 years with RRMM，and Eastern Cooperative Oncology Group (ECOG) performance status was 0–2, measurable disease per International Myeloma Working Group criteria, and documented disease progression following exactly one prior line of systemic therapy. All enrolled patients received K56Pd treatment. Carfilzomib was administered intravenously at 20 mg/m² on day 1 and 27 mg/m² on day 2 of cycle 1, then increased to 56 mg/m² on days 8 and 15 (cycle 1) and subsequently on days 1, 8 and 15 of each following cycle; pomalidomide, 4 mg orally once daily on days 1-21; dexamethasone, 40 mg orally on days 1, 8, 15, and 22. The primary efficacy endpoint was the proportion of patients achieving ≥very good partial response (VGPR).secondary endpoints included overall response rate (ORR), complete response (CR) rate,progression free survival (PFS), overall survival (OS), and safety.The study was approved by the Ethics Committee of the First Affiliated Hospital of Guilin Medical University (Approval No.2024IITLL-09)
Results:
Herein, we reported the preliminary results. Between Jan 24, 2024, and Apr 17, 2025, 31 patients were enrolled. The median age at the start of weekly K56Pd regimen was 69 years old (range, 39-76) and 48.4% were male. Among these eligible patients, 12 (38.7%) of them had received previous autologous hematopoietic stem cell transplantation. Prior therapies included bortezomib (19.4% refractory), lenalidomide (90.3% refractory), and anti-CD38 antibodies (3.2% refractory); 6 (19.4%) were dual-refractory to bortezomib/lenalidomide, and 1 (3.2%) triple-refractory (bortezomib/lenalidomide/anti-CD38). There were 16 patients with high-risk features including ISS stage III (51.6%), extramedullary disease (25.8%), and cytogenetic abnormalities: t(4;14) (12.9%), 1q21 amplification (64.5%), and del(17p) (6.45%).
The median duration of treatment was 15.0 months. All 31 patients completed the initial 2 cycles of treatment, the rate of ≥VGPR was 22.6% (ORR: 90.3%, CR: 19.4%). 22 patients completed 4 cycles of treatment, the rate of ≥VGPR was 63.6% (ORR: 88.2%, CR: 36.4%, sCR: 9.1%). 17 patients completed 6 cycles of treatment, the rate of ≥VGPR was 82.4% (ORR: 88.2%, CR: 35.3%, sCR: 17.6%). After a median follow-up of 8.4 months, the median PFS was 17.0 months (95%CI, NE, NE) and the median OS was not reached. The most common grade 3 treatment related adverse events (TRAE) included anemia (n=3, 9.68%), leukopenia (n=3, 9.68%), infection (n=2, 6.45%), hypertension (n=2, 6.45%) and thrombopenia (n=2, 6.45%). No grade 4 adverse events occurred; no patients died due to TRAE.
Conclusion: The weekly K56Pd regimen demonstrated meaningful clinical benefits and manageable safety in patients with MM at first relapse in real-world settings.
