A real-world study on first-line early switch to kpd regimen in the treatment of multiple myeloma patients with suboptimal induction efficacy or intolerance

Abstract Objective: To evaluate the efficacy and safety of early switch to the KPD regimen (carfilzomib, pomalidomide, dexamethasone) in multiple myeloma patients with suboptimal response or intolerance to first-line induction therapy. Methods: Patients from 12medical centers in Henan Province who did not achieve very good partial response (VGPR) after two cycles of first-line induction therapy (VRD [bortezomib + lenalidomide + dexamethasone], VD [bortezomib + dexamethasone], or VPD [bortezomib + pomalidomide + dexamethasone]) or experienced grade ≥2 adverse events (CTCAE criteria) were switched to the KPD regimen(Carfilzomib [20/27 mg/m² on days 1, 2, 8, 9, 15, and 16], pomalidomide [4 mg on days 1-21] and dexamethasone [20 mg on days 1, 2, 8, 9, 15, and 16]). Treatment response after 2–4 cycles of KPD therapy, its impact on autologous hematopoietic stem cell collection, and adverse events associated with KPD were observed. Results: Totally 57 patients (median age 62 [36–80] years) from 12 hospitals were enrolled from October 23, 2024, to May 31, 2025. There were 7 cases with stage Ⅰ, 14 cases with stage Ⅱ, 26 cases with stage Ⅲ, and 10 cases with NA staged by ISS staging. Among them, 45 patients failed to achieve VGPR after 2 cycles of first-line treatment, and 17 patients were intolerant to bortezomib-induced neurotoxicity (including 5 patients with both unfavorable efficacy and severe neurotoxicity). All 57 patients received KPD regimen re-induction therapy. After 2-4 cycles of KPD treatment, the overall response rate (ORR) was 91.23% (52 cases). Among these, 32 patients (56.14%) achieved complete response (CR) or better, 9 patients (15.79%) achieved very good partial response (VGPR), 11 patients (19.30%) achieved partial response (PR), 4 patients (7.02%) achieved minimal response (MR), and 1 patient (1.75%) kept stable disease (SD). Nine patients successfully completed autologous stem cell collection (median CD34+ cells: 9.84×10⁶/kg [4.01–16.87×10⁶/kg]). In terms of safety, 5 cases (8.7%) experienced neutropenia, 21 cases (36.84%) had anemia, 7 cases (12.3%) developed thrombocytopenia, 13 cases (22.8%) suffered from infection, 11 cases (19.3%) had arrhythmia, and 3 cases (7%) presented with rash. Conclusion: This multicenter real-world observational study suggests that multiple myeloma patients with suboptimal efficacy or intolerance to first-line induction therapy who switch to the KPd regimen early have a high response rate and achieve deeper remission. No new adverse events were observed compared with clinical studies.Keywords: Carfilzomib; Pomalidomide; Dexamethasone; First-line; Multiple myeloma; Efficacy; Safety.