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    Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

    Category: Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

    Weekly Carfilzomib in Combination with Cyclophosphamide and Dexamethasone in Relapsed/Refractory Multiple Myeloma After Bortezomib and Lenalidomide: A Real-World Study

    (PA-467) Weekly Carfilzomib in Combination with Cyclophosphamide and Dexamethasone in Relapsed/Refractory Multiple Myeloma After Bortezomib and Lenalidomide: A Real-World Study

    Friday, September 19, 2025

    Introduction:      Patients with relapsed or refractory multiple myeloma (RRMM) after exposure to both bortezomib and lenalidomide represent a population with poor prognosis and limited treatment options. Carfilzomib, a second-generation proteasome inhibitor, has demonstrated promising efficacy in combination therapies. The weekly carfilzomib, cyclophosphamide, and dexamethasone (KCd) regimen offers a potentially effective and convenient treatment strategy. However, real-world data, particularly from Asian populations, are lacking.

    Methods:   We conducted a single-center retrospective analysis of 33 consecutive RRMM patients treated with weekly KCd between March 2020 and February 2024. All patients had prior exposure to both bortezomib and lenalidomide; 93.9% were lenalidomide-refractory. Carfilzomib was administered weekly (20 mg/m2 on day 1 of cycle 1, then 70 mg/m2 on days 8 and 15 of cycle 1 and on day 1, 8, and 15 of the subsequent cycles), with oral cyclophosphamide (300 mg/m², capped at 500 mg, on day 1, 8, and 15) and dexamethasone (40 mg weekly). Response was assessed using IMWG criteria, and survival outcomes were evaluated via Kaplan–Meier analysis. Adverse events were graded by CTCAE v4.3.

    Results:   The overall response rate was 66.7%, including complete response or better in 15.1% and very good partial response or better in 42.4%. Median progression-free survival (PFS) was 13.5 months (95% CI, 11.47–15.53), and median overall survival (OS) was not reached at a median follow-up of 31.7 months. In patients with high-risk cytogenetics (n=11), ORR was 63.6% with 45.5% achieving VGPR or better. Prior autologous stem cell transplantation and age < 65 years were associated with improved PFS. Grade ≥3 adverse events were mostly hematologic, with neutropenia being most common (15.2%). Non-hematologic toxicities ≥ grade 3 occurred infrequently. No treatment-related deaths or grade ≥3 cardiovascular events were reported. Dose reductions were implemented in 24.2% of patients, primarily for hematologic toxicities.

    Conclusions:   The weekly KCd regimen demonstrated encouraging efficacy and manageable toxicity in pretreated, predominantly lenalidomide-refractory RRMM patients. These findings support the feasibility of KCd as a practical treatment option in real-world settings, particularly in populations with limited remaining therapies.