Weekly Carfilzomib Combined with Daratumumab and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma

Introduction:

Patients with multiple myeloma (MM) are inevitably faced with the challenge of disease recurrence. After receiving different lines of treatment, a reduction in therapeutic efficacy is always observed in relapsed and/or refractory MM (RRMM) patients, leading to diminished outcomes [1]. EQUULEUS[2] and CANDOR[3, 4] studies have established the efficacy of the daratumumab (D), carfilzomib (K), and dexamethasone (d) (DKd) regimen in the landscape of bortezomib and lenalidomide RRMM patients. Based on the approved dosage of carfilzomib at 27mg/m² twice weekly for RRMM, the study explored the efficacy and safety of DKd (carfilzomib 56mg/m², once weekly) in China.

Methods:

From 17th November, 2022 to 15th December, 2023, a total of 29 patients with RRMM who received the DKd regimen as salvage therapy (≥2 lines of therapy) in Zhongshan Hospital, Fudan University were included in the real-world analysis.

These patients received Dara (16mg/kg) weekly on day 1, 8, 15, and 22 for cycle 1-2, day 1 and 15 for cycle 3-6, and day 1 for cycle 7 and beyond; carfilzomib (20 mg/m² initial dose, escalated to 56 mg/m² thereafter) on day 1, 8, and 15 of each 28-day cycle; dexamethasone (40 mg/week for patients aged ≤75 years old, 20 mg/week for patients aged >75 years old) until progression disease (PD) or intolerable adverse effects (AEs). The primary endpoint focused on overall response rate (), and secondary endpoints included progression-free survival (PFS), overall survival (OS), and AEs. PFS is defined as the interval commencing with the initial application of the DKd regimen and terminating at PD or mortality irrespective of cause. OS denotes the duration from the first utilization of the DKd protocol to death from any underlying cause.

Results:

Eastern Cooperative Oncology Group (ECOG) scale at baseline were 2 (21/29) and 3 (8/29). The duration of treatment persisted for 5.64±3.03 months. ORR reached 75.86% (22/29), wherein, 11 patients achieved stringent complete response (sCR), 3 patients received complete response (CR), 5 patients received very good partial response (VGPR), and 3 patients got partial response (PR). The median time to response lasted for 1.59±1.19 months. In both the Revised International Staging System (R-ISS) and R2-ISS subgroups analysis, the ORRs were higher in stage II (11, 78.57% and 6, 75.00%, respectively) and lower in stage III (2, 66.67% and 9, 75.00%, respectively) with no significance compared with stage I. No distinctive differences were revealed in PFS and OS within each subgroup analysis. With median follow-ups of 6.24 months for PFS and 7.62 months for OS, neither median PFS nor OS were reached. The 6-month PFS rate was 74.86%, while OS rate was 100.00%. AEs occurred in 12 cases, with only one case (3.45%) experienced hematologic AE of Grade 3. The most common AEs included thrombocytopenia (5, 17.24%) and neutropenia (3, 10.34%). Seven cases resolved AEs and continued the DKd regimen without dose reduction after symptomatic therapy.

Conclusion:

The DKd regimen exhibited notable effectiveness as a salvage treatment in Chinese patients with RRMM, with manageable toxicities. However, caution should be exercised in interpreting the findings due to the small sample size and lack of a control group, underscoring the need for additional research in larger, randomized controlled trials.

References

1. Ramasamy, K., et al., Improving outcomes for patients with relapsed multiple myeloma: Challenges and considerations of current and emerging treatment options. Blood Rev, 2021. 49: p. 100808.

2. Moreau, P., et al., Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS. Blood Cancer J, 2023. 13(1): p. 33.

3. Usmani, S.Z., et al., Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol, 2022. 23(1): p. 65-76.

4. Usmani, S.Z., et al., Final Analysis of Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone in the CANDOR Study. Blood Adv, 2023.

No relevant conflicts of interest to declare.