CANDOR: Comparing KdD to Kd in Relapsed/Refractory Multiple Myeloma

Take-aways:

• Treatment needs for patients with relapsed/refractory MM remain unmet despite recent therapeutic advances.
• An interim analysis of the phase III CANDOR trial found that median PFS was 1 year longer in patients treated with KdD, compared with those who received Kd.
• KdD may represent a new standard of care for patients with relapsed/refractory MM, particularly those with previous lenalidomide exposure.

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In patients with relapsed or refractory multiple myeloma (MM), treatment with carfilzomib, daratumumab, and dexamethasone (KdD) led to superior progression-free survival (PFS), compared with carfilzomib and dexamethasone (Kd). This is according to an interim analysis of the phase III CANDOR study recently published in Lancet Oncology.

Researchers led by Saad Z. Usmani, MD, FACP, of Memorial Sloan Kettering Cancer Center, analyzed data from 466 adult patients with relapsed/refractory MM from 102 medical centers who were enrolled in the study between June 13, 2017, and June 25, 2018. Patients had Eastern Cooperative Oncology Group Performance status of 0-2 and had experienced at least a partial response to 1 to 3 prior therapies. Approximately 12% of patients had disease that was refractory to both lenalidomide and bortezomib. Patients were randomized to receive either KdD (n, 312) or Kd (n, 154).

Patients were stratified by disease stage, previous proteasome inhibitor or anti-CD38 antibody exposure, and number of previous therapies. Carfilzomib was administered via intravenous (IV) infusion twice per week at 56 mg/m² on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle, and at 20 mg/m² on days 1 and 2 of cycle 1. Patients in the KdD group received IV daratumumab 8 mg/kg on days 1 and 2 of cycle 1 and at 16 mg/kg weekly for the remaining doses of the first 2 treatment cycles, followed by every 2 weeks for cycles 3-6, then every 4 weeks thereafter. On a weekly basis, patients received dexamethasone at 40 mg, or 20 mg if older than 75 years.

At data cutoff, 223 patients (71%) who received KdD and 124 (81%) treated with Kd had discontinued carfilzomib, most commonly because of disease progression (KdD, 95 [30%]; Kd, 70 [45%]). Daratumumab was discontinued in 197 patients (63%) treated with KdD, mainly due to disease progression (112 [36%]). Following discontinuation of treatment, 42 (13%) and 43 (28%) patients in the KdD and Kd groups, respectively, entered follow-up, including 127 (41%) and 88 (57%) who entered long-term follow-up. For patients receiving KdD, median treatment duration was 18.3 months, compared with 9.3 months in the Kd group.

The median follow-up at data cutoff was 27.8 months for patients in the KdD group and 27 months for the Kd arm. In the KdD group, median PFS was 28.6 months, compared with 15.2 months for patients treated with Kd (hazard ratio, 0.59; 95% CI 0.45-0.78; P < .0001).

Overall response rates (ORRs) were 84% and 73% for the KdD and Kd groups, respectively. A total of 103 patients (33%) experienced a complete response or complete stringent response in the KdD arm, compared with 20 (13%) in the Kd group. Very good partial response or better was reported in 216 patients (95%) in the KdD group and 73 patients (47%) in the Kd group.

Among patients who received 1 prior line of therapy in the KdD group, the ORR across lenalidomide subgroups was about 90% versus 67-77% in the Kd arm. The ORR for patients who had undergone 2 to 3 previous therapies, across lenalidomide subgroups, was 76-84% for patients treated with KdD versus 70-71% for those who received Kd.

“The findings of the CANDOR study highlight the clinical benefit of adding an anti-CD38 antibody (daratumumab) to a carfilzomib-based regimen,” the authors wrote. In addition, “progression-free survival benefit was observed across all clinically relevant subgroups, including patients with previous lenalidomide exposure with either 1 or 2 to 3 previous lines of therapy.” According to the researchers, these findings suggest KdD may be superior to other triplet regimens for patients with relapsed/refractory MM who have previous lenalidomide exposure.

No new safety signals were observed in the updated analysis. Grade 3 or higher treatment-emergent adverse events (TEAEs) were reported in 268 patients (87%) treated with KdD and 116 patients (76%) in the Kd group. The most common grade 3 or higher TEAEs across both groups were thrombocytopenia, hypertension, pneumonia, and anemia. In the KdD group and Kd arm, 194 (63%) and 76 (50%) patients experienced serious adverse events (AEs). Twenty-seven patients in the KdD group and 7 (5%) in the Kd group died because of AEs, including septic shock and pneumonia.

Disclosures: Study authors report financial relationships with Amgen and Janssen, the manufacturers of carfilzomib and daratumumab.

Reference

Usmani SZ, Quach H, Mateos MV, 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. 2021 Dec 3;S1470-2045(21)00579-9.