Daratumumab Plus Carfilzomib and Dexamethasone Improves PFS in Myeloma

Ajai Chari, MD

Adding daratumumab (Darzalex) to carfilzomib (Kyprolis) and dexamethasone (DKd) improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma, according to topline findings from the phase III CANDOR study.1

The topline findings showed that the DKd triplet reduced the risk of disease progression or death by 37% compared with carfilzomib and dexamethasone alone (Kd). The median PFS was not yet reached with DKd compared with 15.8 months with Kd alone (HR, 0.630; 95% CI, 0.464-0.854; P = .0014).

"While treatment advances have improved outcomes for patients with multiple myeloma, there remains a need for additional therapeutic options for patients who have relapsed," Ajai Chari, MD, associate professor of medicine, director of clinical research in the Multiple Myeloma Program and the associate director of clinical research, Mount Sinai Cancer Clinical Trials Office, said in a press release.2 "CANDOR confirms in a large phase III study the benefit for patients demonstrated in the earlier phase I study using the same combination."

The open-label phase III CANDOR trial (NCT03158688) randomized 466 patients with relapsed/refractory multiple myeloma treated with 1 to 3 prior therapies to either DKd or Kd. The primary endpoint was PFS. Genmab A/S, which develops daratumumab with Janssen, reported in a press release that no new safety signals emerged with the study drugs compared with historical data. Treatment-emergent adverse advents (TEAEs) occurring in at least 20% of patients in the DKd arm included thrombocytopenia, anemia, diarrhea, hypertension, upper respiratory tract infection, fatigue and dyspnea.

Genmab plans to discuss the CANDOR findings with regulatory authorities and present the data at an upcoming medical meeting.

"We are very pleased that daratumumab has shown efficacy in yet another combination regimen—in this case with carfilzomib, a newer member of the proteasome inhibitor class. We look forward to the potential for this combination to provide an additional regimen for patients diagnosed with relapsed multiple myeloma," Jan van de Winkel, PhD, chief executive officer of Genmab, said in a statement.

Data were previously reported from a phase Ib trial (NCT01998971) exploring the daratumumab triplet.3 The findings included 85 patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy including bortezomib (Velcade) and an immunomodulatory drug. The median number of prior therapy lines was 2 (range, 1-4) and 60% of patients were refractory to lenalidomide.

The overall response rate was 84%, including 79% in lenalidomide-refractory patients. At the time of the data analysis, the median PFS had not been reached. The 12-month PFS rate was 74% across the overall population and 65% in patients refractory to lenalidomide.

The investigators considered the regimen to be well tolerated. Grade 3/4 TEAEs occurring most frequently included thrombocytopenia (31%), lymphopenia (24%), anemia (21%), and neutropenia (21%).

References

1. Genmab announces positive topline results in phase III study of daratumumab in combination with carfilzomib and dexamethasone in relapsed or refractory multiple myeloma. Genmab. Published September 13, 2019. Accessed September 16, 2019. https://bit.ly/2kNde7M.
2. Amgen announces phase 3 CANDOR study combining Kyprolis® (carfilzomib) and Darzalex® (daratumumab) meets primary endpoint of progression-free survival. Amgen. Published September 13, 2019. Accessed September 16, 2019. https://bit.ly/2mgsnPn.
3. Chari A, Martinez-Lopez J, Mateos MV, et al. Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood. 2019;134(5):421-431. doi: 10.1182/blood.2019000722.