Maria-Victoria Mateos, MD, PhD
The benefits of 2 FDA-approved daratumumab (Darzalex)–based triplet regimens were sustained in long-term data from 2 pivotal phase III studies presented at the 2016 ASH Annual Meeting.1,2
In November 2016, the FDA approved daratumumab in combination with lenalidomide (Revlimid) and dexamethasone or bortezomib (Velcade) and dexamethasone for patients with relapsed multiple myeloma following at least 1 prior therapy, based on findings from the phase III CASTOR and POLLUX studies.
At the recent ASH meeting, CASTOR and POLLUX updates were presented, respectively, by Maria-Victoria Mateos, MD, PhD, consultant physician, hematology department, Hospital Universitario de Salamanca, and Saad Z. Usmani, MD, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System.
The CASTOR study randomized 498 patients with relapsed or refractory multiple myeloma to bortezomib and dexamethasone alone (n = 247) or with daratumumab (n = 251). Patients had received a median of 2 prior lines of therapy. Overall, 66% had received prior bortezomib, 76% received a prior immunomodulatory drug (IMiD), and 48% had received prior proteasome inhibitors and IMiD. The median age was 64 years (range, 30-88).
Patients were randomized 1:1 to receive 8 cycles of bortezomib/dexamethasone with or without 16 mg/kg of daratumumab. Bortezomib was administered subcutaneously at 1.3 mg/m2 on days 1, 4, 8, and 11 of each 21-day cycle for a maximum of 8 cycles. Patients received 20 mg of oral dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12 of the first 8 bortezomib treatment cycles. Patients in the daratumumab group were administered an IV infusion of the antibody at 16 mg/kg weekly for the first 3 cycles, on day 1 of cycles 4 to 9, and then every 4 weeks. Treatment was administered until disease progression or unacceptable toxicity.
In the primary analysis, the 12-month progression-free survival (PFS) rate was 60.7% with daratumumab, bortezomib, and dexamethasone versus 26.9% for bortezomib and dexamethasone alone. After a median follow-up of 7.4 months, the median PFS was not reached in the daratumumab arm compared with 7.2 months in the control group (HR, 0.39; 95% CI, 0.28-0.53; P
The overall response rate (ORR) with the addition of daratumumab was 82.9% compared with 63.2% in the control group (P
<.001). The very good partial response (VGPR) or better rate was 59.2% with daratumumab versus 29.1% in the control arm (P
<.001). The complete response (CR) rate was 19.2% with daratumumab versus 9.0% with the doublet (P
The median follow-up for the data Mateos presented at ASH was 13 months (range, 0-21.3). The 12-month PFS was 60% in the daratumumab arm versus 22% in the control arm.
“The progression-free survival benefit continues to be maintained for daratumumab in combination with bortezomib and dexamethasone over time. More patients in the [daratumumab arm] achieved deeper responses with longer follow-up,” said Mateos.
The ORR was 84% in the daratumumab arm, including a 7% stringent CR (sCR) rate, 19% CR rate, 35% VGPR rate, and 22% PR rate. The ORR in the bortezomib/dexamethasone arm was 63%, comprising an sCR rate of 2%, CR rate of 8%, VGPR rate of 19%, and partial response (PR) rate of 34%.
The PFS benefit was sustained regardless of the number of prior lines of treatment. Among patients who had 1 prior line of treatment, the 12-month PFS rate was 77% in the daratumumab arm versus 25% in the control arm (HR, 0.22; 95% CI, 0.14-0.34; P
<.0001). The ORR rates were 91% versus 74%, respectively (P
In the group of patients who had received 2 to 3 prior lines of therapy, the 12-month PFS rate was 44% for the daratumumab cohort versus 22% for the control arm (HR, 0.51; 95% CI, 0.36-0.73; P
= .0002). The ORR rates were 79% versus 58%, respectively (P
Additionally, Mateos said, “MRD negative rates for daratumumab plus bortezomib/dexamethasone were more than 3-fold higher across all sensitivity thresholds in comparison with bortezomib/dexamethasone alone.”
Daratumumab plus bortezomib/dexamethasone also improved outcomes regardless of cytogenetic risk. Among high-risk patients, the median PFS was 11.2 months in the daratumumab arm versus 7.2 months in the control arm (HR, 0.49; 95% CI, 0.27-0.89; P
= .0167). The ORR rates were 82% versus 62%, respectively (P
Among standard-risk patients, the median PFS was not yet reached in the daratumumab arm and was 7 months in the bortezomib/dexamethasone group (HR, 0.29; 95% CI, 0.20-0.43; P
<.0001). The ORR rates were 85% versus 64%, respectively (P
Mateos reported that the overall survival data are not yet mature, but that the curves are beginning to separate.