Daratumumab improves outcomes in relapsed, refractory myeloma

CHICAGO — The addition of daratumumab to a standard-of-care regimens extended PFS among patients with relapsed or refractory multiple myeloma regardless of patients’ cytogenetic risk status, according to study results presented at the ASCO Annual Meeting.

Efforts to target CD38 via combinations of daratumumab (Darzalex, Janssen) with lenalidomide (Revlimid, Celgene) plus dexamethasone, or with bortezomib (Velcade, Takeda) plus dexamethasone appears to improve the poor outcomes typically experienced by patients with high-risk cytogenetic status, Meletios A. Dimopoulos, MD, professor in and chairman of the department of clinical therapeutics at Alexandra Hospital in Athens, Greece, and colleagues wrote.

Meletios A. Dimopoulos

“With longer follow-up, our study showed that there is further improvement in the [PFS] of patients treated with [daratumumab, lenalidomide and dexamethasone], along with improvements in the depth of response, including achievement of minimal residual disease–negative status,” Dimopoulos told HemOnc Today.

Results of the phase 3 POLLUX and CASTOR trials showed the addition of daratumumab to two standard regimens — lenalidomide plus dexamethasone, or bortezomib plus dexamethasone — significantly improved PFS and increased response rates, according to study background.

Dimopoulos and colleagues speculated daratumumab’s novel mechanism of action may improve the poor prognosis associated with high-risk cytogenetic abnormalities in relapsed or refractory myeloma, according to study background.

Researchers examined the efficacy of two combinations — daratumumab, lenalidomide and dexamethasone, and daratumumab, bortezomib and dexamethasone — in patients with relapsed or refractory myeloma who had standard or high-cytogenic risk status.

High-cytogenic risk patients included those with at least one of the following abnormalities: t(4;14) translocation, t(14;16) translocation or deletion 17p. Patients confirmed as negative for these abnormalities were classified as standard risk.

Researchers collected bone marrow aspirates at screening and assessed them centrally via next-generation sequencing.

Efficacy analyses assessed for PFS and objective response rate.

Dimopoulos and colleagues used next-generation sequencing to assess samples from 311 patients in the POLLUX trial (median follow-up, 17.3 months) and 353 samples in the CASTOR trial (median follow-up, 13 months).

Analysis of samples from patients in the POLLUX trial showed the addition of daratumumab to lenalidomide and dexamethasone significantly prolonged median PFS among high-risk patients (not reached vs. 10.2 months; HR = 0.44; 95% CI, 0.19-1.03) and standard-risk patients (not reached vs. 17.1 months; HR = 0.3; 95% CI, 0.18-0.49). Daratumumab also significantly improved ORR in standard-risk patients (95% vs. 82%; P = .002).

Analysis of samples from patients in the CASTOR trial showed the addition of daratumuab to bortezomib plus dexamethasone significantly prolonged median PFS among high-risk patients (11.2 months vs. 7.2 months; HR = 0.49; 95% CI, 0.27-0.89) and standard-risk patients (not reached vs. 7 months; HR = 0.29; 0.2-0.43). Daratumumab also improved ORR among high-risk patients (82% vs. 62%; P = .0167) and standard-risk patients (85% vs. 64%; P = .0003). – by Jennifer Southall

Reference:

Weisel KC, et al. Abstract 8006. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosure: Dimopoulos reports honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen-Cilaq and Takeda; consultant or advisory roles with Amgen, Celgene, Janssen-Cilaq and Takeda; research funding from Amgen and Janssen-Cilaq; and travel, accommodations and expenses from Amgen and Genesis. Please see the abstract for a list of all other researchers’ relevant financial disclosures.