Adding Darzalex to Popular Multiple Myeloma Treatment Regimen May Lead to Durable Responses

Revlimid (lenalidomide), Velcade (bortezomib) and dexamethasone — a combination commonly referred to as RVd — is commonly given to treat patients with multiple myeloma.

Recent findings from the phase 2 GRIFFIN trial presented at the 2022 American Society of Clinical Oncology Annual Meeting showed that the addition of Darzalex (daratumumab) to the regimen may further improve outcomes in patients with transplant-eligible newly diagnosed multiple myeloma.

In particular, the addition of Darzalex improved minimal residual disease (MRD)-negativity rates, which is when there are no traces of leftover disease after treatment has ended. Additionally, adding Darzalex to the triplet therapy improved progression-free survival, which is the time from treatment until disease gets worse.

“(Darzalex) is approved across lines of therapy for the treatment of multiple myeloma, and a primary analysis of the phase 2 GRIFFIN study (adding Darzalex to) RVd significantly improved the stringent complete remission rates compared with RVd, and responses deepened with longer follow-up,” said study author Dr. Cesar Rodriguez, clinical director of Multiple Myeloma at The Mount Sinai Hospital in New York City, during a presentation of the findings.

Participants in the trial were randomly assigned to receive four Darzalex-RVd or RVd induction cycles, autologous stem cell transplant, two consolidation cycles of Darzalex-RVd or RVd and then two years of maintenance therapy with Revlimid with or without Darzalex.

Study results from a median follow-up of 38.6 months showed that 48.1% of patients in the Darzalex plus RVd group had a durable MRD negativity status lasting six or more months, compared with 14.6% in the RVd alone group. MRD negativity that lasted 12 or more months was experienced in 44.2% and 12.6% of the Darzalex plus RVd and RVd groups, respectively.

The Darzalex-containing regimen had better MRD negativity rates for patients with high cytogenic risk, too, at 25% in the Darzalex-containing group and 14.3% in the RVd group lasting six or more months, and 18.8% and 14.3% lasting 12 or more months, respectively. For revised high cytogenic risk, MRD lasting at least six months was 35.7 months and 18.9 months in the Darzalex-containing group and RVd group, respectively, and 33.3% and 16.2% last 12 or more months.

“Data show that all subgroups had higher rates of MRD negativity lasting 12 months or longer at the 10-5 threshold for Darzalex/RVd versus RVd,” Rodriguez said. “At the 10-6 threshold, MRD negativity rates lasting five months or longer were higher for the Darzalex-RVd in most subgroups, except for the revised high cytogenetic risk group, including the 1q gain.”

Additionally, progression-free survival was consistently better in the Darzalex/RVd cohort compared to the RVd cohort in patients who achieved MRD negativity at the 10-5 threshold. Median progression-free survival by durable MRD negativity at 10-5 was not reached in any group because so many patients were still alive without disease progression, so researchers could not calculate the average time until the myeloma progressed.

Patients in both groups tended to have improved progression-free survival when they had lasting MRD negativity, compared to those who did not reach MRD negativity, which, according to the authors, emphasizes the importance of MRD negativity as an important point to consider when studying myeloma outcomes.

Among those who sustained MRD negativity, only one patient on Darzalex plus RVd experienced subsequent disease progression, and one patient on RVd died of an unknown cause. Both patients had high cytogenetic risk at baseline.

“These data are consistent with previous reports that Darzalex-based therapies for newly diagnosed myeloma patients are associated with higher rates of durable MRD negativity, which translated to improved (progression-free survival),” Rodriguez concluded. “These results suggest that Darzalex-RVd therapy in transplant-eligible patients with newly diagnosed myeloma may benefit high-risk subgroups, although larger studies are needed to confirm, especially incorporating patients with revised high-risk cytogenetics, including 1q gain.”

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