Daratumumab Plus RVd Demonstrates Durable MRD Negativity in Multiple Myeloma

Cesar Rodriguez, MD

Daratumumab (Darzalex) plus induction/consolidation lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd) elicited higher minimal residual disease (MRD)-negativity rates vs the RVd combination alone in patients with transplant-eligible newly diagnosed multiple myeloma, including those in high-risk subgroups, according to data from the phase 2 GRIFFIN trial (NCT02874742), presented at the 2022 ASCO Annual Meeting.¹

At a median follow-up of 38.6 months 48.1% of patients in the daratumumab plus RVd arm had a durable MRD negativity status (defined as 10^-5) lasting 6 or more months, compared with 14.6% in the RVd arm. MRD negativity that lasted 12 or more months was experienced in 44.2% and 12.6% of the daratumumab plus RVd and RVd alone arms, respectively.

“Daratumumab is approved across lines of therapy for the treatment of multiple myeloma, and a primary analysis of the phase 2 GRIFFIN study [adding daratumumab to RVd], significantly improved the stringent complete remission rates compared with RVd, and responses deepened with longer follow-up,” said study author Cesar Rodriguez, MD, of the Mount Sinai School of Medicine.

Participants in the trial were randomized 1:1 to receive 4 daratumumab-RVd or RVd induction cycles, autologous stem cell transplant, 2 consolidation cycles of daratumumab-RVd or RVd and then 2 years of maintenance therapy with lenalidomide with or without daratumumab.

The daratumumab-containing regimen induced durable MRD negativity response for patients with high cytogenic risk, defined as those with deletion 17p (del17p), translocation (t[4:14]), or t(14:16) via fluorescence in situ hybridzation. Specifically, 25% of patients in the daratumumab-containing arm and 14.3% in the RVd alone arm had MRD negativity lasting 6 or more months, and 18.8% and 14.3% lasting 12 or more months, respectively.

In an analysis of revised high cytogenic risk—which included patients with del17p, t(4:14), t(14:16), t(14:20), or gain of chromosome 1q—MRD negativity lasting at least 6 months was 35.7% and 18.9% in the daratumumab-containing arm and RVd arm, respectively, and 33.3% and 16.2% lasted 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 daratumumab/RVd vs RVd,” Rodriguez said. “At the 10^-6 threshold, MRD negativity rates lasting 5 months or longer were higher for the daratumumab-RVd in most subgroups, except for the revised high cytogenetic risk group, including the 1q gain.”

Additionally, progression-free survival (PFS) was consistently better in the daratumumab/RVd cohort compared with the RVd cohort in patients who achieved MRD negativity at the 10^-5 threshold. Median PFS by durable MRD negativity at 10^-5 was not reached in any group.

Patients in both groups tended to have improved PFS when they had lasting MRD negativity, compared with those who did not reach MRD negativity, which, according to the authors, emphasizes the importance of MRD negativity as a surrogate end point.

Among those who sustained MRD negativity, only 1 patient treated with daratumumab plus RVd experienced subsequent disease progression, and 1 patient receiving RVd died of an unknown cause. Both patients had high cytogenetic risk at baseline.

“These data are consistent with previous reports that daratumumab-based therapies for newly diagnosed myeloma patients are associated with higher rates of durable MRD negativity, which translated to improved PFS,” Rodriguez concluded. “These results suggest that daratumumab-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.”

Reference

Rodriguez C, Kaufman JL, Laubach J, et. al. Daratumumab (DARA) + lenalidomide, bortezomib, and dexamethasone (RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM): a post hoc analysis of sustained minimal residual disease (MRD) negativity from GRIFFIN. J Clin Oncol. 2022;40(suppl 16):8011. doi:10.1200/JCO.2022.40.16_suppl.8011