Daratumumab Added to RVd Achieved MRD Negativity, PFS Improvement in Newly Diagnosed Myeloma

In the phase 2 GRIFFIN clinical trial (NCT02874742), adding daratumumab (Darzalex) to induction/consolidation lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone (RVd) — a combination commonly referred to as RVd — achieved durable minimal residual disease (MRD)-negativity in patients with transplant-eligible newly diagnosed multiple myeloma, according to findings presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

“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.

Study results from a median follow-up of 38.6 months showed that 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 to 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 arms, respectively.

The daratumumab-containing regimen induced better MRD negativity rates for patients with high cytogenic risk, too, with 25% at the daratumumab-containing arm and 14.3% in the RVd arm lasting 6 or more months, and 18.8% and 14.3% lasting 12 or more months, respectively. For revised high cytogenic risk, MRD lasting at least 6 months was 35.7 months and 18.9 months 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 versus 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 to 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 to those who did not reach MRD negativity, which, according to the authors, emphasizes the importance of MRD negativity as a surrogate endpoint.

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}