Extended GRIFFIN Follow-up Shows Durability of Daratumumab Quadruplet Responses in Transplant-Eligible Myeloma

Take-aways

• After 2-year follow-up, rates of stringent complete response continued to favor D-RVd versus RVd, with higher rates of measurable residual disease negativity.
• Findings appear to support an approach of D-RVd as induction followed by transplant, D-RVd as post-transplant consolidation, and daratumumab and lenalidomide as maintenance.
• With longer follow-up, no new safety concerns were identified.

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According to extended, 2-year follow-up from the GRIFFIN trial, the combination of daratumumab and lenalidomide, bortezomib, and dexamethasone (D-RVd), in conjunction with autologous stem cell transplantation (ASCT) and daratumumab plus lenalidomide maintenance, continued to provide deep and durable responses in patients with transplant-eligible, newly diagnosed multiple myeloma. These results were presented at the 2021 American Society of Hematology Annual Meeting by Jacob Laubach, MD, of Dana-Farber Cancer Institute in Boston.

In his presentation, Dr. Laubach reported that the primary analysis of the phase II GRIFFIN trial, with a median follow-up of 13.5 months, showed a higher rate of stringent complete response (sCR) with D-RVd compared with RVd alone by the end of the post-ASCT consolidation. The present analysis, which included data from a median follow-up of 27.4 months, confirmed a persistent benefit. After 24 months, the rate of sCR was 66.05% for D-RVd, compared with 47.4% for RVd alone (P = .0096).

Together, the results support use of daratumumab plus RVd induction and consolidation with daratumumab maintenance in transplant-eligible patients with previously untreated disease, the authors wrote.

GRIFFIN investigators randomized 207 patients eligible for high-dose therapy and ASCT to receive RVd with or without daratumumab (D-RVd: n, 104; RVd: n, 103). During induction and consolidation, participants received treatment in 21-day cycles:

• lenalidomide 25 mg on days 1-14
• bortezomib 1.3 mg/m² on days 1, 4, 8, and 11
• dexamethasone 40 mg once weekly

In the D-RVd group, patients received daratumumab 16 mg/kg on days 1, 8, and 15 of cycles 1 through 4 and day 1 of cycles 5 and 6.

In the maintenance phase, patients received lenalidomide 10 mg on days 1 through 21 and, if tolerated, 15 mg, with or without daratumumab 16 mg/kg until disease progression or up to 24 months.

After 24 months of maintenance therapy, the rates of the primary endpoint sCR continued to favor D-RVd versus RVd. Rates of measurable residual disease (MRD) negativity were also higher with D-RVd (64.4% vs. 30.1%; P < .0001), particularly among patients who achieved at least a CR (78.0% vs. 47.5%; P = .0003).

MRD negativity (to a sensitivity of 10^-6) also favored D-RVd compared with RVd alone in the entire study population (35.6% vs. 14.6%; P = .0007), as well as among those with CR or better (42.7% vs. 22.0%; P = .0121).

Overall, the rate of sustained MRD negativity persisting for at least 12 months was 3 times greater for patients treated with D-RVd compared with RVd alone (44.2% vs. 12.6%; P < .0001).

The study was not powered for progression-free survival (PFS) analysis, but with a median follow-up of 38.6 months, median PFS was not reached for either treatment arm. “The separation of the PFS rates begins beyond 1 year of maintenance,” reported Dr. Laubach, “and suggests a benefit of prolonged daratumumab and lenalidomide therapy.”

The researchers noted that there were no new safety concerns seen with this extended follow-up. Treatment-emergent adverse events leading to discontinuation were similar in both study arms. One patient in each group died due to treatment-emergent adverse events; neither death was related to the study treatment.

Together, these findings appear to support an approach of D-RVd as induction followed by ASCT, D-RVd as post-transplant consolidation, and daratumumab and lenalidomide as maintenance.

Disclosures: This research was supported by the Janssen Research & Development. Study authors report financial relationships with Janssen Research & Development, the manufacturer of daratumumab.

Reference

Laubach JP, Kaufman JL, Sborov DW, et al. Daratumumab (DARA) plus lenalidomide, bortezomib, and dexamethasone (RVd) in patients (Pts) with transplant-eligible newly diagnosed multiple myeloma (NDMM): updated analysis of Griffin after 24 months of maintenance. Abstract #79. Presented at the 2021 American Society of Hematology Annual Meeting, December 11, 2021.