Conference Coverage

Combo could be new standard for transplant-eligible, newly diagnosed myeloma patients


 

FROM IMW 2019

BOSTON — Daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-RVd) may be a new standard of care for transplant-eligible patients with newly diagnosed multiple myeloma, according to a speaker at the International Myeloma Workshop.

Dr. Peter M. Voorhees, Levine Cancer Institute at Atrium Health in Charlotte, N.C. Jennifer Smith/MDedge News

Dr. Peter M. Voorhees

In the phase 2 GRIFFIN trial, adding daratumumab to RVd deepened responses at all time points and improved rates of stringent complete response and minimal residual disease (MRD) negativity post consolidation.

These results might convince “early adopters of therapy” to change their practice, said Peter M. Voorhees, MD, of Levine Cancer Institute at Atrium Health in Charlotte, N.C., who presented results from GRIFFIN as a late-breaking abstract at the workshop, which is held by the International Myeloma Society.

“But I think you do have to be careful,” Dr. Voorhees added. “We’ll have to see how these patients do over time. Is the MRD sustained, and does that MRD negativity improve progression-free survival?”

Dr. Voorhees presented data on 207 adults with transplant-eligible, newly diagnosed multiple myeloma who were enrolled in the GRIFFIN trial. The patients received RVd, with or without daratumumab, for induction (cycles 1-4). They received granulocyte colony stimulating factor, with or without plerixafor, for stem cell mobilization, and melphalan for conditioning prior to transplant.

Patients received consolidation with D-RVd or RVd (cycles 5-6) and maintenance with lenalidomide alone or in combination with daratumumab (cycles 7-32). Patients could continue maintenance with lenalidomide alone beyond cycle 32.

The D-RVd arm comprised 104 patients, and the RVd arm comprised 103 patients. Baseline characteristics were well balanced between the treatment arms. The median age was 59 years (range, 29-70 years) in the D-RVd arm and 61 years (range, 40-70 years) in the RVd arm.

Most patients had stage I (47% in the D-RVd arm and 49% in the RVd arm) or stage II disease (39% and 36%, respectively) according to the International Staging System. And most patients had standard risk cytogenetics (84% and 86%, respectively).

Response, MRD, and engraftment

The study’s primary endpoint was stringent complete response by the end of consolidation, which was achieved by 42.4% of patients in the D-RVd arm and 32.0% in the RVd arm (odds ratio [OR] = 1.57; P = .068). The overall response rate at that time point was 99.0% and 91.8%, respectively (P = .0160).

Responses deepened over time, and response rates were greater for D-RVd than for RVd at all time points. The complete response rate was 19.2% in the D-RVd arm and 13.4% in the RVd arm at the end of induction; 27.3% and 19.6%, respectively, at the end of transplant; 51.5% and 42.3%, respectively, at the end of consolidation; and 62.6% and 47.4%, respectively, at the clinical cutoff.

D-RVd also improved MRD negativity (10-5) rates at the end of consolidation. MRD negativity was 44.2% in the D-RVd arm and 14.6% in the RVd arm (OR = 4.70; P less than .0001). The rate of MRD negativity in patients with a complete response or better was 28.8% and 9.7%, respectively (OR = 3.73; P = .0007).

Dr. Voorhees noted that D-RVd was favored across all subgroups for MRD negativity and stringent compete response, except among patients with high-risk cytogenetics and stage III disease.

He also pointed out that stem cell mobilization was “feasible” in the D-RVd arm, and daratumumab did not impact engraftment. The median time to neutrophil engraftment was 12 days in both treatment arms. The median time to platelet engraftment was 13 days in the D-RVd arm and 12 days in the RVd arm.

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