Adding daratumumab to induction, consolidation, and maintenance therapy can improve outcomes in patients with newly diagnosed, transplant-eligible multiple myeloma (MM), according to final results from the GRIFFIN trial.
Patients who received daratumumab plus lenalidomide, bortezomib, and dexamethasone (RVd) as induction and consolidation, followed by maintenance with daratumumab and lenalidomide, had superior responses and progression-free survival (PFS), when compared with patients who received RVd as induction and consolidation, followed by lenalidomide maintenance.
These results support the daratumumab regimen as standard care in transplant-eligible, newly diagnosed MM, according to Douglas W. Sborov, MD, of the Huntsman Cancer Institute in Salt Lake City, Utah. Dr Sborov presented these results at the 19th International Myeloma Society Annual Meeting.
In this phase 2 study (ClinicalTrials.gov Identifier: NCT02874742), patients were randomly assigned to treatment with or without daratumumab. There were 103 patients who received RVd induction (cycles 1-4), followed by autologous transplant, RVd consolidation (cycles 5-6), and lenalidomide maintenance (cycles 7-32).
The 104 patients in the daratumumab arm received daratumumab plus RVd induction, followed by autologous transplant, daratumumab plus RVd consolidation, and maintenance with daratumumab and lenalidomide. After 2 years of maintenance on study, patients in either arm could continue receiving lenalidomide alone.
At the final analysis, the median follow-up was 49.6 months. Patients were more likely to complete maintenance in the daratumumab arm than in the RVd arm — 71% and 47%, respectively. After completing study treatment, 61% of patients in the daratumumab arm and 41% in the RVd arm continued to receive lenalidomide maintenance.
The rate of stringent complete response (sCR) improved over time in both treatment arms but was consistently higher in the daratumumab arm. The sCR rate at the end of consolidation was 42% in the daratumumab arm and 32% in the RVd arm. At the end of the study, the sCR rate was 67% and 48%, respectively (P =.0079).
Minimal residual disease (MRD) negativity rates improved over time but were higher in the daratumumab arm than in the RVd arm. At a sensitivity threshold of 10-6, the rate of MRD negativity at the end of consolidation was 11% in the daratumumab arm and 3% in the RVd arm. At the end of the study, the MRD negativity rate was 36% and 16%, respectively.
At the final analysis, the median PFS was not reached in either treatment arm. However, there was a 55% reduction in the risk of progression or death in the daratumumab arm (hazard ratio [HR], 0.45; 95% CI, 0.21-0.95; P =.0324). The 4-year PFS rate was 87.2% in the daratumumab arm and 70.0% in the RVd arm.
The 4-year overall survival rates were similar in the daratumumab arm and the RVd arm — 92.7% and 92.2%, respectively (HR, 0.90; 95% CI, 0.31-2.56; P =.8408). A total of 14 patients died, 7 in each arm.
The final analysis revealed no new safety concerns. The rate of treatment-emergent adverse events (TEAEs) leading to discontinuation was 33% in the daratumumab arm and 31% in the RVd arm. TEAEs led to 1 death in each treatment arm, but neither death was attributed to study treatment.
Disclosures: This study was sponsored by Janssen. Dr Sborov disclosed affiliations with Janssen, GSK, Sanofi, AbbVie, Bristol Myers Squibb, and Pfizer.
Sborov DW, Laubach JP, Kaufman JL, et al. Daratumumab (DARA) + lenalidomide, bortezomib, and dexamethasone (RVd) in patients (pts) with transplant-eligible newly diagnosed multiple myeloma (NDMM): Final analysis of GRIFFIN. Presented at IMS 2022; August 25-27, 2022; Abstract OAB-057.