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The triplet of daratumumab, lenalidomide, and dexamethasone reduced the risk of disease progression or death by 44% compared with lenalidomide plus dexamethasone in newly diagnosed patients with multiple myeloma who were not candidates for high-dose chemotherapy and autologous stem-cell transplant.
Thierry Facon, MD
The triplet of daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone (DRd) reduced the risk of disease progression or death by 44% compared with lenalidomide plus dexamethasone (Rd) in newly diagnosed patients with multiple myeloma who were not candidates for high-dose chemotherapy and autologous stem-cell transplant (ASCT).
Findings from the phase III MAIA study showed that at a median follow-up of 28 months (range, 0.0-41.4), the median progression-free survival (PFS) had not been reached with DRd compared with 31.9 months in the Rd group (HR, 0.56; 95% CI, 0.43-0.73; P <.0001). The PFS rate at 30 months was 71% versus 56%, respectively.
“These results support D-Rd as a new standard of care for patients with transplant-ineligible newly diagnosed multiple myeloma,” said lead author Thierry Facon, MD, of Claude Huriez Hospital in Lille, France.
The overall response rate (ORR) was 93% with DRd compared with 81% with Rd (P <.0001). The stringent complete response (sCR) rate (30% vs 12%), CR rate (17% vs 12%), and very good partial response (VGPR) rate (32% vs 28%) were all higher with DRd versus Rd. The PR rate was higher in the Rd versus DRd group at 28% versus 14%, respectively.
Falcon also reported that the MRD-negative rate was “greater than threefold higher” with DRd versus Rd at 24% versus 7%, respectively.
The open-label, multicenter phase III MAIA trial included 737 newly diagnosed patients with multiple myeloma who were not candidates for high-dose chemotherapy and ASCT. Fifty-two percent of patients were male and 92% were white. The ECOG performance status was 0-1 for 83% of patients.
The median patient age was 73 years (range, 45-90). Only 1% of patients were aged <65 years, while 44% of patients were aged ≥75 years. Facon noted the significance that this proportion of patients aged ≥75 years is much higher than any previous trial in this population.
“We see a very strong clinically significant benefit in extending survival without the cancer getting worse, with no major safety concerns,” said Facon. “In older patients who are not candidates for stem cell transplantation, these are very encouraging results.”
Per the multiple myeloma international staging system, 27% of patients were stage I, 43% of patients were stage II, and 29% of patients were stage III. Of the total population, cytogenetic risk level could be determined for 642 patients. Eighty-six percent of these patients were standard risk and 14% of these patients were high risk.
Patients were randomized to lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) and dexamethasone (40 mg once a week) with or without daratumumab. Daratumumab was administered at 16 mg/kg weekly for the first 8 weeks (cycles 1 and 2), every other week for 16 weeks (cycles 3 to 6), and then every 4 weeks (cycle 7 and beyond) until disease progression or unacceptable toxicity. PFS was the primary endpoint.
The most common grade 3/4 hematologic treatment-emergent adverse events (TEAEs) in the DRd arm were neutropenia (50% versus 35% with Rd), lymphopenia (15% vs 11%, respectively), anemia (12% vs 20%), and thrombocytopenia (7% vs 9%).
The most frequently occurring nonhematologic TEAEs in the DRd arm included pneumonia (14% vs 8% with Rd); fatigue (8% vs 4%, respectively); diarrhea (7% vs 4%); deep vein thrombosis, pulmonary embolism, or both (6% in each arm); asthenia (4% in each arm); back pain (3% in each arm); constipation (2% vs <1%); peripheral edema (2% vs <1%); and nausea (1% vs ≤1%).
Frontline daratumumab was previously approved in multiple myeloma for use in combination with bortezomib (Velcade), melphalan, and prednisone (VMP) for the treatment patients who are ineligible for ASCT. However, the VMP regimen is mostly utilized in Europe, not in the United States.
The ongoing Cassiopeia trial is examining daratumumab in combination with bortezomib (Velcade), thalidomide, and dexamethasone (VTD) as a frontline treatment for transplant-eligible patients with newly diagnosed multiple myeloma (NCT02541383).
Facon T, Kumar SK, Plesner T, et al. Phase 3 Randomized Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant (MAIA). Presented at: ASH Annual Meeting and Exposition; December 4-8, 2018; San Diego, California. Abstract LBA-2.