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Adding daratumumab (Darzalex) to lenalidomide (Revlimid) and dexamethasone -- the DRd regimen -- boosted survival in newly diagnosed multiple myeloma patients ineligible for autologous stem cell transplant, an updated analysis of the MAIA trial showed.

At a median follow-up of 56.2 months, treatment with DRd demonstrated a significant 32% reduction in the risk of death from any cause versus lenalidomide and dexamethasone alone, with estimated 5-year overall survival (OS) rates of 66.3% in the DRd group compared with 53.1% in the control group, reported Thierry Facon, MD, of Centre Hospitalier Universitaire de Lille in France, and colleagues.

"The MAIA study is, to our knowledge, the first randomized phase 3 study that shows a significant improvement in overall survival with daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients ineligible for transplantation with newly diagnosed multiple myeloma," Facon and colleagues wrote in .

Taken together with the findings of the which showed that a daratumumab-based combination significantly improved OS in this population of patients, "the efficacy and safety results of the MAIA study strongly support the frontline use of daratumumab in combination with standard-of-care regimens for patients with multiple myeloma who are ineligible for transplantation," they concluded.

Commenting on the study, Rafael Fonseca, MD, of the Mayo Clinic in Phoenix, told 乌鸦传媒 he agreed with the authors that the results of the study support the frontline use of DRd in this population of patients.

"The results are superior to those published in the SWOG S0777 and ALCYONE studies," said Fonseca, who was not involved in the MAIA trial. "And even though there is no direct comparison between the studies, the outcomes in MAIA are remarkable, even more so now that they have reported on overall survival."

The study showed that the combination of bortezomib (Velcade) plus lenalidomide and dexamethasone (VRd) significantly prolonged progression-free survival (PFS) and OS versus lenalidomide and dexamethasone alone in patients with newly diagnosed multiple myeloma without an intent for immediate transplantation. However, Facon and his colleagues pointed out that a significant OS benefit was not observed in patients 65 years or older, and that patients on the VRd regimen had a high incidence of grade 3 or higher neurological and gastrointestinal adverse events.

Fonseca said that even if one considers DRd and VRd to be comparable in efficacy, "the fact that you can treat myeloma patients without the risk of peripheral neuropathy that occurs with Velcade is very, very important."

In MAIA, 737 patients were randomized 1:1 to receive the two regimens. These patients were 18 years or older (median 73), had newly diagnosed multiple myeloma, an Eastern Cooperative Oncology Group performance status score of 0-2, and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation because of their age (≥65 years) or comorbidities.

At the clinical cutoff date, 32% of patients in the DRd group and 42% in the control group had died (HR 0.68, 95% CI 0.53-0.86). Median OS was not reached in either group.

In the primary analysis of the trial at a median follow-up of 28.0 months, DRd demonstrated a significant improvement in PFS compared with lenalidomide and dexamethasone alone. The estimated proportion of patients who were alive without disease progression or death at 30 months was 70.6% in the DRd group and 55.6% in the control group, translating into a 44% reduction in the PFS hazard.

In this updated analysis, the PFS benefit observed with DRd persisted at a median follow-up of 56.2 months. Median PFS was not reached in the DRd group versus 34.4 months in the control group -- a 47% reduction in the risk of disease progression or death (HR 0.53, 95% CI 0.43-0.66).

The estimated PFS at 5 years was 52.5% in the DRd group and 28.7% in the control group.

According to Facon and colleagues, no new safety concerns were identified with the longer follow-up.

The most common grade 3 or higher treatment-emergent adverse events were neutropenia (54% of patients in the DRd group vs 37% of patients in the control group), pneumonia (19% vs 11%), anemia (17% vs 22%), and lymphopenia (16% vs 11%). Serious adverse events occurred in 77% of patients in the DRd group and 70% of patients in the control group, with treatment-related deaths occurring in 4% and 3%, respectively.

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