Daratumumab Combination Therapy Established Standard of Care for Newly Diagnosed Multiple Myeloma

Daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone provided a significant overall survival benefit compared with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma.

The presentation at the 18th International Myeloma Workshop focused on updated efficacy and safety data for daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone after nearly 5 years of median follow-up in the phase 3 MAIA study (NCT02252172).

“Those results, when looking at [daratumumab plus lenalidomide and dexamethasone], both for PFS [progression-free survival] and OS [overall survival] and a relatively good safety profile, I would say, are now establishing [that combination] as a new standard of care for patients that are not transplant eligible,” said Philippe Moreau, MD, professor of clinical hematology at Centre Hospitalier Universitaire de Nantes, in a presentation of the findings.

The MAIA investigators analyzed data from 737 patients with newly diagnosed multiple myeloma. These patients were ineligible for high-dose chemotherapy and autologous stem cell transplantation because of their age (older than 65 years) or the presence of comorbidities. Participants’ median age was 73 years (range, 45-90). Patients were randomly assigned to daratumumab plus lenalidomide and dexamethasone (n = 368) or lenalidomide and dexamethasone (n = 369).

“One very important point and theory…for elderly patients we know that many of them are not able to receive 2 or 3 lines of treatment so this suggests that the most effective treatment should be used up front and not saved for relapse,” Moreau said.

The primary end point was PFS, with key secondary end points including OS, among others. After a median follow-up of 56.2 months, patients assigned to daratumumab plus lenalidomide and dexamethasone had a 32% reduction in the risk for death compared with those assigned to lenalidomide and dexamethasone.

The median OS was not reached in either group (HR, 0.68; 95% CI, 0.53-0.86; P = .0013). The estimated OS rate at 5 years was 66.3% in the daratumumab plus lenalidomide and dexamethasone group compared with 53.1% in the lenalidomide and dexamethasone group.

The updated median PFS was not reached in patients assigned daratumumab plus lenalidomide and dexamethasone, whereas patients assigned lenalidomide and dexamethasone had a median PFS of 34.4 months (HR, 0.53; 95% CI, 0.43-0.66; P = .248).

Longer follow-up did not result in new safety concerns. The most common grade 3/4 treatment-emergent adverse event was neutropenia, occurring in 54.1% of patients in the daratumumab plus lenalidomide and dexamethasone group and 37% in the lenalidomide and dexamethasone group (TABLE).

_REFERENCE:

_{1. Moreau P, Facon T, Kumar SK, et al. Overall survival and progression-free survival by treatment duration with daratumumab + lenalidomide/dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: phase 3 MAIA study. Oral abstract presented at: 18th International Myeloma Workshop; September 8-11, 2021; Vienna, Austria.}