Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma

Abstract

BACKGROUNDLenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population. METHODSWe randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival. RESULTSAt a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 10 5 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%). CONCLUSIONSAmong patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.

Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies

“…Recently, in the phase 3 MAIA study, D-Rd significantly reduced the risk of disease progression or death and nearly doubled the rate of CR or better. 29 MAIA enrolled patients aged 65 or older, 44% of whom were aged 75 years or older. 29 MM is a disease of the elderly with 35-40% of patients aged 75 years or older at diagnosis.…”

Daratumumab added to standard of care in patients with newly diagnosed multiple myeloma: A network meta‐analysis

“…A comprehensive search of the Embase, Medline, the Science Citation Index, and Cochrane Controlled Trial Register attained 432 articles, of which 6 trials met the predefined inclusion criteria, covering 2674 untreated myeloma patients totally. [6][7][8][9][10][11][12][13][14][15] A diagram of the study flow is presented in Figure 1(1). Their characteristics were summarized in Table 1.…”

“…5 In those relapsed/refractory patients with multiple myeloma, daratumumab added to standard of care significantly prolonged progression-free survival and induced high response quality and had a favorable risk-benefit profile. 6,7 Meanwhile, there were some studies are investigating the use of daratumumab added to standard of care in untreated patients with multiple myeloma, [8][9][10][11][12][13] and most of them only enrolled small number of patients. To better characterize the benefit-to-risk profile of daratumumab combinations in untreated patients, we did this pooled analysis.…”

Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

“…Dara-VMP has recently been approved by both the FDA and EMA, thus becoming one of the standards of care for transplant-ineligible patients. Impressive results in terms of higher MRD negativity rates (24.2% vs. 7.3%, respectively; p < 0.001, threshold 10 −5 ) and reduced risk of progression or death (median NR vs. 32 months after a median follow-up of 28 months, HR 0.56, p < 0.001) were observed when Dara-Rd was compared to Rd in NDMM patients not suitable for autologous stem-cell transplantation (ASCT; MAIA study [38]). In both Dara-VMP and Dara-Rd regimens, the addition of daratumumab did not negatively affect the safety profiles of VMP and Rd, despite a higher rate of grade 3-4 infections being reported in both studies in patients receiving daratumumab (Dara-VMP 23.1% vs. VMP 14.7%; Dara-Rd 32% vs. Rd 23%); also, the frequency of grade 3-4 neutropenia was higher in patients receiving daratumumab in the MAIA study (50% vs. 35%).…”