Literature
Clinical Pearls & Morning Reports
Published May 29, 2019
Does the addition of daratumumab to lenalidomide and dexamethasone increase progression-free survival in newly diagnosed multiple myeloma?
Younger patients with newly diagnosed multiple myeloma who do not have clinically significant coexisting conditions usually receive an induction regimen followed by high-dose chemotherapy and autologous stem-cell transplantation. Facon et al. recently published the results of a prespecified interim analysis of a phase 3 trial assessing the efficacy and safety of daratumumab plus lenalidomide and dexamethasone as compared with lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma who were ineligible for autologous stem-cell transplantation. Read the Original Article here.
Clinical Pearls
Q: What is the standard of care for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation?
A: In the phase 3 Frontline Investigation of Revlimid and Dexamethasone versus Standard Thalidomide (FIRST) trial involving patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, treatment with lenalidomide and dexamethasone administered until disease progression resulted in significantly longer overall survival than treatment with melphalan, prednisone, and thalidomide; these findings established the regimen of lenalidomide and dexamethasone as standard of care.
Q: What is the target of daratumumab?
A: Daratumumab, a human IgG κ monoclonal antibody that targets CD38, has direct antitumor and immunomodulatory activity.
Morning Report Questions
Q: Does the addition of daratumumab to lenalidomide and dexamethasone increase progression-free survival in newly diagnosed multiple myeloma?
A: In the trial by Facon et al., among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, treatment with daratumumab plus lenalidomide and dexamethasone resulted in significantly longer progression-free survival than lenalidomide and dexamethasone alone; the risk of disease progression or death was 44% lower in the daratumumab group than in the control group. The progression-free survival benefit was maintained among patients 75 years of age or older (hazard ratio, 0.63; 95% CI, 0.44 to 0.92). The percentage of patients with a complete response or better was nearly twice as high and the percentage of patients who were negative for minimal residual disease was more than 3 times as high in the daratumumab group as in the control group; these findings are consistent with those of previous trials. 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%).
Q: Did the benefit of daratumumab extend to the subgroup of patients with a high-risk cytogenic profile in the interim report of Facon et al.?
A: The results of this interim analysis showed that the benefit of daratumumab with respect to progression-free survival was not as high in the subgroup of patients who had a high-risk cytogenetic profile as it was in the subgroup of patients who had a standard-risk cytogenetic profile. However, in the previously reported CASTOR (bortezomib–dexamethasone) and POLLUX (lenalidomide–dexamethasone) trials, among patients with relapsed or refractory multiple myeloma who had a high-risk cytogenetic profile, substantial benefits with respect to progression-free survival and minimal residual disease with daratumumab plus standard-of-care regimens were observed after a longer follow-up period.