Adding Daratumumab to Standard Treatment Lowered the Risk of Death, Disease Progression in Patients With Multiple Myeloma

Patients with multiple myeloma who were ineligible for autologous stem-cell transplant and received daratumumab (Darzalex) in addition to standard treatment of lenalidomide and dexamethasone had significantly reduced risk of disease progression or death compared with those receiving standard treatment, according to a study in the New England Journal of Medicine.

“Initial treatment for newly diagnosed multiple myeloma depends on whether a patient may have unacceptable toxic effects from high-dose chemotherapy and may be unable to undergo autologous stem-cell transplantation,” researchers said. “For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care.”

Researchers conducted a randomized, open label, phase 3 trial to examine how patients with multiple myeloma who couldn’t receive stem-cell treatment would respond to the addition of daratumumab to standard treatment. The treatment group received daratumumab, lenalidomide, and dexamethasone while the control group received the standard treatment of lenalidomide and dexamethasone. Of the 737 total patients, 368 patients were assigned to the treatment group while 369 were assigned to the control group. Researchers balanced demographic and clinical characteristics of the groups at baseline. Patients had a median age of 73 years, 14.3% had a high-risk cytogenetic profile, and the median time since diagnosis of multiple myeloma was 0.9 months.

The study’s primary endpoint was progression-free survival. Secondary endpoints included time passed until progression, the percentage of patients with a complete response, a stringent complete response, negative status for minimal residual disease, overall response, a very good partial response or better, overall survival, the time to response, the duration of response, efficacy in the subgroup of patients with a high-risk cytogenic profile, and safety.

A total of 729 patients who underwent randomization, 364 from the treatment group and 365 from the control group, received at least 1 dose of the trial treatment. Treatment was set to continue until disease progression occurred or toxic effects became unacceptable. Researchers obtained serum samples and 24-hour urine samples for efficacy assessment every 28 days for 2 years, then every 8 weeks that followed until disease progression occurred. Complete responses were confirmed with reflex assays for patients who had positive serum immunofixation and daratumumab interference. Researchers evaluated minimal residual disease using Adaptive Biotechnologies’ clonoSEQ next-generation sequencing assay. Adverse events were also evaluated for safety assessments.

At a median follow-up of 28 months, researchers found:

• disease progression or death had occurred in 240, or 26.4%, of patients in the treatment group and 143, or 38.8%, in the control group
• a total of 138 patients had died; 62, or 16.8%, were from the treatment group an 76, or 20.6%, were from the control group
• the estimated percentage of patients who were alive without disease progression at 30 months was 70.6% in the treatment group and 55.6% in the control group
• the percentage of patients with a complete response or better was 47.6% in the treatment group and 24.9% in the control group
• a total of 24.2% of the patients in the treatment group, compared to 7.3% in the control group, had results below the threshold for minimal residual disease

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” researchers concluded.

Reference

Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380:2104-2115

doi: 10.1056/NEJMoa1817249.