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ATLANTA – Adding daratumumab (Darzalex) to a standard regimen for treatment of multiple myeloma led to longer progression-free survival in a phase III study reported here.

Patients treated with bortezomib, melphalan and prednisone (VMP) – a combination favored in Europe and Latin America – achieved a median progression-free survival of 18.1 months, whereas patients who had daratumumab added to the same VMP regimen had not reached a median progression-free survival (P<0.0001) with up to 27 months of follow-up, reported Jesus F. San-Miguel, MD, of the Clínica Universidad de Navarra in Pamplona, Spain.

At month 18 of follow-up, 72% of those in the daratumumab-VMP arm were alive without progression.

During a press conference at the annual meeting of the American Society of Hematology, San-Miguel said that difference translates to a 50% reduction in the risk of having disease progression.

He also reported that 91% of the patients treated with the monoclonal antibody achieved an objective response compared with 74% of the patients treated with the regular VMP regimen (P<0.0001).

The researchers randomly assigned 356 patients with 9 cycles of VMP – bortezomib (Velcade) 1.3 mg/m² subcutaneously twice a week for the first cycle and then once weekly for the following 8 cycles; 9 mg/m² melphalan orally on days 1-4; and prednisone 60 mg/m² on days 1-4.

Another cohort of 350 patients received the same VMP regimen and daratumumab 16 mg/kg intravenously once for the first week and then every 3 weeks. Then patients received daratumumab every 4 weeks until disease progression occurred.

To be eligible for the study, patients had to be ineligible for transplantation for newly diagnosed multiple myeloma; had to be in ECOG status 0-2; had to have adequate kidney function and no more than Grade 2 peripheral neuropathy.

"This is the first phase III randomized trial to evaluate the use of a monoclonal antibody drug for treating newly diagnosed multiple myeloma," San-Miguel said. The combination also induced deeper responses including a greater than 3-fold higher rate of patients achieving a minimal residual disease-negative rate. He noted that 6% of patients receiving VMP achieved a negative minimal residual disease finding compared with 22% of the patients who were also treated with daratumumab (P<0.0001).

He also said the addition of daratumumab was achieved without creating any new safety signal. Infections that occurred more frequently among the patients getting daratumumab resolved. The risk of Grade 3 or Grade 4 neutropenia, thrombocytopenia, or anemia was similar in both treatment arms, but there was a higher rate of pneumonia in patients treated with daratumumab (11% versus 4%).

"Our results support that daratumumab in combination with bortezomib, melphalan, and prednisone should become a new standard of care in transplant-ineligible multiple myeloma patients," said San-Miguel. "Monoclonal antibodies like daratumumab have already been approved for use in relapsed patients; here, we are showing that the benefits extend to newly diagnosed patients, as well."

While the results were impressive, they are unlikely to make a difference in practice in the United States and North America, said Robert A. Brodsky, MD, of Johns Hopkins School of Medicine, Baltimore.

"This treatment is not the standard of care in North America, so this study is not as likely to change practice here. Treatment of multiple myeloma has been a moving landscape because there are so many new drugs, so the question is whether daratumumab upfront would change the standard of care outside of Europe and Latin America."

"The standard of care in the United States varies with the age of the patient, often younger patients will go to transplant," Brodsky, the moderator of the press conference, told 名媛直播. "Treatment regimens also depend on the center. These are all reasonable regimens."

Brodsky noted that the so-called ALCYONE trial "is the first large phase III trial to test upfront a monoclonal antibody – to bring in a non-chemotherapy agent in multiple myeloma."

In his press briefing, San-Miguel acknowledged that the VMP regimen is not used throughout the world, but noted that ongoing studies are testing daratumumab with other combinations used elsewhere.

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