Daratumumab Added to Standard Therapy = Longer Survival in Newly Diagnosed Multiple Myeloma

In patients with newly diagnosed multiple myeloma who were not a good fit for transplant, the addition of daratumumab to bortezomib, melphalan, and prednisone (D-VMP) continues to improve progression-free survival and overall survival compared with bortezomib, melphalan, and prednisone (VMP) alone. These data come from long-term follow-up of patients who participated in a phase 3 clinical trial called ALCYONE.

Progression-free survival is the length of time that a person lives with their cancer without it getting any worse. Overall survival is the length of time from the start of treatment that patients diagnosed with their cancer are still alive. In a clinical trial, measuring progression-free survival and overall survival helps doctors to determine how well a new treatment works.

These updated results from the trial showed that patients treated with D-VMP had a median progression-free survival of 36.4 months, compared with 19.3 months with VMP. After more than 40 months of follow-up, about 75% of patients treated with D-VMP were still alive, versus 62% of patients treated with VMP.

Clinical trials are designed to test the safety and effectiveness of new drugs, and phase 3 clinical trials like ALCYONE are carried out to expand on results from phase 1 and 2 trials, to compare the new treatment with the standard therapies that have already been approved, and to study the overall risks and benefits of the drug. Trials in this phase can last years, and can involve thousands of people.

“For the first time, we demonstrate that the addition of daratumumab to bortezomib, melphalan, and prednisone prolongs overall survival in patients with transplant-ineligible newly diagnosed multiple myeloma, with a 40% reduction in the risk of death versus [bortezomib, melphalan, and prednisone] alone, after a median follow-up of 40 months,” said Maria-Victoria Mateos, MD, one of the study’s lead investigators. “These data confirm the overall survival benefit of adding daratumumab to standard of care in newly diagnosed, transplant-ineligible patients.”

The study included 706 patients from 25 countries with newly diagnosed multiple myeloma. These patients were all ineligible for high-dose chemotherapy and autologous stem-cell transplantation due to either their age (older than 65 years) or comorbidities (other health conditions they had in addition to their cancer).

Patients were randomly assigned to receive either D-VMP (350 patients) or VMP (356 patients). About 30% of patients were over 75 years of age, and most patients had a good performance status, meaning they were able to do all or most of the physical activities they were able to do before their cancer diagnosis.

Overall response rates to treatment were 91% with D-VMP and 74% with VMP, and the quality of responses improved over time. Response rates are one way to tell how effective a new treatment is, and the overall response rate refers to the number of patients who had a partial response (a decrease in the amount of cancer in the body) or a complete response (no evidence of myeloma cells left in their bone marrow or blood). 

Patients who received D-VMP also had significantly higher rates of minimal residual disease (MRD)-negativity: 28% versus 7% with VMP at the time the investigators collected these data.  MRD is a term used to describe the small number of cancer cells in the body after cancer treatment, so an MRD-negative result means that no disease was detected after treatment. Doctors use MRD to measure the effectiveness of treatment and to predict which patients are at risk of relapse.

Regardless of whether or not patients received daratumumab, MRD-negative patients had significantly improved progression-free survival and overall survival.

“However, when we evaluated the proportion of patients who achieved MRD-negativity, at the primary as well as at the updated analysis, D-VMP was always superior to VMP,” said Dr. Mateos. MRD-negativity status also lasted longer in the patients who were given D-VMP: 14% were still MRD-negative at 1 year, compared with 3% in the patients given VMP.

Overall, the new treatment was well-tolerated, and the investigators didn’t see any surprising side effects. About 7% of patients who received D-VMP had to leave the trial due to treatment-related side effects, compared with 9.3% in the VMP group.

“This first report of an overall survival benefit with daratumumab continues to support the use of daratumumab-containing regimens for the treatment of patients with multiple myeloma,” said Dr. Mateos.