Data from the phase III MAIA clinical trial was presented yesterday as part of the Late-Breaking Abstracts Session during the 60th American Society of Hematology (ASH) Annual Meeting in San Diego.

As ASH informed in a press release, interim results from a large international phase III clinical trial show that adding the immunotherapy daratumumab to standard therapy significantly extended the time before cancer got worse in patients newly diagnosed with myeloma who were ineligible for a stem cell transplant.

Patients treated with lenalidomide and dexamethasone plus daratumumab were 44% less likely to die or experience disease progression, compared with patients who received lenalidomide alone, said lead author Thierry Facon, MD, of Claude Huriez Hospital in Lille, France.

He added the trial is important because it’s one of the first to test the combination of daratumumab with a current standard of care in this patient population, and it also enrolled a much higher proportion of patients over the age of 75 than any previous study.

“We see a very strong clinically significant benefit in extending survival without the cancer getting worse, with no major safety concerns,” said Dr. Facon. “In older patients who are not candidates for stem cell transplantation, these are very encouraging results.”

A stem cell transplant is often a recommended treatment option for patients with myeloma who are otherwise in good health. For newly diagnosed patients who aren’t candidates for a stem cell transplant due to age or coexisting health conditions, lenalidomide has been the standard of care since 2013.

Daratumumab is a targeted drug that blocks a protein called CD38, which is found at abnormally high levels in myeloma cells. The drug is currently approved by the U.S. Food and Drug Administration for use in combination with other agents to treat myeloma that has gotten worse after one or more prior rounds of treatment.

The MAIA study

The current trial, known as the MAIA study, enrolled 737 patients with newly diagnosed multiple myeloma who were deemed ineligible for a stem cell transplant. Their median age was 73, with 44% over 75. Slightly over half of the patients were male. The trial was conducted in 14 countries, including the United States, Canada, Australia, Israel, the United Kingdom, and several European countries.

Patients were randomly assigned to be treated with either lenalidomide alone or lenalidomide plus daratumumab. Treatment continued until the patients’ cancer got worse or intolerable side effects occurred. The primary endpoint was the length of time until patients’ cancer worsened, known as progression-free survival (PFS). Key secondary endpoints included minimal residual disease (MRD) negativity, defined as the absence of cancer cells in the bone marrow; the proportion of patients with a reduction of 50 percent or more of serum or urine monoclonal protein, known as the overall response rate; and the rate and severity of adverse side effects.

An interim analysis of the trial’s results after a median follow-up period of 28 months showed that patients treated with lenalidomide plus daratumumab were 44 % less likely to have died or experience disease progression, compared with patients who received lenalidomide alone. Median PFS––the point in time at which half of the patients had disease progression––was 31.9 months for patients treated with lenalidomide alone, and has not been reached yet for those who received the combination.

The complete response rate, or proportion of patients with no detectable disease in the blood or urine and less than 5 % of cancerous cells remaining in the bone marrow, was 47.6 % for patients treated with the combination of drugs, compared with 24.9 % for those who received lenalidomide alone. The proportion of patients who achieved a very good partial response or better–­–defined as a 90 % or greater reduction in levels of M protein in the blood and urine––also was significantly better among patients treated with lenalidomide plus daratumumab (79.3 %, compared with 53.1 % for patients treated with lenalidomide alone). There was more than 3-fold improvement in achieving MRD negativity for the drug combination (24.2 vs 7.3 %) which translates into more patients having longer PFS than standard of care alone. In addition, the drug combination helped more patients achieve a durable MRD response. While the safety profile in MAIA was in line with previous studies, more patients in the drug combination arm than in the arm receiving lenalidomide alone experienced moderate or severe adverse effects of pneumonia and low white blood cell counts.

“These results support the addition of daratumumab to lenalidomid as the new standard of care for patients with transplant-ineligible newly diagnosed multiple myeloma,” Dr. Facon said.