SAN DIEGO – Interim results from a large global phase III trial have shown that adding the anti-CD38 monoclonal antibody Darzalex (daratumumab) to Revlimid (lenalidomide) and dexamethasone (dex) reduced by 44 percent the risk of death or disease progression in patients with newly diagnosed multiple myeloma (MM) who were ineligible for a stem cell transplant.

The trial, called Maia, enrolled 737 MM patients with a median age of 73. It was one of the first studies to test Darzalex with Revlimid and dex, the current standard of care for the blood cancer, in older transplant-ineligible patients who account for the majority of adults with the disease. Results were featured Tuesday during the late-breaking abstract oral session at the American Society of Hematology (ASH) meeting.

"We see a very strong clinically significant benefit in extending survival without the cancer getting worse, with no major safety concerns," said Thierry Facon, a doctor at Claude Huriez Hospital in Lille, France, and principal investigator for the study. "In older patients who are not candidates for stem cell transplantation, these are very encouraging results," he said.

Participants in the study were randomly assigned to treatment with either Revlimid and dex (Rd) alone or Rd plus Darzalex. Treatment continued until the patients' cancer got worse or intolerable side effects occurred. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included minimal residual disease (MRD) negativity, defined as the absence of cancer cells in the bone marrow, as well as overall response rate and the rate and severity of adverse side effects.

Median PFS, the point in time at which half of the patients had disease progression, was 31.9 months for patients treated with Rd alone and has not been reached yet for those who received Rd plus Darzalex. The complete response rate, or proportion of patients with no detectable disease in the blood or urine and less than 5 percent of cancerous cells remaining in the bone marrow, was 47.6 percent for patients treated with Rd plus Darzalex vs. 24.9 percent for those who received Rd alone. Partial responses or better were also greater in the Darzalex-inclusive arm of the study.

Facon also observed a more than threefold improvement in patients achieving MRD negativity while taking Rd plus Darzalex vs. Rd alone, translating into more patients having longer PFS than standard of care alone. In addition, Rd plus Darzalex helped more patients achieve a durable MRD response, the research found.

On the safety front, more patients in the Rd-plus-Darzalex arm than in the Rd-alone arm experienced moderate or severe adverse effects of pneumonia and low white blood cell counts. The safety profile of daratumumab was in line with previous studies.

Real-world data

"These transplant-ineligible patients really represent the majority of patients with myeloma," Mark Wildgust, vice president of global medical affairs for oncology at Johnson & Johnson's Janssen unit, told BioWorld. Forty-four percent of patients in the study were age 75 or older, he said, noting that "it really reflects the age and typical co-morbidities you would typically see in patients with myeloma."

Next steps for the combination will be the submission of the results to a peer-reviewed medical journal and efforts to get regulators to approve conveying the benefits of combining Darzalex with Rd into the product's approved label, Wildgust said.

Developed by Copenhagen-based Genmab A/S and partnered with Janssen Biotech Inc., Darzalex received initial FDA approval in November 2015 as a monotherapy for third-line MM. Since then, its label has been gradually expanded to include new aspects of the relatively uncommon cancer.

In November 2016, Darzalex was approved in combination with Rd or Velcade (bortezomib) and dex, for the second-line treatment of MM. In 2017, it received approval in combination with Pomalyst (pomalidomide) and dex for the third-line treatment of MM. And in May 2018, it received approval in combination with Velcade, melphalan and prednisone for the treatment of patients with newly diagnosed MM who are ineligible for autologous stem cell transplant, making it the first monoclonal antibody approved for newly diagnosed patients with the disease.