Interim results from a large international phase III clinical trial show that adding the immunotherapy daratumumab (Darzalex) to standard therapy significantly extended progression-free survival (PFS) in newly diagnosed patients with multiple myeloma who were ineligible for a stem cell transplant. These findings were presented by Facon et al at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract LBA2).
Patients treated with lenalidomide (Revlimid) and dexamethasone plus daratumumab were 45% less likely to die or experience disease progression compared with patients who received lenalidomide and dexamethasone alone, said lead author Thierry Facon, MD, of Claude Huriez Hospital in Lille, France, in a statement.
He added the trial is important because it is 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.”
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. The median age was 73, with 44% over 75, and 52% of 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 and dexamethasone alone or lenalidomide and dexamethasone plus daratumumab. In both arms, patients were treated until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival. Key secondary endpoints included minimal residual disease (MRD) negativity, 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 and dexamethasone plus daratumumab were 45% less likely to have died or experience disease progression compared with patients who received lenalidomide and dexamethasone alone. Median PFS was 31.9 months for patients treated with lenalidomide and dexamethasone alone, and has not been reached yet for those who received lenalidomide and dexamethasone plus daratumumab.
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 lenalidomide and dexamethasone plus daratumumab, compared with 24.9% for those who received lenalidomide and dexamethasone 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 and dexamethasone plus daratumumab (79.3%, compared with 53.1% for patients treated with lenalidomide and dexamethasone alone). There was more than threefold improvement in achieving MRD negativity for lenalidomide and dexamethasone plus daratumumab (24.2% vs 7.3%) which translates into more patients having longer PFS than standard of care alone, pointed out researchers. In addition, lenalidomide and dexamethasone plus daratumumab helped more patients achieve a durable MRD response. While the safety profile in MAIA was in line with previous studies, more patients in the lenalidomide and dexamethasone plus daratumumab arm than in the lenalidomide and dexamethasone–alone arm experienced moderate or severe adverse effects of pneumonia and low white blood cell counts.
“These results support the addition of daratumumab to [lenalidomide and dexamethasone] as the new standard of care for patients with transplant-ineligible newly diagnosed multiple myeloma,” Dr. Facon said.
This study was supported by Janssen Research & Development, LLC.
Disclosure: See the study authors’ full disclosures at ash.confex.com.
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