Darzalex Combo Approved in Canada for Newly Diagnosed Myeloma Patients Ineligible for Transplant

Health Canada has approved Darzalex (daratumumab), in combination with standard Revlimid (lenalidomide) and dexamethasone, for people newly diagnosed with multiple myeloma who are not eligible for an autologous stem cell transplant.

Under priority review, the approval was based on data from the Phase 3 MAIA trial (NCT02252172), in which Darzalex cut the risk of disease progression or death by 44% compared with standard treatment, nearly doubled response rates, and tripled patients who achieved minimal residual disease negativity.

Based on MAIA’s data, the combination was also approved in the U.S. and is being reviewed in the European Union and Japan for the same patient group.

“It is expected that this regimen should become the new standard to treat newly diagnosed transplant ineligible patients with multiple myeloma,” Nizar Bahlis, MD, associate professor at the University of Calgary, said in a press release.

Darzalex, created by Genmab and developed and commercialized by Janssen Pharmaceuticals, is an antibody that blocks CD38, a protein highly produced by myeloma cells, regardless of disease severity. By targeting CD38, Darzalex not only causes toxicity to the cells but also triggers an immune response against cancer.

The multicenter, randomized MAIA trial was designed to determine if adding Darzalex to standard Revlimid and dexamethasone could improve the outcomes of newly diagnosed multiple myeloma patients not eligible to receive a stem cell transplant.

It included 737 participants, recruited at more than 210 centers across North America, Europe, Australia, and Israel, and randomly assigned them to receive either Darzalex plus Revlimid and dexamethasone or Revlimid and dexamethasone alone until their disease progressed or the therapy caused severe toxicity.

The trial’s main goal was to determine if Darzalex extended the time patients lived without disease worsening, which it did, reducing the risk of disease progression or death by 44%.

In fact, after two years and four months of follow-up, the median progression-free survival in the control group was 31.9 months, while the Darzalex group had not yet reached a value for this measure, meaning more than half of patients were alive and progression-free.

The triple combination also improved responses to treatment, with 93% of patients responding totally or partially and 48% of patients achieving a complete response. In the control group, 81% of patients showed an overall response, and 25% of patients achieved a complete response.

A higher percentage of participants in the Darzalex group were also negative for minimal residual disease — 24.2% versus 7.3%. Minimal residual disease refers to the small number of cancer cells that remain after treatment completion, which can cause relapse.

“In multiple myeloma, it is essential to administer the most effective therapy early, ideally as first-line, to prevent disease relapse and the emergence of resistant clones,” said Bahlis, who is also a member of the Cumming School of Medicine‘s Arnie Charbonneau Cancer Institute.

“The use of [Darzalex] in combination with [Revlimid] and dexamethasone resulted in unprecedented depth and durability of response with the eradication of all detectable disease in a quarter of patients in the study,” he added.

Consistent with previous studies, the rate of some adverse events was higher in the Dazalex group. Still, fewer people receiving the triple combination discontinued treatment due to adverse events — 7.1% versus 15.9%.

Darzalex has three other approvals in Canada for the treatment of people with multiple myeloma, including one as s first-line therapy for transplant-ineligible patients.