Darzalex Combo Leads to Durable Responses in Patients With Advanced Multiple Myeloma, Follow-up Data Show

Janssen‘s Darzalex (daratumumab) in combination with Revlimid (lenalidomide) and dexamethasone continues to lead to strong and durable responses, and prolong the time until disease worsening in patients with relapsed or refractory multiple myeloma, according to three-year follow-up data from a Phase 3 trial.

The findings were reported in a study, “Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study,” published in the journal Leukemia.

Darzalex is an antibody designed to recognize and block the activity of CD38, a protein found on the surface of multiple myeloma cells, to prevent their growth and to eliminate them. It was originally developed by Genmab, and then licensed to Janssen in August 2012.

The U.S. Food and Drug Administration (FDA) approved Darzalex in combination with Revlimid and dexamethasone in 2016 for the treatment of patients with pretreated multiple myeloma. In the following year, the European Commission approved the triple combo for the same indication in the European Union.

Both approvals were based on interim data from the open-label, POLLUX Phase 3 trial (NCT02076009), showing that at a median follow-up of 13.5 months, the triple combo therapy reduced the risk of disease progression or death by 63%, compared to Revlimid plus dexamethasone alone (Rd regimen).

Moreover, the addition of Darzalex to the standard Rd regimen increased the proportion of patients responding to treatment from 76% to 93%. Patients in the trial had previously received at least one line of treatment.

Updated data from POLLUX, covering more than three years of patient follow-up, showed that the triple combo therapy continued to prolong the time until disease progression or death in the overall patient population from 17.5 months to 44.5 months. Similar effects were observed in different patient subgroups, including among those who had received only one prior line of treatment.

The findings also showed that adding Darzalex to the standard Rd combo therapy increased the percentage of patients responding to treatment from 76.4% to 92.9%.

The triple combo also increased the proportion of participants achieving complete responses (56.6% versus 23.2%) and a status of minimal residual disease (MRD) negativity (30.4% versus 5.3%), compared to the standard Rd regimen.

Of note, complete responses refer to complete cancer eradication; a status of MRD negativity is defined as having less than one malignant cancer cell among 10,000 white blood cells.

The Darzalex combo also prolonged the median time to the next therapy from 23.1 months to 50.6 months.

No new safety concerns were reported in the study. Low white blood cell counts (neutropenia) was the most common adverse event observed in the study. It was reported in 63.3% of those treated with the Darzalex combo and in 48.0% of those receiving the standard treatment regimen.

“Taken together, the results from [more than three] years of median follow-up demonstrate [the triple combo] continues to provide significant [survival] benefit and induces deeper and more durable responses, including a greater than five-fold increase in the rate of MRD negativity versus Rd alone in patients with RRMM [relapsed or refractory multiple myeloma],” the researchers wrote.

“These updated findings continue to support the use of D-Rd in patients with RRMM after first relapse,” they said.