medwireNews: Patients with relapsed or refractory multiple myeloma derive a significant progression-free survival (PFS) benefit with the addition of the anti-CD38 monoclonal antibody daratumumab to lenalidomide plus dexamethasone, shows the phase III POLLUX trial.
Meletios Dimopoulos (National and Kapodistrian University of Athens, Greece) and fellow investigators randomly assigned 569 multiple myeloma patients who had failed at least one prior line of therapy to receive lenalidomide plus dexamethasone either with or without daratumumab.
As reported in The New England Journal of Medicine, the risk of disease progression or death was a significant 63% lower for participants given daratumumab in addition to the standard backbone regimen.
The median PFS was not reached in the daratumumab arm and was 18.4 months in the lenalidomide plus dexamethasone arm, with corresponding 12-month rates of 83.2% and 60.1%.
The proportion of patients who achieved an overall response was also significantly higher in the daratumumab versus control group, as was the rate of complete response or better, at 92.9% versus 76.4% and 43.1% versus 19.2%, respectively.
Furthermore, significantly more participants given the triple regimen had results below the threshold of minimal residual disease (MRD; defined as 1 tumour cell/105 white cells), at 22.4% compared with 4.6% in the control arm.
Neutropenia was the most common grade 3 or 4 adverse event, occurring in 51.9% of participants in the daratumumab arm and 37.0% of those in the control arm, followed by thrombocytopenia (12.7 vs 13.5%), and anaemia (12.4 vs 19.6%).
Almost half (47.7%) of the triple regimen-treated patients experienced infusion-related reactions of any grade associated with daratumumab, mainly during the first infusion, but only 5.3% were of grade 3 and none were of grade 4 or 5.
The rate of adverse event-related discontinuation was low and comparable between the daratumumab and control arms (6.7 vs 7.8%), says the team, as was the rate of mortality attributable to adverse events (3.9 vs 5.3%).
In a linked editorial, S Vincent Rajkumar and Robert Kyle, both from Mayo Clinic in Rochester, Minnesota, USA, discuss the new treatment options available for multiple myeloma patients and wonder how best to incorporate these into clinical practice.
They think that “daratumumab–lenalidomide–dexamethasone is the clear standout”, in light of the “impressive” magnitude of benefit and the ease of administration.
“It is therefore our treatment of choice for first relapse in patients whose disease is not refractory to lenalidomide”, Rajkumar and Kyle write.
But they add: “Given the chronic relapsing course of myeloma, the most pressing questions revolve around the appropriate sequence in which these regimens are used, rather than picking winners and losers or excluding a regimen from consideration.”
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