Blood cancers

Daratumumab shows OS benefit in quadruplet therapy for NDMM


The addition of daratumumab to bortezomib, melphalan, and prednisone (VMP) in patients with newly diagnosed multiple myeloma (NDMM) has for the first time been shown to have an overall survival benefit. 

Speaking at ASH 2019 Professor Maria-Victoria Mateos presented an update of the phase 3 ALCYONE study of more than 700 transplant-ineligible myeloma patients randomised to either the standard of care (VMP) or the anti-CD38  monoclonal antibody plus VMP (D-VMP).

Professor Mateos, director of the myeloma unit at the University Hospital of Salamanca in Spain, said previously published results had shown D-VMP led to significantly longer progression-free survival than VMP and was associated with a 50% lower risk of disease progression or death over 16.5 months of follow-up. 

Now, following nine initial cycles of treatment in both arms of the trial and more than three-years of follow-up, the study has been able to show the predicted benefit in overall survival. 

The study, concurrently published in The Lancet, found a benefit in overall survival in the D-VMP group compared to the VMP group (75% v 62%) and across all subgroups analysed on the basis of subsequent lines of therapy, with the exception of patients with high cytogenetic risk. 

She noted about 42% of patients remain on D-VMP.

The most common subsequent therapies were immunomodulatory regimens such as lenalidomide and dexamethasone or a proteasome inhibitor plus an immunomodulatory drug. 

The study found the overall response rate to D-VMP was 91% compared to 74% with VMP alone. 

In particular, 46% of patients in the D-VMP group achieved a complete response compared to 25% in the VMP group. Very good partial responses or better were also observed in 73% of the D-VMP patients compared to 50% of VMP patients. 

A minimal residual disease (MRD) evaluation showed negativity in 28% of D-VMP patients compared to just 7% in VMP patients. 

Professor Mateos told the meeting that maintaining MRD negativity was as important as reaching it. 

MRD negativity was maintained in 16% of D-VMP patients compared to 5% of VMP patients after 6 months and in 14% of D-VMP patients compared to 3% of VMP patients after 12 months.

The progression free survival benefit with D-VMP over VMP continued to increase over time – estimated at 48%  versus 14% at the 42-months follow-up.

Professor Mateos said there were no new safety concerns identified over the longer follow-up. 

Adverse events included anaemia, upper respiratory tract infections and bronchitis. 

The rates of discontinuation of treatment due to adverse events was found to be lower in the D-VMP group than the VMP group (7% v 9%).

“In conclusion, daratumumab with VMP continues to demonstrate a significant PFS benefit versus VMP alone. Responses continue to deepen over time from the primary analysis and patients with sustained MRD negativity had improved outcomes.”

“D-VMP significantly improved the overall survival in patients with transplant-ineligible NDMM.”

She added the daratumumab-based regimen, approved by FDA and EMA, represented a new standard of care.

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