1. Goodwin, Peter M.

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ATLANTA-Adding the anti-CD38 monoclonal antibody daratumumab to standard first-line therapy improved outcomes for patients with multiple myeloma in all risk groups, according to new data reported at the 2017 American Society of Hematology Annual Meeting from the first evaluation of a monoclonal antibody for patients with newly diagnosed multiple myeloma.

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"We show a significant benefit for the experimental arm: 50 percent reduction in risk of progression or death with daratumumab, " said senior study author Jesus F. San-Miguel, MD, Professor of Hematology and Director of Clinical and Translational Medicine at the University of Navarra in Pamplona, Spain, reporting findings from the phase III randomized ALCYONE study (Abstract LBA-4).


With daratumumab approved since 2016 for patients who had been treated previously for multiple myeloma, San-Miguel said the new study compared one of the standards of care being used for patients newly diagnosed with myeloma who were not eligible for transplant-bortezomib, melphalan, prednisone-with the same combination plus the monoclonal antibody daratumumab (targeting CD38 protein overexpressed in multiple myeloma).


"We are showing that the benefits extend to newly diagnosed patients as well," he noted.


Study Details

All 706 patients in the ALCYONE trial received nine 6-week cycles of the standard treatment regimen. Half were randomly assigned to receive daratumumab along with the standard treatment and continued taking the monoclonal antibody once a month after the nine chemotherapy cycles until disease progression.


The improvement in the primary endpoint of progression-free survival (PFS)-with a hazard ratio 0.50 (P <0.0001) at a median follow-up of 16.5 months-was consistent across all demographic and biologic subgroups and the investigators concluded this was driven by significantly better responsiveness to therapy, a higher rate of complete remission, and a tripling of the proportion of patients reporting MRD negativity.


Both study groups showed similar rates of adverse events with the exception of upper respiratory tract infections and pneumonia, which-though more common in those taking daratumumab-resolved in most patients.


Overall response rate was higher (90.9% compared with 73.9% without the antibody) and the rate of "very good partial responses" was also higher (71.1% compared with 49.7%). Complete responses (CR) were almost doubled in the experimental arm (42.6% compared with 24.4%) and the rate of MRD-negativity was 22.3 percent with the monoclonal antibody compared with only 6.2 percent without. Overall survival data were immature.


Minimum Residual Disease

"The treatment was well-tolerated. Our results support that daratumumab in combination with bortezomib, melphalan, and prednisone should become a new standard of care in transplant-ineligible multiple myeloma patients," San-Miguel said. "And hopefully we [will] have improvement of survival for this elderly population that really needs new treatment approaches."


Minimum residual disease (MRD) had already been shown to have been important. "With whatever treatment you use, if you achieve minimum residual disease status, you have significantly longer survival," he noted. "The problem is that with some treatments the chance [of] MRD negativity is significantly low. With daratumumab, you increase the chances of achieving MRD-negativity by three times."


And San-Miguel agreed that for the future MRD status should be monitored as a marker for survival. "It's going to be one of the surrogate markers for survival to find the best [treatment] options."


The investigators concluded that their findings of a doubling of PFS, more deep responses, significantly higher CR rate, and tripling of the MRD-negativity rate-all with no new safety signals-supported the use of the new immunochemotherapy for patients who were ineligible for transplant.


Peter M. Goodwin is a contributing writer.


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