ASH 2017: ALCYONE Trial: Adding Daratumumab to Bortezomib, Melphalan, and Prednisone in Multiple Myeloma

Key Points

  • Patients receiving daratumumab showed a significantly (50%) lower rate of disease progression or death compared to those receiving standard treatment alone, a benefit that was consistent across all demographic and biologic subgroups.
  • This improvement appeared to be largely driven by a 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 occurred somewhat more frequently in those taking daratumumab—but the majority of these resolved.

The first randomized trial to evaluate the use of a monoclonal antibody for treating newly diagnosed multiple myeloma showed that adding the drug daratumumab (Darzalex) to one of the standard treatment regimens reduced the likelihood of disease progression or death by 50%. The regimen also induced significantly deeper responses and higher rates of negative minimal residual disease (MRD). The phase III trial—conducted in patients who were not eligible for a stem cell transplant—suggests daratumumab is a beneficial addition to one of the current first-line therapies for these patients. Findings were presented by Mateos et al at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract LBA-4).

Multiple myeloma is a cancer that starts in plasma cells, a component of the immune system. Stem cell transplantation is used as intensification therapy in young patients. For people who cannot receive a stem cell transplant, one standard treatment involves two chemotherapy drugs, bortezomib (Velcade) and melphalan, together with the steroid prednisone. Daratumumab is a monoclonal antibody designed to directly target tumors while also equipping a patient’s own immune cells to attack the cancer cells. It is approved for patients whose myeloma has relapsed after an initial course of treatment.

“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,” said senior study author Jesus F. San-Miguel, MD, Medical Director of the Clínica Universidad de Navarra in Pamplona, Spain. “Monoclonal antibodies like daratumumab have already been approved for use in relapsed patients; here, we are showing that the benefits extend to newly diagnosed patients, as well.”

Study Findings

The trial enrolled 706 patients. All 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 daratumumab once a month after the first nine treatment cycles. To date, patients have been tracked for a median of 16 months.

In terms of the study’s primary endpoint, progression-free survival, patients receiving daratumumab showed a significantly (50%) lower rate of disease progression or death compared to those receiving standard treatment alone, a benefit that was consistent across all demographic and biologic subgroups. This improvement appeared to be largely driven by a 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 occurred somewhat more frequently in those taking daratumumab—but the majority of these events resolved.

The trial is the first of several ongoing studies to evaluate daratumumab as a front-line treatment for newly diagnosed multiple myeloma to report results.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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