Highlights from

ASH 2019

61st Annual Meeting & Exposition of the American Society of Hematology

Orlando, Florida (USA) 7 - 10 December 2019

ALCYONE: New overall survival results for myeloma

Dr Maria Victoria Mateos (University Hospital of Salamanca, Spain) presented the updated efficacy and safety results from a prespecified, interim analysis of the phase 3 ALCYONE study with over 40 months of follow-up, demonstrating improved overall survival when daratumumab is added to frontline treatment [1,2].

ALCYONE was a multicentre, randomised, open-label, active-controlled, phase 3 trial that enrolled 706 newly diagnosed multiple myeloma patients, who were ineligible for high-dose chemotherapy with autologous stem-cell transplantation, because of their age (≥65 years) or because of substantial comorbidities. Patients were randomly assigned to receive daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP; n=350) or bortezomib, melphalan, and prednisone (VMP; n=356). Patient baseline characteristics were well balanced between treatment arms. Median age was 71 (range 40–93) years, and 29.9% of patients were ≥75 years of age.

All patients received up to nine 6-week cycles of subcutaneous bortezomib, oral melphalan, and oral prednisone. Patients in the D-VMP group also received intravenous daratumumab (16 mg/kg of bodyweight, once weekly during cycle 1, once every 3 weeks in cycles 2 through 9, and once every 4 weeks thereafter as maintenance therapy until disease progression or unacceptable toxicity).

The initial analysis of the ALCYONE study already reported a significant progression-free survival benefit with D-VMP versus VMP alone at a median follow-up 16.5 months (HR 0.50; 95% CI 0.38-0.65; P<0.001) [3].

In the current analysis, at a median follow-up of 40.1 months (interquartile range 37.4-43.1), a significant benefit in overall survival was observed for the D-VMP group (HR 0.60; 95% CI 0.46-0.80; P=0.0003). The Kaplan-Meier estimate of the 36-month rate of overall survival was 78.0% (95% CI 73.2-82.0) in the D-VMP group and 67.9% (95% CI 62.6-72.6) in the VMP group. Progression-free survival, the primary endpoint, remained significantly improved for the D-VMP group (HR 0.42; 95% CI 0.34-0.51; P<0.0001). The most frequent adverse events during maintenance daratumumab monotherapy in patients in the D-VMP group were respiratory infections (19% patients had upper respiratory tract infections; 15% bronchitis; 12% viral upper respiratory tract infections; 12% cough), and 10% experienced diarrhoea.

Thus, D-VMP prolonged overall survival in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, and the updated results of the ALCYONE study continue to support the addition of daratumumab to frontline treatment regimens.

Keywords: ALCYONE; Multiple Myeloma; daratumumab; bortezomib; melphalan; prednisone

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