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Daratumumab plus VMP a potential therapy for transplant-ineligible multiple myeloma

Roshini Claire Anthony
05 Jan 2018
Prof Jesus San-Miguel

The addition of daratumumab to a bortezomib-melphalan-prednisone (VMP) regimen appears to improve progression-free survival (PFS) over VMP alone in individuals newly diagnosed with multiple myeloma who are ineligible for stem-cell transplantation, according to findings from the phase III ALCYONE* trial.

“In this first phase III randomized study with a monoclonal antibody in [newly diagnosed multiple myeloma], daratumumab plus VMP [D-VMP] reduced the risk of progression or death by 50 percent,” said senior study author Professor Jesus San-Miguel from the Clínica Universidad de Navarra, Pamplona, Spain, who presented the results at ASH 2017.

Researchers of this multinational, open-label trial randomized 706 patients (median age 71 years, median 0.8 months since diagnosis) with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation to receive VMP (subcutaneous bortezomib [1.3 mg/m2 BIW on weeks 1, 2, 4, and 5 of cycle 1 and QW on weeks 1, 2, 4, and 5 of cycles 2–9], oral melphalan [9 mg/m2 QD on days 1–4 of each cycle], and oral prednisone [60 mg/m2 QD on days 1–4 of each cycle]), or D-VMP (with additional intravenous daratumumab [16 mg/kg at doses of 20 mg QW in cycle 1, Q3WK in cycles 2–9, and Q4WK until disease progression or toxicity]) for up to nine cycles (42 days per cycle).

After a 16.5-month median follow-up period, PFS was longer in patients in the D-VMP compared with the VMP arm (not reached vs 18.1 months), with a PFS rate of 71.6 percent vs 50.2 percent at 18 months (hazard ratio, 0.50, 95 percent confidence interval, 0.38–0.65; p<0.001). [ASH 2017, abstract LBA-4; New Engl J Med 2017;doi:10.1056/NEJMoa1714678]

Compared with patients in the VMP arm, those on D-VMP had a better overall response rate (90.9 percent vs 73.9 percent; p<0.001) with a better median duration of response (not reached vs 21.3 months) and a higher rate of complete response or better (42.6 percent vs 24.4 percent; p<0.001). 

More patients on D-VMP than VMP tested negative for minimal residual disease (MRD**; 22.3 percent vs 6.2 percent; p<0.001).

“D-VMP induced significantly deeper responses including a more than threefold higher MRD-negative rate,” said San-Miguel.

“In this trial, negative status for [MRD] was associated with longer [PFS] than positive status, irrespective of trial treatment,” said San-Miguel and co-authors.

The most common grade 3–4 adverse events (AEs) were neutropenia (39.9 and 38.7 percent of patients on D-VMP and VMP, respectively), thrombocytopenia (34.4 and 37.6 percent, respectively), and anaemia (15.9 and 19.8 percent, respectively). Grade 3–4 infections occurred more frequently in patients on D-VMP compared with VMP (23.1 percent vs 14.7 percent), the most common being pneumonia (11.3 percent vs 4.0 percent).

Serious AEs occurred in 41.6 and 32.5 percent of patients on D-VMP and VMP, respectively, though treatment discontinuation due to AEs was less common with D-VMP than VMP (4.9 percent vs 9.0 percent).

“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,” said San-Miguel.

“Three phase III studies have now demonstrated a consistent doubling of PFS and more than threefold increase in MRD-negativity rate when combining [daratumumab] with [standard-of-care] regimens,” said San-Miguel and co-authors.

“ALCYONE strongly supports D-VMP as a standard of care in transplant-ineligible [newly diagnosed multiple myeloma],” he said.

 

 

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Most Read Articles
Dr. Jay Zhu, Dr. Lai Fung Li, Prof. Chae-Yong Kim, 27 Nov 2019
The current standard of care for glioblastoma multiforme (GBM), an aggressive primary brain tumour with a rapid disease course, consists of maximum safe surgical resection followed by radiotherapy with concomitant temozolomide (TMZ) chemotherapy and subsequent TMZ maintenance. At the 16th Annual Meeting of the Asian Society of Neuro-Oncology (ASNO) in Taipei, Taiwan, experts reviewed the evidence and shared their clinical experience on the use of tumour treating fields (TTFields), a novel treatment modality for GBM.