Daratumumab, Bortezomib, Dexamethasone Trio Improves Refractory Multiple Myeloma Outcomes

Triple therapy with daratumumab, bortezomib and dexamethasone proposed as new standard of care for multiple myeloma patients with relapsed or refractory disease

medwireNews: Addition of the anti-CD38 Monoclonal antibody daratumumab to bortezomib plus dexamethasone significantly improves progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma, shows the phase III CASTOR trial.

The research was presented at the annual meeting of the American Society of Clinical Oncology in Chicago, Illinois, USA.

Researcher Antonio Palumbo, from the University of Torino in Italy, who presented the data on behalf of his colleagues, said that the trio “should be considered a new standard of care” for patients being treated with the current standard, namely the combination of bortezomib and dexamethasone.

After a median follow-up of 7.4 months, median PFS was not reached for the 251 previously treated participants randomly assigned to receive intravenous daratumumab (16 mg/kg once a week for cycles 1–3, followed by once every 4 weeks for cycles 4–8) alongside bortezomib plus dexamethasone. This was significantly longer than the median of 7.2 months observed in the 247 patients given just bortezomib and dexamethasone, and equated to a hazard ratio (HR) of 0.39, which is “unprecedented” in randomised trials of novel therapies in this patient population, Antonio Palumbo told the press.

Addition of daratumumab significantly extended the time to progression, with the median not reached in the daratumumab group versus 7.3 months in the control group (HR=0.30), and also improved the overall response rate, at 83% versus 63%.

Furthermore, daratumumab “significantly deepened responses”, with a “doubling” of the proportion of patients achieving a complete response (19 vs 9%) and a very good partial response (59 vs 29%), said the presenting author.

The median duration of response was not reached for patients who received the triple therapy, while for those given the two-drug regimen, responses lasted for a median of 7.9 months.

The most frequent grade 3 or 4 adverse events experienced by daratumumab-treated patients were thrombocytopenia (45.3%), anaemia (14.4%), neutropenia (12.8) and lymphopenia (9.5%). Nine percent of patients given the trio had a grade 3 infusion-related reaction, but no grade 4 reactions were observed.

The toxicity profile was consistent with that reported for single-agent daratumumab or bortezomib plus dexamethasone, said Antonio Palumbo. Moreover, the rates of discontinuation attributed to treatment-emergent adverse events were similar for the two groups, at 7.4% for the daratumumab arm and 9.3% for the control arm.

Reference

Palumbo A, Chanan-Khan AAA, Weisel K, et al. Phase III randomized controlled study of daratumumab, bortezomib, and dexamethasone versus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: CASTOR study. J Clin Oncol 2016; 34 (suppl; abstr LBA4)

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016