Can Adding Clarithromycin to Lenalidomide/Dexamethasone Improve Outcomes in Myeloma?
Posted: Friday, September 10, 2021
Findings from a phase III trial reported in Blood Cancer Journal suggest that the addition of the antibiotic clarithromycin to the combination therapy of lenalidomide and dexamethasone may result in worsened progression-free survival in transplant-ineligible, newly diagnosed patients with multiple myeloma, particularly the elderly. Because case-control evaluations have suggested the addition of clarithromycin may be of benefit, María-Victoria Mateos, MD, PhD, of Hospital Universitario de Salamanca, Spain, and colleagues sought to analyze the outcomes associated with this treatment in a phase III setting.
The study included 286 patients, aged 65 years and older, with newly diagnosed multiple myeloma. None of the enrolled patients were eligible to undergo autologous stem cell transplantation. Between December 15, 2015, and December 31, 2018, patients were randomly assigned to receive continuous lenalidomide and dexamethasone with (n = 143) or without (n = 143) clarithromycin. Treatment continued until disease progression or intolerable toxicity occurred.
At a median follow-up of 19 months, the group given clarithromycin experienced a higher rate of complete response than those who were not given the antibiotic (22.6% vs. 14.4%). However, median progression-free survival was comparable between both arms (23 months with clarithromycin vs. 29 months without it).
The patients who received clarithromycin had a higher percentage of toxic deaths (n = 36, 72% vs. n = 22, 55%). Both arms had similar grade 3 or 4 adverse events, with neutropenia (12% with clarithromycin vs. 19% without) and infections (30% with clarithromycin vs. 25% without) occurring most commonly for each group. At data cutoff on February 7, 2020, 108 patients (75%) in the clarithromycin group and 82 patients (57.3%) in the lenalidomide/dexamethasone-alone group had discontinued treatment.
“The results of our trial also highlight the relevance of evaluating phase I/II clinical data in the context of phase III clinical trials, since such design offers us the strongest scientific evidence regarding efficacy and safety of new treatments as compared to the standard of care,” noted the authors.
Disclosure: For full disclosures of the study authors, visit nature.com.