Clarithromycin plus bortezomib does not confer any additional efficacy and is a toxic combination among patients with multiple myeloma (MM), according to a study published in Experimental Hematology & Oncology.
Evidence from previous studies suggested that clarithromycin may lead to synergistic effects in treatment regimens with immunomodulatory drugs for MM, such as lenalidomide plus dexamethasone, but there is a lack of data supporting actual clinical efficacy.
For this phase 2 study, researchers randomly assigned 58 newly diagnosed patients with MM receiving bortezomib, cyclophosphamide, and dexamethasone (VCD) to clarithromycin or placebo arms. Only patients who were eligible for high-dose melphalan with stem cell support were included in the study.
The study was designed to have a total enrollment of 160 patients, but was prematurely terminated after 58 patients due to safety reasons.
There were no significant differences in the rates of very good partial response or better response between patients in the clarithromycin group compared with patients in the placebo group (P= .59), but grade 3 and greater gastrointestinal complications (eg, neutropenic enterocolitis, paralytic ileus, peptic ulcer) occurred in more patients in the clarithromycin arm (7 patients) versus patients in the placebo arm (1 patient). Gram-negative bacterial septicemia was reported among 5 patients in the clarithromycin arm compared with 1 case of pneumococcal septicemia in the placebo arm.
Patients in the clarithromycin group also reported having more clinically relevant neurotoxicity, as well as reduced global quality of life.
The authors concluded that “our data do not indicate any additional effect of clarithromycin when added to the VCD regimen, and due to treatment toxicity our trial does not encourage further clinical studies on the combination of clarithromycin and bortezomib.”
Gregersen H, Do T, Kristensen IB, et al. A randomized placebo-controlled phase II study of clarithromycin or placebo combined with VCD induction therapy prior to high-dose melphalan with stem cell support in patients with newly diagnosed multiple myeloma[published online August 13, 2018]. Exp Hematol Oncol. doi: 10.1186/s40164-018-0110-0