CXCR4–CXCL12 axis blockade with ulocuplumab safe in relapsed/refractory myeloma

The first-in-class fully human IgG4 monoclonal antibody ulocuplumab that inhibits the binding of CXCR4 to CXCL12 appears to be safe in the treatment of patients with relapsed/refractory myeloma, yielding a high response rate when added to lenalidomide and dexamethasone with acceptable adverse events (AEs), according to the results of a phase Ib/II trial.

The trial included 46 patients (median age, 60 years), 30 of which were enrolled in arm A (ulocuplumab alone and in combination with lenalidomide and dexamethasone) and 16 in arm B (bortezomib and dexamethasone).

The median number of prior therapies was three, with 70 percent of the patients having received more than the median. This trial involved a dose-escalation and a dose-expansion part, and researchers applied a 3+3 design on both treatment arms. Ulocuplumab dose was increased to a maximum of 10 mg/kg without reaching the maximum tolerated dose.

Frequently reported treatment-related AEs were neutropoenia in arm A (13 patients, 43.3 percent) and thrombocytopoenia in arm B (six patients, 37.5 percent). There were documented deaths related to study drugs.

Efficacy data favoured arm A. The group of patients treated with the combination of ulocuplumab plus lenalidomide and dexamethasone achieved higher rates of response (partial response or better; 55.2 percent) and clinical benefit (72.4 percent) compared with the group given bortezomib and dexamethasone (25.0 percent and 50.0 percent, respectively). The efficacy advantage in arm A was observed even in patients previously exposed to immunomodulatory agents.

The findings indicate that CXCR4 inhibitors are a promising class of antimyeloma drugs that merit further investigation in clinical trials, the researchers said.