Clarithromycin-Based Quadruplet Therapy Demonstrates Promising Clinical Responses for Treatment of Relapsed/Refractory Multiple Myeloma

An all-oral combination of clarithromycin, ixazomib, pomalidomide, and dexamethasone (ClIPd) demonstrated high response rates and prolonged progression-free survival (PFS) in patients with relapsed/refractory (R/R) multiple myeloma (MM), including those with high-risk cytogenetics, according to study results published in Blood Neoplasia.

Researchers evaluated the clinical efficacy and safety of clarithromycin, ixazomib, pomalidomide, and dexamethasone as a combination treatment in a phase 1/2 clinical trial. The primary end points were maximum tolerated dose and recommended dose, secondary end points included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). 

Overall, 28 patients treated with clarithromycin, ixazomib, pomalidomide, and dexamethasone were evaluable. Most patients were male (72%), and the median age among all patients was 64 years, with a range of 54 to 82. The median number of prior lines of therapy was 2. The ORR was 75% and the DCR was 100%. A very good partial response (VGPR) was met by 13 patients and 6 patients achieved a complete response (CR). High-risk cytogenetics abnormalities were not associated with inferior response rates (odds ratio [ORR], 1.32; 95% confidence interval [CI], 0.49 to 19.82).  

The median PFS was 22.2 months (95% CI, 13.3 to not reached) and the median duration of response (DOR) was 19.8 months (95% CI, 12.4 to not reached).  The median follow-up was 35.6 months (95% CI, 28 to 54) and the median OS was not reached (95% CI, 22.1 to not reached). 

In terms of safety, 97% of patients experienced at least 1 adverse event, of which 59% were grade 3 or 4. Hematologic adverse events (26%) included neutropenia (16%) and infections (13%) were the most common nonhematologic adverse event among patients. Of 19 serious adverse events reported, 2 were possibly related to treatment with clarithromycin, ixazomib, pomalidomide, and dexamethasone.

The researchers concluded, “ClIPd is an all-oral quadruplet regimen that is relatively well-tolerated and offers convenient dosing with relatively high rates and durable responses and is feasible for patients in whom parenteral therapy is not feasible or preferred.”

Source:

Rosenberg AS, Maverakis E, Costello C, et al. Clarithromycin, Ixazomib, Pomalidomide, Dexamethasone for Relapsed/Refractory Myeloma: Survival and Correlative Analysis. Blood Neoplasia. Published online August 22, 2025. doi:10.1016/j.bneo.2025.100067