Efficacy assessments resulted in the early termination of a phase 2 study of the combination of ibrutinib with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma (R/R MM). The findings from this study were published in European Journal of Haematology.

Although the last decade has seen the availability of a number of novel agents and drug combinations for patients with multiple myeloma, the treatment of relapsed/refractory disease remains an unmet medical need.

In this open label, single-arm phase 2 clinical study (ClinicalTrials.gov Identifier: NCT02902965), the combination of ibrutinib, a Bruton tyrosine kinase inhibitor, with bortezomib, a proteasome inhibitor, and dexamethasone was evaluated in 76 patients who had received 1 to 3 lines of prior therapy and had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Median patient age was 67.5 years.

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The overall response rate to the drug combination was 57%. At a median follow-up of 19.6 months, median progression-free survival (PFS) was 8.5 months, and the median overall survival had not been reached.

Regarding safety, the rate of grade 3 or higher adverse events was 73% of patients; of these, the most common were thrombocytopenia (34%), pneumonia (16%), anemia (15%), and asthenia (14%). Grade 3/4 atrial fibrillation occurred in 4% of patients.

Of note, fatal adverse events occurred in 15% of patients, and were attributed, in order of frequency, to infection, including pneumonia (n=8); cerebral hemorrhage (n=1); sudden death (n=1); and unknown cause (n=1).

Following initiation of treatment in 74 patients, the clinical trial was suspended due to the high rate of serious and fatal infections. However, these patients continued to receive study treatment following the implementation of risk-minimization procedures, such as lowered doses of dexamethasone, infection prophylaxis, and the establishment of a Safety Review Committee.

Although re-initiation of study enrollment was approved 6 months after study suspension following the observation of very few serious and no fatal infections with the introduction of risk-minimization procedures, the study was terminated since it was deemed unlikely to reach the primary end point, PFS, following an evaluation of treatment efficacy.

The study authors commented that “clinical studies evaluating the safety and efficacy of novel combinations are critical to identifying more effective salvage treatment options for patients with multiple myeloma. The information gained from these studies of novel combinations, regardless of the outcome, can help to inform future studies seeking to address this unmet clinical need.”

Disclosure: This study was sponsored by Pharmacyclics Switzerland GmbH, an AbbVie company.

Reference Hajek R, Pour L, Ozcan M, et al. A phase 2 study of ibrutinib in combination with bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma [published online December 28, 2019].  Eur J Haematol. doi: 10.1111/ejh.13377