BTK Inhibitor Combination Therapy for Resistant Multiple Myeloma
Posted: Monday, June 15, 2020
Combination therapy using the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib plus carfilzomib with dexamethasone showed anticancer activity in patients with relapsed or refractory multiple myeloma. This phase I/IIb trial was published in Hematological Oncology by Ajai Chari, MD, of Mount Sinai School of Medicine, New York, and colleagues.
“The overall response rate of 71% was comparable to existing regimens used to treat patients with relapsed or refractory multiple myeloma containing bortezomib,” commented the investigators.
Patients recruited to this study had measurable multiple myeloma and had undergone at least two prior lines of therapy with no response or disease progression. In total, 59 patients received the recommended phase II dose, consisting of 840 mg of ibrutinib plus 36 mg/m2 of carfilzomib with dexamethasone in a 28-day cycle.
Of the patients in this cohort, 69% were refractory to bortezomib, and 90% were refractory to their last treatment. The overall response rate to ibrutinib plus carfilzomib was 71%, with 3% achieving a stringent complete response and 3% achieving complete response. The median durations of response and clinical benefit were both 6.5 months, and the median progression-free survival was 7.4 months. The median overall survival in all patients was 35.9 months. High-risk patients had an overall response rate of 67% compared with the overall response rate of 73% in patients who were not at high risk. The median overall survival in high-risk patients was 13.9 months.
In total, 85% of patients experienced a grade 3 or higher treatment-related adverse event. Common grade 3 or higher adverse events included anemia, thrombocytopenia, and hypertension. Other adverse events that occurred in more than 20% of patients included diarrhea, fatigue, nausea, cough, insomnia, and upper respiratory tract infection. No patients died while on this treatment.
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