Dose reduction data of the Bruton tyrosine kinase (BTK)-inhibitor ibrutinib, the first FDA approved therapy for Waldenström macroglobulinemia (WM), were presented at the 2021 American Society of Hematology (ASH) Annual Meeting to evaluate the time to dose reduction, the symptoms leading to dose reduction, the rate of improvement in symptoms after dose reduction, and the hematologic response at 12 months after dose reduction.

The BTK-inhibitor ibrutinib “produces overall response rates (ORR) >90 percent and long-term disease control in both treatment naïve (TN) and previously treated patients. Despite the remarkable efficacy of ibrutinib, dose reduction is often required for intolerance,” explained Shayna Sarosiek, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues.

A total of 385 patients received treatment with ibrutinib in the clinic from May 2012 through October 2020. The starting dose was 560 mg, 420 mg, 280 mg, and 140 mg. Common reasons for ibrutinib initiation included anemia, constitutional symptoms, and symptomatic hyperviscosity. The median age of patients requiring dose reduction was 71 years (range, 46-96) at the time of dose reduction.

“Of the 95 patients requiring a dose reduction, 40 patients (42% of all patients with dose reductions) had improvement in at least 1 of the medication side effects after the initial dose reduction. Twenty-two patients (23%) had complete resolution of adverse effects. Twenty-six patients (27%) had no change in symptoms, and 10 of these patients required an additional dose reduction,” explained Dr Sarosiek and colleagues.

Notably, 5 patients had improvement or resolution in symptoms after the second dose reduction. Of the patients with available 1-year hematologic follow-up data, 21 percent had improvement in hematologic response and 73 percent maintained their hematologic response. Interestingly, the hematologic response worsened in 6 percent of patients after dose reduction.

“In conclusion, one quarter of WM patients in this series on ibrutinib required a dose reduction due to development of intolerable medication side effects. In the majority of these patients, adverse effects improved or resolved with dose reduction. Importantly, hematologic response remained stable or improved in most patients despite dose reduction,” concluded Dr Sarosiek and colleagues.

Shayna S, Gustine J, Flynn CA, et al. Dose Reductions Related to Adverse Effects in Patients with Waldenström Macroglobulinemia Treated with the BTK-Inhibitor Ibrutinib. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 3529.