Patients with symptomatic Waldenström macroglobulinemia (WM) benefit from first-line treatment with ibrutinib, which Steven P. Treon, MD, PhD, Bing Center for Waldenström Macroglobulinemia, Dana Farber Cancer Institute, Boston, MA, and colleagues describe as being highly active and safe in this setting (J Clin Oncol. 2018;36:2755-2761).
Seeking to examine the safety and efficacy of ibrutinib monotherapy in symptomatic, untreated patients with WM, Dr Treon and colleagues conducted a prospective clinical trial. They also sought to determine the effect of CXCR4 mutation status on patient outcomes.
Ibrutinib 420 mg was administered daily to 30 symptomatic, treatment-naïve patients with WM until disease progression or unacceptable toxicity occurred. All patients had their tumors genotyped for MYD88 and CXCR4 mutations.
The MYD88 mutation was present in all study participants; 14 (47%) patients had a CXCR4mutation. Compared with baseline levels, median serum immunoglobulin M levels declined from 4370 mg/dL to 1513 mg/dL, bone marrow involvement reduced from 65% to 20%, and hemoglobin levels increased from 10.3 g/dL to 13.9 g/dL after ibrutinib treatment (P = .001 for all comparisons).
Overall and major responses occurred in 100% and 83% of all patients, respectively. Patients with wild-type CXCR4 mutation had higher major and very good partial responses than patients with CXCR4 mutation (94% vs 71% and 31% vs 7%, respectively). Time to major responses was also more rapid among patients with wild-type CXCR4 versus CXCR4mutation (1.8 v 7.3 months, respectively; P = .01)
At a median follow-up of 14.6 months, 2 patients with CXCR4 mutation had disease progression. According to Dr Treon and colleagues, the estimated progression-free survival at 18 months is 92% (95% confidence interval, 73%-98%).
More than 5% of patients had grade 2/3 treatment-related toxicities including arthralgia (7%), bruising (7%), neutropenia (7%), upper respiratory tract infection (7%), urinary tract infection (7%), atrial fibrillation (10%), and hypertension (13%). No grade 4 or unexpected toxicities occurred.
“Responses exceeded 5 years in previously treated patients in the pivotal trial, whereas among patients with rituximab-refractory disease, the 18-month PFS was 86% with shorter follow-up, demonstrating durable benefit for ibrutinib in WM,” Dr Mellby and colleagues said.
“Overall, treatment was well tolerated, with no unexpected toxicities. Ibrutinib is safe and effective in treatment-naïve patients with symptomatic WM,” they concluded.—Hina Khaliq