Ibrutinib monotherapy promising for untreated Waldenström macroglobulinemia
medwireNews: Phase II trial results suggest that the Bruton tyrosine kinase inhibitor ibrutinib has high activity and is well tolerated in symptomatic, treatment-naïve patients with Waldenström macroglobulinemia.
Treatment with ibrutinib 420 mg/day until disease progression or unacceptable toxicity led to a major response – defined as a complete, very good partial, or partial response – in 83% of 30 patients, while an overall response – which additionally includes a minor response – was achieved by all trial participants.
After a median follow-up of 14.6 months, no patient had died and only two had progressed, giving an estimated 18-month progression-free survival rate of 92%, report Steven Treon (Dana Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues in the Journal of Clinical Oncology.
Interestingly, they found that the major and very good partial response rates were higher among the 53% of patients with wild-type CXCR4 status than for their counterparts harboring mutations in the gene, at 94% versus 71% and 31% versus 7%, respectively. And the time to major response was significantly shorter, at a median of 1.8 and 7.3 months, respectively.
Moreover, both patients who experienced disease progression during the course of the study tested positive for CXCR4 mutations.
“In response to these findings, a clinical study of ibrutinib plus the anti-CXCR4 monoclonal antibody ulocuplumab has been initiated” for Waldenström macroglobulinemia patients with CXCR4 mutations, the study authors write.
Reporting on the safety profile, they say that ibrutinib was “well tolerated […] and no unexpected toxicities were encountered.”
Hypertension was the most common adverse event of grade 2 or 3, occurring in 13% of participants, followed by atrial fibrillation in 10% and arthralgia, bruising, neutropenia, and upper respiratory and urinary tract infections in 7% each.
The author of a related editorial observes that the most recent version of the National Comprehensive Cancer Network Guidelines lists 12 options for the first-line treatment of Waldenström macroglobulinemia.
He stresses that choosing between the options will involve not only the consideration of benefits and response rates, but also immediate and late toxicity profiles as well as cost.
Although ibrutinib is not an inexpensive drug, says Morie Gertz (Mayo Clinic, Rochester, Minnesota, USA), “with its high activity [it] is a welcome addition to the current armamentarium.”
The commentator concludes: “The future is bright for patients with [Waldenström macroglobulinemia] who now have many choices for treatment type, and the likely outcome is that few patients will succumb to this disease in the future.”
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