"Ibrutinib for Previously Treated Waldenström's Macroglobulinemia". The New England Journal of Medicine. 2015.
Links to original sources: Wiki Journal Post Full Journal Article
Contents
1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcomes 8.2 Secondary Outcomes 9 Funding 10 Further Reading
Does ibrutinib improve clinical outcomes in symptomatic patients with previously treated Waldenström's macroglobulinemia?
In previously treated patients with Waldenström's macroglobulinemia, ibrutinib was effective in achieving a high overall response rate of 90.5% and promoting durable responses with a 2-year progression-free-survival rate of 69.1%.
Waldenström's macroglobulinemia is a malignant B-cell lymphoma with limited treatment options upon progression. Ibrutinib, a Bruton's tyrosine kinase inhibitor, has proven to be a promising therapy due to the high prevalence of MYD88L265P mutation that activates tumor-cell growth via Bruton's tyrosine kinase pathway. CXCR4WHIM mutations confer in vitro resistance to ibrutinib, thus creating a need to understand the impact of these mutations on treatment outcomes.
As of 2015, no guidelines have been published that reflect the results of this trial for the use of ibrutinib in Waldenström's macroglobulinemia.
Prospective, multicenter study of 63 symptomatic patients with previously treated Waldenström's macroglobulinemia.
Inclusion Criteria Symptomatic patients requiring treatment, one or more prior regiments, adequate counts, no central nervous system involvement, no significant cardiovascular disease.
Exclusion Criteria Central nervous system lymphoma, significant cardiovascular disease, use of warfarin, or medications prolonging the QT interval.
Baseline Characteristics Patients had received a median of two prior therapies. Baseline MYD88L265P mutation present in 89%, CXCR4WHIM in 34%.
420 mg of ibrutinib orally per day for up to twenty-six 4-week cycles, with further treatment continuation upon re-consent.
Overall response rate was 90.5%, with a major response rate of 73.0%. Median serum IgM levels decreased and hemoglobin levels increased significantly.
Estimated 2-year progression-free survival was 69.1%, with an overall survival rate of 95.2%. Responses were highest among patients with MYD88L265P and wild-type CXCR4 genotype.
The study was supported by Pharmacyclics, Janssen Pharmaceuticals, various foundations, and private donations.
Full details and supplemental material can be accessed at the NEJM with ClinicalTrials.gov number NCT01614821.