"Ibrutinib for Previously Treated Waldenström's Macroglobulinemia".
The New England Journal of Medicine. 2015.

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

Clinical Question

Does ibrutinib improve clinical outcomes in symptomatic patients with previously treated Waldenström's macroglobulinemia?

Bottom Line

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%.

Major Points

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.

Guidelines

As of 2015, no guidelines have been published that reflect the results of this trial for the use of ibrutinib in Waldenström's macroglobulinemia.

Design

Prospective, multicenter study of 63 symptomatic patients with previously treated Waldenström's macroglobulinemia.

Population

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%.

Interventions

420 mg of ibrutinib orally per day for up to twenty-six 4-week cycles, with further treatment continuation upon re-consent.

Outcomes

Primary Outcomes
Overall response rate was 90.5%, with a major response rate of 73.0%. Median serum IgM levels decreased and hemoglobin levels increased significantly.

Secondary Outcomes
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.

Funding

The study was supported by Pharmacyclics, Janssen Pharmaceuticals, various foundations, and private donations.

Further Reading

Full details and supplemental material can be accessed at the NEJM with ClinicalTrials.gov number NCT01614821.