Ibrutinib in Previously Treated Waldenström’s Macroglobulinemia  

Oleh:

Treon, Steven P. ; Tripsas, Christina K. ; Meid, Kirsten ; Warren, Diane

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The New England Journal of Medicine (keterangan: ada di Proquest) vol. 372 no. 15 (Apr. 2015), page 1430-1440.
Topik: tumor cells; ibrutinib; serum; toxic effects; waldenstroms macroglobulinemia; treatment
Fulltext: nejmoa1501548.pdf (495.72KB)

Ketersediaan

Perpustakaan FK Nomor Panggil: N08.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

BACKGROUND MYD88L265P and CXCR4WHIM mutations are highly prevalent in Waldenström’s macroglobulinemia. MYD88L265P triggers tumor-cell growth through Bruton’s tyrosine kinase, a target of ibrutinib.CXCR4WHIM mutations confer in vitro resistance to ibrutinib. METHODS We performed a prospective study of ibrutinib in 63 symptomatic patients with Waldenström’s macroglobulinemia who had received at least one previous treatment, and we investigated the effect ofMYD88 and CXCR4 mutations on outcomes. Ibrutinib at a daily dose of 420 mg was administered orally until disease progression or the development of unacceptable toxic effects. RESULTS After the patients received ibrutinib, median serum IgM levels decreased from 3520 mg per deciliter to 880 mg per deciliter, median hemoglobin levels increased from 10.5 g per deciliter to 13.8 g per deciliter, and bone marrow involvement decreased from 60% to 25% (P<0.01 for all comparisons). The median time to at least a minor response was 4 weeks. The overall response rate was 90.5%, and the major response rate was 73.0%; these rates were highest among patients with MYD88L265PCXCR4WT (with WT indicating wild-type) (100% overall response rate and 91.2% major response rate), followed by patients with MYD88L265PCXCR4WHIM (85.7% and 61.9%, respectively) and patients with MYD88WTCXCR4WT (71.4% and 28.6%). The estimated 2-year progression-free and overall survival rates among all patients were 69.1% and 95.2%, respectively. Treatment-related toxic effects of grade 2 or higher included neutropenia (in 22% of the patients) and thrombocytopenia (in 14%), which were more common in heavily pretreated patients; postprocedural bleeding (in 3%); epistaxis associated with the use of fish-oil supplements (in 3%); and atrial fibrillation associated with a history of arrhythmia (5%). CONCLUSIONS Ibrutinib was highly active, associated with durable responses, and safe in pretreated patients with Waldenström’s macroglobulinemia.MYD88 and CXCR4 mutation status affected responses to this drug.

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