Prospective Clinical Trial of Ixazomib, Dexamethasone, and Rituximab as Primary Therapy in Waldenström Macroglobulinemia
| Autor: | Patricia Severns, Steven P. Treon, Joshua Gustine, Lian Xu, Guang Yang, Toni Dubeau, Zachary R. Hunter, Jorge J. Castillo, Kirsten Meid |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Boron Compounds
Male Cancer Research medicine.medical_specialty Glycine Phases of clinical research Gastroenterology Dexamethasone Ixazomib 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Maintenance therapy Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Aged Aged 80 and over business.industry Waldenstrom macroglobulinemia Middle Aged medicine.disease Survival Analysis Rash Clinical trial Regimen Treatment Outcome Immunoglobulin M Oncology chemistry 030220 oncology & carcinogenesis Female Rituximab Waldenstrom Macroglobulinemia medicine.symptom business Biomarkers 030215 immunology medicine.drug |
| Zdroj: | Clinical Cancer Research. 24:3247-3252 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: Proteasome inhibition is of proven efficacy in patients with Waldenström macroglobulinemia (WM). However, WM remains incurable with standard treatments. Novel agents, safe and effective, are needed. Patients and Methods: We designed a prospective phase II study evaluating the combination of ixazomib, dexamethasone, and rituximab (IDR) as primary therapy in symptomatic patients with WM. Protocol therapy consisted of oral ixazomib, 4 mg, with intravenous or oral dexamethasone, 20 mg, on days 1, 8, and 15 every 4 weeks for induction cycles 1 and 2, and in combination with intravenous rituximab, 375 mg/m2, on day 1, every 4 weeks for cycles 3 to 6. Maintenance therapy followed 8 weeks later with IDR given every 8 weeks for 6 cycles. Results: Twenty-six patients were enrolled. All patients had the MYD88 L265P mutation, and 15 patients (58%) had a CXCR4 mutation. The median time to response was 8 weeks, which was longer (12 weeks) in WM patients with CXCR4 mutations (P = 0.03). The overall response rate was 96%, and the major response rate was 77%. With a median follow-up of 22 months, the median progression-free survival was not reached. Grade ≥2 adverse events reported in >1 patient included infusion-related reactions (19%), rash (8%), and insomnia (8%). Conclusions: IDR offers a highly effective and well tolerated, neuropathy-sparing regimen for primary therapy in patients with WM. This trial is registered at www.clinicaltrials.gov under ID NCT02400437. Clin Cancer Res; 24(14); 3247–52. ©2018 AACR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|