Rituximab and Subcutaneous 2-Chloro-2′-Deoxyadenosine Combination Treatment for Patients With Waldenström Macroglobulinemia: Clinical and Biologic Results of a Phase II Multicenter Study
- 1 May 2010
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 28 (13), 2233-2238
- https://doi.org/10.1200/jco.2009.23.6315
Abstract
Purpose: To assess the efficacy of 2-chloro-2′-deoxyadenosine (2-CdA) given subcutaneously (SC) in combination with rituximab in the treatment of newly diagnosed/pretreated patients with Waldenström macroglobulinemia (WM) and to correlate the response to treatment with biologic findings (immunophenotypic and pharmacogenomic analysis). Patients and Methods: From December 2003 to February 2007, 29 patients were enrolled. Intended therapy consisted of a combination of rituximab (375 mg/m2) on day 1 followed by 2-CdA 0.1 mg/kg (SC injection) for 5 consecutive days, administered monthly for four cycles. Anemia (n = 16), neurologic symptoms (n = 6), symptomatic cryoglobulinemia (n = 4), and thrombocytopenia (n = 3) represented the reasons for starting treatment. The expression of ζ chain–associated protein kinase 70 (Zap-70) and of seven genes involved in 2-CdA metabolism as markers of response to the combination treatment was evaluated. Results: With a median follow-up of 43 months, the overall response rate observed was 89.6%, with seven complete responses (CR), 16 partial responses, and three minor response, without any difference between newly or pretreated patients (P = .522). The therapy was well tolerated, except for transitory cardiac toxicity (n = 2) and intolerance to rituximab (n = 2). No major infections were observed despite the lack of antimicrobial prophylaxis. No patients developed transformation to high-grade non-Hodgkin's lymphoma nor myelodysplasia. Low expression levels of human concentrative nucleoside transporter 1 (hCNT1) were correlated with the failure to achieve a CR (P = .024), whereas no association with Zap-70 expression was found. Conclusion: The combination of rituximab and SC 2-CdA is safe and effective in patients with WM requiring treatment. The pharmacogenomic analysis associated with the study suggests hCNT1 might be beneficial in predicting clinical response to such a combination treatment.This publication has 23 references indexed in Scilit:
- Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180Journal of Clinical Oncology, 2009
- International prognostic scoring system for Waldenström macroglobulinemiaBlood, 2009
- Increased Incidence of Transformation and Myelodysplasia/Acute Leukemia in Patients With Waldenström Macroglobulinemia Treated With Nucleoside AnalogsJournal of Clinical Oncology, 2009
- Update on Treatment Recommendations From the Fourth International Workshop on Waldenström's MacroglobulinemiaJournal of Clinical Oncology, 2009
- Update on treatment recommendations from the Third International Workshop on Waldenstrom's MacroglobulinemiaBlood, 2006
- Guidelines on the management of Waldenström macroglobulinaemia*British Journal of Haematology, 2006
- Immunophenotypic Profile of Lymphoplasmacytic Lymphoma/Waldenström MacroglobulinemiaAmerican Journal of Clinical Pathology, 2005
- Nucleoside transporters in chronic lymphocytic leukaemiaLeukemia, 2004
- Differential Expression of Human Nucleoside Transporters in Normal and Tumor TissueBiochemical and Biophysical Research Communications, 2001
- Cladribine (2‐CDA) given as subcutaneous bolus injections is active in pretreated Waldenström's macroglobulinaemiaBritish Journal of Haematology, 1997