Rituximab and subcutaneous 2-chloro-2′-deoxyadenosine combination treatment for patients with Waldenström macroglobulinemia: Clinical and biologic results of a phase II multicenter study

Daniele Laszlo, Giovanna Andreola, Luigi Rigacci, Alberto Fabbri, Cristina Rabascio, Patrizia Mancuso, Giancarlo Pruneri, Davide Radice, Antonello Pinto, Ferdinando Frigeri, Liliana Calabrese, Atto Billio, Francesco Bertolini, Giovanni Martinelli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2233-2238
Number of pages6
JournalJournal of Clinical Oncology
Volume28
Issue number13
DOIs
Publication statusPublished - May 1 2010

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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