pentostatin and Waldenstrom-Macroglobulinemia

The purine nucleoside analogues, either alone or in combination with other chemotherapeutic agents, are increasingly used in the treatment of patients with indolent B-cell lymphoproliferative disorders. The initial studies in Waldenström's macroglobulinaemia (WM) are very promising. Approximately 40% of patients who have received prior therapy with alkylating agents respond, while response rates of up to 90% have been documented in untreated patients. However, it is not known whether the purine analogues offer any significant advantage over alkylating agents such as chlorambucil. In this review the treatment options in WM and in particular the role of the purine analogues are discussed.

Topics: Alkylating Agents; Antimetabolites; Chlorambucil; Cladribine; Clinical Trials as Topic; Drug Resistance; Drug Therapy, Combination; Guidelines as Topic; Humans; Middle Aged; Pentostatin; Plasmapheresis; Purine Nucleosides; Quality of Life; Vidarabine; Waldenstrom Macroglobulinemia

Topics: Adenosine Deaminase; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cladribine; Humans; Lymphoma; Lymphoma, B-Cell; Lymphoma, T-Cell, Cutaneous; Pentostatin; Vidarabine; Waldenstrom Macroglobulinemia

Waldenström's macroglobulinemia (WM) is an indolent lym phomaand is responsive to therapy regimens containing alkylating agents, purine analogs and rituximab if treatment becomes necessary. We initiated a multicenter phase II trial to determine the safety and efficacy of a regimen containing pentostatin, cyclophosphamide and rituximab (PER) in patients with WM. Between May 2005 and December 2010, 25 patients with WM were included in the study. Twenty-one patients received PER as first-line therapy. In these patients, 2-year progression-free survival was 83.6% and 2-year overall survival was 100%. Thirteen patients (52%) received R maintenance therapy. In these patients, the 2-year progression-free survival was 91.67% and 2-year overall survival was 100%. We have provided evidence that PER is a safe and effective regimen for WM. Although R maintenance therapy after PER seemed to induce a better long-term outcome, this study was not powered to address this issue.

Topics: Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Female; Humans; Male; Middle Aged; Pentostatin; Rituximab; Treatment Outcome; Waldenstrom Macroglobulinemia

Pentostatin has demonstrated significant activity as a single agent in patients with low-grade B-cell and T-cell lymphomas and is less myelosuppressive than other purine analogues.. We conducted a phase II trial with the combination regimen of PC-R (pentostatin/cyclophosphamide with or without rituximab) in 14 patients with Waldenstrom's macroglobulinemia (WM) and 3 patients with lymphoplasmacytic lymphoma (LL) without monoclonal serum immunoglobulin M (IgM), followed by a maintenance regimen with rituximab (375 mg/m2 every 3 months) for patients exhibiting a complete response (CR) or a partial response (PR) after 4-6 cycles. Nine patients were untreated, and 8 had been previously treated with 1-3 regimens. The first 9 patients received PC therapy (pentostatin 4 mg/m2 plus cyclophosphamide 600 mg/m2), and 8 patients received the same combination with rituximab 375 mg/m2 on day 1. Cycles were repeated every 3 weeks.. An objective tumor response after PC and PC-R was confirmed in 11 of 17 evaluable patients (64.7%), with 2 CRs (11.7%) and 9 PRs (52.9%). In patients who received rituximab (n = 13) simultaneously or subsequently, the overall response rate was 76.9%. Grade 2/3 nausea and grade 2 vomiting was generally mild based on World Health Organization criteria. Grade 3 hematologic toxicity occurred after 9 of 49 cycles (18.3%), and grade 4 toxicity occurred after 2 cycles (4%). Ten patients were subsequently treated with rituximab every 3 months for 2-9 cycles to date (median, 4 cycles). No patients have had disease relapse to date, and all exhibited stable IgM serum levels. In 3 patients with a PR after completion of chemotherapy, remission has improved further, with normalization of the IgM level in 1 patient and another patient exhibiting a CR.. Our data indicate that PC-R is safe and highly effective in patients with WM. Maintenance therapy with rituximab for WM as a single infusion every 3 months can be administered safely and can improve remission status.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Female; Humans; Immunoglobulin M; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Pentostatin; Remission Induction; Rituximab; Waldenstrom Macroglobulinemia

Topics: Blood Proteins; Blood Viscosity; Coformycin; Female; Hemoglobins; Hemolysis; Humans; Immunoglobulin M; Immunoglobulins; Middle Aged; Paraproteins; Pentostatin; Platelet Count; Ribonucleosides; Waldenstrom Macroglobulinemia