Cladribine combined with rituximab (R-2-CdA) therapy is an effective salvage therapy in relapsed or refractory indolent B-cell non-Hodgkin lymphoma

Abstract

Although cladribine has been reported to be an active purine analog against indolent B-cell non-Hodgkin lymphoma (B-NHL), there are few reports of combination use of cladribine and rituximab. This multicenter phase II study evaluated the efficacy and toxicity of cladribine with rituximab (R-2-CdA) therapy in relapsed or refractory indolent B-NHL. Twenty patients with the median age of 58.5 yrs (range, 42-72) were enrolled and received R-2-CdA therapy from April 2005 to July 2007. The median number of prior regimens was 2 (range, 1-3), and fifteen patients (75%) were previously treated with rituximab-containing regimens. Disease histology included follicular lymphoma in 16 patients, MALT lymphoma in two patients, nodal marginal B-cell lymphoma in one patient, and lymphoplasmacytic lymphoma in one patient. The overall response rate (ORR) was 90%, with a complete response rate (CRR) of 70%. Estimated median progression-free survival (PFS) time was 22.4 months (95%CI, 10.9-32.6 months) at a median follow-up time of 27 months (range, 12-43). Two-year PFS and 2-yr overall survival (OS) were 52.6% (95%CI, 31.0-73.2%) and 89.5% (95%CI, 66.1-97.3%), respectively. Grade 3 or grade 4 toxicities were neutropenia in 74% and thrombocytopenia in 11%. R-2-CdA therapy was demonstrated to have a high activity with durable PFS and acceptable toxicity in relapsed or refractory indolent B-NHL mostly pretreated with rituximab-containing therapy. Although a large-scale trial is needed for confirmation, R-2-CdA therapy could be a good salvage therapy option in relapsed or refractory indolent B-NHL.

Oral clofarabine for relapsed/refractory non-Hodgkin lymphomas: results of a phase 1 study

“…[14–16] Intravenous cladribine produces response rates of 30–45%, also increased when combined with rituximab. [17–19] While the majority of chemotherapy agents employed for relapsed/refractory NHL are administered intravenously, patients may prefer oral agents provided they offer similar therapeutic efficacy. [20] An oral formulation of fludarabine was reported to show an overall response rate of 65% in a phase 2 trial in relapsed indolent B-cell NHL, though 70% of patients experienced grade 3 or 4 neutropenia.…”

A single center experience: rituximab plus cladribine is an effective and safe first-line therapy for unresectable bronchial-associated lymphoid tissue lymphoma

“…Hirokazu et al reported high efficacy of R-2-CdA therapy as a salvage approach relapsed or refractory indolent B-NHL, with a ORR of 90% and CR of 70%. However, the 20-patient cohort in this study was mainly comprised by patients with follicular lymphoma, and only consisted 2 with MALT lymphoma (25). In a retrospective study involving 89 patients with marginal zone lymphoma, the use of R-2-CdA therapy resulted in an ORR of 89.3%, with 53.6% CR and 60 months of median of TTP, and a trend of early relapse in patients who did not receive rituximab was reported (44).…”

“…Monotherapy of cladribine is now considered the standard first-line treatment for hairy cell lymphoma (37,38). In addition, cladribine had shown satisfying effects in other indolent type of B-cell neoplasms, including marginal zone lymphoma, both as a single agent and in combination with other agents (22,24,25,34). Prolonged efficacy and longterm safety had been reported for cladribine in several publications (23,26).…”

“…Both the anti-CD20 monoclonal antibody rituximab (R) and the nucleoside analogue 2-chlorodeoxyadenosine (cladribine, 2-CdA) have demonstrated high efficacy and minimal side effects in the treatment of MALT lymphoma (21)(22)(23). The combination of rituximab and cladribine (R-2-CdA) has also been tested and showed promising results in both non-gastric MALT lymphoma and refractory/relapsed indolent B-NHL (24)(25)(26). Nonetheless, the effect and safety of R-2-CdA therapy in untreated BALT lymphoma with unresectable advanced lesions had not been assessed.…”

Modulation of deoxycytidine kinase (dCK) and glycogen synthase kinase (GSK-3β) by anti-CD20 (rituximab) and 2-chlorodeoxyadenosine (2-CdA) in human lymphoid malignancies

“…In one patient, however, 2-CdA was delivered subcutaneously due to lack of venous access. In another patient, 2-CdA was delivered daily over 5 days as iv infusion over 2 hours according to Nagai et al [ 25 ]. Toxicity was graded according to the US National Cancer Institute using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.…”