Long‐term safety and activity of cladribine in patients with extranodal B‐cell marginal zone lymphoma of the mucosa‐associated lymphoid tissue (MALT) lymphoma

Abstract

The purine analogue 2-chloro-deoxyadenosine (2-CDA, cladribine) +/- rituximab has been successfully tested in mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) patients. However, studies using cladribine in other indications have reported the potential for prolonged hematological side effects and secondary hematologic and non-hematologic malignancies. To date, there have been no data on long-term effects of cladribine in MALT lymphoma patients. We have analyzed a large number of 49 patients treated with cladribine at our institution 1997-2011. All patients were treated within clinical trials and had undergone a standardized follow-up protocol minimizing a potential bias in the detection of late sequels and relapses. After a median follow-up time of 61 months (interquartile range: 43-72) for 49 analyzed patients, 35 (71%) are alive, while 14 (29%) have died. In the entire collective, three cases (6%) of prolonged pancytopenia including manifest myelodysplastic syndrome in one patient (2%), three cases (6%) of secondary lymphoid malignancies, and five cases (10%) of non-hematologic cancers were documented. In terms of outcome, 42/49 (86%) patients responded to cladribine-containing treatment, and only 10/42 (24%) responding patients needed further treatment after a median time to progression of 14 months (interquartile range, 8-34). Currently, 25/35 (71%) patients being alive are in ongoing complete remission and 2/35 (6%) in ongoing stable disease, respectively. Eight patients (23%) are free of lymphoma after second-line therapy, with the median overall survival not having been reached. Our data suggest that cladribine might be safely applied in patients with MALT lymphoma, also in terms of long-term toxicities. These data also confirm the potential of cladribine to induce durable remissions. Copyright © 2015 John Wiley & Sons, Ltd.

Cladribine in combination with entinostat synergistically elicits anti-proliferative/anti-survival effects on multiple myeloma cells

“…Purine nucleoside analogues are antimetabolites that inhibit lymphocyte proliferation by interfering DNA synthesis. As a specific one, cladribine was designed to treat hairy cell leukemia (HCL); and it has been proved to be safe and effective in some B cell originated leukemia [44,45]. However, its activity in MM remains elusive.…”

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

“…Both the monoclonal anti-CD20 antibody rituximab and the nucleoside analogue cladribine have demonstrated certain efficacy in the management of B-NHLs and some efficacy data was also reported in MALT lymphoma (22,23,26,(32)(33)(34). Cladribine is a deoxyadenosine purine nucleoside analogue that has potent cytotoxic effects on both resting and proliferating lymphocytes (35,36).…”

“…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.…”

“…Attributing to the novel understanding in the pathogenesis and genetics of the disease together with the development of precise diagnostic tools, the risk adapted therapeutic concepts, which encouraging organ preservation and focusing more on quality of life, had been proposed and widely accepted. Given these, systemic therapy with satisfying efficacy and mild toxicities seems to be a better choice for patients with advance-stage BALT lymphoma.Both the monoclonal anti-CD20 antibody rituximab and the nucleoside analogue cladribine have demonstrated certain efficacy in the management of B-NHLs and some efficacy data was also reported in MALT lymphoma (22,23,26,(32)(33)(34). Cladribine is a deoxyadenosine purine nucleoside analogue that has potent cytotoxic effects on both resting and proliferating lymphocytes (35,36).…”

“…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).Undoubtedly, the role of rituximab in the management of B-cell neoplasms is essential, especially in diffuse large B-cell lymphoma and follicular lymphoma. Although its use in MALT lymphoma has not been officially approved for this indication in China, rituximab has been reported to have high effectiveness in this disease, both in monotherapy and in combination immune-chemotherapy (21,33,39-42).…”