Cladribine in the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma

BACKGROUND: The treatment of relapsed or refractory Non-Hodgkin lymphoma (NHL) depends on the number of drugs of choice, and additional treatments can achieve remission for many patients. Cladribine (2-chlorodeoxyadenosine, 2-CdA) is a purine nucleoside analogue, and generally approved for indolent NHL relapsed after or refractory to previous chemotherapy. We conducted this analysis to determine efficacy and toxicity of 2-CdA in the treatment of relapsed or refractory NHL.

PATIENTS AND METHODS: 29 relapsed or refractory NHL patients treated with cladribine in a single institution from 2002 to 2007 were entered in a retrospective analysis.

RESULTS: The median age was 64 years. Seventeen patients (59%) were male, twenty (69%) with indolent lymphoma consisting mainly of follicular lymphoma and mantle cell lymphoma, and twenty-eight (97%) previously treated with 1 to 10 regimens (mean 2.7). Cladribine was administrated 24% as a monotherapy and 22% with other chemotherapeutic agents. The dose and duration of administration were variable among the patients, however, most common regimen was 0.9mg/kg/day for seven consecutive days, for 1 to 6 cycles, depending on response. Response rate was 72% (CR and PR were 31%, 41%, respectively). Median overall survival was of 2.9 years. Patients showed improved survival rate in performance status 0 or 1 (Willcoxon: P<0.0001, Log-rank: P<0.0001), more than 3 cycles of cladribine (Willcoxon: P<0.028, Log-rank: P=0.126), or combination chemotherapy (Willcoxon: P=0.042, Log-rank: P=0.040). Main reason for death was disease progression. Myelosuppression was the most common adverse effect. Eight patients (28%) experienced CTCAE grade 4 neutropenia, fourteen (48%) lymphocytopenia, and three (10%) thrombocytopenia, respectively. Two episodes (6.9%) of grade 3–4 infections were observed. There was no treatment related mortality.

CONCLUSIONS: Cladribine is effective even in heavily pretreated patients with NHL. It also has favorable safety, and can be considered as a good alternative treatment for relapsed or refractory NHL.