The role of rituximab in combination with pentostatin or cladribine for the treatment of recurrent/refractory hairy cell leukemia

Abstract

BACKGROUND.The purine analogs pentostatin and cladribine have revolutionized the treatment of hairy cell leukemia (HCL) with overall responses in greater than 85% of patients and a median progression‐free survival of up to 15 years. They continue to be effective at second‐ and even third‐line therapy; however, alternative treatments are needed for patients who are or have become refractory to these agents or whose remissions are shorter with each course of therapy.METHODS.The authors conducted a retrospective review of 8 patients who received pentostatin or cladribine combined concurrently (n = 6 patients) or sequentially (n = 2 patients) with rituximab at second‐line therapy (n = 3 patients) and at subsequent lines of therapy (n = 5 patients). Results from a previously reported database of 219 patients with HCL (73 patients who received second‐line therapy and 20 patients who received third‐line therapy) were used as a historic control group against which to measure benefit.RESULTS.All 8 patients responded to therapy, with 7 complete responses (CRs) (87.5%) and minimal toxicity. All patients who had CRs were negative for minimal residual disease (MRD). At a median follow‐up of 29 months (range, 5–39 months) 1 patient developed recurrent disease, and the estimated 2‐year recurrence rate was 20% (0% after second‐line therapy and 25% after subsequent lines of therapy). In the historic control group, the CR rates were 70% after second‐line therapy and 45% after third‐line therapy, and the recurrence rates at 2 years were 15% and 33%, respectively.CONCLUSIONS.The combination of purine analogs with rituximab was safe and effective for patients with recurrent and/or refractory HCL, and the current results suggested an added benefit compared with standard treatment. Cancer 2007 © 2007 American Cancer Society.

Hairy cell leukemia

“…Few preliminary data have reported that the combined use of rituximab after a purine nucleoside analogue, or given concomitantly with these agents, may produce a higher percentage of CR without evidence of residual disease and cumulative toxicity. [26][27][28] This chemotherapy-immunotherapy combination could increase the economic implications but, at the same time, in terms of cost/benefit balance, it is important to evaluate this aspect over a long period of time, because it could potentially be possible to reduce the number of further treatments for the patients.…”

Multifocal brain involvement in a patient with hairy cell leukemia successfully treated with rituximab and cladribine

“…[9][10][11] After completion of his treatment, his symptoms, splenomegaly, and lymphadenopathy resolved. The white blood cell count was 4.52 3 10 /L.…”

Orphan drugs for the treatment of hairy cell leukemia

“…In contrast to the purine analogs, responses to Rituximab are achieved in 30 --50% of patients and less than 20% are CR. By contrast the combination of chemoimmunotherapy (Rituximab plus DCF or CDA) in patients who experience early relapse, multiple relapses or do not achieve a response to single agent purine analog demonstrates that this combination is highly effective [69,70]. Else et al reported the efficacy of a combination of DCF or CDA with Rituximab in eight multiple relapsed or refractory HCL patients with impressive results [69].…”

“…By contrast the combination of chemoimmunotherapy (Rituximab plus DCF or CDA) in patients who experience early relapse, multiple relapses or do not achieve a response to single agent purine analog demonstrates that this combination is highly effective [69,70]. Else et al reported the efficacy of a combination of DCF or CDA with Rituximab in eight multiple relapsed or refractory HCL patients with impressive results [69]. An update of this study in 18 patients that had previously received one to six therapies has shown an ORR of 100%, a CR rate of 89% and that 16 of 18 patients treated with this combination remain in CR with a median follow-up of 36 months; one PR patient relapsed at 10 months [71].…”