Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence

Abstract

The purine analogs pentostatin and cladribine are effective treatments for hairy cell leukemia (HCL). However, alternative treatments are needed for patients with recurrent disease. We reviewed retrospectively data from 18 patients who were retreated with either pentostatin (n = 12) or cladribine (n = 6) in combination with rituximab, after 1-6 (median 2) previous treatments with either purine analog as a single agent. All 18 patients responded to therapy, with a complete response (CR) rate of 89%. This compared favorably with CR rates of 68% after second-line therapy and 47% after third-line therapy in 88 patients retreated one or more times with a purine analog alone. Toxicity with the combination treatment was minimal. At a median follow-up of 36 months (range 5-83 months) all 16 complete responders remained in CR, while one partial responder developed recurrent disease at 10 months. The estimated recurrence rate at 3 years was 7%. This compares with 21% after second-line therapy and 42% after third-line therapy in the 88 patients retreated with a purine analog alone. Furthermore, it was a marked improvement on the 55% recurrence at 3 years previously seen in these same 18 patients after their own first-line treatment with single-agent pentostatin or cladribine (p = 0.006). The combination of a purine analog with rituximab was safe and effective for patients with recurrent HCL. The results suggest an added benefit compared with single-agent purine analog therapy.

Rituximab therapy for hairy cell leukemia: a retrospective study of 41 cases

“…The longest follow-up in our cohort (median 45 months for these patients) may explain this difference. However, even in case of combination with PA, relapse rate in our study (11 % after a median follow-up of 24.5 months) is still higher than published data, although to a lesser extent [15,16].…”

“…Moreover, molecular responses were obtained in 70 % of these patients. In the relapse setting, the efficacy of rituximab combined with either cladribine, pentostatin, or even fludarabine is also substantial with similar response and relapse rates, even though the number of reported patients is much lower [16,17].…”

An unusual indication for splenectomy in hairy cell leukaemia: a report of three cases with persistent splenomegaly after chemoimmunotherapy

“…As pentostatin is usually administered until maximum response and then two more doses beyond as consolidation (Else et al , 2011), this phenomenon may expose the patient to an unnecessary amount of chemotherapy if they are not considered to be in CR.…”

“…In that context, the combination of pentostatin or cladribine with rituximab was tested and found to be effective (Else et al , 2011), and is now recommended in the UK for recurrent or refractory HCL (Jones et al , 2012). …”

Orphan drugs for the treatment of hairy cell leukemia

“…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]. Therefore the vast majority of these patients achieve a long-lasting CR to this combination.…”