In a phase II study reported in the Journal of Clinical Oncology, Robert J. Kreitman, MD, and colleagues found that achievement of minimal residual disease–free complete remission for patients with hairy cell leukemia was enhanced by adding concurrent rituximab to first-line cladribine; a lesser beneficial effect was observed with the addition of delayed rituximab.
Robert J. Kreitman, MD
As stated by the investigators, “Single-agent purine analog, usually cladribine, has been the standard first-line therapy [for hairy cell leukemia] for 30 years. High complete remission rates often include minimal residual disease, leading to relapse and repeated treatments. Rituximab can clear minimal residual disease, but long-term results are unknown and optimal timing of rituximab undefined.”
Study Details
In the trial, 68 patients with purine analog–naive classic hairy cell leukemia were randomly assigned to receive 0.15 mg/kg of cladribine intravenously on days 1 to 5 with eight weekly doses of rituximab at 375 mg/m2 started on day 1 (concurrent group, n = 34) or ≥ 6 months later after detection of minimal residual disease in their blood (delayed group, n = 34). Minimal residual disease tests included blood and bone marrow flow cytometry and bone marrow immunohistochemistry.
Patients in either group could receive a second course of rituximab ≥ 6 months after the first. The primary endpoint was 6-month minimal residual disease–free complete remission rates with concurrent treatment vs cladribine monotherapy in the delayed group.
Minimal Residual Disease–Free Complete Remission Rates
At 6 months after concurrent treatment vs cladribine monotherapy, complete remission rates were 100% vs 88% (P = .11), minimal residual disease–free complete remission rates were 97% vs 24% (P < .0001), and blood minimal residual disease–free rates were 100% vs 50% (P < .0001). At a median follow-up of 96 months, 94% vs 12% of patients remained minimal residual disease–free.
Compared with concurrent treatment, deferred rituximab in 21 evaluable patients in the delayed group was associated with a lower rate of minimal residual disease–free complete remission (67%, P = .0034) and a reduced duration of minimal residual disease–free status (hazard radio favoring concurrent treatment = 0.094, P = .0081). A second course of delayed rituximab was received by six patients in the delayed group. A total of 12 patients in the delayed group remained minimal residual disease–free at restaging at 6 to 104 months (median = 78 months) after receipt of the last delayed rituximab treatment.
Adverse Events
Compared with cladribine monotherapy, concurrent treatment was associated with an increased frequency of grade 3 or 4 thrombocytopenia (59% vs 9%, P < .0001), with these events being transient and reversible. Prophylactic platelet transfusions, in the absence of bleeding, were given to 35% vs 0% of patients (P = .0002). By 4 weeks, concurrent treatment was associated with higher neutrophil counts (P = .017) and platelet counts (P = .0015).
The investigators concluded: “Achieving minimal residual disease–free complete remission of hairy cell leukemia after first-line cladribine is greatly enhanced by concurrent rituximab and less so by delayed rituximab. Longer follow-up will determine if minimal residual disease–free survival leads to less need for additional therapy or cure of hairy cell leukemia.”
Dr. Kreitman, of the National Institutes of Health, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and Genentech. For full disclosures of the study authors, visit ascopubs.org.
