Abstract 3717: Randomized phase II trial of cladribine with or without immediate rituximab for newly diagnosed or previously treated hairy cell leukemia to eliminate minimal residual disease: Interim report

Abstract

Abstract Purine analogs including cladribine can induce complete remission (CR) in a high percentage of patients with previously untreated hairy cell leukemia (HCL), but late relapses are common and disease-free survival curves show no convincing evidence of cure. Many patients in CR after cladribine have minimal residual disease (MRD) which strongly expresses CD20, and the anti-CD20 Mab rituximab, particularly with a purine analog, can eliminate MRD to undetectable levels. To determine the potential benefit of adding rituximab to cladribine for initial or 2nd-line treatment of HCL, a randomized trial was begun in 150 HCL patients with 0-1 prior courses of cladribine requiring therapy. Patients receive cladribine 0.15 mg/Kg by 5 daily 2-hr i.v. infusions, and 8 weekly i.v. infusions of rituximab 375 mg/m2. Rituximab in half the patients is begun with the 1st dose of cladribine, and in the other half is delayed at least 6 months when MRD is detectable in blood. Endpoints include determining whether MRD rates are lower at 6 months with immediate rituximab, and whether blood MRD-free survival is longer when rituximab is delayed at least 6 months or begun with cladribine. HCL variant (HCLv) patients, known to respond poorly to initial cladribine alone, are not randomized and receive rituximab with cladribine. Bone marrow and blood are assessed for MRD by immunohistochemistry, PCR and flow cytometry at 1 and 6 months after cladribine. At this time 14 patients are enrolled, including 6 untreated and 8 with 1 prior course of cladribine, the latter group including 1 with HCLv. So far, the overall response rate is 100% with 10 (83%) CRs in 12 evaluable patients at 61-243 (median 202) days of follow-up. By 1 month, 0 of 5 patients after cladribine alone vs 5 (71%) of 7 after cladribine with immediate rituximab were MRD-free (p=0.028), including the patient with HCLv. Neutropenic fever was more frequent in patients receiving immediate rituximab, and was associated with both infusional reactions and reversible infections. We conclude that rituximab with cladribine can result in early clearing of MRD which is frequently present after cladribine alone. Additional accrual and follow-up is needed to determine whether simultaneous cladribine and rituximab can reduce MRD rates at 6 months, whether MRD-free survival might be longer or shorter with delayed rituximab, and whether rituximab added to cladribine for 1st or 2nd line treatment of HCL can prevent or delay clinical relapse. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3717.