LAUSR

Hairy cell leukemia variant (HCLv) responds poorly to purine analog monotherapy. Rituximab concurrent with cladribine (CDAR) improves response rate, but long-term outcomes are unknown. We report final results of a phase II study of CDAR for patients with HCLv. Twenty patients with 0-1 prior courses of cladribine and/or rituximab, including 8 previously untreated, received cladribine 0.15 mg/kg days 1-5 with 8 weekly rituximab doses 375 mg/m2. Patients received a 2nd rituximab course ≥6 months after cladribine, if/when minimal residual disease (MRD) was detected in blood. The complete remission (CR) rate from CDAR was 95%, 95% confidence interval (95%CI) 75-100%. Sixteen of 20 patients (80%, 95% CI: 56-94%) became MRD-negative by bone marrow at 6 months. The median duration of MRD-negative CR was 70.1 months and 7 of 16 are still MRD-negative up to 120 months. With median follow-up of 69.7 months, 11 patients received delayed rituximab and the 5-year progression-free survival (PFS) and overall survival (OS) were 63.3% and 73.9%, respectively. Five patients with TP53 mutations had shorter PFS (median: 36.4 months vs unreached, p=0.0024) and OS (median: 52.4 months vs unreached, p=0.032). MRD-negative CR at 6 months was significantly associated with longer PFS (unreached vs 17.4 months, p<0.0001) and OS (unreached vs 38.2 months, p<0.0001). Lack of MRD in blood at 6 months was also predictive of longer PFS and OS (p<0.0001). After progression following CDAR, median OS was 29.7 months. CDAR is effective in HCLv with better outcome in patients who achieved MRD-negative CR.