Randomized Phase Ii Study Of Cladribine With Simultaneous Or Delayed Rituximab In Patients With Untreated Hairy Cell Leukemia.

7003 Background: Single-agent purine analog therapy, usually cladribine, has been the standard 1st-line therapy of hairy cell leukemia (HCL) for ~30 years. Relapse is attributed to minimal residual disease (MRD) persisting despite complete remission (CR). Rituximab can clear MRD, but there are no long-term data for how frequently and for how long this happens, or even how frequently MRD remains after cladribine. We therefore conducted a randomized phase II trial of 1st-line cladribine with concurrent vs delayed rituximab. Methods: The primary endpoint was to determine if 8 weekly doses of rituximab (375 mg/m2 iv) begun the same day as 5 daily doses of cladribine (0.15 mg/kg iv) reduce HCL MRD 6 months later compared to cladribine alone. Secondary endpoints included testing delayed rituximab, 8 weekly doses beginning if/when MRD is detected in blood (or if HCL-related cytopenias persist preventing consideration of CR) ≥ 6 months after cladribine. Both groups could receive a 2nd course of rituximab if the same situation recurred ≥ 6 months after starting the 1st course of rituximab. MRD was assessed in blood (PB) and bone marrow (BM) using flow cytometry (FC), consensus PCR, and immunohistochemistry. Results: Sixty-eight patients were randomized 1:1 to concurrent vs delayed arms. At 6 months after cladribine, 97% concurrent vs 24% delayed (p < 0.0001) patients were MRD-free by all tests. 100% concurrent vs 41% delayed patients were MRD-free by all tests except BMA FC (p < 0.0001). At a median follow-up of 87.3 months, delayed rituximab was required by 1 concurrent patient vs 27 courses in 21 delayed patients. MRD-free survival after 1st rituximab was not reached for 34 patients after concurrent rituximab, with 32 still MRD-free after a median of 72 months (94% MRD-free survival), compared to median MRD-free survival 60.1 months after delayed rituximab, with 10 (48%) of 21 remaining MRD-free (p < 0.0001, hazard ratio for concurrent rituximab 0.09). Conclusions: Achievement of MRD-free CR after 1st line cladribine for HCL is greatly enhanced by concurrent rituximab. Use of delayed rather than concurrent rituximab could achieve MRD-free CR but durability was clearly inferior to concurrent rituximab. Longer follow-up will determine if MRD-free survival leads to cures of HCL, increased CR duration, and/or less need for additional therapy. Clinical trial information: NCT00923013.