Phase II study of cladribine (2CDA) followed by rituximab for eradication of minimal residual disease (MRD) in hairy cell leukemia (HCL)

Abstract

6620 Background: HCL is an indolent lymphoproliferative malignancy characterized by infiltration of the bone marrow, liver, and spleen by neoplastic B-cells with cytoplasmic hair-like projections. Despite the success of the nucleoside analogs 2CDA and pentostatin in achieving long-term remissions in HCL, some patients (pts) continue to relapse and the relapse-free survival curve does not appear to achieve a plateau. Rituximab has been used effectively to treat pts with relapsed HCL. We investigated whether the prolonged administration of rituximab one month after therapy with 2CDA can effectively eradicate MRD in pts with newly diagnosed HCL or those who have relapsed after one prior therapy. Methods: 2CDA 5.6 mg/m2 is administered over 2 hours daily for 5 days. One month later, rituximab 375 mg/m2 is administered weekly for 8 weeks. MRD is assessed by flow cytometry as well as by IgH polymerase chain reaction (PCR) assay using framework-1, -2 and -3 primer sets. MRD is evaluated at one month following 2CDA and after completion of rituximab. Results: To date, ten pts have been enrolled onto the study. Eight pts had received no prior therapy, one pt had relapsed after prior 2CDA therapy 9 years ago and one pt had received chlorambucil only. Two pts had the variant form of HCL. Six pts have completed all therapy, 3 are receiving rituximab, and 1 pt has completed 2CDA only. So far, six (100%) of the evaluable pts have achieved a complete remission (CR) with no evidence of MRD by flow in 6 and by PCR in 3. PCR remained positive in 1 pt and was not evaluable in 2 pts. Eight of 9 pts with evaluable flow studies one month after completing 2CDA remained positive; 1 pt was negative after 2CDA only and 6 became negative after completing rituximab. Five of 6 pts with evaluable PCR studies one month after completing 2CDA remained positive; 1 pt was negative after 2CDA only and 3 became negative after rituximab. Conclusions: We conclude that assessment and eradication of MRD by flow and PCR in HCL is feasible. Longer follow-up is necessary to determine whether MRD status at completion of therapy can predict relapse. This may allow design of regimens that may further improve long-term disease-free survival in HCL. No significant financial relationships to disclose.