Preliminary safety and efficacy of the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib (IBR) in patients (pts) with hairy cell leukemia (HCL).

Abstract

7063 Background: Effective treatments (tx) for classical (c) HCL pts refractory to or ineligible for nucleoside analogs (NA) are limited, and there is no accepted standard for either tx-naïve or relapsed variant (v) HCL. IBR, an oral small molecule inhibitor of BTK, is active in several indolent B-cell malignancies, but its activity in HCL has not been previously assessed. We report preliminary safety and efficacy data from a CTEP-supported phase 2, multicenter study. Methods: Pts with cHCL (relapsed after ≥1 NA or unfit for NA) and vHCL who require tx are eligible if ECOG ≤2, free of infection and end-organ function preserved. Pts receive continuous IBR 420 mg daily in 28-day cycles. Response, including bone marrow biopsy with immunohistochemistry for MRD, is assessed after 8 and 12 cycles. Pts may continue IBR indefinitely absent unacceptable toxicity or progressive disease. Results: 8 pts (1 tx-naïve and 1 relapsed vHCL, 6 relapsed cHCL) have been dosed (range 1-8 cycles) and all remain on tx. Common treatment-related adverse events were grade (Gr) 1/2 diarrhea, rash, arthralgia/myalgia, and transient Gr 1-3 elevation of hepatic transaminases. 3 cases of Gr 3 neutropenia and 2 cases of febrile neutropenia have been observed during cycle 1, all responding to tx interruption and/or brief course GCSF. Redistribution lymphocytosis (peaking at day 8) occurred in both vHCL pts and 1 V34.4 subtype cHCL pt with circulating disease at baseline. Soluble IL2 receptor (sIL2R) levels decreased after tx in all pts and correlated with improvements in symptoms and peripheral blood counts. Marrow clearance (>90% pre-, <2% post-tx) was observed in the first pt undergoing response assessment after 8 cycles. Pretreatment imunoblots demonstrated the presence of pBTK in several pts that was substantially reduced after IRB. This did not correlate with loss of pERK, suggesting that ERK phosphorylation ex vivo may not be a reliable indicator of IBR activity. Conclusions: IBR appears well tolerated and demonstrates early evidence of activity in both cHCL and vHCL. sIL2R levels may correlate with response. Accrual continues at 5 US sites. Updated safety and efficacy data will be presented. Clinical trial information: NCT01841723.