PHASE Ib PILOT STUDY OF ITACITINIB WITH ALEMTUZUMAB IN PATIENTS WITH T-CELL PROLYMPHOCYTIC LEUKEMIA Open Access

• The JAK1 inhibitor, itacitinib, combined with CAMPATH was safe and well-tolerated in patients with T-cell prolymphocytic leukemia

• Itacitinib improved constitutional symptoms in patients with T-PLL and resulted in encouraging response and survival outcomes with CAMPATH

T-cell prolymphocytic leukemia (T-PLL) is a mature T-cell neoplasm with an aggressive clinical course. Overall prognosis is poor, and treatment relies on alemtuzumab due to inadequate response to conventional chemotherapy. Three-quarters of cases harbor activating mutations in the JAK-STAT pathway (JAK1, JAK3, STAT5B, IL2RG). We report safety and efficacy from a phase 1b study evaluating the combination of the JAK1 inhibitor itacitinib with alemtuzumab. Patients (n=15) were >18 years, with treatment-naïve (n=8) or relapsed/refractory (n=7) T-PLL with adequate organ function, ECOG PS < 2, and platelet > 30 K/μL. Cycle 1 included a lead-in phase with itacitinib monotherapy on Days 1-14. Beginning Day 15, patients also received alemtuzumab 30 mg IV three times weekly for up to 4 (28-day) cycles or until best response. At best response, up to 8 cycles of maintenance with single-agent itacitinib was allowed. Median age was 65 years (range, 39-83). Ten patients (67%) had complex cytogenetics, 11 (73%) had chromosome 14 abnormality, and 13 (87%) were TCL1A positive by FISH. Among frontline patients, overall response rate (ORR) was 88% (CR: 75%), median event-free survival (EFS) and overall survival (OS) were 11.6 and 19.5 months, respectively. Three frontline patients proceeded to allogeneic stem cell transplantation. The ORR in the relapsed/refractory cohort was 57% (CR: 43%), median EFS and OS were 11.1 months. Most (85%) adverse events were grade 1-2 and none were attributed to itacitinib. Continued studies evaluating JAK inhibitors in patients with T-PLL are warranted. The trial is registered with ClinicalTrials.gov (NCT03989466).