Phase 2 Study of Ruxolitinib in Patients with Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia

Background Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid malignancies with an estimated median survival of 2 years. No effective therapy has been established. The majority of CNL and Methods The clinical trial is an open-label, phase 2 study of single agent ruxolitinib in CNL/aCML patients, regardless of CSF3R mutation status. A minimum of a 7-day washout period was required for patients on therapy aimed at reducing white blood cell count. The primary endpoint is overall response rate (partial response [PR] and complete response [CR]), which was evaluated in patients who completed 6 continuous 28-day cycles. Patients who did not reach the end of cycle 6 were considered non-responders. CR was defined as normalization of the white blood cell count, spleen volume, and marrow hyperplasia and/or dysplasia. Secondary endpoints include evaluation of ruxolitinib safety and tolerability, and clinical and laboratory correlates of response. The starting dose of ruxolitinib was guided in part by baseline platelet count. Dose modifications were allowed based on investigator discretion. Patients who remained on treatment for ongoing clinical benefit could enter an extension phase after 24 cycles of ruxolitinib treatment. Results At the time of data cutoff (October 2017), we enrolled 40 patients (median age 73.2 years; 17 females and 23 males) with a diagnosis of CNL (N=20) or aCML (N=20). The median daily starting dose was 20mg (range 10-40mg) and daily dose during the study was 30mg (range 10-50mg), administered twice daily. Twenty (50%) patients were positive for CSF3R-T618I mutation (15 CNL and 5 aCML). The median number of cycles completed was 7.0 cycles (range Conclusions Ruxolitinib provides clinical benefit in at least a third of CNL and aCML patients and is well-tolerated in this patient population. The greatest clinical benefit was among those with CSF3R-T618I mutation. However, most hematologic responses are partial in nature, reflecting a composite evaluation of the white blood cell count, spleen volume, and marrow hyperplasia and/or dysplasia. Further characterization of the clinical and genetic correlates of response, including a subset of patients with complete responses, may help optimize selection of patients for ruxolitinib therapy. Disclosures Dao:Incyte: Consultancy. Collins:Arog Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; Celgene Corporation: Research Funding; Agios: Research Funding. Cortes:novartis: Research Funding. Deininger:Blueprint: Consultancy; Pfizer: Consultancy, Membership on an entity9s Board of Directors or advisory committees. Druker:Henry Stewart Talks: Patents & Royalties; Third Coast Therapeutics: Membership on an entity9s Board of Directors or advisory committees; ARIAD: Research Funding; Novartis Pharmaceuticals: Research Funding; McGraw Hill: Patents & Royalties; Bristol-Meyers Squibb: Research Funding; Fred Hutchinson Cancer Research Center: Research Funding; MolecularMD: Consultancy, Equity Ownership, Membership on an entity9s Board of Directors or advisory committees; Gilead Sciences: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity9s Board of Directors or advisory committees; GRAIL: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Cepheid: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Oregon Health & Science University: Patents & Royalties; ALLCRON: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Equity Ownership, Membership on an entity9s Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity9s Board of Directors or advisory committees; Aileron Therapeutics: Consultancy; Monojul: Consultancy; Beta Cat: Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy; Patient True Talk: Consultancy; Leukemia & Lymphoma Society: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity9s Board of Directors or advisory committees; Millipore: Patents & Royalties. Gotlib:Incyte: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Research Funding; Kartos: Consultancy; Deciphera: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Blueprint Medicines: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Promedior: Research Funding. Oh:Gilead: Research Funding; CTI Biopharma: Research Funding; Incyte: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Janssen: Research Funding. Tyner:Vivid Biosciences: Membership on an entity9s Board of Directors or advisory committees; Janssen: Research Funding; Array: Research Funding; AstraZeneca: Research Funding; Incyte: Research Funding; Aptose: Research Funding; Genentech: Research Funding; Takeda: Research Funding; Constellation: Research Funding; Gilead: Research Funding.