PB1746 PRACINOSTAT PLUS AZACITIDINE IN OLDER PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML): A CASE REPORT FROM A PHASE 2 STUDY
Authors: A. Yacoub, S. Mappa
Journal: HemaSphere (2019)

Background: Older patients with newly diagnosed AML have limited treatment options and poor prognosis. They usually have poor tolerance and low response rates to intensive chemotherapy, poor candidacy for allogeneic stem cell transplant, and modest responses with the commonly used low‐intensity palliative regimens. A recent phase 2 study has shown that the pan‐histone deacetylase inhibitor pracinostat combined with azacitidine was well tolerated and active in older patients unfit for intensive chemotherapy, leading to a complete remission (CR) rate of 42% and median overall survival of 19.1 months (Garcia‐Manero G. Blood Advances , 2019). Aims: To describe novel and rare findings in an older patient with AML who received treatment with pracinostat and azacitidine. Methods: The patient is a 67‐year‐old man who presented with AML and severe symptomatic anemia, resulting in unstable angina and non–ST‐elevation myocardial infarction. Due to comorbidities that included advanced chronic obstructive pulmonary disease and symptomatic angina, the patient was deemed unfit for induction chemotherapy or allogeneic stem cell transplantation. The patient was enrolled in a phase 2 open‐label, single‐arm study (NCT01912274) assessing the safety and efficacy of pracinostat combined with azacitidine in older (≥65 years) patients with newly diagnosed de novo, secondary, or therapy‐related AML ineligible for induction chemotherapy. The patient received oral pracinostat 60 mg/day, 3 days/week, for 3 consecutive weeks plus azacitidine 75 mg/m 2 daily for 7 days in a 28‐day cycle. Bone marrow (BM) biopsies were performed at screening, cycles 2, 4, and 6, and every 3 cycles thereafter until CR or as clinically indicated. A peripheral blood sample was also obtained from the patient at baseline, to determine the presence of any possible mutations. Results: The mutation analysis revealed that the patient presented with 5 mutations: CBL p.P433L variant allele frequency (VAF) 0.386243, fms‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD) VAF 0.2738, nucleophosmin (NPM1) p. L287fs 0.2167, RAD21 p. R172fs 0.2632, and Wilms tumor protein 1 (WT1) p.V379fs 0.3089. The patient has received over 48 cycles of pracinostat combined with azacitidine and remains on treatment to date (&gt;49 months). After the first 2 treatment cycles, the patient achieved a BM partial remission, with CR being attained by cycle 6 and maintained for over 43 months. Due to treatment‐related neutropenia, the administration of cycles 5, 48, and 49 was delayed by 1, 2, and 1.5 weeks, respectively. Due to treatment‐related pneumonia, the administration of cycle 43 was delayed for approximately 7 weeks. He remained on therapy with no treatment‐related toxicities, and significant improvement in his performance status and quality of life. Summary/Conclusion: This case demonstrates the potential of pracinostat in combination with azacitidine to be a long‐term effective and safe regimen for older patients with newly diagnosed AML, achieving long‐lasting CR beyond what is expected with single‐agent azacitidine. These results bear increased relevance for patients with an unfavorable baseline mutation status and a consequent particularly poor prognosis.