PF273 VENETOCLAX IN COMBINATION WITH LOW DOSE CYTARABINE AND/OR ACTINOMYCIN D IN REAL LIFE RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA PATIENTS
Authors: A. Zucenka, R. Pileckyte, V. Vaitekenaite, A. Surauciute, L. Griskevicius
Journal: HemaSphere (2019)

Background: Relapsed/refractory acute myeloid leukemia (R/R AML) patients remain a group with dismal prognosis and very few effective treatment options. Aims: To evaluate the safety and efficacy of Venetoclax (Ven) combined with low dose cytarabine (LDAraC) and/or Actinomycin D (ActD) in R/R AML patients. Methods: We performed a single institution retrospective analysis of Ven treated R/R AML / mixed phenotype acute leukemia (MPAL) patients. Treatment regimens consisted of Ven 600 mg p/o daily + Cytarabine 20 mg/m2 D1–10 (Ven/LDAraC), Ven 600 mg p/o daily + Actinomycin D 12.5 μg/kg D1–5 + Metformin 3 g p/o daily (Ven/ActD/Met) or Ven 600 mg p/o daily + Cytarabine 20 mg/m2 D1–10 + two, three or five doses of Actinomycin D 12.5 μg/kg during D1–5 (ACTIVE). Ven was initiated in a daily ramp-up dosing reaching 600 mg on the 6th day. Venetoclax was obtained through a compassionate use program for R/R AML patients (AbbVie). Results: 18 R/R AML and 1 MPAL patients were enrolled. 16/19 (84%) patients had previously received intensive chemotherapy and 7/19 (37%) had previously been allotransplanted. 7 patients received Ven/LDAraC, 2 patients received Ven/ActD/Met and 7 patients were treated with ACTIVE regimen. 2 patients received both Ven/LDAraC and Ven/ActD/Met, 1 patient was treated with both Ven/ActD/Met and ACTIVE. Patient characteristics and response results are summarized in Table 1. 12/19 (63%) patients responded (CR/CRi/MLFS) with 5 (56% of CR/CRi) patients achieving MRD negativity. The highest CR/CRi rate (5/8, 63%) was observed with ACTIVE treatment. 4 responders had previously relapsed after alloSCT and are currently in CR. 4 other responders were allotransplanted with 2 in ongoing CR (1 after reinduction). 5 of these eight patients received Ven/LDAraC ± donor lymphocyte infusion (DLI) maintenance post alloSCT. 4 patients were not candidates for alloSCT due to age or poor performance status and one responder remains in CR on Ven/LDAraC maintenance. Overall, a total of 5 relapses and 10 deaths were observed. Nine patients are currently alive with 7 remaining in CR (6 MRD negative). The median observation time was 3 months. The median EFS and OS was 4 and 6 months, respectively. At 6 months, 32% remain event-free and 46% are alive. The most common treatment related grade 3–4 adverse events were infectious complications (12/19, 63%): sepsis (5/19, 26%), pneumonia (5/19, 26%), catheter related infections (3/19, 16%) and febrile neutropenia (3/19, 16%)). Other non-infectious treatment related grade 3 adverse events were tumor lysis syndrome (3/19, 16%), mucositis (1/19, 5%) and hyperbilirubinemia (1/19, 5%). There were no Ven/LDAraC ± ActD related deaths.Summary/Conclusion: In R/R AML patients, Ven/LDAraC ± ActD showed high response rates with some patients becoming MRD negative. A number of responses are ongoing with maintenance treatment and DLI. Infectious complications were common, and the incidence of clinically relevant mucositis was low.