Acute Myeloid Leukemia

Background : The addition of the BCL-2 inhibitor venetoclax to HMAs improves survival compared to HMAs alone. This study was conducted to assess the response rates after the addition of venetoclax to the lowintensity cladribine (CLAD) + low dose AraC (LDAC) backbone for this group of patients.

Method : The Phase II clinical trial was conducted in adults older than 60 years or unfit patients with newly diagnosed AML. Cladribine 5 mg/m2 IV over 30 minutes was administered on days 1–5 followed by AraC 20 mg subcutaneously twice a day on days 1–10. Maintenance consisted of two cycles of cladribine 5mg/m2 IV on days 1–3 + AraC 20 mg subcutaneously twice a day on days 1–10 alternating with two cycles of azacitidine 75 mg/m2 on days 1–7, for up to 18 cycles. Venetoclax 400 mg was administered on days 1–21 with dose adjustments for CYP3A inhibitors

Results : CLAD/LDAC plus venetoclax alternating with azacitidine plus venetoclax was found to be effective as a lower-intensity regimen in older patients and was well tolerated producing durable MRD negative remission and meaningful blood count recovery. The rates of relapse-free survival and OS were good in a oneyear follow-up

Background : The ongoing, phase 3, open-label, randomized trial is being conducted to investigate the efficacy of gilteritinib + azacitidine vs. azacitidine alone in adults with FLT3 mutated AML ineligible for intensive induction chemotherapy.

Method : The trial is being conducted in patients with FLT3 mutated AML who are either ≥65 years old and ineligible for intensive induction chemotherapy or are 18–64 years old with specific comorbidities making them ineligible for intensive induction chemotherapy.

Results : No new safety signals have been observed in this ongoing trial and gilteritinib 120 mg daily + azacitidine has a complete remission rate of 67%.

Background :Around 30% of newly diagnosed (ND) unfit patients with AML are retinoic acid receptor alpha-positive (RARA+). RARA + AML is correlated with venetoclax resistance, which can lead to a poor prognosis. The combination of SY-1425 and azacitidine is currently being evaluated in the RARA + ND unfit patients with AML. Initial data of SY-1425 + azacitidine show that a high response rate and rapid onset of responses can be obtained with this combination in the RARA+ ND unfit AML cohort

Method : For this study, both RARA + and retinoic acid receptor alpha-negative (RARA-) ND unfit patients with AML were enrolled and given 75 mg/m2 of azacitidine in vitro or subcutaneously daily on days 1–7. SY1425 (6 mg/m2 /day) was given twice daily on days 8–28 of each 28-day cycle.

Results :Data obtained suggest that the combination of SY1425 and azacitidine was generally well-tolerated when compared to a single agent. Moreover, a higher complete response rate and rapid time to initial response were observed with this combination.

Background :SY-1425 along with azacitidine demonstrates a high CR rate and a rapid onset of response in RARA + ND unfit patients with AML. Initial data from the phase 2 trial studying the combination of RARA + relapsed/refractory (R/R) cohort are presented.

Method : RARA+ R/R patients with AML were given 75 mg/m2 of azacitidine (intravenous/subcutaneous) daily for days 1–7 followed by SY-1425 (6 mg/m2 /day) twice daily in divided doses on days 8– 28 for each 28-day cycle.

Results :SY-1425 + azacitidine was observed to be welltolerated in the pretreated R/R AML population. The initial result of OS indicates that SY-1425 + azacitidine is a potentially novel regimen for the treatment of RARA+ R/R AML.

Background :For patients with AML, it is important to preserve and measure perceptions of health-related quality of life (HRQoL) when evaluating new treatment regimens especially for those ineligible for intensive chemotherapy and with a poor prognosis. The HRQoL from two Phase 3 trials, Viale-A (NCT02993523) and Viale-C (NCT03069352) were evaluated in patients with AML receiving venetoclax with azacitidine (Viale-A) or LDAC (Viale-C).

Method : Viale-A and Viale-C trials were conducted in treatment-naive patients with AML, who were ≥18 years of age, and were ineligible to receive intensive chemotherapy. In Viale-A, patients were randomized 2:1 to receive venetoclax and azacitidine or placebo and azacitidine. In Viale-C, patients were randomized to receive venetoclax and LDAC or placebo and LDAC. Patient-reported outcomes data were collected on Day 1 of every 28-day cycle in both the trials and time to deterioration was also assessed.

Results :Results show a longer time to deterioration in patients who received venetoclax combinations compared azacitidine or LDAC monotherapy suggesting that venetoclax is associated with better HRQoL.