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Encouraging results of novel triplet combination for AML

Presented by
Dr Patrick Reville, MD Anderson Cancer Center, TX, USA
ASH 2021
Phase 2
A regimen of cladribine plus low-dose cytarabine plus venetoclax alternated with 5-azacitidine plus venetoclax showed encouraging efficacy in patients with newly diagnosed acute myeloid leukaemia (AML). Moreover, the displayed efficacy was consistent across European LeukemiaNet (ELN) risk groups and patients ‚Č•70 years of age. The results of this phase 2 trial need to be confirmed in larger trials but are really very promising [1].

Dr Patrick Reville (MD Anderson Cancer Center, TX, USA) and colleagues included patients with newly diagnosed AML of ‚Č•60 years of age to evaluate a regimen of cladribine plus low-dose cytarabine plus venetoclax, alternating with 5-azacitidine plus venetoclax.

Participants (n=60) followed 1 or 2 cycles (28 days per cycle) of induction therapy (cladribine, 5 mg/m2, once daily on day 1 to 5; cytarabine, 20 mg, twice daily on day 1 to 10; venetoclax, 100 mg, 200 mg, or 400 mg [dose depending on the use of CYP3A4 inhibitors], for 21 days). Subsequently, they received 2 cycles of 5-azacitidine (75 mg/m2) on days 1 to 7 and venetoclax on the first 7 to 14 days, depending on measurable residual disease and tolerability. Hereafter, 2 cycles of maintenance cladribine, low-dose cytarabine, and venetoclax were alternated with 2 cycles of 5-azacitidine plus venetoclax, up to 18 cycles. The primary outcome was a composite complete response (CR/CRi) rate.

In total, 93% of the patients achieved the composite CR rate, with 80% of the patients reaching CR and 13% of the patients achieving CRi. Early mortality rates were low, with 1 deceased patient after 4 weeks and 4 mortalities after 8 weeks. The observed response rate was consistent across subgroups: ELN Adverse (96%), Adverse/Complex Cytogenetics (89%), FLT3-mutated (88%), MLL-rearranged (75%), and secondary AML (93%). The disease-free survival (DFS) rate was 60% after 24 months; median DFS was not yet reached (see Figure). Similarly, median event-free survival and median overall survival were not yet reached after 24 months, with rates of 56% and 64%, respectively.

Figure: 24-month disease-free survival [1]

DFS, disease-free survival; NE, not estimable; SE, standard error.

The rate of serious adverse events was low. Febrile neutropenia (55%) and pneumonia (23%) were the most common grade 3 events. Tumour lysis syndrome was observed in 1 patient.

  1. Reville PK, et al. Phase II Study of Venetoclax Added to Cladribine (CLAD) and Low Dose AraC (LDAC) Alternating with 5-Azacytidine (AZA) in Older and Unfit Patients with Newly Diagnosed Acute Myeloid Leukemia (AML). Abstract 367, ASH 2021 Annual Meeting, 11‚Äď14 December.


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