Developments in the treatment of acute myeloid leukemia (AML): Despite recent progress in AML in older patients, outcomes remain poor. A phase 2 study (Abstract 25) of venetoclax added to Cladribine + Low Dose AraC (LDAC) alternating with 5-azacytidine demonstrated high rates of MRD negative CRs and excellent tolerability in older adults with newly diagnosed AML: the 1-year overall survival (OS) was 70%, and 1-year recurrence-free survival (RFS) was 66%. Importantly, the regimen was well tolerated among the older patient population with an eight-week mortality of only 4%. The venetoclax plus azacitidine combination reported a significant improvement in median OS n treatment-naïve patients with FLT3-mutant AML (Abstract 1904) who were unfit to receive intensive chemotherapy, highlighting the efficacy of bcl-2 inhibition in combination with hypomethylating agents across the spectrum of AML.
Next steps in myelofibrosis treatment: Ruxolitinib, a JAK inhibitor, has been a major advance in managing spleen size and symptoms in myelofibrosis but does not appear to alter the natural history of the disease. Therefore, JAK inhibitors are being combined with other agents and newer drugs are being investigated in hopes of improving current treatment outcomes. ASH 2020 saw early promising results with the addition of navitoclax to ruxolitinib (Abstract 52) in patients with relapsed/refractory myelofibrosis, as well as a favorable overall survival with imetelstat, a telomerase inhibitor in the 2nd line setting (Abstract 53). In the front line setting, the addition of CPI-0610, a bromodomain protein inhibitor, to ruxolitinib appears safe and effective (Abstract 55) whereas momelotinib, a JAK inhibitor, demonstrated robust overall survival and sustained efficacy outcomes in the first line and previously JAK inhibitor treated patients (Abstract 54).
A potential treatment alternative for chronic myeloid leukemia (CML): While tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML, a minority of patients may not respond to currently available agents. The efficacy and safety results from the ASCEMBL trial (Abstract LBA-4), an open label phase 3 study of asciminib, a first-in-class STAMP inhibitor, vs bosutinib in patients with chronic phase CML previously treated with two or more TKIs demonstrated that asciminib significantly improved the rate of major molecular response at 24 weeks compared with bosutinib, meeting the study’s primary objective.
Combination therapies for myelodysplastic syndromes (MDS): It is crucial to build on the success of hypomethylating agents in MDS, especially to improve outcomes in higher risk patients. At ASH 2020 Pevonedistat, a first-in-class NEDD8-activating enzyme (NAE) inhibitor, in combination with azacytidine achieved impressive CR rate of 52%, ORR of 79%, and OS of 24.2 months in patients with higher risk MDS (Abstract 653). The venetoclax and azacytidine combination continues to impress in MDS achieving an ORR of 41% and median OS of 12 months in relapsed disease (Abstract 3109) and an ORR of 79% with median OS of 27.5 months when used frontline (Abstract 656).