Novel Therapies for De Novo or Relapsed/Refractory AML with TP53 Mutations : A Glimmer of Hope (ASH 2022)
We screened 2300 articles and included articles citing novel therapies such as "Venetoclax" (VEN), "Hypomethylating agents (HMA), 5-azacytidine (5-AZA), "checkpoint inhibitors, and "MDM2 inhibitors"...VEN with low-dose cytarabine (LDAC) had 27% CR, whereas LDAC alone had 7%.Checkpoint inhibitors such as nivolumab showed favorable responses, as in the phase II study of nivolumab in combination with azacitidine in relapsed/refractory (R/R) AML; it demonstrated acceptable toxicity and an overall response rate (ORR) of 33%. However, increased response rates were seen in HMA-naïve patients.HDAC inhibitors : In two phase II trials incorporating AZA vs AZA + entinostat, the CR was 46% vs 44%..., the combination therapy of Decitabine and valproic acid showed CR of 34% and mOS of 11.9 months...described a remission of 82% with a median OS of 14.7 months in Eprenetapopt + 5-AZA. The most common grade ≥ 3 hematological adverse events were anemia, neutropenia, thrombocytopenia, and leukopenia.MDM2 Inhibitors : In the MIRROS trial, a phase III trial incorporating idasanutlin + cytarabine + placebo + cytarabine in R/R AML; 436 patients were enrolled...Still a daunting challenge, a combination of these therapies may ultimately be necessary to obtain adequate and sustained responses. Participation in clinical trials for all newly diagnosed AML patients should be encouraged to promote the development of innovative therapeutics.