Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Targeted Therapy For Adults Diagnosed With Acute Myeloid Leukemia
Marie-Eve Bordeleau, et al.
The Abstract concludes: Using an unbiased pharmacogenomic approach, we identified ABT-199, a compound with the potential to eradicate NPM1c+ AML, which has already been tested in a phase 2 clinical trial for AML. Our results shed light on determinants of ABT-199 sensitivity which could readily impact AML therapy by providing a rationale for prioritizing patients with NPM1, RAD21, IDH1 and/or IDH2 mutations for ABT-199 AML trials. Our results also uncover potential mechanisms of resistance to ABT-199, providing grounds to design combination therapies to overcome ABT-199 chemoresistance.
Andrew Wei, MD, et al.
The Abstract concludes: Venetoclax in combination with LDAC led to rapid, deep, and durable responses in patients with AML who were ineligible for intensive chemotherapy. Venetoclax plus LDAC demonstrated an improved CR rate (26% vs. 8%), CR/CRi rate (54% vs. 11%) and median overall survival (10 months vs. 5 months) compared to the historical rates with LDAC alone. Furthermore, a majority of patients achieved transfusion independence during venetoclax therapy. Strong and moderate CYP3A inhibitors, including azole antifungals, were safely coadministered with appropriate venetoclax dose adjustments. These results demonstrate that venetoclax, in combination with LDAC, represents an effective therapeutic option for patients with AML who are not suitable for standard induction therapy.
Daniel A Pollyea, et al.
The Abstract concludes: Venetoclax in combination with either azacitidine or decitabine led to high rates of rapid and deep responses that were durable in patients with AML ineligible for standard induction chemotherapy. A majority of patients who were transfusion dependent at baseline achieved transfusion independence after initiating venetoclax therapy. These results suggest that venetoclax, in combination with hypomethylating agents, may provide a potent therapeutic option for patients with AML who are not eligible for intensive chemotherapy.
Abhishek Maiti, et al.
The Abstract concludes: The DEC10-VEN regimen had an acceptable safety profile and excellent response rates with CR/CRi of 92% in ND AML, 71% in sAML, and 44% in R/R AML with MRD- in 52% of ND AML, 40% of sAML and 50% of R/R AML. Trial is continuing to accrue (NCT03404193).
Eytan M. Stein, et al.
The Abstract concludes: This trial demonstrates the significant clinical activity of enasidenib in previously untreated IDH2 mutated AML patients who do not choose to receive intensive chemotherapy. Enasidenib in this trial was associated with a low early death rate and an acceptable toxicity profile. These results justify further exploration of single agent enasidenib in newly diagnosed AML and of novel combination strategies building upon the efficacy of enasidenib in newly diagnosed AML patients ≥ 60.
288 Incidence of Differentiation Syndrome with Ivosidenib (IVO) and Enasidenib (ENA) for Treatment of Patients with Relapsed or Refractory (R/R) Isocitrate Dehydrogenase (IDH)1- or IDH2-Mutated Acute Myeloid Leukemia (AML): A Systematic Analysis By the U.S. Food and Drug Administration (FDA)
Kelly J. Norsworthy, et al.
The Abstract concludes: An algorithmic analysis of AEs and laboratory tests using the Montesinos criteria led to recognition of additional cases of DS not identified by investigators for patients treated with IDH inhibitors IVO and ENA. DS occurred in roughly one in five patients treated with both drugs and grade 3 or higher adverse reactions were present in over half of cases. Leukocytosis was not always present. Patients with DS had numerically lower response rates, but firm conclusions regarding the impact on response cannot be inferred based on this post-hoc subgroup analysis. Increased recognition of signs and symptoms of DS through the framework of the Montesinos criteria may lead to earlier diagnosis and treatment, which may decrease severe complications and mortality. Furthermore, integration of the algorithmic approach into clinical trials of differentiating therapies may help to prospectively monitor the incidence and severity of DS.