This is a synopsis of a Peer Exchange series featuring James K. McCloskey, MD, and Lori A. Leslie, MD, of John Theurer Cancer Center, Hackensack University Medical Center.

In this discussion, James K. McCloskey, MD, Chief of the Leukemia Division at the John Theurer Cancer Center, discusses recent data from ASH and potential impacts on leukemia management. Dr. McCloskey notes that leukemia encompasses a heterogeneous group of diseases including most myeloid malignancies, bone marrow failure syndromes, and acute lymphoblastic leukemia (ALL). Advances have differed between diseases like chronic myeloid leukemia (CML) and acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or myelofibrosis. However, a common theme is exploiting understanding of genetic drivers of these diseases to develop targeted molecular agents. Early clinical research showed efficacy of these agents in relapsed/refractory settings as single agents. Now, combination regimens and new molecular pathways are improving upfront outcomes, despite research challenges due to the rarity of molecular subtypes. Recent abstracts at ASH continue exploring applications of molecularly targeted agents to enable more precise, personalized leukemia treatment.

Specifically regarding CML, tyrosine kinase inhibitors (TKIs) like imatinib have greatly improved survival over the last 20 years. However, some patients develop resistance or intolerance leading to investigations of alternate TKIs like ponatinib. The OPTIC trial compared ponatinib to standard dose imatinib, demonstrating superior major molecular response (MMR) rates by 12 months for ponatinib, with manageable side effects. Alternatively, the PACE trial explored ascending doses of ponatinib for patients resistant or intolerant to prior TKIs. Lower ponatinib doses demonstrated clinical activity in these difficult-to-treat patients, enabling continuation of TKI therapy.

In ALL, introducing targeted agents like the CD3/CD19 bispecific antibody drug conjugate blinatumomab and CD3 BiTE immunotherapy tafasitamab to chemotherapy backbones have led to improved remission rates and survival, especially in high-risk and relapsed/refractory patients. The comprehensive PhALLCON study is further exploring combinations with these immunotherapies to boost responses. The selective BET protein inhibitor INCB057643 also showed promise in early phase studies for relapsed/refractory patients, warranting further investigation.

Overall, these varied therapeutic approaches represent the wider paradigm shift toward molecularly targeted and immunotherapy-based combinations to drive more durable remissions, longer survival, and eventual cures for leukemia patients.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.