Dr. Cortes on Better Understanding Areas of Interest in ALL

Jorge E. Cortes, director, Georgia Cancer Center, Augusta University, discusses important questions in acute lymphoblastic leukemia (ALL) to address, such as improved understanding of the role of allogenic stem cell transplant (ASCT) and the use of tyrosine kinase inhibitor (TKI) combinations. 

ASCT has traditionally been the standard-of-care treatment for patients with ALL, Cortes begins. However, the recent development of more effective therapeutic agents may indicate a reduced need for ASCT in select patients. Accordingly, the identification of patients who would gain the most benefit from ASCT is a key topic of interest for continued research and discussion, Cortes states. The future use of ASCT will likely be determined according to minimal residual disease (MRD) status. For example, patients who have high MRD-positivity levels may still require transplant, he says. 

Next, the best use of TKIs in AML is a topic of considerable interest, Cortes continues. Data on the use of ponatinib (Iclusig) compared with imatinib mesylate (Gleevec) has been encouraging. Moreover, historical data indicate that ponatinib may also show superiority when compared with other kinase inhibitors, such as dasatinib (Sprycel), Cortes explains. Although there is currently no direct comparison of these agents, this regimen may still be preferable to dasantinib in most patients, Cortes says. Additionally, ponantib administered in combination with chemotherapy is not an option for patients who are ineligible for chemotherapy, he notes.

Several novel strategies or modifications to standard TKI approaches are being investigated for this patient population, Cortes says. These include the potential substitution of monoclonal antibodies for chemotherapy. Research on the use of cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (Adriamycin), and dexamethasone (mini-hyper-CVAD) has been particularly promising, Cortes details. These strategies will allow more patients to experience benefit from TKIs while eliminating intensive chemotherapy completely, he says.

Ultimately, chemotherapy-based or monoclonal antibody-based TKI regimens will both have a role in the future treatment of patients with ALL, and their use will depend on individual patient factors, Cortes concludes. 

Editor’s Note: Dr. Cortes reports serving as a consultant or in an advisory role and receiving research funding from Novartis AG, Takeda, Pfizer, and Sun Pharmaceuticals.