Jorge Cortes, MD, is director of the Georgia Cancer Center at Augusta University.

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.

Videos

Jorge E. Cortes, MD, discusses important questions in acute lymphoblastic leukemia to address, such as improved understanding of the role of allogenic stem cell transplant and the use of tyrosine kinase inhibitor combinations. 

Dr. Cortes on Better Understanding Areas of Interest in ALL

Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University, discusses emerging therapies in chronic myeloid leukemia (CML).

Research efforts are underway to develop novel therapies for patients with CML, Cortes says. For example, several new TKIs are emerging in CML, including the STAMP inhibitor asciminib (ABL001), Cortes explains. A new drug application (NDA) seeking the approval of asciminib for the treatment of patients with CML received a priority review designation from the FDA on August 25, 2021. The NDA is supported by data from the phase 3 ASCEMBL trial (NCT03106779), in which asciminib demonstrated a 24-week major molecular response rate of 25.5% vs 13.2% with bosutinib (Bosulif) in patients with Philadelphia chromosome–positive CML in chronic phase who received at least 2 prior TKIs. 

Additionally, other novel agents, including the BCR-ABL TKIs vodobatinib (K0706), HQP1351, and PF-114, have demonstrated early efficacy signals in CML and are under further investigation in phase 2 studies, Cortes concludes.

Jorge E. Cortes, MD, discusses emerging therapies in chronic myeloid leukemia. 



Dr. Cortes on Emerging Therapies in CML 

Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University, shares advice for navigating among first- and second-generation TKIs in the frontline treatment of patients with chronic myeloid leukemia (CML).

Currently, 4 drugs are approved by the FDA for the frontline treatment of patients with CML: the first-generation TKI imatinib (Gleevec), as well as 3 second-generation TKIs, which include dasatinib (Sprycel), erlotinib (Tarceva), and bosutinib (Bosulif), according to Cortes. When deciding on a treatment strategy, the first consideration should be whether a second-generation TKI should be used or imatinib is a more appropriate choice, Cortes says. 

Imatinib can have some advantages over second-generation TKIs in certain clinical scenarios, such as cost and less arterial occlusive events and pleural effusions. However, fewer patients achieve deep molecular responses with imatinib compared with the newer-generation TKIs, and responses do not tend to be as rapid. If patients do not have the goal of treatment-free remission or for those who have concerns regarding certain adverse effects, imatinib may be the stronger option to begin with, Cortes concludes.

Jorge E. Cortes, MD, shares advice for navigating among first- and second-generation TKIs in the frontline treatment of patients with chronic myeloid leukemia.

Dr. Cortes on Navigating Among Frontline TKIs in the CML Paradigm

Jorge E. Cortes, MD, director of the Georgia Cancer Center at Augusta University, discusses the benefits of ruxolitinib (Jakafi) in patients with myeloproliferative neoplasms (MPNs).

Ruxolitinib is a very effective option for patients with myelofibrosis, particularly those who are very symptomatic or have a large spleen, says Cortes. Ruxolitinib is not known to change the natural history of the disease nor does it completely eliminate it; thus, it only benefits the specific subsets of patients who are extremely symptomatic or have large spleens, Cortes reiterates. However, many patients fall under these categories, adds Cortes.

Additionally, ruxolitinib has received regulatory approval for patients with polycythemia vera and essential thrombocythemia who do not respond to initial lines of therapy. Limited therapeutic options are available in this space; thus, ruxolitinib serves as an important option for those patient populations, concludes Cortes.

Jorge E. Cortes, MD, discusses the benefits of ruxolitinib (Jakafi) in patients with myeloproliferative neoplasms.

Dr. Cortes on the Benefit of Ruxolitinib in MPNs

Jorge E. Cortes, MD, professor and deputy chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses the results of quizartinib in patients with relapsed/refractory acute myeloid leukemia (AML).

The phase III randomized controlled QUANTUM-R trial evaluated the safety and efficacy of the FLT3 inhibitor quizartinib in patients with relapsed/refractory 

-ITD—mutant AML. The first report from this trial was presented at the 2018 European Hematology Association Congress, showing that single-agent quizartinib significantly prolonged overall survival (OS). The median OS for patients treated with quizartinib was 27 weeks (95% CI, 23.1-31.3), and 20.4 weeks (95% CI, 17.3-23.7) for patients treated with salvage chemotherapy. Cortes says that the OS hazard ratio of quizartinib was relative to salvage chemotherapy at 0.76 (95% CI, 0.58-0.98; 

Additionally, the percentage of patients that are alive at 1 year is 26% in the quizartinib arm, and 20% in the control arm of salvage chemotherapy. Cortes says that with a statistically significant median OS, this trial is very positive for patients with 

Jorge E. Cortes, MD, professor and deputy chair, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses the results of quizartinib in patients with relapsed/refractory acute myeloid leukemia. 

Jorge Cortes, MD

Articles

Dr. Cortes on Better Understanding Areas of Interest in ALL

Dr. Cortes on Emerging Therapies in CML

Dr. Cortes on Navigating Among Frontline TKIs in the CML Paradigm

Dr. Cortes on the Benefit of Ruxolitinib in MPNs

Dr. Cortes on the Results of Quizartinib in Relapsed/Refractory AML