Kendra Sweet, MD, an assistant member of the Department of Malignant Hematology at Moffitt Cancer Center, as well as an assistant professor in the Department of Oncologic Sciences at University of South Florida Morsani College of Medicine, discusses key findings from the OPTIC trial with ponatinib (Iclusig) in chronic myeloid leukemia (CML).

the interim analysis of the randomized phase 2 OPTIC trial

, which were presented during the 2020 ASH Annual Meeting & Exposition, showed high response rates with good survival outcomes in patients with CML who progressed on prior second-generation TKIs. Moreover, the study evaluated various doses of ponatinib. Patients were started at 45 mg of daily ponatinib, which was decreased to 15 mg daily in the presence of a response. The data suggest that patients require a 45-mg starting dose of ponatinib, Sweet explains. Additionally, the safety results confirmed that toxicity was significantly improved with the 15-mg dose compared with the 45-mg dose. 

Another key takeaway was that patients with 

 mutations, who are known to respond well to ponatinib, may benefit from earlier integration of the agent. The survival advantage may be because these patients receive fewer prior lines of therapy compared with patients who do not harbor 

 mutations and receive additional second-generation TKIs.

Videos

Kendra Sweet, MD, discusses key findings from the OPTIC trial with ponatinib in chronic myeloid leukemia.  



Dr. Sweet on Key Findings From the OPTIC Trial With Ponatinib in CML 

Kendra Sweet, MD, an assistant member of the Department of Malignant Hematology at Moffitt Cancer Center, as well as an assistant professor in the Department of Oncologic Sciences at University of South Florida Morsani College of Medicine, discusses efforts made to mitigate toxicities associated with ponatinib (Iclusig) in patients with chronic myeloid leukemia (CML).

Ponatinib was the subject of controversy when it was temporarily pulled from the market due to significant arterial occlusive events observed in patients who were receiving treatment in the PACE trial, according to Sweet. Although this warranted further investigation of the agent, Sweet notes that much has been learned in the years following the trial. If what is currently known about the drug and its adverse effects (AEs) were known during the course of the PACE trial, Sweet says the results may have been different.

After utilizing ponatinib in practice over the past 7 years, Sweet shares that she has not observed the level of toxicities that had been reported in the trial; this is likely due to more widespread knowledge of these AEs and efforts are being made to mitigate these toxicities up front. Some techniques to reduce the risk of these AEs include the utilization of cardioprotective measures and referring patients to a cardiologist up front, Sweet concludes.

Kendra Sweet, MD, discusses efforts made to mitigate toxicities associated with ponatinib in patients with chronic myeloid leukemia.



Dr. Sweet on the Awareness and Mitigation of AEs Associated With Ponatinib in CML

Kendra Sweet, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, assistant professor, Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, discusses treatment selection with TKIs in chronic myeloid leukemia (CML).

Currently, the TKIs imatinib (Gleevec), nilotinib (Tasigna), dasatinib (Sprycel), and bosutinib (Bosulif) are approved for the frontline treatment of patients with CML, says Sweet. Additionally, the third-generation TKI ponatinib (Iclusig) is approved for later-line use, Sweet explains.

In the frontline setting, treatment selection is largely dependent on physician preference, patient comorbidities, the safety profile of the drug, and insurance, says Sweet. In most instances, Sweet will select imatinib for patients with newly diagnosed CML who have low Sokal scores. Conversely, one of the second-generation TKIs may be preferable for patients with intermediate- or high-risk Sokal scores, Sweet says. 

Second- and later-line treatment selection is based on patient comorbidities, the reason for stopping first-line therapy, and mutational profile, concludes Sweet.

Kendra Sweet, MD, discusses treatment selection with TKIs in chronic myeloid leukemia.  



Dr. Sweet on Treatment Selection With TKIs in CML 

Kendra Sweet, MD, an assistant member in the Department of Malignant Hematology at Moffitt Cancer Center, discusses discontinuation of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML).

Due to the success of TKIs in the treatment landscape of CML, investigators have been working toward a regimen that safely discontinues therapy in patients. Data over the last decade have supported the discontinuation of TKIs, and the high cure rate of patients with CML lends to the idea of stopping therapy to spare patients from unnecessary toxicities.

TKI discontinuation was first tested in 100 patients who were being treated with imatinib (Gleevec) in the Stop Imatinib (STIM) trial in 2007. The largest trial of TKI discontinuation to date is the EURO-SKI trial. This trial included 755 patients who used a TKI for at least 3 years and had a deep molecular response for at least 1 year. After treatment, molecular relapse-free survival was 61% at 6 months and 50% at 24 months.

Kendra Sweet, MD, an assistant member in the Department of Malignant Hematology at Moffitt Cancer Center, discusses discontinuation of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia.
 

Kendra Sweet, MD

Articles

Dr. Sweet on Key Findings From the OPTIC Trial With Ponatinib in CML

Dr. Sweet on the Awareness and Mitigation of AEs Associated With Ponatinib in CML

Dr. Sweet on Treatment Selection With TKIs in CML

Dr. Sweet Discusses TKI Discontinuation in CML