Panelists discuss how when choosing between asciminib and ponatinib for chronic myeloid leukemia treatment, key considerations include the patient’s mutation status, prior tyrosine kinase inhibitor therapy response, cardiovascular risk factors and comorbidities, and the differing safety profiles of the 2 drugs, with ponatinib generally having more cardiovascular concerns but broader mutation coverage vs asciminib’s more favorable tolerability but more specific targeting of BCR::ABL1.

Beyond T315I mutations: When to Consider Ponatinib or Asciminib in CML Second-Line Treatment

Video content above is prompted by the following:

What do you consider when making a treatment decision between asciminib and ponatinib?

What disease-specific factors do you consider?

Videos

Panelists discuss how for patients with chronic myeloid leukemia who develop the T315I mutation, ponatinib and asciminib have demonstrated efficacy in the PACE and ASCEMBL trials, respectively, with ponatinib showing a major cytogenetic response rate in patients with T315I mutation and asciminib demonstrating superior major molecular response vs bosutinib.

Managing T315I Mutations in CML: Second Line Treatment Options - Ponatinib & Asciminib

We know that a T315I mutation in the kinase domain confers resistance to our frontline therapies for chronic myeloid leukemia (bosutinib, dasatinib, imatinib, and nilotinib). What therapies are available for patients who develop this mutation while taking their first-line tyrosine kinase inhibitor?

Please briefly review the ASCEMBL and PACE trials and key outcomes.

Panelists discuss how mutation analysis should be considered when treatment fails to meet milestones or patients show loss of response to tyrosine kinase inhibitor (TKI) therapy, as this information helps determine whether to continue the current TKI or switch to an alternative agent based on the specific resistance profile.

Interpreting Milestones: Prioritizing the Patient Picture

If milestones are not reached, how do you determine whether to switch therapy or continue the current tyrosine kinase inhibitor?

 kinase domain mutation result for analysis?

Panelists discuss how in standard clinical practice, response to first-line tyrosine kinase inhibitor therapy is monitored through regular molecular testing of BCR::ABL1 transcript levels, with key evaluations to assess whether patients achieve target milestone responses that predict long-term outcomes.

Evaluating Early Treatment Response in CML: Expert Insights on Monitoring

The NCCN guidelines had recent updates for evaluating early treatment response milestones. In a patient on first-line tyrosine kinase inhibitor, how do you monitor and evaluate response in your clinical practice?

Stephen A. Strickland, MD, MSCI, director of leukemia research, Sarah Cannon Transplant & Cellular Therapy Network, discusses a step-by-step approach for the diagnosis and workup of esophageal squamous cell carcinoma (ESCC).

The preferred diagnostic approach for ESCC is like that of esophageal adenocarcinoma (EAG), Strickland begins. Patients with ESCC are usually symptomatic before presenting at the clinic and have therefore undergone basic cancer workup. However, de novo patients will require a thorough history of present illness in addition to a workup, Strickland says. Common adverse events (AEs) in ESCC include dysphasia and associated weight loss. It is important to understand the severity of this AE and its effects on weight and caloric intake, Strickland advises.

After obtaining information on a patient’s symptom burden, a mitigation approach like nasogastric intubation may be appropriate, Strickland continues. An esophagogastroduodenoscopy (EGD) should then be performed to visualize the location of the tumor mass. Tumor biology and resectability can differ according to anatomic location, so obtaining this information can inform subsequent treatment approaches. Performing a biopsy can also lead to better pathological tissue diagnosis, he says.

Biomarker analysis is a critical next step in ESCC diagnosis, Strickland states. Several key biomarkers differentiate ESCC from EAG. Although common biomarkers like PD-L1, mismatch repair (MMR) status and HER2 status are less specific to this disease type, they are still important to test for to obtain a full picture of the disease, Strickland notes.

A PET-CT scan should then be conducted to allow for staging, Strickland recommends. This imaging modality provides information on F-fluorodeoxyglucose (FDG) avidity and assesses distant metastasis in the chest, abdomen, and pelvis, he explains.

Importantly, NCCN guidelines do recommend EGD followed by endoscopic ultrasound, Strickland notes. This can help assess the depth of invasion and suspicion level for involved regional lymph nodes. However, surgical case studies have shown that patients with clinical dysphasia have angreatly increased likelihood of having involved local regional lymph nodes. Therefore, these patients may not require an endoscopic ultrasound, Strickland concludes.

Stephen A. Strickland, MD, MSCI, discusses a step-by-step approach for the diagnosis and workup of esophageal squamous cell carcinoma.

Stephen A. Strickland, MD, MSCI

Articles

Beyond T315I mutations: When to Consider Ponatinib or Asciminib in CML Second-Line Treatment

Managing T315I Mutations in CML: Second Line Treatment Options - Ponatinib & Asciminib

Interpreting Milestones: Prioritizing the Patient Picture

Evaluating Early Treatment Response in CML: Expert Insights on Monitoring

Dr. Strickland on the Diagnosis of ESCC