, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, we had the pleasure of speaking with Ashkan Emadi, MD, PhD. Dr Emadi is the chair of the Department of Medical Oncology and the Alexander Bland Osborn Endowed Chair and Distinguished Professor of Medical Oncology at the West Virginia University (WVU) School of Medicine; as well as physician-in-chief of Medical Oncology and the associate center director for Translational Research at the WVU Cancer Institute in Morgantown.

In our exclusive interview, Dr Emadi discussed how the combination of venetoclax (Venclexta) plus pegcrisantaspase induced complete remissions in heavily pretreated patients with relapsed/refractory acute myeloid leukemia, including in those with prior exposure to venetoclax. He detailed data on the combination from a phase 1 study published in 

, the significance of the findings, and more.

That’s all we have for today! Thank you for listening to this episode of 

. Check back on Mondays and Thursdays for exclusive interviews with leading experts in the oncology field.

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Podcasts

Ashkan Emadi, MD, PhD, discusses how the combination of venetoclax  plus pegcrisantaspase induced complete remissions in heavily pretreated patients with relapsed/refractory acute myeloid leukemia.

Venetoclax Plus Pegcrisantaspase Induces Remissions in R/R AML: With Ashkan Emadi, MD, PhD

Dr Emadi on Initial Responses With Venetoclax Plus PegC in R/R AML

"Interestingly, 1 out of every 3 patients who had prior exposure to venetoclax and were treated with [venetoclax plus PegC] achieved a complete remission with a partial or incomplete count recovery. In a sense, this shows that…this combination's mechanism interferes with the mRNA cap binding to the ribosome, resulting in the decrease of the MCL1, which can [resensitize patients to] venetoclax."

Ashkan Emadi, MD, PhD, chair, Department of Medical Oncology; Alexander Bland Osborn Endowed Chair, Distinguished Professor of Medical Oncology, West Virginia University (WVU) School of Medicine; physician-in-chief, Medical Oncology; associate center director, Translational Research, WVU Cancer Institute, discusses differential responses achieved with venetoclax (Venclexta) plus pegcrisantaspase (PegC) for patients with relapsed/refractory acute myeloid leukemia (AML), including those with prior venetoclax exposure, according to findings from a phase 1 study (NCT04666649).

In this study, patients with AML received at least 1 dose of PegC in combination with venetoclax. Efficacy-evaluable patients completed at least 1 cycle of the combination therapy. Notably, the trial permitted the enrollment of patients with prior venetoclax exposure to reflect real-world clinical practice; these patients comprised 67% of the study population.

Results showed that the overall composite complete remission (CR) rate with partial or incomplete count recovery in patients with prior venetoclax exposure was 33%, Emadi reports. This suggests that the regimen’s mechanism of interfering with mRNA cap binding to the ribosome may resensitize venetoclax-resistant leukemic cells, he says. Interestingly, responses correlated with alterations in proteins involved in mRNA translation, Emadi adds. Patients with 

 mutations demonstrated a composite CR rate of 100%, indicating that the combination therapy effectively targets a key vulnerability in these cells.

Highlighting the biological rationale for these findings, Emadi explains that AML cells, particularly those with 

 mutations, exhibit dependence on ribosomal biogenesis and mRNA translation for survival. By targeting mRNA capping at the ribosome, the combination exploits this dependency, hitting a critical weakness in these leukemic cells, he states.

In a planned phase 2 study, Emadi and colleagues plan to evaluate patients with both 

-mutated and wild-type AML; separate analyses will be conducted to stratify outcomes based on 

Safety analysis revealed that the most common treatment-related adverse events of any grade were antithrombin III decrease (52%), elevated transaminases (36%-48%), fatigue (28%), and hypofibrinogenemia (24%). Importantly, no thromboembolic or hemorrhagic events, nor clinical pancreatitis, were observed.

These findings suggest that venetoclax plus PegC could offer a novel therapeutic approach for patients with AML, particularly those with 

mutations or those who have relapsed after prior venetoclax therapy, Emadi concludes.

Videos

Ashkan Emadi, MD, PhD, discusses responses achieved with venetoclax plus PegC in patients with venetoclax-pretreated, relapsed/refractory AML.

Ashkan Emadi, MD, PhD

Articles

Venetoclax Plus Pegcrisantaspase Induces Remissions in R/R AML: With Ashkan Emadi, MD, PhD

Dr Emadi on Initial Responses With Venetoclax Plus PegC in R/R AML