Wendy Stock, MD, is the Anjuli Seth Nayak Professor of Medicine at UChicago Medicine and co-leader of the Clinical and Experimental Therapeutics research program at the University of Chicago Medicine Comprehensive Cancer Center

Dr Stock on the Multifaceted Role of Molecular Testing in Ph+ ALL

“In Ph-positive ALL, unlike in CML, many patients experience an early emergence of resistance mutations, particularly the [

] T315Imutation. This is why, in the current [treatment] era, we’ve started to incorporate the third-generation TKI ponatinib up front to try to prevent the emergence of resistant clones, especially the T315I clone. We do not traditionally test for the presence of that mutation at baseline, but if there’s any hint of treatment resistance, one might look for that clone—particularly if incorporating a second-generation TKI, like dasatinib [Sprycel], as frontline treatment.”

Wendy Stock, MD, the Anjuli Seth Nayak Professor of Medicine at UChicago Medicine and co-leader of the Clinical and Experimental Therapeutics research program at the University of Chicago Medicine Comprehensive Cancer Center, discussed best practices for molecular testing in patients with Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia (ALL).

One factor that distinguishes Ph-positive ALL from chronic myeloid leukemia is the frequent and early emergence of resistance mutations, particularly the 

 T315I clone, Stock began. To counteract this rapid resistance development, hematologists have begun integrating the third-generation TKI ponatinib (Iclusig) in the up-front setting to try to avoid the development of those resistant clones, she said.

 T315I mutation is not traditionally tested for at initial diagnosis, Stock explained. However, if there is any indication of emerging treatment resistance during therapy, testing for this clone becomes necessary, she emphasized. This is particularly crucial if a second-generation TKI, such as dasatinib (Sprycel), is incorporated as initial frontline treatment, she noted.

Furthermore, high-risk stratification in Ph-positive ALL requires identifying other molecular features, collectively known as the Ikaros-plus signature, according to Stock. The mutation or deletion of the 

 gene is common in this disease, affecting approximately 80% of patients, she reported. The Ikaros-plus signature constitutes the loss or mutation of 

 in combination with deletions or mutations in other genes, including the 

 genes, she added. Although testing for the Ikaros-plus signature is not universally performed up-front, it is considered a reasonable approach to take, she continued. Determining the presence of this signature is instrumental in guiding therapeutic decisions regarding necessary risk stratification and assessing whether the patient requires additional chemotherapy, she stated.

Beyond molecular genetics, a nonmolecular feature serving as an important prognosticator is initial white blood cell count, which is considered one of the more adverse prognosticators for outcome, she explained. Monitoring treatment response relies on serial bone marrows for morphologic monitoring of the disease, supplemented by much more sensitive molecular techniques, she summarized. Next-generation sequencing is now being employed in Ph-positive ALL to track the immunoglobulin gene rearrangement, she noted. Since this rearrangement is an intrinsic component of the leukemic clone, the eradication of this trackable clone might be the most important prognostic marker for achieving excellent disease-free survival, she concluded.

Videos

Wendy Stock, MD, discussed the role of molecular testing in Ph-positive ALL and best practices for implementing this testing across clinical scenarios.

Catherine E. Lai, MD, MPH, an associate professor and physician leader of the Leukemia Clinical Research Unit at the University of Pennsylvania Perelman Center for Advanced Medicine, moderates a discussion with Selina M. Luger, MD, FRCPC; Gail J. Roboz, MD; and Wendy Stock, MD, on how being female affected their careers in ways such as limited maternity leave, the pressure they felt to overcompensate in their professional lives, and the importance of setting a successful example for the women who would follow in their footsteps. They also share the scientific achievements they most want to be remembered for in the leukemia field.

Luger is an attending physician, professor of medicine, and interim director of the Penn-Vinmec Oncology Center of Excellence at the Hospital of the University of Pennsylvania. Roboz is a professor of medicine and the director of the Clinical and Translational Leukemia Program at the Weill Medical College of Cornell University and the NewYork-Presbyterian Hospital. Stock is the Anjuli Seth Nayak Professor of Medicine and a professor in the Comprehensive Cancer Research Center at the University of Chicago Medicine.

In this episode, Luger, Roboz, and Stock discuss the unique challenges and successes that motherhood brought to their early careers. They note the importance of being selective and prioritizing a healthy work/life balance, even at the expense of certain career opportunities. They also share their satisfaction with how the dynamic between their personal and professional lives ultimately panned out.

Additionally, the 3 experts highlight some of the moments they’re most proud of from their careers, including bringing pediatric-inspired regimens to adults, running safe clinical trials with advances in drug development, and building leukemia programs at their institutions. They also reflect on the cooperative nature of clinical research and the collaborations with colleagues and patients that they’ve most enjoyed over the years. 

Selina M. Luger, MD, FRCPC, Gail J. Roboz, MD, and Wendy Stock, MD, discuss how being female affected their careers and share the scientific achievements they most want to be remembered for in the leukemia field.



Women in Oncology: Prioritization and Passionate Legacies

Catherine E. Lai, MD, MPH, an associate professor and physician leader of the Leukemia Clinical Research Unit at the University of Pennsylvania Perelman Center for Advanced Medicine, moderates a discussion with Selina M. Luger, MD, FRCPC; Gail J. Roboz, MD; and Wendy Stock, MD, on how they turned leukemia career “lemons” into “lemonade.”

In this episode, Luger, Roboz, and Stock discuss times when their plans veered in directions different from what they expected, such as the challenges of spearheading a leukemia program, designing a trial that never happened, and developing a well-researched regimen that nevertheless fell short. In highlighting their most memorable roadblocks, they share how they turned these obstacles into inspirations for further advancement in the field of leukemia treatment.

The 3 experts also reflect on what they learned from each of these experiences, including the details of designing studies, the value of research that leads to networking, and how leaving one institution opens other doors and is a catalyst for gaining the necessary confidence for effective leadership. Additionally, they express their gratitude that moments like these helped them speak up about their work and develop their authoritative voices.

Selina M. Luger, MD, FRCPC; Gail J. Roboz, MD; and Wendy Stock, MD, discuss how they turned their leukemia career “lemons” into “lemonade.”

Women in Oncology: Resilience That Leads to Innovation

Catherine E. Lai, MD, MPH, an associate professor and physician leader of the Leukemia Clinical Research Unit at the University of Pennsylvania Perelman Center for Advanced Medicine, moderates a discussion with Selina M. Luger, MD, FRCPC; Gail J. Roboz, MD; and Wendy Stock, MD, on what motivated them to continue working toward improvements in the leukemia field, even when outcomes were dismal and treatment options were scarce.

In this episode, Luger, Roboz, and Stock discuss the importance of building on the concepts of already-effective treatments when innovating new therapies, and how the simultaneous evolution of technology and supportive care gave them hope for the future of leukemia treatment. They also reflect on their formative experiences with translational research as a valuable tool for learning more about the disease with each patient they treated, either through predicting a patient’s response to therapies or studying their response to determine next steps.

Additionally, the 3 experts highlight how being involved with clinical trials made them feel that there was always progress on the horizon in leukemia. They also give advice to current oncology fellows on how to take initiative during their fellowship and pursue a variety of opportunities for the beginnings of a well-rounded career.

Selina M. Luger, MD, FRCPC; Gail J. Roboz, MD; and Wendy Stock, MD, discuss what motivated them to continue working toward improvements in the leukemia field, even when outcomes were dismal and treatment options were scarce.

Women in Oncology: Bringing Advances From the Lab Into the Clinic

Catherine E. Lai, MD, MPH, an associate professor and physician leader of the Leukemia Clinical Research Unit at the University of Pennsylvania Perelman Center for Advanced Medicine, moderates a discussion with Selina M. Luger, MD, FRCPC; Gail J. Roboz, MD; and Wendy Stock, MD, on the issues that were most prominent in leukemia treatment when they began their careers.

In this episode, Luger, Roboz, and Stock discuss the challenges that accompanied the lack of progress in leukemia treatment when they began their fellowships and express their excitement about encouraging developments that have since emerged in the arena, such as hyperfractionated cyclophosphamide, vincristine, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) and high-dose cytarabine. They also share their thoughts on being some of the first people at their institutions to use treatments like arsenic trioxide in acute promyelocytic leukemia and autologous stem cell transplant in chronic myeloid leukemia (CML).

Additionally, the 3 experts explain how they enacted their early fascination with the biology behind the disease through studying gene deregulations and mutations, measuring minimal residual disease, and conducting quantitative southern blot monitoring of CML. They also reflect on how far the leukemia field has advanced as a whole, from struggling with the limited choices in their armamentarium to having an array of more effective therapies for a variety of leukemia subtypes.

Selina M. Luger, MD, FRCPC; Gail J. Roboz, MD; and Wendy Stock, MD, discuss the challenges that accompanied the lack of progress in leukemia treatment when they began their fellowships and express their excitement about encouraging developments that have since emerged in the arena.

Wendy Stock, MD

Articles

Dr Stock on the Multifaceted Role of Molecular Testing in Ph+ ALL

Women in Oncology: Prioritization and Passionate Legacies

Women in Oncology: Resilience That Leads to Innovation

Women in Oncology: Bringing Advances From the Lab Into the Clinic

Women in Oncology: How Early Treatments Paved the Way for Future Advances