NCI Rising Scholars: Cancer Research Seminar Series (Upcoming Webinars)

Ipilimumab plus decitabine for patients with MDS or AML in posttransplant or transplant-naïve settings.
Jacqueline S Garcia, M.D., K08 Awardee
Dana-Farber Cancer Institute

Dr. Jacqueline S. Garcia is an Assistant Professor of Medicine at Harvard Medical School. She is a clinical/translational investigator in the Adult Leukemia Program at the Dana-Farber Cancer Institute and an attending physician at the Brigham & Women’s Hospital. She graduated from University of Illinois at Chicago College of Medicine and completed her internship and residency training in Internal Medicine at the University of Chicago. She next completed Hematology and Oncology Fellowship training at Stanford University. She joined Dana-Farber in 2015. Dr. Garcia’s research focuses on the design and execution of scientifically based early phase clinical and proof-of-concept studies in advanced myeloid malignancies, including MDS, myelofibrosis and acute myeloid leukemia. Much of her research centers on identifying novel therapeutic opportunities to leverage the anti-apoptotic pathway in chemoresistant leukemia and to address or prevent post-transplant relapse in the context of investigator-initiated trials (IIT). She is a Principal Investigator for several clinical trials, including IIT, ETCTN/CTEP, and pharmaceutical studies. Her research has received support from the National Institutes of Health/National Cancer Institute, Leukemia and Lymphoma Society, and Conquer Cancer Foundation.

Recurrence of acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) after transplant has exceedingly poor outcome. In a prior study at our center, single agent CTLA-4 checkpoint inhibitor (ipilimumab) generated remissions in cases of AML with low disease burden at relapse with induction of graft-versus-host disease. We asked if we could augment the rate of remission with combination decitabine plus ipilimumab in patients regardless of disease burden and if the alloreactive environment generated after transplant was required for response. In the context of a phase 1 multi-site clinical trial supported by the NCI/ETCTN, we enrolled and treated 48 patients with decitabine/ipilimumab in cohorts separated by transplantation status to assess for safety and preliminary efficacy. We also collected blood/bone marrow from each patient at the same time points before, on-therapy and at time of relapse when relevant to study the local and systemic tumor immune infiltrates. We discovered that immune-related adverse events were frequent and manageable in most patients, the recommended phase 2 dose was the same regardless of transplant status, and we identified responders in both cohorts. Multiplex immunofluorescence (MIF) analyses of paired sequential bone marrows revealed increases in CD4+ T cells after ipilimumab, but we did not consistently observe increases in activated CD8+ T cells among responders. Immune monitoring using Cytof revealed increases in T regulatory cells after ipilimumab but no correlation with response. Transcriptome-based analyses and MIF revealed differences in AML patients with leukemia cutis (skin) compared to those with marrow involvement, including infiltration of memory T cells and higher expression of CTLA-4 and FOXP3. Altogether, detailed immune and molecular correlatives identified potential mechanisms of response and resistance to combination therapy in advanced MDS/AML patients.

Publication

An integrated isothermal nucleic acid amplification test to detect HPV16 and HPV18 DNA in resource-limited settings.
Kathryn A Kundrod, Ph.D., NCI Cancer Research Training Awardee
National Cancer Institute

Kathryn Kundrod, PhD, MPH is a Cancer Prevention Fellow at the National Cancer Institute (NCI), where she is focused on increasing access to cervical cancer screening with Dr. Philip Castle in the Clinical Genetics Branch of the Division of Cancer Epidemiology and Genetics. Through her fellowship, Dr. Kundrod is currently on rotation with the White House Office of Science and Technology Policy (OSTP), where serves as Senior Advisor for Cancer Moonshot Policy Coordination. Prior to joining NCI, Dr. Kundrod completed a PhD and postdoctoral fellowship in bioengineering at Rice University. During her training, she developed point-of-care HPV tests for early cervical cancer detection in resource-limited settings, as well as a COVID-19 saliva test for use in a surveillance laboratory that she managed. Dr. Kundrod earned a Master of Public Health (MPH) degree from the Harvard T.H. Chan School of Public Health during her Cancer Prevention Fellowship.

Globally, there is an urgent need for low-cost and accessible cervical cancer screening tests. The most sensitive method of cervical cancer screening is testing for high-risk human papillomavirus (HPV) DNA, but current HPV DNA tests are not widely available in resource-limited settings, where the burden of cervical cancer is highest. This talk will outline the recent development of a prototype test that detects two types of HPV DNA – HPV16 and HPV18 – to help meet the need for low-cost cervical cancer screening. The developed test is low-cost, manufacturable, and point-of-care-friendly, enabled by two technologies, isothermal amplification and lateral flow detection, that reduce the cost and complexity of the test. Moreover, the test requires six user steps, produces a result in 45 minutes, and can be performed using small benchtop instruments. In field testing in low- and high-resource settings, the developed test yielded a clinically relevant limit of detection of 1,000 HPV16 or HPV18 DNA copies. Taken together, these results demonstrate the feasibility of an integrated point-of-care HPV DNA test. With the inclusion of additional high-risk HPV types, this test has the potential to meet the need for a point-of-care cervical cancer screening test in resource-limited settings.

Publication

Barriers and facilitators of Hispanic/Latino parents caregiving for a childhood cancer survivor: a qualitative study.
Carol Y Ochoa, Ph.D., M.P.H., K00 Awardee
University of California, San Diego

Dr. Carol Ochoa-Dominguez is a Postdoctoral fellow at the University of California San Diego in the Department of Radiation Medicine and Applied Sciences and a Member in Training of the Cancer Control Program at Moores Cancer Center. She is a cancer health disparities researcher; broadly, her research experience has centered on three areas of focus: 1) cancer survivors, 2) informal caregivers, and 3) cancer screening. Within this work, she uses a mixed-method approach to explore whether there are any racial/ethnic differences, the role of social determinants, and specific cultural factors that may be related to these outcomes.
Dr. Ochoa-Dominguez completed her doctoral degree in 2022 from the Department of Population and Public Health Sciences at the University of Southern California, where she was funded by the National Cancer Institute’s T-32 and F99/K00 awards. Before starting her doctorate training, she served as the Cancer Survivorship workgroup ORISE Fellow from 2016-2017 within the Division of Cancer Prevention and Control at the CDC. She also received her MPH in Behavioral Science and Health Education from the Rollins School of Public Health at Emory University in 2016 and her BA from UCLA in 2013.

We extend previous research on Hispanic/Latino caregiver experiences by exploring in-depth the perceived barriers and facilitators of parents in a safety-net clinic who are the primary caregivers throughout their child’s cancer journey. While there have been studies published on Hispanic/Latino caregivers of older adults, there has been little published on identifying the barriers and facilitators of caregiving experiences of parents. Given the intersecting complexities of this safety-net children’s clinic in Los Angeles, which serves primarily Hispanic, recently immigrated, Spanish-speaking, and Medicaid population, it is important to assess whether this vulnerable population has unique barriers and facilitators from previously published literature. Semi-structured phone interviews were conducted among 15 Hispanic/Latino parents caring for their child who was diagnosed with cancer. All interviews were conducted in English or Spanish based on the participant’s language preference. The interviews were recorded using a digital audio device and transcribed by a bilingual professional transcription service. To conserve the meaning of the interviews, they were transcribed and analyzed in the language in which they were conducted. Two bilingual coders independently reviewed transcripts coded them following reflexive thematic analysis and using elements of grounded theory methodology on Dedoose. This study revealed that multilevel factors impact Hispanic/Latino parents’ cancer care management. At the individual level, the magnitude of the caregiving responsibility acted as a barrier, while parents' self-described “relationship with God” acted as a facilitator. Interpersonal relationships, including familial flexibility and fluid roles in relation to caregiving and a positive relationship with the medical care team, were facilitators for caregivers. However, others' perceptions or misconceptions of their child’s illness were a barrier to caregiving. At the organizational and policy level, external financial resources and assistance navigating the application process were beneficial for parents. While issues related to financial hardship and uncertain immigration and citizenship status resulted in caregiver distress and challenges navigating the healthcare system. These findings can guide recommendations to address caregiver burden for this at-risk population at various levels, including suggestions for the healthcare system and policy level.

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