Hematology/Oncology Research and Clinical Updates - March 2021

Robert Dreicer, MD

Message from Medical Oncology Section Head, Dr Robert Dreicer

The past academic year has seen some notable accomplishments. The late fall saw the opening of the new UVA Breast Care Center. Our breast medical oncologists, including Drs. Brenin (Medical Director of the UVA Cancer Center Infusion Center), Dillon and Millard, were significant contributors to this excellent facility’s highly successful opening providing a full range of clinical and clinical investigative care for our medical breast cancer patients.

Although the UVA Cancer Center’s submission for renewal of our NCI designated status has not yet been renewed at the time of this report, the sections clinical investigators have been significant contributors to our clinical trials programs’ evolving growth and success.

Melanoma/and related disorders
Drs. Elizabeth Gaughan, Varinder Kaur, and William Grosh (retired 12/31/2020)
APP: Jennifer Eccles

Breast Medical Oncology
Drs. Christiana Brenin, Patrick Dillon and Trish Millard
APP: Paul “Mike” Marshall

Thoracic Medical Oncology
Drs. Ryan Gentzler and Richard Hall
APP: Marie Thomas

Head and Neck Oncology
Dr. Varinder Kaur

Gastrointestinal Medical Oncology and Unknown Primary Neoplasms
Drs. Tri Le, Paul Kunk, and Matthew Reilley
APP: Jenna Ally

Genitourinary Medical Oncology
Drs. Michael Devitt and Robert Dreicer
APP: Jennifer Eccles

Sarcoma
Drs. Michael Douvas, William Grosh, and Johann Hsu

Infusion/Urgent Care
APPs: Julia Gyampoh and Melody Noble

Tamila Kindwall-Keller, MD

Message from Stem Cell Transplant Associate Clinical Director, Dr Tamila Kindwall-Keller

The Stem Cell Transplant and Cellular Therapy Program is entering its 10th year of serving patients in Virginia. Our first transplant was performed in January 2012, and at the end of February 2021, we have completed 743 transplants. We receive referrals from all over Virginia, including Virginia Beach, Northern Virginia, and Appalachia / SW Virginia. In the calendar year 2020, we performed transplants for various hematologic malignancies, including multiple myeloma, non-Hodgkin’s lymphoma, acute leukemia, myelodysplastic syndrome, and myeloproliferative disorders. Since the inception of the CAR T-cell program, we have given commercial and research CAR T-cells to 13 patients. Our cell processing lab helps support cellular therapy trials in digestive health, vascular surgery, cardiology, and pulmonary/critical care for SARS-CoV2 patients. We are working with the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) to open cooperative group clinical trials at UVA for our patients. Both Dr. Varadarajan and Dr. Volodin are working with Dr. Larry Lum’s lab to bring the novel Bispecific Activated Armed T-Cells to our patients through clinical trials. The physicians would like to thank all the team members and consultants who have helped us take amazing care of our patients over the past ten years; we would not be where we are today without them.

We look forward to bringing all the new cellular therapies developed over the next ten years to our UVA patients.

Stem Cell Transplant
Drs. Karen Ballen, Tamila Kindwall-Keller, Indumathy Varadarajan, and Leonid Volodin
APPs: Hania Aloul, Joshua Humphrey, Jessica Kassay-McAllister, and Christine Mazimba

Elizabeth Gaughan, MD

Message from UVA Community Oncology Section Head, Dr. Elizabeth Gaughan

The UVA Community Oncology Section includes seven providers serving patients with the spectrum of hematologic and solid tumor diagnoses at three Central Virginia locations. They provide oversight for the multidisciplinary infusion centers, including 42 active infusion chairs. Due to our convenient office locations, we can see patients quickly and facilitate referrals to sub-specialists at the Emily Couric Clinical Cancer Center, when appropriate. The team actively supports the education, research, and administrative priorities of the Division.

The UVA Cancer Center Augusta recently welcomed a weekly clinic for Dr. David Brenin along with the Mobile Mammography Coach. We anticipate opening nine additional infusion chairs at the Augusta clinic to serve the UVA patient population in FY21 further. Optimization efforts are underway for the clinical trial efforts at UVA Cancer Center Pantops, the backbone for expanding these services to our other regional sites. The UVA Cancer Care Culpeper team is looking forward to the spring 2021 expansion of PET services in the Culpeper area linked with UVA Nuclear Medicine.

Augusta Location
Dr. Nicholas Paphitis
APP: Meera Kumar

Culpeper Location
Drs. Ali Mahjoub and Pranav Patel
APP: Michelle Otto

Charlottesville/Pantops Location
Dr. Johann Hsu
APP: Kathleen Oleson

Dr Robert Dreicer

Message from Hematologic Malignancies Section Head, Dr. Craig Portell

Our Hematologic Malignancy Service continues to grow and expand in clinical care and research. A highlight of the year was creating a dedicated T-cell lymphoma team, led by Dr. Enrica Marchi and Dr. Owen O’Connor. They joined us from Columbia University in New York, NY. The lymphoma team also welcomed Dr. Emily Ayers from the University of Pennsylvania. The lymphoma team continues to have a strong presence with the NCI cooperative groups and leads multi-institution studies combining novel agents with either chemotherapy or other targeted drugs. There continues to be an expanding role for immunotherapy in lymphoma and CLL with CAR T-cell therapy and bispecific antibodies making strong headways at UVA. In myeloma, an explosion of new drugs and likely CAR T-cell therapy soon has increased life expectancy and made myeloma a chronic disease. Dr. Laahn Foster and Dr. John Densmore study combinations of novel drugs, both in the refractory setting and in patients with minimal residual disease. And leukemia does not stop for the pandemic, and neither does the team of Dr. Firas El Chaer, Dr. Fran Garrett-Bakelman, Dr. Michael Douvas, and Dr. Mike Keng. They have partnered with our primary science colleagues with several exciting new studies, using nanotechnology and PIM inhibition, genuinely creating a bench-to-bedside approach.

Lymphoma and CLL
Drs. Emily Ayers, Enrica Marchi, Craig Portell, and Michael E. Williams
APPs: Kim Leake and Heather Youngberg

Myeloma
Drs. Laahn Foster and John Densmore
APP: Heather Youngberg

Leukemia
Drs. Michael Douvas, Michael Keng, Francine Garrett-Bakelman and Firas El Chaer
APP: Kim Leake

Karen Ballen, MD

Message from Hematology Section Head, Dr. Karen Ballen

In Hematology, under Dr. Louise Man’s direction, we opened our Adult Comprehensive Hemophilia Center, a grant-supported collaborative effort with Pediatrics, to serve adult patients with Hemophilia Bleeding Disorders. Dr. Kelly Davidson has been instrumental in expanding our Sickle Cell Program and advocating for adult patients from Virginia’s Commonwealth. She has partnered with our Hospitalist Team to design individualized care plans to reduce hospitalizations. Dr. Hillary Maitland is leading our efforts to reduce deep vein thrombosis throughout UVA Health, and is working on a research project to reduce blood transfusion requirements in dialysis patients.

Hematology
Drs. Kelly Davidson, Hillary Maitland, and Louise Man
APPs: Julie Armatas and Kathryn Strickler

Hemophilia Program

The Adult Comprehensive Bleeding Disorder Clinic (also known as the “Hemophilia Treatment Center” clinic) was started in mid-2020. Just like the comprehensive pediatric Clinic, the adult program promotes optimal health in patients with congenital bleeding disorders through a model of integrated, multidisciplinary, comprehensive care. Dr. Louise Man leads this program; other members of this multidisciplinary team include Julie Armatas (nurse practitioner), Ellen Brock (nurse coordinator), Adonice D’Atre (social worker), Marc Gilgannon (physical therapist), and Lindsay Comstock (research and resource nurse).

CAR-T

On October 12, 2020, after five years of thorough planning, the UVA Breast Care program moved into the new 18,500 square foot Breast Care Center (BCC) at 652 Peter Jefferson Parkway. This is an off-grounds location, a one-stop-shop with the full complement of physicians involved in breast care, imaging, laboratory, and treatment facilities – all under one roof.
The site is designed to make it easier for patients to access coordinated breast care in a single, convenient location. From mammography, ultrasound, and biopsy, to survivorship, genetics, PM&R, infusion therapy, and clinical trial participation, almost all breast care services provided by UVA are now available to patients in a single visit. Flourish “feel better” boutique is also on-site and offers Dignicap support, allowing patients to minimize hair loss during chemotherapy.

The new UVA BCC is run by a tripartite all-female leadership team – Dr. Shayna Showalter from Surgical Oncology, Dr. Carrie Rochman from Breast Imaging Dr. Christiana Brenin from Medical Oncology. This team has been working together for nearly a decade and has finally come together under one roof to provide the coordinated multidisciplinary care that our patients so deserve. There are three surgeons, three medical oncologists, two plastic surgeons, six breast imagers, two genetic counselors, and 2 APNs who practice out of the BCC. We are delighted to be sharing this beautiful and bright space, with the bonus of having ample and free ground-level parking, a drastically improved experience for our patients!

Breast Care Center

Emily Couric Cancer Center, Infusion Center

Key Infusion Center Initiatives

• January 2020 – Opened template to include 37 chairs
• March 2020 – Establishment of the Urgent Care Clinic, providing telemedicine as well as in-person clinic visits
• March 2020 – Facilitated relocation of apheresis to ECCC
• April 2020 – On-boarded second APN to support clinical activities
• May 2020 – Expansion of care to include Intravesical Chemo/BCG
• August 2020 – Supported PO Chemotherapy focused clinical trials
• June 2020 – Expanded Pre-infusion template from 84 to 97 appointments daily
• May to July 2020 – Supported organizational financial mitigation directives
• September 2020 – APN’s assume “Doc of the Day” Coverage for Emily Couric Cancer Center (ECCC)

Key Staff Metrics

• 25% of nursing team certified as oncology nurses (COC standard)
• 32 % of nursing team enrolled in BSN or higher degree program (Magnet standard)

For 2021

• February 21, 2021 – Stem cell mobilizations moving to the infusion center, and extended weekend hours: 8:30 – 4:30 pm Saturday and Sunday
• March 2021 – Opened template to include all infusion chairs (46 in total)
• March 2021 – Extended weekday holiday hours – 8:30 – 4:30

Richard Hall, MD

Message from the Fellowship Program Director, Dr. Richard Hall

Writing a summary “letter” for Medicine Matters this spring is challenging. In past years, I would highlight our fellows’ accomplishments and share large program initiatives to constantly improve our educational curriculum. This year, however, I think our fellowship team is slowly exhaling – having held our breath for far too long as the pandemic around us raged.

One welcome change over the past year is that our hematology/oncology fellowship program successfully petitioned the Medical Center to expand our annual complement of fellows from three to four fellows per year. This expansion has been long-awaited. Like many of you, we adapted to our circumstances and successfully recruited an outstanding group of new fellows who will start with us in July 2021 – Nate Roberts MD (Wake Forest), Chris Thomas (Kentucky), Will Thomas (UAB), and Phi Young (UVA). In addition to our annual program expansion, we welcomed Melissa Yacur, MD, as a transfer from George Washington University in January 2021.

Over the coming year, our program leadership team will re-evaluate and refine our educational curriculum and implement new initiatives. The pandemic has uncovered opportunities to grow and improve how we educate fellows to adapt to a rapidly changing hematology/oncology treatment landscape. We have several project ideas for inter-institutional educational projects, and we are looking forward to the coming spring and summer months to spend more time together.

Dr. Lawrence Lum’s Lab

Lawrence Lum, MD

In 2016, the targeted T cell immunotherapy was established by the Cancer Center’s recruitment of Dr. Lum. Research and cGMP facilities and clinical infrastructure were created to support investigator-initiated clinical trials using bispecific antibody-targeted T cells (BATs) for solid and liquid cancers. Together with principal investigators for clinical trials, there are now FDA-approved protocols for growing and administering BATs to treat patients with metastatic breast cancer, pancreatic and hormone-refractory prostate cancer, primary glioblastoma, multiple myeloma, and pediatric neuroblastoma/osteosarcoma. A new, more powerful killer T cell created by transducing T cells with co-activating genes armed with bispecific antibodies is in the clinical pipeline for solid tumors and hematologic malignancies.

In addition, to the manufacture of targeted T cells for cancer treatment, Dr. Lum is studying the effects of irradiation on immune functions, convalescent immune plasma on patients with COVID-19 infections, lymphocyte functions in patients treated for Hodgkin’s disease with ibrutinib, immune function in men receiving Sipuleucel-T, and the regulation of T cell trafficking by CXCR3. The laboratory is developing T regulatory cells to treat Type 1 Diabetes, GVHD, and other autoimmune diseases and bispecific antibody targeting T cells to treatment with COVID-19 infection.

Research Team Science Award

Tom Loughran Jr., MD, and collaborators, received the 2020 School of Medicine Dean’s Excellence in Faculty Research Team Science Award. Dr. Loughran leads the team along with his long-term collaborator Mark Kester, Ph.D. (Pharmacology). The two are multiple PIs for a National Cancer Institute (NCI) program project (P01) grant entitled Targeting Sphingolipid Metabolism for Treatment of AML. The P01 aims to define the dysregulated sphingolipid metabolism in AML and target this pathway to enhance therapeutic efficacy. The three major projects are led by the Loughran and Kester labs at UVA along with Dr. Myles Cabot at East Carolina University. Other Hem/Onc team members of the 12-person team included David Feith, PhD., and Su-Fern Tan, PhD (Loughran group), Fran Garrett-Bakelman, MD Ph.D. (Systems Metabolomics Core), and Michael Keng, MD (clinical trial PI). The team’s excellence is exemplified by the successful renewal of the Program Project grant in 2020 for an additional 5-year term and over 50 co-authored publications while funded by the NCI.

Three UVA team members direct core facilities for the Program Project (Todd Fox, Ph.D., Pharmacology, Targeted Sphingomics Core; Kevin Janes, Ph.D., Biomedical Engineering, Systems Metabolomics Core; Mark Conaway, Ph.D., Public Health Sciences, Biostatistics Core). An additional core includes Penn State Cancer Institute (David Claxton, MD) and Memorial Sloan Kettering Cancer Center investigators (Martin Tallman, M.D. and Ross Levine, MD). This core provides access to AML patient samples and in vivo models that utilize human AML cell lines, primary AML xenografts, or genetically engineered mouse models for preclinical therapeutic testing. The Systems Metabolomics Core has developed an innovative approach to collate multiparameter datasets (mutational profiling, sphingolipid-omics, gene expression, enzyme activity, and proteomics) from human AML cell lines and patient samples to more precisely define sphingolipid dysregulation and therapeutic vulnerabilities as well as to identify diagnostic and prognostic biomarkers in AML.

The primary goal of this translational research team is to develop new sphingolipid-targeted therapeutics for AML. Towards that end, the recent program project renewal includes a phase I clinical trial in relapsed/refractory AML with ceramide nanoliposomes (CNL). These nanoformulations enhance the delivery of the pro-death C6-ceramide sphingolipid. This FDA- and IRB-approved trial will begin patient accrual this spring. Next, a phase II study will combine CNL with the standard of care therapy for relapsed/refractory AML (CNL plus low-dose AraC and Venetoclax, a.k.a. the CAV trial). These trials will leverage the multi-institutional program project team to enhance accrual and to complete extensive correlative studies across the projects and cores. The team looks forward to reporting research and clinical trial results in future editions of Medicine matters.

Filed Under: Basic Research, Clinical Research

Tags: April 2021 Medicine Matters, April Medicine Matters, April Medicine Matters Newsletter, DOM, faculty, Hematology, medicine matters, oncology, Research

Hematology/Oncology Research and Clinical Updates – March 2021