Sylvester Pursues Landmark Research Presented at International Hematology Conference
Researchers with Sylvester Comprehensive Cancer Center, part of UHealth – University of Miami Health System and the University of Miami Miller School of Medicine, presented more than eighty-five abstracts, participated in and moderated multiple panels and served on leadership committees at the 64th American Society of Hematology (ASH) Annual Meeting in New Orleans.
“ASH was a great success for so many reasons, including the record number of presentations by Sylvester researchers at an ASH annual meeting,” said Stephen D. Nimer, M.D., director of Sylvester, Oscar de la Renta Endowed Chair in Cancer Research and executive dean for research at the Miller School of Medicine.
In 1993, when Craig Moskowitz, M.D., Sylvester’s physician-in-chief, started attending ASH, the meeting attracted about 1,000 attendees. Now it’s a “mini city,” according to Dr. Moskowitz, a lymphoma specialist who presented an abstract. “For hematologic cancers, ASH is the most important worldwide meeting. This is where, as a scientist, you make your contacts with industry. This is where we get investigator-initiated studies and increase participation in clinical research.”
Sylvester did more than participate: Cancer center researchers are also among the leaders of ASH, according to Dr. Nimer, who was senior author on poster presentations for two abstracts.
“Sylvester has great representation in ASH leadership. We can help shape the direction of hematology research and clinical care this powerful society’s work,” Dr. Nimer said.
It is extremely important that Sylvester be involved with ASH, according to Mikkael A. Sekeres, M.D., M.S., chief of hematology at Sylvester. Among Dr. Sekeres’ roles in ASH, he is chair of the communications committee and a member of the executive committee and of the program committee, which helped to set the meeting agenda.
“ASH sets the policy for the hematology agenda throughout the year and for the next few years. If we’re not in leadership positions and not part of that conversation, we’re not influencing where hematology should go,” Dr. Sekeres said. “The hematology research we presented at the annual meeting today will set the standards for how we deliver care for patients with hematologic diagnoses in the future.”
New Myeloma Research Institute Brings Impressive Team
News of the launch of Sylvester’s Myeloma Research Institute also made a big splash at this year’s ASH meeting, which was attended by more than 25,000 people worldwide.
“At ASH, we had nine oral presentations focusing on multiple myeloma,” said C. Ola Landgren, M.D., Ph.D. “We have studies on precision medicine, where we’re trying to understand how different drugs work in different disease settings. We have over 2,000 cases where we have integrated information from whole genome or whole exome sequencing with treatment and clinical data. Using integrated computational approaches, we can better provide optimal treatment decisions for individual patients for improved clinical outcomes. Our translational research program is designed to dissect molecular mechanisms underlying resistance to therapy.”
Dr. Landgren played many roles at ASH. He chaired a satellite symposium focusing on the role of minimal residual disease (MRD, or the lowest detectable presence of malignant cells) negativity in hematologic cancers and spoke on the role of MRD testing in multiple myeloma at the symposia. Dr. Landgren, who chaired ASH’s Abstract Review Committee for Myeloma Clinical Trials and co-chaired the session “Risk Adapted Therapy in Myeloma,” authored forty-one myeloma-focused abstracts presented at the meeting.
Among those from the Myeloma Research Institute who presented, Francesco Maura, M.D., associate director, gave oral presentations for two abstracts on the treatment of multiple myeloma.
“We are working on genomic data, which is basically looking at the DNA and alterations that affect the cells and understanding how we can use that information to find the right treatments for the right patients,” Dr. Maura said.
Sylvester hematologist and oncologist Benjamin Diamond, M.D., was part of a team that presented on radiotherapy in multiple myeloma and myeloid neoplasms. Developing cancer after being treated for multiple myeloma is a major concern, according to Dr. Diamond. Most myeloma patients are treated with stem cell transplants, which likely puts the cancer into remission but also exposes them to high-dose chemotherapy, putting them at increased risk for developing secondary leukemia.
“We’re looking at sequencing data to try and figure out if there are any genes or mutations that are predisposing these people to developing these problems in the future,” Dr. Diamond said.
Sylvester hematologist and oncologist David Coffey, M.D., presented on the use of a research tool in drug discovery called the Vk*MYC transgenic model of multiple myeloma, which is highly representative of human multiple myeloma.
Monika Chojnacka, Ph.D., a student at the Sylvester myeloma institute, presented work using whole genome sequencing and RNA sequencing of clinical samples to find rare structural variants that account for most structural variants seen in multiple myeloma.
Dickran Kazandjian, M.D., associate director of the myeloma institute, presented at the ASH Scientific Workshop on Advancing Decentralized Clinical Trials in Hematology and participated in several abstracts throughout the meeting.
Sylvester hematologist and oncologist James Hoffman, M.D., presented at the ASH Satellite Symposia focusing on the role of B cell maturation antigen (BCMA)- targeted therapies in multiple myeloma and participated in several abstracts.
More Advances in Leukemia Research
One of the areas that Sylvester researchers focus on is acute myeloid leukemia (AML) in older adults.
“We focus on that area because it is serving the needs of our population in South Florida, and that’s the goal of a comprehensive cancer center like Sylvester. We’ve done the research to make sure that the standards and therapies that we administer to those in their 80s and even 90s work just as well without causing more toxicity in older adults,” said Dr. Sekeres, who was involved in seventeen ASH presentations and was an author of an abstract on toxicity and outcomes in octo- and nonagenarians with AML.
Ellen Madarang, Pharm.D., BCOP, hematology clinical pharmacist, was among the primary authors on the octogenarian and nonagenarian study, as was Jillian Lykon, Pharm.D., BCOP, hematology/oncology clinical pharmacy coordinator at UHealth.
“Patients in their 80s and 90s often are underrepresented in clinical trials,” Dr. Lykon said. “In this study, we collaborated with five other institutions, and found that octogenarians and nonagenarians that got venetoclax and hypomethylating agent therapy do require some dose adjustments but actually responded pretty well — with a median overall survival of about nine months, which is a lot longer than with the therapies we had previously.”
The work being done at Sylvester in leukemia and related conditions is much needed, according to Terrence Bradley, M.D., a member of Sylvester’s Cancer Epigenetics Program, who moderated the AML session and presented at ASH.
“This is a population of critical unmet need,” said Dr. Bradley.
Justin M. Watts, M.D., Pap Corps Endowed Professor of Leukemia at Sylvester, presented a study on combining a novel drug, APVO436, with venetoclax and azacitidine in AML patients who have relapsed or did not respond to previous treatment.
“We demonstrated very encouraging clinical activity, particularly in patients who had not been treated with venetoclax previously,” said Dr. Watts, the lead principal investigator on the study. “We are now planning an 80-patient phase 2 study.”
Moving Forward in the Fight against Lymphomas
Sylvester researchers presented several abstracts on various aspects of lymphoma.
Sylvester researcher Alvaro J. Alencar, M.D., presented a study evaluating pirtobrutinib, a drug that is not yet approved by the FDA.
“This is a class of agents that is showing incredible activity, even in patients that were very resistant to previous lines of therapy. That by itself is phenomenal,” Dr. Alencar said.
Sylvester physician-scientist Justin Taylor, M.D., presented several abstracts and chaired the review committee for abstracts submitted to “Chronic Lymphocytic Leukemias: Basic and Translational.”
Despite excellent outcomes for chronic lymphocytic leukemia patients treated with covalent BTK inhibitors, many patients become resistant to the therapy. Dr. Taylor and colleagues studied a new type of drug called degraders, which were shown to overcome this resistance by causing the BTK protein to degrade.
“We used laboratory models to mimic what might happen in humans and showed that the novel BTK degrader overcame resistance,” Dr. Taylor said.
Dr. Taylor and colleagues used a variety of technologies to do this work, including one called CRISPR gene editing. He is among the authors on another study presented at ASH that translated those findings to patients.
“This is the first in-human study of a BTK degrader,” he said. The preliminary results showed that the drug was safe and resulted in responses in a group of refractory CLL patients.
Minority Patient Inclusion: A Global Approach
“A big push for Sylvester is working on diversity, equity, and inclusion, and I worked with thought leaders in this space at ASH to make sure that it is top of mind among all cancer researchers moving forward,” said Namrata Sonia Chandhok, M.D., a hematologic oncologist at Sylvester who was on a multi-institutional committee at ASH for diversity, equity and inclusion in clinical trials. Dr. Chandhok also was an abstract reviewer for the ASH meeting.
Sylvester researcher Juan Carlos Ramos, M.D., presented several studies with Georgios Pongas, M.D., and investigators from South America that are focused on HTLV-1 associated adult T-cell leukemia-lymphoma (ATLL).
“Adult T-cell leukemia-lymphoma is a disparate disease,” said Dr. Ramos. “It is caused by a retrovirus [HTLV-1] that is endemic in the Caribbean, affecting mostly African descendants, and in South America where Indigenous populations are at stake.”
Drs. Ramos and Pongas also shared preliminary clinical trial results demonstrating that complete molecular responses can be achieved in patients with ATLL treated with belinostat and zidovudine-interferon-a. “Our goals are to prevent and treat ATLL with novel approaches, including a vaccine and cell-based immunotherapies that are being developed here at Sylvester,” Dr. Ramos said.
Izidore S. Lossos, M.D., director of the lymphoma program at Sylvester, presented data showing that many clinical trials indirectly discriminate against inclusion of minorities, including Hispanic non-whites. Dr. Lossos also authored thirteen other oral and poster presentations, including a Miller School-led study of the largest sequencing data to date in patients with extranodal marginal zone lymphoma.
A Finger on the Pulse of Cancer Care
“Our patients always ask: ‘Do you share information and know what others are doing?’ ASH gives us the opportunity to hear the latest and greatest in our field, and to network,” Dr. Nimer said.
The conference also provided the opportunity to advocate for Sylvester, according to Dr. Nimer.
“We are fortunate to be in Miami, where our patient population looks like what the rest of the U.S. is going to look like in the next decade or two,” he said. “The research we do now can impact the direction the rest of the country takes in the future.”
Tags: American Society of Hematology, Division of Hematology, Dr. Francesco Maura, Dr. Ola Landgren, Dr. Stephen Nimer, Miller School of Medicine, Myeloma Research Institute, Sylvester Comprehensive Cancer Center