Of the 1.8 million cases of cancer diagnosed in the U.S. this year, only around 10,000 will be T-cell lymphomas. Most community oncologists will see just a few cases of T-cell lymphoma in a lifetime. Building consensus on the best way to treat these rare and fast-growing diseases has been a challenge, and outcomes have been the poorest of any other type of blood cancer.
Fortunately, there are researchers who have dedicated their careers to advancing our understanding of T-cell lymphoma and developing more effective treatments. Two of these researchers are now making UVA Cancer Center their base of operations.
Owen A. O’Connor, MD, PhD, is an international authority on lymphoma. He has spent the past two decades studying the 30 different subtypes of T-cell lymphoma and working to ensure that these rare diseases receive the same consideration and research dollars as more common malignancies. In 2018, he was awarded an American Cancer Society Clinical Research Professorship, the most prestigious grant awarded by the ACS. He is a long-time member of the Lymphoma Research Foundation’s Scientific Advisory Board. And his research has contributed to the development and FDA approval of two drugs to treat T-cell lymphoma.
In the summer of 2020, O’Connor was appointed professor at the UVA School of Medicine and he moved his lab from Columbia University Medical Center in New York to UVA Cancer Center. “The director of the UVA Cancer Center, Dr. Tom Loughran, is renowned for his discovery of a form of T-cell lymphoma, LGL [large granular lymphocytic] leukemia,” says O’Connor. “In working together … we realized similarities in our research findings, and we began discussing the prospect of working together more closely, sharing some of the resources and drug development skill sets we’ve developed.”
This transition is an opportunity to “work hand-in-hand with international authorities on cancer research to develop breakthrough therapies and think outside the box to manage lymphoid malignancies,” O’Connor adds.
Carrying the Torch
Accompanying O’Connor to UVA is his longtime collaborator Enrica Marchi, MD, PhD, a former mentee of Pier Luigi Zinzani, MD, PhD, an international authority on T-cell lymphoma based in Bologna, Italy. “Dr. Zinzani contacted me and told me that he had one of the best young physicians he’d ever encountered working with him at the University of Bologna,” says O’Connor. “He said he would like to send Dr. Marchi to my lab in New York to get experience doing translational laboratory research to see if we might mentor her together so that she can be [part of] that next generation of innovative leaders in the field.”
Marchi rose to the challenge. Working closely with O’Connor doing translational research on novel treatment strategies for T-cell lymphoma, she obtained her PhD and became passionate about the work. “I decided that I wanted to pursue my career goals in the U.S. and become a physician-scientist, translating from the laboratory to the clinic our most interesting and promising novel agents and drug combinations,” says Marchi. That meant, despite being a trained hematologist in Italy, she would have to repeat much of her medical training.
“Dr. Marchi went back to repeat her residency and fellowship, which for some can be very difficult having done it before, but she excelled,” says O’Connor. “She got relicensed and board-certified in the U.S. and, based on her demonstrated success in the lab, she was driven to continue work in drug development as it pertained to T-cell lymphoma.” Marchi joined the faculty at Columbia, where she emerged as one of the “top rising innovators,” according to O’Connor. “She’s been invited to lecture around the world and she has also helped us get one of the most prestigious grants from the government, an RO1.
Home for Advancement and Collaboration
As they work to make UVA a leading center for T-cell lymphoma research, O’Connor and Marchi, the co-directors of the UVA Program for T-Cell Lymphoma Research, agree that they have a strong platform to build upon. “You cannot bring an entire clinical laboratory research operation to a place that does not have the structure to welcome it,” says Marchi. “UVA has that capability to make it work. There is a great research team here that helps with the development of clinical trials. There are top-notch labs and there is a nanotechnology institute that is pioneering nanoparticles, which is another area of interest to us. There was really everything we needed to work well here in a collaborative environment that supports bench-to-bedside research.”
“I have continued to be incredibly impressed by the commitment of the people at UVA, their attention to detail and their absolute enthusiasm to make substantial strides in advancing the care of cancer of all sorts,” adds O’Connor. “It is unbelievably exhilarating, and it’s an exciting opportunity to work with them and work with Dr. Marchi and my friends at UVA to build a program that will receive national and international attention in T-cell lymphoma care and research, as well as new drug development.”
Of course, to advance treatment of such a rare disease more quickly and effectively will require the efforts of many. “Because this disease is so rare, to do clinical trials is very challenging,” says O’Connor. “That’s why I envisioned putting together a global team to harmonize efforts of [developing] clinical trials in a way that hastens advances in the field.”
That team of international experts from Europe, North America, Australia and Asia now make up the Global T-Cell Lymphoma Consortium. UVA will be the headquarters for this collaborative effort to enroll more patients in trials so that researchers can quickly get information that allows them to determine the next best steps in treating these diseases.
Opt for Specialized Care
These latest additions to the UVA Cancer Center team are examples of UVA’s commitment to providing highly specialized cancer care. Patients with rare cancers, in particular, benefit from the expertise of highly skilled physician-scientists like Marchi, who will be caring for T-cell lymphoma patients in addition to working in the lab.
O’Connor’s advice for referring providers: “When you see patients with these diseases, you have a golden opportunity to work with people really dedicated and focused on this rare orphan disease,” he says. “I would encourage all physicians not specializing in these specific diseases to actively seek out those collaborative interactions with those who spend their life thinking about it, so we can learn together.”
To refer a patient to UVA Cancer Center, call UVA Physician Direct at 800.552.3723.
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At a Glance: T-Cell Lymphoma Research
According to O’Connor, the field of cancer research is moving so fast that many of the lessons we’ve learned in the past about how to treat this disease are no longer applicable. Chief among them is the belief that chemotherapy is the best treatment option for lymphoma, particularly T-cell lymphomas.
O’Connor and Marchi have focused much of their research on the development of more targeted, chemotherapy-free therapies that destroy cancer cells without affecting healthy ones. Their latest studies show the potential of combination therapies rather than single agents to stop cancer cells from dividing.
“We have seen that the combination of epigenetic drugs and immunotherapies can produce compelling activity that lasts a long time,” says O’Connor. “It’s nothing more than the natural evolution of cancer therapies. Identifying drugs that work, then trying to create a biological rationale for studying them together, in time leads to better and better treatments that can change our conventional paradigms of care.”
Highlights of this research can be found at the links below:
The rapidly changing landscape in mature T‐cell lymphoma (MTCL) biology and management
The combination of hypomethylating agents and histone deacetylase inhibitors produce marked synergy in preclinical models of T‐cell lymphoma
Oral 5-azacytidine and romidepsin exhibit marked activity in patients with PTCL: a multicenter phase 1 study
T-cell Lymphoma Clinical Trials at UVA
T-cell lymphoma studies currently enrolling at UVA include:
Durvalumab in Different Combinations With Pralatrexate, Romidepsin and Oral 5-Azacitidine for Lymphoma
Study of Pembrolizumab Combined With Decitabine and Pralatrexate in PTCL and CTCL
T-cell lymphoma studies coming soon include:
A Randomized, Phase IIB, Multicenter, Trial of Oral Azacytidine Plus Romidepsin versus Investigator’s Choice in Patients with Relapse or Refractory Peripheral T-cell Lymphoma (PTCL)