As part of his work with a new CAR T-cell consortium, Matthew Cortese, MD, MPH, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, shares that certain types of hard-to-treat lymphomas may be more receptive to immunotherapies than previously thought.
“We’ve been able to show for the first time that certain types of lymphoma, including transform follicular lymphoma, Richter transformation, transform marginal zone lymphoma and B cell lymphomas, do extremely well with cell therapy,” he says.
For one patient, the introduction of venetoclax, a small molecule that has been shown to help repair a damaged immune system in as little as 30 days in patients with chronic lymphocytic leukemia, allowed him to successfully provide relief from her hyper-progressive lymphoma. “She was recommended to seek hospice, but we were able to turn her around and give her more time,” Dr. Cortese says. “We were able to treat and arrest her disease progression, get her infection under control and she was able to meet her great-granddaughter. We got her over a year (of more time). That led to the development of my Richter transformation study, which has been greenlit by the FDA.”
Dr. Cortese and his team at Roswell Park also continue to work on trials to boost treatment efficacy while minimizing toxicity by considering different treatment sequences to create more durable remissions. He’s also working across disease types on research into complement biology, where he’s had promising results in ovarian cancer patients.
“We’re trying to mitigate the risk of neurotoxicity from cell therapy as well as building relationships with industry partners and patients and stakeholders in the community to develop novel trial approaches to make toxicity less and efficacy more,” he says.
Hi, my name is Matt Cortiz. I'm an assistant professor of oncology in the department of medicine lymphoma section working with colleagues here to treat and kill blood cancers here at Roswell Park Comprehensive Cancer Center in Buffalo, New York. It is my pleasure to talk about some of the great work we do at Roswell Park. Uh, basically bringing precision medicine to the bedside from the bench to be pioneers in some of the targeted therapy approaches and emerging and, and always evolving and improving standards of care. This includes some of our clinical trials in cell therapy. As many of you know, Russell Park has invested a great deal of money with some state support to develop this GMP facility to develop novel cell therapies and immunotherapeutics for patients with all kinds of cancer, in particular blood cell cancers that I specialize in. We do lots of work with. centers around the country, including some of the work that I helped with in a CAR T cell consortium, where we've basically shown for the first time that certain subtypes of lymphoma, like transformed follicular lymphoma, Richter transformation, transformed marginal zone lymphomas all do extremely well with cell therapy, and that's basically in relation to diffuse large B cell lymphoma. We were the first to show as part of this consortium, overall survival benefit, for example, for those with transformed follicular lymphoma with CART. It's also my pleasure to work in the translational space as we try to better understand and leverage some of the newer small molecules and other immunotherapies at our disposal. I've had the privilege to work with Dr. Hernandez Eliza Latui in our lymphoma translational Research Center with some rockstar students, including new upcoming PhD candidates at Roswell Park, who we've successfully recruited. Looking at multiomics and how the immune system is repaired with certain small molecules like phonetic plaques, for example, and CLL we've shown that the immune system is repaired very effectively in as little as 30 days uh with phonetic plaques, and then we've actually shown how that works in an upcoming publication. And we're showing how there's immense synergy and potential to boost car T cell efficacy using some of these novel agents and a deeper understanding of how they truly work. Sequencing of treatments, trying to use as little effective medication as safely as possible. To deliver the best possible results, we all are looking for those minimal residual disease or MRD negative durable remissions with very little toxicity. It's culminated so far for me in an upcoming clinical trial that I've written for Richter transformation, uh, using nemtorutinib and pembrolizumab, um, with this new, you know, chemo-free approach to that horrible and devastating type of chemo refractory lymphoma. We're not done yet, so that's just one small trial out of a mix of many other studies going on. I've had the luxury of collaborating with uh some of our basic scientists on complement biology, for example, and so far some very promising results in ovarian cancer, uh, minimizing uh malignant ascites, you know, these abnormal fluid collections in the body for patients. Um, and of course trying to move the needle for solid tumors with my colleagues as well. We've actually also taken that approach in a different direction and we're looking at trials to mitigate the risk of neurotoxicity from cell therapy, for example, as well as building relationships with industry partners and obviously patients and and our stakeholders in the community and elsewhere to develop these novel trial approaches to again make toxicity less and efficacy more. There's been several examples that I've had the privilege to care for patients. And and touch their lives and they've also touched me back. A victory of sorts for an elderly patient who basically came in very much infected, hyper progressive lymphoma was recommended to seek hospice care, and we actually were able to turn her around with a targeted therapy. In this case it was Richter transformation with a drug like Venolax, and we were able to arrest the disease progression, get her infection under control, treat her. And she was able to basically meet her, her great granddaughter, and that was one of her things on her bucket list. We got her another, you know, over a year and of course this is before, you know, the non-covalent BTK inhibitors were available. Unfortunately, you know, we do still lose patients, right? And in this case it was trying to get them to CAR T cell therapy and that led to the development of my Richter transformation study, which has been greenlit by the FDA and available on clinicalTrials.gov. I've been blessed to represent Rossell Park on the NCCN steering committee. And panel for CLLSLL and transformation and we're rewriting the standards of care collaboratively with places around the country for that particular disease as well. As the only comprehensive cancer center in upstate New York, Roswell Park has a mission to help you, help your patients and help our communities, and I would like to encourage anyone who's listening and watching. If you have any patients who are highly complicated, complex, disease wise or or other factors, if you have difficult, highly morbid patients who have lots of end organ damage, they're beat up, if you need clinical trials available and and to see what the latest science is either. Today or what it will be shortly in the near future we can help you and either directly through direct care or we're happy to consult with you as well. I want everyone here to know that Roswell Park Conference of Cancer Center has your back. We're not here to steal patients. We're here to help you help the community and advance clinical science together basically to make better treatments for everyone.
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