The Latest Advances and Optimal Strategies for Peripheral T-Cell Lymphoma Treatment – Media Medic

Media Medic posted on LinkedIn:

“The 5th Tianjin International Lymphoma Academic Conference, serving as an academic platform to foster international academic exchange and cooperation, has actively played its role as a bridge, facilitating in-depth exchange and collaboration in the field of international lymphoma. During the conference, ‘Hematology Frontier’ specially invited Dr. Lihua Qiu from Tianjin Medical University Cancer Institute and Hospital and Dr. Swaminathan Iyer from The University of Texas MD Anderson Cancer Center to engage in a China-International dialogue, reviewing the latest therapeutic advances in peripheral T-cell lymphoma (PTCL) and the optimization direction of treatment strategies.

Hematology Frontier：In light of the recent breakthroughs in PTCL treatment, what are your thoughts on the evolution of therapeutic strategies, and how do these advancements compare between China and your regions?and what considerations should be taken into account when updating treatment protocols between different healthcare systems?

Dr. Swaminathan Iyer: I think it’s a very important question because T cell lymphoma are rare, at least in the US and there are multiple types and they are very aggressive. There’s no standard therapies and they relapse, so there are many challenges.And one of the big differences that we see between the united states and china is that you see a lot more T-cell Lymphoma, particularly the NK/T-cell lymphoma in certain parts of china more than the the world is as one small place and I believe that we have to learn from each other. China has spearheaded many therapies, many chemotherapy agents, novel therapies, because of the numbers and because of the biotechnology sector. We, in fact, are doing many studies in the us in collaboration with many companies in china, whether it is the novel, PI3Kδ inhibitor, or whether it is the JAK I think it’s a two way street between the us and china. The numbers are smaller in the us and there are many biotech companies, but I think it’s a lot of these innovations are coming from china.

Dr. Lihua Qiu: Peripheral T-cell lymphoma (PTCL) is relatively common in China, posing significant challenges in treatment. Over the past two decades, domestic and international scholars have conducted extensive exploratory work aimed at enhancing therapeutic efficacy and improving survival outcomes. Encouragingly, remarkable progress has been made in this field. Firstly, we recommend that eligible patients undergo autologous hematopoietic stem cell transplantation upon achieving complete remission after initial treatment, as data indicate its beneficial effects on prognosis. On the other hand, the continuous emergence of novel drugs developed in China has opened up new avenues for PTCL treatment. Over a decade ago, epigenetic drugs, particularly histone deacetylase inhibitors, were developed internationally, demonstrating an objective response rate of 20% to 30% in the realm of small-molecule targeted therapies. Building upon this foundation, recent years have witnessed rapid advancements in new drug development, with objective efficacy reaching new heights. These drugs include PI3K inhibitors (such as linperlisib), EZH2 inhibitors (like tazemetostat), and JAK1 inhibitors (like golidocitinib), all of which have demonstrated exceptional efficacy, elevating the treatment response rate to a higher level of 40% to 50%, bringing renewed hope to PTCL patients.Specifically, regarding the unique disease entity prevalent in China, the most common subtype of PTCL—NK/T-cell lymphoma —exhibits distinct Chinese characteristics, necessitating a treatment strategy vastly different from that for common PTCL types in Europe and the United States. In the standard treatment of common PTCL types in Western countries, CHOP combined with novel agents , CHOP+X, has become the cornerstone regimen, widely applied in the treatment of PTCL subtypes other than NK/TCL. However, for NKTCL, pegaspargase serves as the cornerstone therapeutic agent, with regimens such as P-GemOx incorporating this drug, achieving remarkable clinical efficacy. These achievements underscore the uniqueness, innovation, effectiveness, and contribution of China’s treatment strategies in this field.

Hematology Frontier: What are the current challenges in PTCL treatment that need to be addressed, and how do you see the role of collaborative research in overcoming these hurdles?

Dr. Swaminathan Iyer: I think T-cell Lymphoma are many challenges.The first one is the number of diagnosis it’s not one disease. According to the recent WHO and ICC there are at least 32 different entities. There are many others that don’t quite fit the description, so we try and push them towards one of these areas. The initial diagnostic pathways are based on morphology followed by immunophenotype and molecular studies. Broadly this more morphological immunophenotype approach has helped us with the diagnosis but they still remain a challenge for the pathologist because they need a lot of clinical information t o put the context to what they see in the microscope. The second is therapies. We have borrowed a lot of therapies from B cell lymphoma. As professors mentioned, a CHOP as a standard of care, but it may not work for everybody there, so we use something like DDGP regimens. And even these where they work very well in early stages, many of the T cell lymphomas have advanced stages, high international prognostic index that puts us in a challenge that we have to consolidate them with an autologous stem cell transplantation or an allogeneic transplantation. The third problem is that many of these lymphomas are have EBV and EBV becomes a challenge and EBV causes problems, not only because it transforms the lymphoid cell lines, whether it’s T cells or B cells and it can bring other issues such as hemophagocytic lymphohistiocytosis. And finally I think there are not many therapies. If you look at the United States approval, there are three major approvals product. Is since most of these patients relapse having three options is not enough, so we need a more therapeutics, more clinical studies. So that’s where I think the collaborations and the learning from each other helps because china sees so many peripheral lymphoma and we at MD Anderson are the forefront of some of these diagnostic and therapeutic modalities for T cell lymphoma. I think it’s very natural that we work together in this particular area and come up with solutions.And we have had discussions with various groups here in china to try and come up with a simple, collaborative retrospective databases, including pathology reviews, molecular pathways and also in clinical studies, so I think there’s long ways to go, but I think it might be a good start for us to have this collaboration, particularly in peripheral lymphoma.

Dr. Lihua Qiu: Currently, participation in clinical trials is the preferred recommendation for the treatment of PTCL patients. Given the high degree of heterogeneity in PTCL, future research directions should focus on improving prognosis, with a primary emphasis on refined and optimized treatment strategies tailored to different pathological subtypes. The cornerstone of this strategy lies in implementing personalized “divide and conquer” therapeutic approaches for each specific pathological subtype to deepen our understanding of pathological types, extensive scientific research, particularly at the genomic level, is imperative. This necessitates significant investment in basic research to screen and identify target genes that play pivotal regulatory roles or function akin to rate-limiting enzymes. Based on these discoveries, efforts should be directed towards the development of novel drugs, with rigorous evaluations of their efficacy, aiming to achieve significant breakthroughs in treatment. It is noteworthy that the relatively low incidence of PTCL in European and American countries compared to its higher prevalence in China underscores the importance of international multi-center collaboration. Through cross-border cooperation, we can more effectively validate the therapeutic effects of novel drugs, share research outcomes, and thereby accelerate treatment advancements, ultimately benefiting patients worldwide. This collaborative model not only contributes to enhancing the overall level of treatment but also serves as a vital pathway towards medical progress.

Hematology Frontier：How do you envision the future of PTCL treatment, especially with the advent of novel agents and precision medicine approaches?

Dr. Swaminathan Iyer: We are at the inflection, for molecular therapies based on various targets that has been discovered. First thing I want to say is that a lot of advances in understanding of the biology of the various sub-type of T cell lymphoma are ongoing and several discoveries have been made. For example, the PTCL will not otherwise specified is not just a basket of diagnosis.That’s actually three different diagnosis.And today we can sub-type them easily. One of the first themes I would say is sub typing. And the second is molecular analysis.Using Next-Generation Sequencing, we are able to find not just mutations, but also up regulated pathways in these T cell lymphomas. Why？Because it gives us insights into the biology. In the battle section, we’ve had developments of various novel agents, whether it’s PI3K inhibitors or JAK1/2 inhibitors.Several of these agents are now in clinical studies.Phase two have been completed. Recent presentations at ASH from last year and from EHA this year have shown that they have remarkable responses and durable complete remissions, so that gives hope, now there are also newer therapies in the realm of the T cell lymphoma. And now there is a target unifying target directed against CD94, which seems to be helpful and will have data on ASH this year. The third point is HLH which ii mentioned earlier, either due to EBV or due to the micro-environment and now there is a target therapeutic in the EHA, we had a late breaking abstract which has shown to benefit these patients. Finally, I think we are not very behind in terms of CAR-T development, even though we started a little late and there were challenges for developing CAR-T, for T-cell lymphoma, the various targets that investigating CD 70 is an active investigation at MD Anderson. We’ve done aloe CD 70 and NK CD70. CD5 is another target. Various groups are doing CD5 CAR-T.CD7 is another target for T-cell lymphoma. So I think we are making progress with normal therapeutics with monoclonal antibodies bispecific monoclonal antibodies and also CAR-T. And I think clearly the clinic on the ongoing studies a in a year or two from now, I think you’ll hear more mature data and will be confident to say that we have better therapies for T-cell lymphoma.

Dr. Lihua Qiu: In the realm of PTCL treatment, remarkable progress have been achieved in recent years. Specifically, for patients achieving CR1 after first-line therapy, autologous hematopoietic stem cell transplantation consolidation has emerged as a crucial therapeutic modality. For recurrent and refractory cases, allogeneic hematopoietic stem cell transplantation is widely recognized as the only definitive and effective treatment strategy currently available.From a subtype perspective, internationally, anaplastic large cell lymphoma stands as the first significant subtype whose treatment landscape has undergone a fundamental transformation with the introduction of brentuximab vedotin. This not only updated treatment guidelines but also significantly enhanced treatment outcomes, presenting an extremely promising therapeutic outlook. In China, the application of regimens such as PGemOx for NKTCL has brought hope of cure to numerous patients. Additionally, breakthroughs have been made in the treatment of angioimmunoblastic T-cell lymphoma. The advent of numerous novel drugs, including Mitoxantrone Hydrochloride Liposome among chemotherapeutics and PI3K inhibitors, JAK1 inhibitors, and EZH2 inhibitors among molecular targeted therapies, has significantly improved treatment efficacy, with single-agent response rates reaching as high as 40% to 50%. This achievement marks a significant step forward in treatment. In contrast, while advancements in the treatment of peripheral T-cell lymphoma not otherwise specified , have been less pronounced than those for the aforementioned subtypes, research and development continue unabated.Looking back at the history of treatment, from the traditional CHOP regimen to the current CHOP+X combination therapies, and particularly over the past decade, the incorporation of epigenetic drugs such as HDAC inhibitors (including romidepsin, pralatrexate, and domestically developed chidamide) has further enhanced treatment outcomes, resulting in an improvement of approximately 20% to 30% in efficacy.Looking ahead, with the continuous advancement of science and technology, the revelation of new mechanisms of action and the continuous emergence of new drugs, have brought unlimited possibilities for the treatment of peripheral T-cell lymphoma. We firmly believe that the saying, “The road ahead is long and arduous, but with perseverance, we will reach our destination. Keep moving forward, and the future is full of promise” inspires us to continue exploring and bring more effective treatments to patients worldwide.”

Professor Swaminathan P. Iyer is a specialist in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. His expertise includes hematology-oncology, chronic myeloid leukemia (CML), acute myeloid leukemia, multiple myeloma, hematopoietic stem cells, myelodysplastic syndromes, stem cell transplantation and chemotherapy.

Dr. Lihua Qiu is the Deputy Chief Physician in the Department of Lymphoma at Tianjin Medical University Cancer Hospital and a Visiting Scholar at Moffitt Cancer Center. He serves on several key committees, including the Lymphoma Committee of the Tianjin Anti-Cancer Association and the Chemotherapy Professional Committee of the China Medical Education Association. Specializing in tumor chemotherapy and the clinical research of malignant lymphoma, Dr. Qiu has published over 20 papers in national and international journals.