Editor's note: On December 5, 2020, the 62nd annual meeting of the American Society of Hematology (ASH) will be held online, bringing together blood oncologists and academics from around the world to announce some of the biggest advances in hematology.At the annual expert face-to-face session, researchers share the issues that blood academics focus on in the industry.
Oncology Frontier invite Prof. Mark Roschewski, a lymphoma direction expert at the National Cancer Institute (NIH), discussing issues of concern in the field of lymphoma.
Q1.How can we better treat patients with untreated follicular lymphoma? Could you please introduce the updated studies focus on untreated FL?
Prof. Mark Roschewski: Patients with follicular lymphoma have a lot of treatment options currently and most of them are effective at obtaining remissions. There is still 15-20% of cases that are high-risk for early progression after standard therapy and identifying who these patients are is a huge priority. Those are the patients who should be prioritized for novel approaches. The biggest issue is identifying regimens that are able to obtain durable remissions that last years without indefinite or prolonged therapy. A number of targeted agents and targeted agent combinations are being tested in this regard. The ultimate goal is to identify regimens that have fewer toxicities than chemotherapy – particularly long-term effects and provide more options. There is also an interest in prediction medicine biomarkers that may useful for selecting specific treatments.
Q2.Why patients with large B-cell lymphoma fail CAR T-cell therapy & how to manage them?
Prof. Mark Roschewski: The complete picture of why CAR-T does not work in every case is not fully known. In some cases, it relates to a loss of the target (i.e. CD19) but other mechanisms also play a role and may have to do with T-cell fitness, persistence, and function. A number of studies are addressing these mechanisms now. We do not yet know anything about molecular features that predict response to CAR-T at this point.
Q3. Could you please introduce overall strategies for secondary CNS lymphoma?
Prof. Mark Roschewski: Secondary CNS lymphoma is a real clinical problem. Typically, these are aggressive lymphomas that have secondarily involved the CNS after initial therapy but also include cases with concomitant peripheral disease and CNS at first presentation. These patients are difficult to cure because they have often just completed induction therapy and have limited bone marrow reserve. In addition, the number of treatments available is small and often include agents that have just been given (like MTX). We see that a substantial subset of these patients have underlying B-cell receptor signaling and respond to BTK inhibitors such as ibrutinib. We are testing that now in an ongoing clinical trial. Other options include CAR-19 therapies which have had some success at inducing remissions. In all cases of remission, stem cell transplant is often considered and both autologous stem cell transplant as well as allogeneic transplant are often considered. The problem of course with these approaches is that they are not available to all patients and often require a remission to be most effective.
Q4.Could you introduce advances in ctDNA for lymphoma prognosis?
Prof. Mark Roschewski: Circulating tumor DNA is an emerging biomarker that can be used in many ways for lymphoma. The current applications are all research, but include baseline prognostication, response assessment (measure of MRD), and as surveillance tools after therapy to help guide therapy. At this point, no clinical utility has been demonstrated.
Q5.Could you please summarize how to utilize MRD to improve outcomes in lymphoma patients?
Prof. Mark Roschewski: MRD in aggressive lymphomas is probably the best way to identify patients who will require additional therapy to achieve cure. I think about the way that MRD has revolutionized the way we treat acute lymphocyte leukemia and that is model here. If we can identify patients who are in remission by scans but have persistent disease, we can prioritize them for salvage therapy. The earlier this can be determined, is probably better so there is significant interest in interim monitoring to avoid therapy that will not be curative.