'The HemOnc Pulse' Live: Unanswered Questions in Aggressive Non-Hodgkin Lymphoma

In this podcast episode from the “HemOnc Pulse” Live meeting in Chicago, an expert panel explores unanswered questions in managing aggressive non-Hodgkin lymphoma, in particular diffuse large B-cell lymphoma.

The panelists included Grzegorz Nowakowski, MD, a Professor of Oncology and Medicine in the Division of Hematology at the Mayo Clinic; Jane Winter, MD, a Professor of Medicine in the Division of Hematology and Oncology at the Northwestern University Feinberg School of Medicine; and Alan Skarbnik, MD, Director of the Lymphoma and Chronic Lymphocytic Leukemia Program and of Experimental Therapeutics, Malignant Hematology at Novant Health.

To begin, the panel observed that the past 25 years of R-CHOP study data have not shown the desirable significant increase in patient overall survival (OS), Dr. Winter remarking that PFS improvements alone are “not good enough given all the downstream therapies we have.” The speakers agreed with Dr. Nowakowski that “[R-CHOP] is ‘a’ standard of care, but it is not ‘the’ standard of care,” though not an inferior therapy.

In deciding between R-CHOP or POLA-R-CHP in a patient, Dr. Skarbnik said the two regimens have similar efficacy and toxicity, but R-CHOP has a cost benefit. An issue raised by the audience, though, was that studies comparing cost benefits between these regimens are inconclusive. Another concern raised was that whether a study uses molecular testing rather than immunohistochemistry on the cell of origin has implications for its data’s usefulness for individualizing management. The panel also touched on the debate over the reliability of subset analyses, Dr. Winter saying about such analyses “we have to use our judgment and, yes, there’s a risk. But, as you know, the risk is small.”

The panel addressed specific questions about their own treatment algorithms. To the issue of how to use chimeric antigen receptor T (CAR-T) cell therapy in patients expected to fail POLA-R-CHP, Dr. Nowakowski expects these patients would still benefit from such management but answering this question requires real-world data, which are difficult to gather. Another area of uncertainty in management where more data are needed is whether to choose R-CHOP or POLA-R-CHP in second-line therapy. Dr. Nowakowski also mentioned a trial currently underway investigating if CAR-T therapy may be improved if it is preceded by CD19 therapy.

In the final topic discussed by the panel, central nervous system prophylaxis, there was again the issue of data uncertainty, recent retrospective studies having increased doubts about the benefit from methotrexate. Dr. Skarbnik believes, among these unanswered questions, “this one…is important because it does carry toxicity, affects patients, and I feel it could be answered in a randomized fashion.” Dr. Nowakowski concurred but, again, noted that such data, needed from thousands of patients, would be difficult to obtain. Even with such uncertainty, Dr. Winter said that “I find that difficult to decline prophylaxis in those with the highest risk.”