Source / Disclosures
Source: Healio interview
Disclosures: Bellomo does not report any relevant financial information.
With the emergence of targeted therapies and new treatments, allogeneic hematopoietic cell transplantation has taken precedence over immunotherapy in the treatment of lymphoma.
Healio spoke with Courtney Bellomo, MD, a hematologist and stem cell transplant specialist with New York Oncology Hematology, a private and community oncology practice in the Albany area of New York, and a HemOnc today Next Gen Innovator, on the history of the use of allogeneic HSCT, where treatment fits into the current lymphoma treatment landscape and more.
Healio: How allogeneic HSCT been used historically in the management of lymphoma?
Bellomo: Allogeneic HSCT is really intended for patients with relapsed / refractory lymphoma. Patients who do not respond to conventional chemotherapy and who also do not respond to autologous HSCT are those patients who have typically been treated with allogeneic HSCT in the past. The exception to this are patients with T cell lymphoma, which can be aggressive from the start and for whom we sometimes bypass the autologous transplant. The chemotherapy-resistant group of patients was the one who underwent allogeneic HSCT, usually in the third line setting. We have also done this for our lymphoma patients when the autologous transplant was not effective as well as sometimes for those with mature leukemias.
Healio: Where does allo come fromgenetic HSCT fit into the current lymphoma treatment landscape?
Bellomo: Chimeric antigen receptor T cell therapy is changing the treatment paradigm. Follicular lymphoma is a prime example. The patient who is on third-line treatment for follicular lymphoma would likely be considered for allogeneic HSCT. We know that most follicular lymphomas are indolent, but about 20% have frequent relapses and behave aggressively and these patients would have been treated with autologous HSCT, which would always happen. But now, instead of allogeneic HSCT, we are looking at CAR T cell therapy for these patients and the side effect profile of these two treatments is very different. CAR T cell therapy can leave a patient with long-term pancytopenia or hypogammaglobulinemia, which is much more manageable than graft versus host disease, which can occur with HSCT. There is a role to play here in “taking” people away from that. CAR T-cell therapy will also change the paradigm for the use of autologous HSCT. For a patient with third-line follicular lymphoma who has undergone numerous treatments, we might have considered an autologous transplant for him in the past, but he is now eligible for CAR T therapy. that the paradigm changes in indolent lymphomas. In aggressive lymphomas, we would always do some kind of allogeneic HSCT in the hopes that it worked, but we knew that for a lot of people it didn’t work. So now we have a good option for them. CAR T cell therapy not only changes the use, but also the way we discuss the prognosis with patients.
Healio: ImmunotherapyYes Has significantly changed treatment for lymphoma, especially diffuse large B cell lymphoma. Is allogeneic HSCT still have a role in DLBCL?
Bellomo: Honestly, I’m not sure that’s the case – that’s an unanswered question at this point. In general, we treat these patients with CAR T cell therapy and if they relapse after CAR T cell therapy then we have more options, including targeted monoclonal antibodies or bispecific antibodies currently on the market. A lot of people are hoping that we can get these patients to have allogeneic HSCT, but most don’t go that far. Patients who are not eligible for CAR T therapy are not eligible for allogeneic HSCT. For those who relapse after CAR T cell therapy, it is difficult to bring them into remission because allogeneic HSCT only really works for the patient in remission. From a scientific standpoint, the question remains whether this would work. If we manipulate a patient’s T cell immunity and it doesn’t cure their cancer, would someone else’s T cell immunity still be effective? Our suspicion is yes, but we do not yet have an answer.
Healio: For which patients with allo T cell lymphomagenetic HSCT be a good option?
Bellomo: I don’t think the treatment paradigm is changing for these patients because we don’t have targeted CAR T cell therapy for T cell lymphomas. For most systemic T cell lymphomas, except for T cell lymphomas. skin T cells, we are considering autologous consolidation HSCT from the start. For anyone who relapses, allogeneic HSCT is the way to go if they are physically fit and can go into remission.
For most T cell lymphoma patients, generalized first-line therapy is only 40% effective, and then only 20-30% at best for all other lines of therapy. This means that there is a 70-80% chance that someone will not be in remission. But that’s still the way to go right now if someone relapses or doesn’t respond to chemotherapy – we’re bringing them to autologous HSCT. We can get them to an allogeneic HSCT with a low disease burden, but it won’t work if it is a serious disease. It is a matter of how they are doing about their disease course.
Healio: What strategies have summer used to improve results with allogenetic HSCT overtime?
Bellomo: This is a difficult question. We are constantly improving in the management of graft versus host disease with new therapies on the market, but as far as conditioning regimens and these changes go, I’m not sure.
Healio: What role do you think hellogenetic HSCT will play in the future?
Bellomo: We will continue to use allogeneic HSCT, certainly for our leukemias, and more than likely for our T cell lymphomas. We can continue to use it for chronic lymphocytic leukemia or Richter’s transformation because we know in the population of the Richter transformation as CAR T cell therapy is not as helpful.
The hardest part will be determining its use once commercially available CAR T-cell products are available. Right now we use the patient’s own immune system, but what happens when CAR T cell therapy or other variants are allogeneic? Then we can have minimal graft versus host disease but a different immune system, so we can almost combine these two technologies. This is where I think it’s going to be a bigger and more difficult question for allogeneic HSCT. I suspect that for leukemia a complete new reboot of the immune system with allogeneic HSCT is probably going to be helpful, but will allogeneic CAR T cells overcome allogeneic HSCT in lymphoma? Maybe, but we don’t have the science yet to know what it’s going to look like like.
Healio: Is there anything else you would like to mention for our readers?
Bellomo: It’s going to be fascinating to see where this all ends up. For example, for myeloma patients, where will autologous HSCT fall compared to CAR T cell therapy? What will CAR T look like with regard to maintenance therapy for patients? Where will allogeneic HSCT fall if CAR T cell therapy works well for second relapse leukemia? Where are all of these things going to be placed in a treatment discussion and how is that going to impact the timing of these treatments?
In general, many trials of cell therapy have excluded people with allogeneic HSCT, not all, but most of them. This is because there is a real concern about the risk: if we activate T cell immunity, will we create graft versus host disease in patients who have had allogeneic HSCT? It will not only be a question of use, but also a question of timing as we do not want to activate the immune system and cause debility due to graft versus host disease. The timing is going to be important as well as the cost and the use. All of these questions remain.
Just recently I asked a colleague at the Dana-Farber Cancer Institute about one of my patients, for whom we had previously administered allogeneic HSCT, if we now take them for CAR T-cell therapy. He said 100% CAR T cell therapy. When CAR T cell therapy is found to be effective in myeloma and follicular lymphoma, for example, allogeneic HSCT will be abandoned. In places where CAR T cell therapy may not be as effective, we may still be thinking about allogeneic HSCT, but then which should come first? It’s still something we’re trying to figure out.
For more information:
Courtney Bellomo, MD, can be contacted at [email protected]