Transplant eligibility in R / R DLBCL and CAR T cell therapy

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Mazyar Shadman, MD, MPH: Over the past 2 years we have had access to a number of new agents or treatment modalities, and I’m just wondering what your standard practice is. We are awaiting some of the recently announced press releases of some comparative trials comparing standard of care to CAR [chimeric antigen receptor] T cell therapy, but for now at least we don’t have any details on these studies. Our standard approach would be to use second-line chemotherapy, platinum therapy, to achieve complete remission or maybe good partial remission as we move on to autologous stem cell transplantation. There are of course some patients who are not eligible for a stem cell transplant. I was wondering what is your approach in general with relapsing, and then also for patients who are not eligible for a transplant?

Brian T. Hill, MD, PhD: It’s a very similar approach. The norm in the United States and around the world is still taking patients who have relapsed from, say, R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] or a similar first line treatment with diffuse large B cell lymphoma and try to put them into remission, which will hopefully last a very long time. Platinum-based chemotherapies that are typically used as second-line regimens, such as R-ICE [rituximab, ifosfamide, carboplatin, etoposide] or R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin] are generally effective in doing so. Once you are in remission, consolidation with high doses of chemotherapy and rescue of autologous stem cells is the standard approach. But we know, unfortunately, that not everyone who needs a transplant is successful, and there are several reasons for this. One of the most common is not even being referred for 1 because you have to go to a transplant center. The other common thing that we see, unfortunately, is that people who relapse, when treated with, say, R-ICE [rituximab, ifosfamide, carboplatin] or similar chemotherapy, do not respond well. It is easy if they achieve complete remission to switch to a transplant, but many patients do not. Overall, the rate of complete remission with platinum-based chemotherapy has been reported somewhere in the 30-40% range, with overall response rates in the 50-60% range. Was this also your experience? Do you see a lot of patients who don’t respond to lifesaving treatment, as we call it?

Mazyar Shadman, MD, MPH: Yes, we do, and the success rate for getting a stem cell transplant in terms of responding to next lines of chemotherapy is around 50%, and then looking at an overall cure rate in this setting beyond the first line of about 20% to 30%. Not being eligible for a transplant occurs for 2 reasons, as we have discussed. To give someone high-dose chemotherapy, they must show you that they are sensitive to the chemotherapy. But I wonder about the criteria to qualify someone ineligible for transplantation, mainly for comorbidities or age and factors like that. We both come from large transplant centers. It’s hard for us to refer someone for a transplant, but it does happen. It’s a moving target. The assessment of risks and benefits changes as you have alternative options. Two years ago, I had no choice. I may have accepted a patient for a transplant with some additional comorbidities. With the treatments we are going to talk about, this assessment is different. Is this your experience? Is that what you saw? In general, what type of patient do you consider not eligible for the transplant from the point of view of comorbidity?

Brian T. Hill, MD, PhD: You must have a certain level of physical condition and organ functional status, but you are correct that the biggest determinant of what we consider eligible for transplantation is probably their sensitivity to chemotherapy. The reason fewer transplants are done, and we’ve seen this in national databases, is that if you’re not in full remission after second-line treatment, you had no options before. But now we know that even for people who have relapsed after a transplant or are not in good remission before the transplant, we have CAR T cell therapy as an option.

Maybe we should mention to the public what CAR T cell therapy is. Many people know that you can collect T cells from patients in peripheral blood and have them made, genetically engineered to express the chimeric antigen receptor. , which redirects them to the target CD19, which is present in all B cells. After a brief period of lymphodepletion, if the cells are re-administered to the patient, they have strong antitumor effects and tumor destruction, which can lead to responses and even complete remission in patients refractory to previous chemotherapy. From this perspective, we have these options for patients who might have previously been considered eligible for a transplant. Transplantation might not be their best option and maybe we should go straight to CAR T cell therapy.

This transcript has been edited for clarity.

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