I have a patient, 50M, who presented to me for apparent relapsed follicular lymphoma (previously treated in 2013 with BR and in 2017 with R-CHOP). We biopsied one of his masses (he had extremely bulky diffuse disease) and it came back as follicular lymphoma grade 2 but with very high proliferation index, and his other indices made me clinically very concerned for transformation of disease. I ended up treating him with R-DHAP (he is on the second cycle now) and had a very strong clinical response, though I won’t be able to get more than two cycles in him due to concern about collection. At this point we are planning on CAR-T but if he has a CR on PET scan, would you consider doing a BEAM auto and holding CAR-T in reserve for him? His KPS is 100 now and he has no other comorbidities.
This is a tricky situation and one that we don't have great data for to help guide decision making. Based on this information, I share your concern for transformed disease. The ZUMA-7 and TRANSFORM studies suggested that CART is superior to standard of care (chemo + auto transplant) in primary refractory or early relapsed DLBCL, including patients transformed from follicular lymphoma. However in those studies they lump all of the standard of care patients together and don't specifically tell us how the population of patients who achieve a CR before auto transplant do compared to CART. Furthermore, we don't yet have data for patients who achieve a CR following first line therapy after histologic transformation. Therefore, when I'm in these situations I usually prefer auto transplant for several reasons. First, it is ideal to do an auto transplant when the patient demonstrates chemosensitive disease and is in a CR. If you pass up on that opportunity now you may not be able to get him back into a CR and/or he may develop chemorefractoriness in the future. Second, it will be more difficult to collect stem cells after CART. Not only will he have received additional chemotherapy because of the lymphodepletion, but many patients remain have prolonged pancytopenia/bone marrow suppression after CART which can make it more difficult to adequately collect stem cells. Third, I always worry about the quality of the T-cells that I'm collecting for CART, especially right after chemo. By doing an auto transplant now and monitoring the patient closely, if he should relapse you could potentially collect his cells before giving any additional chemotherapy and thus collect healthier T-cells. So I believe that sequencing auto transplant first gives patients the best chance and most opportunities for long term remission.