Ian W. Flinn, MD, PhD: Amit, let’s turn to you. Can you walk us through the recommended treatment options for second-line therapy? Kami just talked about a trial looking at CAR [chimeric antigen receptor T-cell therapy, but we have transplant in that setting. What is your standard of care?
Amitkumar Mehta, MD: I think the standard of care is still a consolidated bone marrow transplant for patients who are chemotherapy-sensitive. If you look at the recent data, even for patients who had a partial response, if you pursue the transplant, they still have a progression-free survival at 3 years of about 40%. In those patients, the first question I ask is whether they are a candidate for transplant. I always say that beauty lies in the eyes of the beholder. You cannot make a decision on your own. I always like to have a consultation with my transplant colleagues. If they don’t have any red flags that this patient is absolutely not eligible for transplant, the plan is to consider salvage chemotherapy: R-ICE [rituximab, ifosfamide, carboplatin, etoposide], R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin], or gemcitabine–based treatment. None of them, except for R-ICE [rituximab, ifosfamide, carboplatin, etoposide] and R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin], which were compared head-to-head, turn out to be similar in terms of response rates.
When investigators looked at the GCB [germinal center B-cell] and ABC [activated B-cell] subtype, there was a subgroup analysis where the GCB subtype had a bad response with R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin]. So in some patients, if they can handle cytarabine, that is my favorite approach. Once they get salvage treatment, if they respond, if there is a response on the PET [positron emission tomography] scan, then I consider consolidated autologous stem cell transplantation.
I agree with everybody else. At the academic centers, these are the patients, especially primary-refractory patients, who are an area of need. They may qualify for multiple clinical trials. When ZUMA-7 was up and running, that was a trial for which we would consider these patients; it randomized patients between salvage transplant versus axi-cel [axicabtagene ciloleucel]. There are many others also looking at that approach. If the patient qualifies, we would probably consider enrolling him or her on the trial.
Ian W. Flinn, MD, PhD: John, Amit just went through a variety of salvage regimens, but the question comes up, not infrequently: Should we be using a CD20 [antibody] at all? If we do, should we be switching to a different anti-CD20? Should we switch from rituximab to obinutuzumab? How are you approaching this? If you decided that you did want to do it, is it even feasible? Can you get that approved?
John M. Burke, MD: I haven’t personally made the switch to obinutuzumab or ofatumumab or anything like that. Based on the GOYA study, where obinutuzumab was not better and did add a little toxicity in the frontline setting, it’s not a strategy that I have tried. Back many years ago when I was training, the group I was with at Memorial Sloan Kettering Cancer Center looked at the value of adding rituximab to ICE [ifosfamide, carboplatin, etoposide], and it really didn’t add much benefit. But I think most people probably still do it, myself included. If I have a patient with CD20-positive large B-cell lymphoma who relapses, I’ll generally add rituximab to the salvage regimen, whether it’s ICE [ifosfamide, carboplatin, etoposide] or DHAP [dexamethasone, cytarabine, cisplatin].
That’s been my practice. I don’t know the answer to your question, Ian, about using obinutuzumab or some other anti-CD20 antibody, whether it would be authorized. I don’t know.
Transcript Edited for Clarity