Selecting Among Available Treatment Options for Patients With Relapsed/Refractory DLBCL

Caron Jacobson, MD, and Matthew Lunning, DO, FACP, assess the available treatment options for patients with R/R DLBCL.

Grzegorz S. Nowakowski, MD: Right now, the reality is that about 30% to 40% of our patients will relapse after R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone], and typically, those relapses happen relatively soon after therapy. Those are associated with poor prognosis. Caron, how do you choose treatment for patients with relapsed/refractory disease? What are your pathways in the clinic?

Caron Jacobson, MD: Because of some of the randomized studies in the second line of CAR [chimeric antigen receptor] T-cell therapy, the first question is: how soon did they relapse after their frontline therapy? If it’s within the first year and they’re a candidate for CAR T cells, 2 of the studies, which we’ll talk about later, would say we should be moving forward with CAR T-cell therapy in that setting.

If they’re relapsing after a year from their initial therapy, then I ask myself: are they an autologous stem cell transplant candidate? In which case, I’d treat them with second-line chemotherapy—either standard options like R-ICE [rituximab, ifosfamide, carboplatin, etoposide] or R-DHAP [rituximab, dexamethasone, cytarabine, cisplatin]—or a clinical trial, because there are clinical trials with some of these new agents that we started to talk about today—looking at them in combination with standard chemotherapy. If they have a good response, take them to autologous stem cell transplant. If they don’t, then it’s CAR T-cell therapy. That’s how I usually approach it.

Frederick Locke, MD: That’s exactly how we do it at Moffitt Cancer Center as well. That brings up the question of who is a candidate for CAR T-cell therapy versus transplant? There has been some thought that they have similar eligibility criteria, but in reality, we’re able to get some of the older patients with more comorbidities through CAR T-cell therapy—patients on whom we wouldn’t have necessarily done autologous transplant. It’s important that those patients get referred in and considered, and at least have the conversation and discussion rather than make assumptions about it based on what we’re used to in the transplant setting.

Matthew Lunning, DO, FACP: I take pause when I get a CAR T-cell referral and I say that this is a large cell lymphoma referral. It’s part of my job to look at the landscape and understand that CAR T cell is 1 piece of the landscape in relapsed/refractory diffuse large B-cell lymphoma. Because while the disease may be shunting you toward CAR T cell, other factors may not. What are those? Logistics, caregivers, financial ramifications, and insurance ramifications. All those things are factored in. You may want to do CAR T-cell; the intent may be to do CAR T cell, but you just can’t do it, so you have to be able to pivot, and maybe give another therapy while you work on or fine-tune their CAR T cell ability in that situation. It’s incredibly frustrating when you want to go to CAR T but you can’t, but we all sometimes live in this reality.

There are meaningful therapies that have response rates and can have some durability in the relapsed/refractory setting. But we have to be very choosy in what those therapies are, because if they’re going to engage the same antigen that the CAR T cell is, what are the ramifications of that? Often in the short term—maybe if you can have time away from those therapies—there may be less of an issue, but we’re in a relative data-free zone in regard to that. This is a major chess match against a grandmaster opponent in this situation. What piece you move matters, even if the queen is your CAR T cell.

Grzegorz S. Nowakowski, MD: I like your comment that we should look at the whole picture as large cell lymphoma referral rather than CAR T cell referral because it fits in the landscape of rapidly changing therapies in this space. What therapies are you typically considering in your patients who aren’t CAR T-cell candidates due to medical reasons, insurance, logistics, or just refusal?

Matthew Lunning, DO, FACP: The landscape has been a landslide from the standpoint of what was there has flown away, and we’re looking at new territory in regard to relapsed/refractory diffuse large B-cell lymphoma. What they did in their first-line setting or second-line setting, how they tolerated certain therapies, and what they received matters. Personally, it also depends on my intent. Is my intent to go to CAR T-cell therapy? Are they not a transplant candidate? Because usually the reasons that they aren’t is because their disease is refractory, not that we didn’t want to take them to an autologous stem cell transplant in certain circumstances.

Transcript edited for clarity.

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