John P. Leonard, MD: I want to get into stem cell and CAR [chimeric antigen receptor] T [cell] and more aggressive approaches in a minute. Before we get to that, I’m going to ask for Kami’s thoughts on the less aggressive approaches or the nontransplant approaches. Let’s say a patient who had R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] is in their late 70s, relapses 2 years later and is not a transplant candidate. What’s the chemotherapy approach for that patient? And we now have the CD79B antibody-drug conjugate polatuzumab. How do you think about the approach to the nontransplant candidate at this point?

Kami Maddocks, MD: Typically a patient who is a nontransplant candidate, if they’ve had a prior response to chemotherapy, the first thing I’m going to offer them is R-GemOx [rituximab, gemcitabine, oxaliplatin]. About half the patients or a little better than half will get a response, although it’s usually less than half who have received prior rituximab again, which is going to be everybody we see anymore. In less than 6 months, patients will get a response.

We do now have this CD79B antibody-drug conjugate polatuzumab available in combination with bendamustine or rituximab chemotherapy. In the United States this is approved as third-line therapy, although it sometimes can be given in the second-line setting. It’s approval is after a patient will have failed another treatment at relapse. This approval was based on a randomized study that compared it with BR [bendamustine, rituximab].

I’ll be honest, the responses to bendamustine-rituximab, while it is active in large cell, are very short lived. The trial showed that adding the polatuzumab to BR significantly improved the rate of overall response, complete remission, and the progression-free survival close to a year. This is an option I offer patients who are candidates for treatment for the chemotherapy because it includes BR.

The downsides are that it does cause more cytopenias—and that can be a problem when patients received prior chemotherapy—and the neuropathy. For most of the patients in the study, their neuropathy improved or resolves, but neuropathy is often a problem in patients who have had R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] and have had a vinca alkaloid before. Those are the challenges with having that in mind.

John P. Leonard, MD: It sounds like your approach is a chemotherapy for the nontransplant candidate, a chemotherapy-based approach as a second line, and then going to polatuzumab as part of the third line. Is that more typical? Nathan I’m going to ask your approach in a second as well.

Kami Maddocks, MD: Other options for patients are the oral therapies lenalidomide and ibrutinib, and both have shown to have activity in nontransplant patients. Ibrutinib’s activity tends to be limited to the non–GC [germinal cancer] patients, whereas lenalidomide’s activity is unclear but suggested for those patients. I’ll offer ibrutinib in some of the non-GC patients, and I’ll offer R-len [rituximab, lenalidomide] in some of the patients if I feel that’s a reasonable approach.

John P. Leonard, MD: I’ll mention because we touched on polatuzumab that there are randomized trials as part of up-front therapy comparing the R-CHOP R-CHP-POLA [rituximab, cyclophosphamide, doxorubicin, prednisone, polatuzumab vedotin] vs. R-CHOP, as well as studies using R-GemOx. Nathan, in your approach in the nontransplant candidate, do you also use chemotherapy, polatuzumab, chemotherapy, novel agents? What’s your general approach there?

Nathan H. Fowler, MD: There are a couple ways to talk about it. In patients who are not transplant eligible, long-term remission from any chemotherapy-based regimen is only about 15% of patients. If you’re not transplant eligible and you have a relapsed large-cell lymphoma, everything is palliative. We are, in general, trying to hold this thing in base.

I know you can try a lot of different things, but if I have something a patient who is at very high risk of dying of this disease, then I really have to think about the toxicity of any salvage regimen because we want to ensure that we maintain as much quality of life as possible. It’s very different in patients who have a localized relapse because I’ll radiate if I’m not going to transplant. If they are older and have a lot of systemic disease, I’ve seen a lot of good responses with R2 [lenalidomide, rituximab].

We’re seeing some very interesting outcomes in elderly patients with CAR T-cell therapy, so trying to get them into some type of cellular therapy or clinical trial is a great option. Polatuzumab—I do use this. I’m not that impressed with bendamustine as a drug for salvage relapsed large cell lymphoma.

Transcript Edited for Clarity