Brian Hill, MD, PhD: The question often comes up: What percentage of patients are refractory or relapse after standard frontline therapy? Depending on the risk category, this could be as high as 30% or 35% of patients who initially respond to R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] and then relapse, or a primary refractory. Primary refractory disease is fairly rare, probably less than 5% of patients. But it does occur, and it typically results, or is manifest by, a positive PET [positron emission tomography] scan or a progressive disease during primary care for your R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]. The more common scenario, which is going to occur in about up to a third of cases, is relapse after achieving a remission. Usually those relapses occur in the first year or 2 after completion of primary therapy.

Andre Goy, MD: For the patient with refractory/relapsed lymphoma, these patients can receive salvage chemotherapy and then high-dose therapy and transplant. The question is, is that who can qualify for this? Well, for the patients who are in first relapse and have chemotherapy-sensitive disease—the more chemotherapy sensitive, the better—reaching a PET-negative prior to high-dose therapy and transplant clearly has an impact. The issue here is that some of these patients are not great candidates for transplant high-dose therapy, but also some of these patients do not respond well to the second line. The primary refractory patients and the early relapse do very poorly in that setting. So this is not something that we actually recommend necessarily.

When you look at the overall in a patient in the R-chemotherapy [rituximab chemotherapy] era, the outcome of patient after high-dose therapy and autologous stem cell transplantation is still in the range of only 10% to 15% of the patients that you save. This is not the perfect option at this point, but thankfully we have other options we’ll talk about, including cell therapy.

The patients who are eligible for transplantation are really an unmet need. Similarly, so are the patients who fail after transplantation. There is some option now, so we’ll talk about CAR T [chimeric antigen receptor T cell] and cell therapy in a minute. But it may be easier to use. The polatuzumab data refer to BR [bendamustine, rituximab], which was very impressive and is approved. It was 40 patients per arm, but the CR [complete response], which was the primary end point, was 40% versus 15% and with a very significant difference in duration of response and survival. This is interesting. The R2 [lenalidomide, rituximab]–ibrutinib is something that we presented updated at ASH [American Society of Hematology Annual Meeting] in a non–GC [germinal center] subtype. It’s important because we go with age: Up to two-thirds of elderly patients, over 70 and above, can be ABC [activated B-cell] or non-GC subtype, so this is really 1 of the unmet needs we alluded to before.

For these patients, R2 [lenalidomide, rituximab]–ibrutinib, during the chemotherapy-free part, we had a response rate of 60% and some very durable response. Patients were well over 3 years with the disease control with R2 [lenalidomide, rituximab]–ibrutinib, particularly in a non-GC diffuse large cell lymphoma. This is something to keep in mind. Finally, there are the L-MIND data, which is lenalidomide plus anti-CD19, tafasitamab, and the response rate in this situation was also very impressive and very durable. This is really potentially an option and that has been combined in a frontline setting in the context of BR/POLA [polatuzumab], or bendamustine-rituximab and POLA [polatuzumab], so we’re trying to integrate this novel therapy in the frontline setting.

In patients who are not candidates for transplant, this is really again an unmet need. Those are perfect candidates for clinical trials, and we’ll talk a little more about cell therapy in that setting. But in reality, the patients who are truly not eligible for autologous stem cell transplant because of frailty or comorbidities are not going to be necessarily great candidates for CAR T cell, at least at this point.

Julio Chavez, MD, MS: What’s a typical response and duration of response after R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]? This is a challenging question, and it all depends on where you get the data. If we talk about outcomes in real life, the R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] outcomes are worse, as opposed to clinical trials in which there is an inherent selection bias. We tend to select the healthier and less sick patients in trials, so they will probably tolerate better the treatment and they will complete the treatment, and also patients will have less aggressive disease.

In general, what I see in my general practice is about 60% to 70% of patients are cured with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]; the rest, 30% to 40% of patients will either relapse or remain refractory. In terms of long-term remission, probably the most important data that we have is on the GELA [Groupe d’Etude des Lymphomes de l’Adulte] study, the French study that compared R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] versus CHOP [cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], that showed that about 50% of patients were still alive at 10 years’ follow-up.

Transcript Edited for Clarity