DLBCL: Treating Patients Following Relapse on Frontline Therapy

Ian W. Flinn, MD, PhD: Thankfully many patients don’t relapse, but there is a group of people who do. Some have some of these high prognostic risk factors, some do not. Can you talk a little about what you do after frontline therapy? How do you approach that patient?

Loretta J. Nastoupil, MD: Fortunately, a good portion of patients do very well. We’re particularly nervous about identifying those who will not do well. And so, prior to initiation of treatment, we’re always trying to risk stratify patients and see if there’s something other than CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] chemotherapy. We utilize PET [positron emission tomography] scans in the midst of therapy, with all of the caveats in terms of the positive predictive value and how important the interim PET is. But we’re always looking for any sign that a patient is going to fail.

A small portion of patients fail in the midst of CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone]-like therapy. It’s a larger portion who fail within the first 12 months of treatment. Another small percentage will have late relapses. My approach to those 3 different scenarios is different. We saw some data emerge at ASH [the American Society of Hematology 2020 annual meeting] utilizing an interim PET in these predefined high-risk patients—those who had double-hit features and high IPI [international prognostic index score] who had an interim PET after 2 cycles of CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] or CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone]-like therapy. If they failed to achieve a Deauville score of 1 to 3, they may be eligible for intervention with something like axi-cel [axicabtagene ciloleucel], or CAR [chimeric antigen receptor] T-cell therapy.

Again, there are caveats to that. These are patients who were treated at centers that had access to CAR T-cell therapy. These are patients who had a Deauville score of 4, and maybe they would have gone on to do well. Nevertheless, it identifies how we might utilize the tools at our disposal to find or identify those high-risk patients for whom we might start down a path separate from more intensification of chemotherapy. But again, I recognize that there is a portion of patients who do very well with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], and we’re stuck with surveillance imaging.

I think the other technology that might emerge and might be useful in this setting is cell-free DNA. This could potentially help identify patients who are going to fail outside of our traditional imaging approaches such as PET and CT scans. We saw some differentiating data at ASH 2020 with the adaptive approach not being an effective strategy, but maybe the CAPP-Seq [cancer personalized profiling by deep sequencing] cell-free DNA is a strategy that might be employed. I think it’s too soon to decide what the preferred method is, but I do think there is optimism surrounding that strategy to identify high-risk patients, maybe even before they fail on a PET scan.

I think the other thing that I don’t put as much emphasis on in the relapsed setting is cell of origin, or even double-hit cases. I have not adopted an approach for which I might approach them differently. I just know that if they fail early, they do poorly. If they fail late, they might do better.

Ian W. Flinn, MD, PhD: Kami, to follow up on what Loretta was saying, do you find that to be the same? Let’s take 2 equivalent patients, or 2 patients who relapse 9 months after completing R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. I think Loretta was saying it really doesn’t matter at that point whether they were a GCB [germinal center B-cell] or non-GCB patient. The approach is going to be relatively the same. Is that what you do at The Ohio State University Wexner Medical Center? What do you do for that patient?

Kami J. Maddocks, MD: I completely agree with that. The biggest indicator is going to be if they’re primary refractory or have an early relapse. We have been fortunate enough to currently have and had the prior trial looking at sending patients to CAR T. Patients are randomized to standard of care with salvage chemotherapy and autologous stem cell transplant versus early CAR T. I try to get patients on that study because I think this may be a population that benefits from that.

I think that is best for those patients. Outside of a study, we don’t have a different practice for our standard of care for these patients. Hopefully that will change.

Transcript Edited for Clarity