R/R DLBCL: A Glance at Using Novel Therapies Moving Forward

Ian W. Flinn, MD, PhD: Kami, let’s ask you to look into your crystal ball. In solid tumors, the checkpoint inhibitors, the immunotherapies are often the mainstay of treatment for many diseases. Today R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], as we started the conversation discussing, is really our most common therapy for patients with diffuse large B-cell lymphoma. But we do have exciting data with these other forms of immunotherapy. Do you foresee a day when we’re abandoning chemotherapy? If that is possible, what would it take for us to get to that point?

Kami J. Maddocks, MD: The first thing to recognize is the progress that we have made in the last handful of years in relapsed/refractory diffuse large B-cell lymphoma. Previously, if you were going to get to autotransplant, you didn’t have curable disease and you didn’t have effective outcomes. Now we have CAR [chimeric antigen receptor] T-cell therapy for the patients who can’t get to autotransplant or relapsed autotransplant, and we have bendamustine and rituximab with polatuzumab-tafasitamab-lenalidomide, which have all improved outcomes in patients who otherwise would get palliative therapy.

Moving forward, when you look at the role of CAR T, I do think that this is going to be used earlier in therapy in a large number of patients. There will be select patients who relapse late and are going to benefit from chemotherapy and transplant. But as Loretta mentioned, a lot more are going to be getting CAR T at first relapse. And for those high-risk patients—whether we define them as not achieving an early response to CHOP [cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]–based chemotherapy by either a PET [positron emission tomography] scan or circulating tumor DNA—I think we will be moving on to CAR-T earlier.

In regard to CAR T as primary therapy, based on the way it’s given now, it’s hard to imagine using it as frontline therapy. Just considering the logistics of giving this therapy, patients with aggressive large B-cell lymphoma can’t wait 3 to 4 to 6 weeks to get their first line of therapy, right? So that’s saying that there’s not going to be a role, especially in the frontline setting. We’re a far way off from that.

I do think about things like Jason Westin’s SMART START study that looked at the role of limited therapy and nonchemotherapy in select patients leading in. Then they used a normal course of chemotherapy. In select patients, they were able to reduce the amount of chemotherapy, potentially not giving it in some patients. I think that’s in the future. 

We’ve come to recognize that large B-cell lymphoma is very heterogeneous, and these patients cannot all receive 1 treatment. We’ve looked at therapies directed at these different subsets of patients. At the same time, when you look at the therapies that have been approved—CAR T, bendamustine and rituximab with polatuzumab-tafasitamab-lenalidomide—these are active across different subsets of patients. So looking at incorporating some of these treatments into the management of patients and using them as combinations may be beneficial to these patients.

Ian W. Flinn, MD, PhD: It sounds as if there is a lot of opportunity out there, and it is a problem. I guess it’s something to strive for.

Transcript Edited for Clarity