Dr Anna Sureda on the Evolving Treatment Landscape for Relapsed/Refractory DLBCL, Follicular Lymphoma

Anna Sureda, MD, PhD, president of the European Group for Blood and Marrow Transplantation (EMBT), head of the clinical hematology department at the Catalan Institute of Oncology, explains how the treatment landscape for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma has evolved significantly, with chimeric antigen receptor (CAR) T-cells, bispecific monoclonal antibodies, and other novel therapies now offering promising options beyond traditional chemotherapy and stem cell transplantation.

She expanded upon this topic last month at the European Hematology Association (EHA) 2024 Congress during the sessions "New Frontiers in Relapsed/Refractory B Cell Lymphomas: Current and Future Roles for Bispecific T Cell Engagers (TCE)" and "Pursuing New Heights in Lymphoma Care With Bispecific Antibodies."

This transcript has been lightly edited for clarity.

Transcript

Could you provide an overview of the current treatment landscape for relapsed/refractory DLBCL and follicular lymphoma?

Starting with diffuse large B cell lymphoma [DLBCL], until a few years ago, when we had a relapse patient, we were thinking about autologous stem cell transplantation as a treatment option if the patient was transplant eligible. Sometimes in those patients, relapsing after an autologous transplant, or after several lines of chemotherapy, an allogeneic stem cell transplantation was also taken into consideration. Of course, the rest of the treatment was based on the use of different chemotherapy strategies.

In the last few years, this treatment landscape has significantly changed. I would like to mention, first of all, probably the 2 strategies that I think are going to significantly change the way that we treat patients. The first one is the introduction of CAR T-cells. We know that autologous anti-CD-19 CAR T-cells constitute a curative treatment strategy for a significant proportion of patients who have failed at least 2 prior lines of therapy. CAR Ts have moved to the second line, and there are prospective clinical trials looking at the role of CAR Ts in high-risk novel diffuse large B-cell lymphoma.

The other group of drugs that I would like to mention are bispecific monoclonal antibodies that are coming into the field. They have more recent developments with respect to CAR Ts, and, nowadays, have been approved and starting to be reimbursed in Europe in third line or plus. Of course, they are also quickly moving to earlier lines of therapy.

We have other classes of different treatment strategies, so we have to think about ADCs, or antibody-drug conjugates. The two best examples are polatuzumab vedotin given in combination with rituximab and bendamustine. Also, loncastuximab tesirine has been approved for patients with multiple relapses if they have large B cell lymphoma. Also, anti-CD-19 monoclonal antibodies, like tafasitamab, are basically combined with lenalidomide for patients who are not transplant eligible. So, as you can see, the treatment landscape is very much populated in this specific disease.

If we move to follicular lymphoma, the evolution has some similarities. Until recent years, we were basically treating these patients with chemotherapy. Of course, associated with monoclonal antibodies using rituximab as a maintenance therapy strategy.

For those patients with relapsed disease, we have the possibility to use a chemo-free strategy, the R² regimen, including lenalidomide and rituximab. Those patients that have an early relapse, the ones that we call POD24 positive, have always been considered a high-risk population of patients, and, of course, autologous stem cell transplantation has been for many years the standard of care for them. At some point, we were also considering allogeneic stem cell transplant.

These treatment strategies have been significantly modified in the last few years with the introduction of small molecules and targeted therapies, but, once again, I want to mention CAR T-cells. They are still pending to demonstrate the curative potential in these patients basically because the follow-up after CAR T-cell infusion in patients included in pivotal trials is not so long, but they are able to give really impressive overall response rates, complete remission rates, and progression-free and overall survival.

Of course, bispecifics constitute probably the second group of tracks that have demonstrated to be very effective in the inpatient setting with patients with relapsed/refractory disease and moving really fast to earlier lines of therapies.