Treatment Options for Relapsed-Refractory DLBCL

Matthew J. Matasar, MD:There are a number of treatment regimens that are available in the treatment of relapsed or refractory large-cell lymphoma. There are certainly chemoimmunotherapy programs that we choose among based on patient disease characteristics, patient preferences, toxicity profiles, and disease biology.

For patients who may have had a long duration of remission after R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisolone] chemotherapy, the regimen of rituximab and EPOCH [etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride] chemotherapy, or R-EPOCH [rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride]—remember, that was originally designed and developed as a salvage regimen. It’s still appropriate for some subset of patients, particularly those who may not have received a full course of doxorubicin-based therapy in the first line or enjoyed a long duration of remission following R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisolone] first-line therapy.

Other regimens that we used in the transplant-eligible population: Typically, platinum-based programs continue to remain the standard of care, although we know that response rates even in that most promising setting are still suboptimal.

For transplant-ineligible patients in the second line, we typically are choosing either a chemoimmunotherapy program such as R-GemOx [rituximab, gemcitabine, and oxaliplatin], BR [bendamustine, rituximab], sometimes R-ICE [rituximab, ifosfomide, carboplatin, etoposide phosphate], or the like. R-EPOCH [rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride] chemotherapy, or R-CEPP [rituximab, cyclophosphamide, etoposide, procarbazine, and prednisone], which can be administered either intravenously or orally for more frail patients. And then for patients with certain disease characteristics and certain disease biology, like nongerminal cell or double expressor lymphoma, you may look at using either rituximab combined with lenalidomide or rituximab combined with ibrutinib. Again, with palliative intent.

In the third-line setting, options become a little more varied yet. We have 2 therapeutic approaches that now have FDA approval for the treatment of third-line and beyond relapsed diffuse large B-cell lymphoma. The first of these is CAR [chimeric antigen receptor] T-cell therapy, and we have 2 currently approved CAR T-cell agents.

The first is known as axi-cel, or axicabtagene ciloleucel. The second is tisagenlecleucel. These are 2 CAR T-cell therapies that have slightly different toxicity profiles and slightly different activity profiles, both of which are approved and highly active in diffuse large B-cell lymphoma.

The second option that we now have as an FDA-approved strategy is combination bendamustine and rituximab with polatuzumab vedotin-[piiq], which is an antibody drug conjugate delivering MMAE [monomethyl auristatin E] and targeting CD79b, a surface antigen that is ubiquitously expressed on B-cell lymphomas, including relapsed diffuse large B-cell lymphoma.

Transcript edited for clarity.