The 2022 Tandem Meetings | The evolving treatment landscape of R/R LBCL

I think there are, fortunately we are investigators practicing in the field of really novel, promising constructs that are looking very efficacious as well as very safe in patients with relapsed/refractory large B-cell lymphoma. Previously all we had was chemotherapy. And I think now the field is moving forward. In the field of immunotherapy, I think we have had multiple drug approvals for patients with relapsed/refractory large B-cell lymphoma. These are technically considered chemo-free or just targeted chemotherapy agents. For example, the FDA currently has approved for example, tafalen, tafasitamab and lenalidomide for primary refractory large B-cell lymphoma who are transplant-ineligible. And then there is CAR-T therapy, of course, in the third-line setting. And then now in the second-line setting axi-cel was approved for patients with high-risk, large B-cell lymphoma. There was polatuzumab plus bendamustine rituximab that is approved for patients who have failed two lines of treatment and are transplant-ineligible. And then there’s loncastuximab, which is the antibody-drug conjugate, which also showed very impressive responses in transplant-ineligible patients who have had two or more prior lines of treatment. So I think this is what we currently have, but in addition to that, I think things are beginning to look very promising.

And I think one of the most promising constructs in my opinion would be bispecific antibodies. So there was a lot of data that was presented at ASH and these data looked very impressive. For example, the data that was presented for mosunetuzumab, glofitamab, mosunetuzumab plus polatuzumab. These were patients who were heavily pretreated, aggressive large cell lymphoma. Other relapsed/refractory B-cell lymphoma patients were also included. I think most striking was the fact that some of these patients had been exposed to prior CAR-T therapy. And it seemed like these bispecific antibodies seem to have efficacy in those patients as well. I think most importantly, also to notice the fact that the toxicity profile was very manageable. So of the multiple other agents that are currently being worked up in the immunotherapy forum, I would say bispecific antibodies catch my attention the most.

And then of course we do continue to improve upon the chimeric antigen T-cell receptor constructs. So we currently have a CD19 CAR-T therapy and thus these many clinical trials, which have really helped. At least 40% of patients would’ve otherwise succumbed to their disease historically in the past.

The new unmet need is patients who relapse after CAR T-cell therapy. And I think there has been excellent data with bispecific CAR-T therapy with CD22 CAR-T therapy besides just large cell lymphoma. I think there was some excellent data that was presented at TCT by Dr Natalie Grover in patients with relapsed/refractory Hodgkin lymphoma with a CD30, a CCR4 expressing CAR-T construct, and the results look very promising so far. So I think the field continues to evolve and we just have just so much more optimism for patients who have relapsed/ refractory B-cell lymphoma with all of these promising novel molecules.