ASH 2025 | Treatment sequencing in R/R follicular lymphoma: bispecifics and CAR T-cell timing

Certainly we continue to see progress in our approach to patients with relapsed or refractory low-grade follicular lymphoma. We had important readouts from the first FDA approval of bispecific antibody-based combination treatment in the second-line setting, work led by my friend Lorenzo Falcone in the so-called ER-squared regimen, mosunetuzumab plus lenalidomide and rituximab. And this led to FDA approval for this treatment. It is quite intensive treatment. It’s a year of therapy with a fair amount of treatment visits, but extraordinarily favorable outcomes with an overall response rate of 95% and a complete response rate of 87%. These data are still maturing. We’ll see how durable those remissions are, but early signal is certainly quite favorable. But I think this highlights our emerging understanding that bispecific antibodies can and indeed likely should be used in earlier lines of treatment, whether as monotherapy or in combination, and which bispecific antibody is best and with which partners continues to unfold, even as we do first-line studies trying to leverage bispecific antibodies, even for the treatment of newly diagnosed follicular lymphoma. In diffuse large B-cell lymphoma, we’ve really hammered the message that early referral for CAR T-cell therapy is the standard of care, and increasingly, you know, the so-called CAR ineligible patient population continues to narrow as we gain increased confidence in our ability to manage the toxicities of CAR and recognize its maximal curative potential in this context. For relapsed follicular lymphoma, that story is not so clear. And indeed, I believe that the field in some ways is moving towards favoring bispecific-based approaches and reserving CAR T-cell therapy for bispecific antibody refractory disease or in disease that has lost expression of CD20, which is the target of all of our commercially available bispecific antibodies right now. And CAR T-cell therapy for follicular lymphoma is becoming increasingly reserved for post-bispecific or for the true histologic transformation patients who are being treated more aligned with a diffuse large B-cell lymphoma paradigm.

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