What Happens When You Add Mosunetuzumab + Polatuzumab to CAR‑T (axi‑cel)? | Jay Spiegel, MD

So, my name is Jay Spiegel. I'm an assistant professor at the University of Miami Sylvester Comprehensive Cancer Center, and I'm presenting an abstract today on combining two active drugs—mosunetuzumab and polatuzumab—with axi-cel, which is a CAR-T therapy for recurrent, refractory aggressive large B-cell lymphomas.

CAR-T therapy has been approved since 2017 for aggressive large B-cell lymphomas and can put many patients into complete response—meaning we can't detect the tumor anymore, about 60%. However, long-term remission, where patients remain alive and disease-free, is only about 30–40%. This suggests that most patients’ disease eventually comes back, even if CAR-T is initially effective.

We designed this trial to see if we could increase the number of patients achieving long-term responses. Over time, new active agents targeting the immune system, like mosunetuzumab, and novel chemotherapy agents like polatuzumab, became available. So we decided to combine them with CAR-T therapy in what we call a “total therapy” approach—before, during, and after CAR-T.

This phase 2 trial aimed to enroll about 30 patients, and we are reporting on the first 25. The trial structure involved giving mosunetuzumab and polatuzumab before the CAR-T infusion. Patients then received CAR-T along with one dose of mosunetuzumab, and were eligible for three more doses of mosunetuzumab and polatuzumab afterward.

Our primary goal was to evaluate the complete response rate three months after CAR-T infusion, as a measure of effectiveness. We aimed to exceed a 40% complete response rate. At day 90, the complete response rate was 92%, which is very exciting. Even more encouraging, this response appears durable—at one-year follow-up, 79% of patients remain in remission. Typically, patients who are in remission at one year rarely relapse.

Regarding safety, CAR-T therapy can cause cytokine release syndrome (CRS) and neurotoxicity. Using axi-cel, which is generally associated with more toxicity than other CAR-T products like liso-cel, we observed CRS in about 95% of patients, mostly low grade and easily treatable. Neurotoxicity occurred in about 60% of patients, with grade 3 toxicity in 29%, similar to what we see with axi-cel alone.

We also monitored long-term risks such as infections and low blood counts. About 40% of patients experienced a grade 3 infection requiring IV antibiotics or hospitalization—all were treatable. Some patients had prolonged low white blood cell counts, but by one year after CAR-T, blood counts had largely recovered.

In summary, this combination therapy shows a very high response rate that appears durable. Toxicity is consistent with what is expected for CAR-T therapy. Our goal is to follow up with a second study that randomizes this combination against CAR-T alone to determine whether it truly improves outcomes.

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