ASH 2025 | Three-year follow-up of a Phase Ib trial of mosunetuzumab plus polatuzumab vedotin in R/R DLBCL

I presented the three-year follow-up of the fixed-duration treatment of mosunetuzumab, a CD20 T-cell engager, in combination with polatuzumab, a CD79B-directed antibody drug conjugate, in patients with relapsed/refractory large B-cell lymphoma. This is a Phase Ib study, and initial results, the primary analysis, has already been presented, which showed an exceptional durable efficacy, as well as safety profile for the doublet. So, just so that I can make the audience aware, mosunetuzumab and polatuzumab were given in a time-limited fashion. Mosun was initially given in cycle 1 as a ramp-up, followed by every three-week administration. If patients had achieved a complete response after cycle eight, mosun was stopped. And if they had achieved less than a complete response, they would continue it up to 17 cycles. Polatuzumab was administered every three weeks for a total of six cycles. A total of 98 patients were enrolled. These were transplant-ineligible patients. They had to receive one or more prior line of CD20 chemoimmunotherapy in the past. They had to have an ECOG of 0 to 2 and these patients were enrolled on the expansion cohort of this Phase Ib follow-up study with a fixed duration combo. The baseline characteristics of this patient were the median age was 68 with a range that was wide with the oldest patient that was an octogenarian. In addition to which, it’s important to also bear in mind that the prior line of treatment median was 2 with a range of 1 to 8. Majority of patients were stage 3, stage 4. More than 50% of patients had elevated LDH, extranodal sites of involvement, and an IPI score of three to five. So it was a very heavily pretreated population. Now let’s take a look at the data. With regards to the follow-up data, the overall response rate for the entire cohort was 62%, which translated into a complete response rate of over 50%. In addition to which, on this study, there were four cohorts that were pre-specified and analyzed, namely primary refractory early relapsing, as well as patients who had received prior CAR-T. 36% of patients had actually received prior CAR-T, of which 70% were refractory. So in these four cohorts, the overall response rate was absolutely comparable to the overall cohort. In terms of duration of response was also durable and in the range of 40 months. Now let’s look at the progression-free survival and the overall survival data. The three-year progression-free survival was over 40% for the entire cohort, translating into a three-year progression-free survival of over 45% in terms translating into a three-year overall survival of more than 45%. So, in net, the efficacy continues to look quite durable, where a significant subset of patients continue to be in response. With regards to safety signals, there were no new safety signals that were seen. There were two infections that were reported, primarily COVID-19 and influenza in the same patient. With regards to B-cell depletion, majority of the patients regained B-cell function 12 months after completion of the protocol. So the net is that at the three-year mark, this combination is a very safe outpatient delivery absolutely is possible and feasible, extremely efficacious regimen in a transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma population.

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