This was a randomised phase II trial of a novel combination of mosunetuzumab, a bispecific CD20/CD3 directed antibody, in combination with polatuzumab vedotin which is an antibody-drug conjugate. Patients were randomised to the control arm which included rituximab with polatuzumab vedotin, so it was essentially mosunetuzumab polatuzumab versus rituximab polatuzumab. This was a phase II trial for patients with previously treated diffuse large B-cell lymphoma trying to determine whether the change from rituximab to mosunetuzumab would provide additional benefit to patients.
What was the study design?
This was a randomised trial so 40 patients were assigned to the control arm with rituximab polatuzumab and 40 to mosunetuzumab with polatuzumab, so these patients received a bispecific T-cell directed [??] therapy in combination with the antibody-drug conjugate.
What are the key results?
In this study patients were enrolled after a median of 2-3 lines of treatment and there was a median of about 2 in mosunetuzumab polatuzumab and 3 in rituximab polatuzumab. Some of these patients were heavily pretreated with prior CAR T-cell therapy, about a third of them, and most of these patients were refractory to their CAR T-cell therapy. Half of these patients were also primary refractory to their initial treatment and some of them had very early relapse.
The results were very encouraging. We saw a total response rate of 77% in the experimental arm in comparison with 50% in the rituximab polatuzumab. The rate of complete responses was 57%. It was also very encouraging that these responses were durable among patients who achieved a complete response – over 80%, 82%, remaining at complete response after one year of follow-up. Altogether, if we look at the results of survival with progression free survival and overall survival, these are also very encouraging in comparison with other similar regimens and settings with progression free survival at one year now at 64% and overall survival of 74% for these patients who were previously refractory to their therapy
What stands out, really, among similar trials is the safety of this regimen. Clinicians are quite accustomed to delivering polatuzumab and mosunetuzumab appears to not only provide additional benefit but also is quite safe with only a 10% rate of cytokine release syndrome which was almost exclusively grade 1 and very easily manageable.
What is the clinical significance of these results?
These results led to a global phase III trial now which compares the mosunetuzumab and polatuzumab vedotin compared to standard chemotherapy with rituximab and GemOx. But the principal significance of this is that this is a novel regimen for patients with previously treated disease which is not directly compared to other options that exist like CAR T-cells or other bispecific-based combinations but really stands out in terms of its safety and the durability of responses. So we think that this regimen may be a really good option for settings, community settings, smaller hospitals or [??] settings where more intense therapies are not available.
It’s [??] hospitalisation for patients so we think this is a great option that will be developed as a potential, highly effective, really with comparable efficacy to other currently existing modalities, treatment for patients in settings where this would be the safest regimen to deliver.
