IMS 2024 | A Phase Ib/II trial of sonrotoclax plus dexamethasone in patients with R/R MM harboring t(11;14)

I’ll summarise the Phase Ib/II study of sonrotoclax plus dexamethasone. And this study was presented or updated at the recent IMS meeting in Brazil for patients with relapsed/refractory myeloma who have the genetic change of 11;14 translocation. Approximately 15% to 20% of people with multiple myeloma will harbour the genetic change of 11;14 translocation. And in these patients, the myeloma cells express a pro-survival molecule called BCL2. Sonrotoclax is an inhibitor of BCL2 and is more potent and selective at BCL2 inhibition compared to the first-generation BCL2 inhibitor venetoclax. So in this study, patients with relapsed/refractory myeloma were given sonrotoclax at various doses up to a dose of 640 milligrams orally daily, which ended up being the recommended dose for the expansion phase of the study. And dexamethasone was given at 40 milligrams weekly orally, and treatment was given until disease progression. So in this update, 32 patients were treated with sonrotoclax and dexamethasone, and these patients had a median age of around 70 years and up to 80 years old. They were heavily pretreated. They had a median of three prior lines of treatment and up to 12 prior lines of therapy. All patients had prior exposure to a PI and an IMiD, and around 72% of patients had prior exposure to an anti-CD38 monoclonal antibody. And overall, around 50% of patients were triple-class refractory. And amongst the patients who were evaluable for efficacy, the overall response rate was 75% and 50% had a deep response, that is a VGPR or better. And CR or better occurred in around 21% of patients, with some even achieving MRD negativity. The median time to response was fast, Iit occurred in less than one month and a median duration of response was eight months. And the longest duration of response at the time of data cutoff was 18 months, which I feel is quite remarkable. Importantly, the combination of sonrotoclax and dexamethasone was very well tolerated. And the main adverse events were fatigue, which was mainly mild, and severe fatigue occurred in two patients. Insomnia or sleeplessness occurred in one patient, and this was mainly due to dexamethasone. And there was also a smattering of other adverse events, which were mainly grade 1 or grade 2. Hematologic adverse events were quite low, occurring notably in only four patients out of the 32 patients and of these only two patients had grade 3 thrombocytopenia and one patient had grade 3 neutropenia. So in summary, I think the combination of sonrotoclax and dexamethasone is very well tolerated. It’s effective in a group of quite heavily pre-treated myeloma patients. This study is currently ongoing and it’s exploring additional arms with different combinations of sonrotoclax and I do anticipate that sonrotoclax will be an important therapy for patients with 11;14 translocation going forward.