ASH 2025 | VIBER-M: venetoclax, iberdomide, & dexamethasone for multiple myeloma with t(11;14) in early relapse

At this ASH meeting, we had the opportunity to present the initial results of our Viber-M study. This is an academic investigator-initiated study that was conducted through the Australasian Leukaemia Lymphoma Group, or ALLG, and it was presented by Dr. Shirlene Sim. This was a Phase 1b-2 study exploring venetoclax in combination with iberdomide and dexamethasone for patients in early relapse of multiple myeloma with the 11;14 translocation. Around 15-20% of patients with multiple myeloma will have the 11;14 translocation and this cytogenetic abnormality is clinically important because it predicts for a sensitivity to BCL2 inhibitors such as venetoclax. More importantly, this patient population has now emerged as a population of ongoing unmet need, partly due to the fact that they have less incremental benefit to IMiDs, proteasome inhibitors, and an anti-CD38 monoclonal antibody. Venetoclax is a first-in-class BCL2 inhibitor that was previously shown to be quite effective for patients with 11;14 translocation. And iberdomide is a cereblon E3 ligase modulator that has immunomodulatory activities as well as direct tumor effects in myeloma cells. And preclinical studies have demonstrated that combining BCL2 inhibitors with immunomodulatory drugs can increase apoptosis and deepen the response. 

So in the Viber-M study, we only enrolled patients with 11;14 translocation and who have only had one or two prior lines of treatment. And the data presented here is a pre-planned analysis of the first 20 patients with the data of only the first three cycles of treatment. These patients had a median age of 65 and they mainly had one prior line of treatment and the majority were lenalidomide exposed or lenalidomide refractory. Venetoclax was given orally daily in a 28-day cycle and iberdomide was given as an oral dose daily from days 1 to 21 in a 28-day cycle and dexamethasone was given as an oral weekly dosing. And an intra-patient dose escalation design allowed individual patients to safely increase the dose of venetoclax from 200mg to 400mg by the beginning of cycle 3 and iberdomide up to 1.6 milligram by cycle 3. The dose of iberdomide was subsequently capped at 1.0 milligram upon emerging data at the time from other studies showing that this was the recommended phase 3 dose. 

From a safety perspective, the main side effects we saw was neutropenia. Grade 3 and 4 neutropenia occurred in around 45% of patients. Grade 3 and 4 thrombocytopenia only in around 10% of patients. And grade 3 and 4 anemia was even less. Now, despite the grade 3 and 4 neutropenia, the rate of grade 3 and 4 infections were quite low. It only occurred in about 10% of patients. And then there were other side effects, including gastrointestinal symptoms, constipation, diarrhea, that generally occurred in around 10 to 20% of patients only. 

From an efficacy perspective, we saw quite an encouraging early response. We saw a response rate of 80% with a VGPR of 25%. Now, remember that this is only in the first three cycles, so follow-up was quite short, and we do expect that the depth of response will continue to improve with time. So overall, our early data would suggest that the combination of venetoclax, iberdomide and dexamethasone is a rational combination and is deliverable and effective for patients with 11;14 translocation in early line relapse and the study is currently still ongoing and we really look forward to updating you all with more mature data as the study progresses.

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