Iberdomide Maintenance Therapy after ASCT in Myeloma | Tanye Wildes, MD | IMS 2024

Hi, my name is Tanya Wilds. I'm an associate professor at the University of Nebraska Medical Center. I had the opportunity to present a phase two trial of ibertamides maintenance therapy following high dose therapy and autologous stem cell transplantation on behalf of the principal investigator of the study, my colleague and friend, Dr. Sarah Holstein, also at the University of Nebraska. In this study, we are enrolling patients between days 80 and 110 after transplant who had achieved at least a partial response and had not had any evidence of disease progression after initial diagnosis or start of treatment. So we are enrolling participants who have newly diagnosed multiple myeloma, have undergone initial therapy, and undergone high dose therapy and autologous stem cell transplantation. We're enrolling them between days 80 and 110 post transplant, and they are then started on ibertamide maintenance therapy at a dose of one milligram, days one through 21, Q28, very much mirroring standard practice with lenalidomide when used with a one week break. The study drug is then continued until progression or intolerance or toxicity requires discontinuation. The primary objective of the study is to assess the one year completion rate, basically demonstrating initial feasibility of ibertamide as a maintenance therapy. Secondary objectives will look at safety of the drug, second primary malignancies, progression free survival, overall survival, and MRD testing. Exploratory objectives will be exploring immunophenotype across time. Patients will also undergo bone marrow biopsy to assess MRD status by using next generation flow at a sensitivity of 10 to the minus fifth. What we presented here at IMS was a pre-planned interim analysis after the first 11 participants had completed one year on therapy. As far as baseline characteristics of the first 11 patients, the average age was 58. Most of the patients had received a daratumab based therapy. All patients received bortezumab based initial induction therapy. Most patients had already achieved a very good partial response prior to heading into transplant. There were some patients who did have high risk cytogenetic abnormalities, but most had standard risk disease. As far as the primary objective of this pre-planned interim analysis, it was specified a priori that if fewer than six participants were able to complete the first year of therapy, then this would invoke the futility stopping role, meaning that with continuing enrollment we wouldn't likely be able to demonstrate the feasibility of continuing ibertamide as a maintenance therapy. So after the first 11 patients had reached the one year mark, we were able to demonstrate that we should continue enrollment. As far as tolerability, overall the side effect profile observed was very similar to that as we would expect. The non-hematologic toxicities included risk of infection. Grade two infections were primarily noted. There was one episode of grade two diarrhea, one episode of grades three rash. As far as the hematologic toxicity, the most common was actually grade three neutropenia. And dose modifications were undertaken if after a first event of ANC less than 1.0, estimation and recurrence of this. The subsequent dose levels included the first dose reduction to 0.75 milligrams of ibertamide and a second dose reduction to 0.6 milligrams of ibertamide. So far in the first 11 patients there had been four dose reductions. One of these was for the hematologic toxicities and three for the non-hematologic toxicities. Notably because of FDA requirements, the non-hematologic toxicities required dose modification regardless of whether the toxicities or the adverse event was considered attributable to the study drug. As far as the efficacy of note, we saw an increase in the number of patients who had achieved a stringent complete response between the time of their staging prior to transplant and at one year of therapy on ibertamide. Heading into transplant, about 36% of participants had achieved a stringent complete response. And by one year of ibertamide maintenance, 100% of patients had achieved a stringent complete response. As far as MRD testing, nine of the 11 participants had already achieved a minimum residual disease negativity at the start of ibertamide maintenance. The two patients who had not yet achieved MRD negativity deepened the response and were MRD negative at one year post transplant. So this was an early look based on a pre-specified analysis after the first 11 participants in this phase two study had undergone therapy with ibertamide. We did demonstrate that there was utility in continuing the study. Enrollment is actually near complete and we will be looking forward to the full mature data with this. This in combination with the EMN 26 trial, which is also examining ibertamide as post transplant maintenance and then ultimately a randomized phase three trial comparing ibertamide with lenalidomide will help inform the role of ibertamide as post transplant maintenance therapy. Thank you.