Paul G. Richardson, MD, on Multiple Myeloma: Mezigdomide Plus Dexamethasone in Relapsed and Refractory Disease

2022 ASH Annual Meeting and Exposition


Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, discusses preliminary results from the dose-expansion phase of the CC-92480-MM-001 Trial, which showed promising efficacy in patients with relapsed and refractory multiple myeloma, including those with prior BCMA-targeted therapies. Patients in these two groups had an overall response rate of 40% and 50%, respectively. The results support the development of mezigdomide, currently being evaluated in combination with standard therapies in multiple myeloma as part of a large, ongoing phase I/II trial (NCT03989414) and planned phase III studies (Abstract 568).


Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Well, it's my pleasure to present at this meeting the results of our mezigdomide dexamethasone combination dose expansion part of a phase I/II trial. This was exclusively in relapsed and refractory myeloma patients who were triple-class refractory. That meant that three classes of drugs had failed them and they were also allowed to have received prior BCMA therapy, which is an important new aspect of myeloma management. Because obviously BCMA has been a very exciting advance as the target. But the question obviously then arises when treatment fails in that space, what are effective agents there? What are the effective agents that can meet that challenge? So we allowed BCMA exposed patients as well as triple-class refractory patients to receive mezigdomide combined with low-dose dexamethasone. And the dexamethasone was given on a weekly schedule. mezigdomide was given three weeks on and one week off. And mezigdomide is this really very interesting oral agent. It's what's called a CELMoD. These are very powerful drugs that engage the cereblon E3 ligase complex inside the myeloma cell and result in profound pathobiologic changes within the myeloma cell through the targeted degradation of Ikaros and Aiolos. They also have enormous immune system effects. They stimulate specific T-cells and NK cells and have an immune effect on the tumor as a result. So really a very exciting class of drug. And in that context we were able to show a response rate of 40%, actually 41% to be precise overall for the whole 101 patients on intent to treat. What we were able to also show in the subgroups was a 30% response rate in patients with extramedullary disease. And what was really interesting, in about a third of patients who had BCMA exposure, we showed a 50% response rate. So really nice response data. In the original phase one portion of the study, we demonstrated a response rate in the small number of patients at the RP2D and there was the recommended phase two dose. We've shown a response rate of 55%. So all of this data was very consistent in terms of the safety. Again, very consistent, very similar to what we saw in the phase one portion with neutropenia, some thrombocytopenia, some fatigue. But beyond that everything else was very, very uncommon in terms of any non-hematologic side effects. And above all, we didn't see thrombosis, we didn't see neuropathy, we didn't see cardiac issues. We found that the drug was generally well tolerated. So in terms of future directions, we know that mezigdomide is extremely active in combination and there are trials ongoing combining the mezigdomide with bortezomib, carfilzomib and monoclonal antibodies. And these studies hopefully will bear fruit within the next three to four years or so in terms of a readout. In the meantime, to have this exciting data is really quite important because it tells us that we've got an oral agent with a convenience of that, that we can actually literally take off-the-shelf for our patients. And in that spirit, one of the other things that was important among the safety profile was to us we did have some infections. They were at a much lower rate than you would normally see with say, an antibody based therapy. And also we only had one COVID death despite seeing some COVID infection because of the timing of the trial. In that context of over 100 patients, there was only one person who died of COVID. So really important information to share with the community and hopefully very exciting new addition to the army in the relative near future.

Related Videos


Jia Ruan, MD, PhD, on Mantle Cell Lymphoma: Phase II Findings on Acalabrutinib/Lenalidomide/Rituximab

Jia Ruan, MD, PhD, of Meyer Cancer Center, Weill Cornell Medicine, and NewYork-Presbyterian Hospital, discusses trial results demonstrating that the triple chemotherapy-free combination of acalabrutinib, lenalidomide, and rituximab is well tolerated, highly effective, and produces high rates of minimal residual disease (MRD)-negative complete response as an initial treatment for patients with mantle cell lymphoma, including those with TP53 mutations. Real-time MRD analysis may enable treatment de-escalation during maintenance to minimize toxicity, which warrants further evaluation. An expansion cohort of acalabrutinib/lenalidomide/obinutuzumab is being launched (Abstract 73).


Tycel J. Phillips, MD, on Mantle Cell Lymphoma: New Findings on Glofitamab Monotherapy

Tycel J. Phillips, MD, of the City of Hope National Medical Center, discusses data that showed fixed-duration glofitamab monotherapy induced high and durable complete response rates in patients with mantle cell lymphoma (MCL) who received obinutuzumab pretreatment. This is one of the largest data sets and longest follow-ups reported with a CD20/CD3 bispecific monoclonal antibody for patients with relapsed or refractory MCL (Abstract 74).


Paolo F. Caimi, MD, on DLBCL: Outcomes After R-ICE Chemoimmunotherapy

Paolo F. Caimi, MD, of the Taussig Cancer Institute, Cleveland Clinic, discusses new findings showing that patients with diffuse large B-cell lymphoma (DLBCL) who achieve a complete response after salvage therapy with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) can achieve long-term disease control, regardless of the time to relapse from initial therapy, particularly if they proceed to autologous stem cell transplant (ASCT). These results suggest that second-line chemotherapy followed by ASCT and/or CAR T-cell therapy for chemosensitive and chemorefractory patients may maximize patient outcomes, regardless of time to relapse (Abstract 156).


Irene Roberts, MD, on Leukemogenesis in Infants With Trisomy 21

Irene Roberts, MD, of Oxford’s Weatherall Institute of Molecular Medicine, discusses children with Down syndrome, who have a more than 100-fold increased risk of developing acute myeloid leukemia before their fourth birthday compared to children without Down syndrome. Their risk of acute lymphoblastic leukemia is also increased by around 30-fold. Dr. Roberts details current knowledge about the biologic and molecular basis of this relationship between leukemia and Down syndrome, the role of trisomy 21 in leukemogenesis, and the clinical implications of these findings.

Multiple Myeloma

Julie Côté, MD, on Multiple Myeloma: Real-World Results of Autologous Stem Cell Transplantation in Newly Diagnosed Patients

Julie Côté, MD, of CHU de Québec–Université Laval, discusses findings from the Canadian Myeloma Research Group database, which showed that integrating bortezomib and lenalidomide into the autologous stem cell transplant (ASCT) sequence produces a median overall survival rate ≥ 10 years in most patients with newly diagnosed multiple myeloma. These observations highlight the contribution of post-ASCT maintenance, particularly lenalidomide given until disease progression, when used in multiple patient groups including those with and without high risk, as well as those requiring a second induction regimen (Abstract 117).