New drug combination halves myeloma progression risk in trial
Mezigdomide extends remission in hard-to-treat disease
Written by |
Treatment with a regimen based on the experimental therapy mezigdomide reduced the risk of disease progression or death by more than 50% compared with standard care among people with hard-to-treat myeloma in a Phase 3 clinical trial
Mezigdomide’s developer, Bristol Myers Squibb (BMS), shared the findings at the 2026 American Society of Clinical Oncology annual meeting, being held May 29-June 2 in Chicago and online, in a presentation titled, “Mezigdomide, carfilzomib, and dexamethasone (MeziKd) vs carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM): Results from the phase 3 SUCCESSOR-2 trial.”
“Multiple myeloma is a persistent disease and there remains an urgent unmet need for patients as early as first relapse,” Cristian Massacesi, MD, executive vice president, chief medical officer, and head of development at BMS, said in a company press release. “Importantly, these compelling data further validate our targeted protein degradation platform.”
Myeloma is a form of blood cancer marked by the out-of-control growth of plasma cells, a type of immune cell, in the bone marrow. Mezigdomide belongs to a class of medications called CELMoDs (Cereblon E3 Ligase Modulators), which are designed to kill myeloma cells by targeting a protein called cereblon.
“Mezigdomide is a very potent, oral CELMoD and we’re committed to bringing it forward as a potential new standard of care for relapsed/refractory multiple myeloma across multiple settings,” Massacesi said.
Trial compares combo regimen against standard treatment
The new data come from analyses of nearly 500 patients in the Phase 3 SUCCESSOR-2 clinical trial (NCT05552976). The study enrolled adults with myeloma that was relapsed or refractory, meaning the cancer had failed to respond or come back following prior treatments. Most participants had received two or more prior lines of therapy and had not responded to anti-CD38 antibodies or lenalidomide (sold as Revlimid and generics), both of which are standard myeloma treatments.
All participants in SUCCESSOR-2 received the approved myeloma treatments Kyprolis (carfilzomib) and dexamethasone. Some received these standard therapies only, while others were given the two drugs in combination with mezigdomide, a regimen known as MeziKd.
The trial’s main goal was to determine whether the MeziKd regimen would outperform standard treatment in prolonging progression-free survival (PFS), the time patients remain alive without the cancer worsening. BMS previously announced that the study had hit its goal, and now the company has shared specifics: Median PFS was 18 months with MeziKd, compared with 8.3 months on the standard therapy. That works out to a 52% decrease in the chance of disease progression or death with MeziKd.
“Maintaining durable disease control becomes an increasing challenge with each line of therapy for patients with relapsed or refractory disease and increasing resistance to therapy, so achieving extended progression-free survival of a year and a half is especially meaningful. These promising results at ASCO underscore MeziKd’s potential, particularly for those patients who need additional options after both early and later relapse,” said Paul Richardson, MD, a professor at Harvard Medical School.
The improved PFS with MeziKd was consistently observed across subgroups in the Phase 3 trial, including patients with more prior lines of treatment, individuals with high-risk genetic alterations, and elderly patients aged 75 and older.
The MeziKd regimen showed a higher overall response rate (80.2% vs 53.4%), referring to the number of patients whose cancer burden decreased with treatment. Rates of complete response or better, essentially meaning the cancer went away, were also higher with MeziKd than the standard therapy (26.7% vs 8.9%).
Median overall survival in the study has not been reached; in other words, as of the latest follow-up, most participants are still alive. So far, 21.5% of patients given MeziKd have died, as have 26.7% of those on standard therapy. These deaths were mainly due to disease progression.
Safety data for MeziKd were overall consistent with the known profiles of each drug in the combination therapy. Serious safety issues were reported in 83.7% of patients given MeziKd and 56.5% of those on standard therapy. The MeziKd regimen had notably higher rates of infections (34% vs 15.6%) and neutropenia (low counts of a specific type of immune cell; 61.1% vs 9.1%). Death due to infection occurred in 2.4% of patients on MeziKd and 1.1% of those on the standard regimen.
“The combination of MeziKd demonstrated a promising median progression-free survival rate of 18 months in multiple settings of relapsed, refractory multiple myeloma, along with a consistent safety profile and the convenience of oral administration and ability to implement across diverse care settings,” Richardson said.
BMS said it will share the study results with healthcare regulatory authorities.
