Bristol Myers Squibb (BMS) has revealed clinical data for two pipeline candidates in multiple myeloma (MM) at the European Hematology Association Congress (EHA) 2026, held from June 11–14.
While the drugmaker already has multiple therapies approved for the type of blood cancer, BMS is hoping to expand its presence in the market by addressing certain MM patients with unmet needs.
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The treatment landscape for relapsed or refractory (R/R) MM is rapidly evolving, GlobalData anticipates notable growth in the MM therapeutics market across the eight major markets (8MM: the US, France, Germany, Italy, Spain, the UK, Japan, and China), according to GlobalData’s Multiple Myeloma: Eight-Market Drug Forecast and Market Analysis 2022–32 report. The market is expected to grow over the forecast period to $29bn in 2032.
Phase III SUCCESSOR-2 meets endpoints
BMS presented updated results from the global, multicenter, open-label, Phase III SUCCESSOR-2 trial. The study evaluated BMS’s mezigdomide, an investigational oral cereblon E3 ligase modulator (CELMoD), in combination with Amgen’s Kyprolis (carfilzomib), a proteasome inhibitor, as well as dexamethasone versus Kyprolis and dexamethasone alone, as a second-line or later therapy in patients with R/R MM who had received prior treatment with lenalidomide and at least two cycles of an anti-CD38 monoclonal antibody.
MeziKd met the trial’s primary endpoint of progression free survival (PFS), extending median PFS to 18.0 months versus 8.3 months with Kd alone and reducing the risk of disease progression or death by 52%. The regimen also improved response depth, with an overall response rate of 80.2% in patients receiving MeziKd versus 53.4% in patients receiving Kd, and a complete response or better rate of 26.7% in patients receiving MeziKd versus 8.9% in patients receiving Kd. Overall survival (OS), a key secondary endpoint, remained immature but showed a positive trend favoring MeziKd.
Any-grade treatment-emergent adverse events (TEAEs) occurred in 99.3% of patients receiving MeziKd versus 95.7% with Kd alone, while grade 3 or 4 TEAEs were higher at 83.7% in patients receiving MeziKd versus 56.5% in patients receiving Kd, mainly driven by neutropenia and infections. MeziKd could become a new standard of care in second-line or later R/R MM for this patient population, although its higher toxicity burden will be an important consideration for its uptake.
Commercially, mezigdomide is entering the fast-changing R/R MM landscape. The regimen is unlikely to displace chimeric antigen receptor (CAR) T-cell therapies or bispecific antibody therapy in fit patients with access to specialist centers, particularly as Johnson & Johnson (J&J)’s Tecvayli (teclistamab), Talvey (talquetamab), and Carvykti (ciltacabtagene autoleucel) continue to move earlier in the treatment algorithm. Its strongest opportunity is instead in the large and growing post-CD38, post-lenalidomide population where clinicians need an effective, immediately available, non-cellular therapy that can be delivered outside highly specialized centers and may preserve B-cell maturation antigen (BCMA) or G protein-coupled receptor class C group 5 member D (GPRC5D)-directed options for later use.
MeziKd should be viewed as a commercially attractive and clinically meaningful new option, rather than a universal new standard across all R/R MM settings. If approved, its adoption will depend on how regulators, payers, and clinicians weigh the strength of the PFS benefit against higher hematologic toxicity, immature OS data, and the growing availability of highly active T-cell-redirecting alternatives.
CAR-T Achieves 96% Response
BMS also presented updated safety and efficacy results from the Phase I trial (NCT04674813) of its CAR T-cell therapy, arlocabtagene autoleucel (arlo-cel), in R/R MM.
Arlo-cel is an autologous CAR-T therapy that targets G-protein-coupled receptor 5D (GPCR5D), an orphan receptor that is highly specific to MM cells. The presented trial tested the safety and efficacy in patients who had undergone one to three prior regimens (median: two regimens). A total of 31 adult patients were enrolled, pre-treated with lymphodepleting chemotherapy, then administered with arlo-cel at a dose of 150 million cells. At 24 months, all patients experienced treatment-emergent adverse events (TEAEs), of which 87% where grade 3 or higher, mostly hematologic, with 81% experiencing neutropenia, 29% thrombocytopenia, and 26% anemia. Cytokine release syndrome, a key safety measure for CAR-T therapy, was frequent (84% patients), as were infections (61%). However, all cases of both were grade 1 or 2 and clinically manageable, and no deaths were observed. Immune effector cell-associated neurotoxicity syndrome was present in 10% of patients, all also grade 1 or 2 and manageable. Consistent with other GPCR5D directed therapies, TEAEs were reported in epithelial tissues, including the nail (36%), skin (26%), and mouth (42%). This is believed to be a symptom of off-target activity against GPRCR5D expressed in these tissues.
The overall response rate (ORR) was 96%, with 67% complete responses (CRs). The 18-month duration of response (DoR) was 64.6%, and PFS was 62.6%. The 18-month overall survival held at 100%. Minimal residual disease (MRD) negativity, generally an indicator of long-term response and an FDA-recommended endpoint for accelerated approval in MM, was found in 56.3% patients. The positive efficacy reports here are encouraging and contend against BCMA direct CAR-Ts for patients after a similar number of lines of therapy. BMS is looking to demonstrate this in a larger cohort in a Phase III trial (QUINTESSENTIAL 2; NCT06615479), which is now underway.
It is important to note that this study focuses on patients who have typically only undergone two prior lines of therapy, yet only one patient was included who was R/R after BCMA therapy. BCMA-targeting therapies are moving increasingly earlier into the clinical landscape as more CAR-T and antibody drugs are entering the market, supported by large amounts of positive clinical data and awareness. Without strong long-term efficacy data, it will be challenging for GPCR5Ds, a relatively new drug class, to directly contend with these established treatments in the first or second line, especially as they introduce alarming adverse events in the skin, mouth, and nails. Opportunity will more likely be found if further trials can demonstrate efficacy in BCMA R/R patients, as these are an increasing group with an urgent need for better options.
BMS still has a way to go in building arlo-cel’s clinical case, and GlobalData forecasts that arlo-cel’s likelihood of achieving pre-registration status is 20%. Nevertheless, if the high efficacy reading is sustained, GlobalData’s analyst consensus forecast estimates that arlo-cel could achieve global sales of $290m by 2032.
