Bristol Myers Squibb’s golcadomide, a first-in-class, oral CELMoD (cereblon E3 ligase modulator), has shown compelling activity as monotherapy and in combination with rituximab in patients with heavily pretreated relapsed/refractory follicular lymphoma (R/R FL) in the Phase I/II CC-99282-NHL-001 study (NCT03930953).
Relapsed or refractory (R/R) follicular lymphoma (FL) remains a therapeutic challenge despite recent advances in CAR-T cell therapies and bispecific antibodies. The treatment landscape continues to seek oral, chemotherapy-free regimens that deliver deep responses as treatment remains fragmented by toxicity, limited durability in later lines and accessibility challenges. Bristol Myers Squibb’s golcadomide, a first-in-class, oral CELMoD, has shown compelling activity as a monotherapy and in combination with rituximab in patients with heavily pretreated R/R FL in the Phase I/II CC-99282-NHL-001 study (NCT03930953). Golcadomide induces a closed, active conformation of cereblon, leading to potent degradation of Ikaros and Aiolos. This results in both direct tumour cytotoxicity and immune stimulation, distinguishing golcadomide mechanistically from priorgeneration immunomodulatory drugs such as lenalidomide.
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At the American Society of Hematology (ASH) 2025 Annual Meeting, held from 6 to 9 December in Orlando, Florida and online, updated data from the extended follow-up of Part B Cohort D was presented. Among 56 efficacy-evaluable patients, the overall response rate (ORR) was 89%, including a 61% complete response rate (CRR). Activity was dose-dependent, with the 0.4mg regimen achieving a 97% ORR and 78% CRR, compared with the 0.2mg dose, which achieved a 77% ORR and 41% CRR. Responses were maintained across difficult-to-treat subgroups, including those with prior lenalidomide exposure and prior T-cell-redirecting therapies, where response rates remained between 91% and 100%. Early durability signals were notable, with more than 12-month remissions observed even in heavily pretreated patients.
Safety was manageable and aligned with golcadomide’s on-target effects. Grade 3 or 4 neutropenia occurred in 59% of patients with the 0.2mg dose and in 68% of patients with the 0.4mg dose, with lower rates of anaemia and febrile neutropenia in both groups. No patients discontinued treatment or died due to golcadomide-related toxicity.
Golcadomide’s performance is being closely watched as it represents the most mature CELMoD data in indolent lymphomas. Its oral administration and fixed-duration dosing provide significant advantages over CAR-T therapies and bispecifics, both of which require hospital-based delivery and ongoing safety monitoring. The ongoing Phase III GOLSEEK-4 study will determine whether the golcadomide + rituximab combination therapy can establish itself as a chemotherapy-free standard in second-line or later FL. A positive outcome could drive a shift toward outpatient, fixed-duration immunomodulatory regimens, particularly in regions with limited access to CAR T-cell therapies.
While the efficacy signal at the 0.4mg dose has been notable, sustained remission data and effective management of myelosuppression will be key to long-term adoption. The CELMoD class also faces internal portfolio competition as Bristol Myers Squibb develops iberdomide and mezigdomide across haematologic malignancies. Nonetheless, golcadomide’s preferential lymphoid organ distribution and encouraging tolerability profile may position it as the leading CELMoD for Bcell lymphomas. According to GlobalData’s analyst consensus forecast, golcadomide is projected to achieve annual sales of $200 million by 2031 if Phase III results confirm durable benefit, with potential to modestly shift market share away from bispecific antibodies and later-line cellular therapies.
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By GlobalData
