Résumé
Approximately 40% of patients with DLBCL relapse after initial chemoimmunotherapy, leading to poor outcomes. Golcadomide is a potential, first-in-class, oral CELMoD agent for lymphoma treatment, with preferential distribution to lymphoid organs. Golcadomide drives the closed, active conformation of cereblon to induce rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing (agnostic of cell-of-origin) and immune modulation. We report extended follow-up results for golcadomide+rituximab in patients with R/R DLBCL in phase 1/2 CC-99282-NHL-001 (NCT03930953).
Patients with R/R DLBCL and at least two prior lines of therapy (≥1 in part B if prior anti-CD20 treatment) received golcadomide at various doses in part A. In part B, golcadomide was dosed orally 0.2 mg or 0.4 mg (14 days on/14 days off) with or without rituximab for up to 2 years. Primary objectives included safety and recommended phase 2 dose determination.
As of December 30, 2024, 77 patients (golcadomide + rituximab 0.2 mg, n = 39; 0.4 mg, n = 38) were included. Median age, 66 years; median prior lines, 4 (53% CAR-T therapy; 36% bispecific antibody therapy; ≥44% refractory to last therapy). Eleven patients (14%) were ongoing; 4 (5%) completed 2 years of treatment; 62 (81%) discontinued treatment, mostly due to progression. Most common any-grade treatment-emergent adverse events were neutropenia (68%) and anemia (44%). Grade 3/4 neutropenia and febrile neutropenia occurred in 64% and 10% of patients, respectively. GCSF was administered in 44/52 patients with neutropenia and 7/8 patients with febrile neutropenia. One grade 5 pneumonia was considered related to study treatment. Efficacy-evaluable patients (n = 71) had 47% objective response rate (ORR) (58% at 0.4 mg) and 32% complete response rate (CRR) (44% at 0.4 mg). Patients with prior T-cell–redirecting therapy (n = 34) had 44% ORR and 29% CRR. At median follow-up (13.1 months), median duration of response was 11.7 months, and durable response was >12 months in 15 patients. Circulating tumor DNA reduction from baseline was observed across mutant variants in responders.
Golcadomide+rituximab continues to demonstrate manageable safety with no new signals. Durable responses were observed in heavily pretreated patients, independent of cell-of-origin and tumor microenvironment status. These data support the ongoing development of golcadomide in patients with R/R non-Hodgkin lymphoma. Presented at 2025 EHA Annual Congress; modified using BMS AI.