Dr Morillo on the Safety Profile of Golcadomide in R/R Follicular Lymphoma

Mainly, AEs were hematologic, whereas non-hematologic AEs were infrequent. [Neutropenia] was transient and well manageable with granulocyte colony-stimulating factor, so it is an expectable AE, but it is well manageable, and in general, it won’t be an issue [when] using this combination.

Daniel Morillo, MD, a clinical investigator and consultant physician in the Department of Hematology and Hemotherapy at Fundación Jiménez Díaz University Hospital and the START Madrid–FJD Early Phase Unit, discussed the safety profile of the potential first-in-class oral CELMoD golcadomide (CC-99282) plus rituximab (Rituxan) from the phase 1/2 CC-99282-NHL-001 trial (NCT03930953) in patients with relapsed/refractory follicular lymphoma, presented at the 2026 EHA Congress.

In cohort D of part B of the 2-part, multicenter, first-in-human study, patients with relapsed/refractory follicular lymphoma received golcadomide at 0.2 mg (n = 22) or 0.4 mg (n = 38) on a 14-days-on/14-days-off schedule, plus rituximab. At a February 26, 2026, data cutoff and a median follow-up of 17.08 months (range, 2.1-35.1), treatment-emergent adverse effects (TEAEs) were predominantly hematologic, whereas non-hematologic TEAEs were infrequent and mostly low grade, Morillo said.

Neutropenia was the most common TEAE, occurring at grade 3 or higher in 64% of patients in the 0.2-mg cohort and 68% of those in the 0.4-mg cohort. This was an expected, on-target effect of Ikaros degradation in neutrophil precursors, and it was transient and manageable with granulocyte colony-stimulating factor support, Morillo said. The median time to neutrophil recovery was 8 days, and grade 3/4 febrile neutropenia occurred in 9% and 13% of patients in the 0.2-mg and 0.4-mg cohorts, respectively.

Despite the high rate of neutropenia, rates of febrile neutropenia, pneumonia, and sepsis remained low, with no notable signal for serious infection, Morillo said. Non-hematologic TEAEs, such as fatigue, nausea, and diarrhea, were largely grade 1/2, and no grade 5 treatment-related AEs were reported.

Overall, the toxicity profile was predictable and manageable without new safety signals at longer follow-up, Morillo concluded. The ongoing phase 3 GOLSEEK-4 study (NCT06911502) is further evaluating golcadomide at 0.4 mg plus rituximab as a fixed-duration regimen for patients with second- or later-line follicular lymphoma.