Can golcadomide plus R-CHOP become the first-line standard of care in high-risk BCL?

Golcadomide plus R-CHOP delivered a high rate of durable complete metabolic responses (CMR) regardless of the cell of origin in participants with aggressive B-cell lymphoma (BCL). The progression-free survival data of this phase 1b study were promising at 12 months follow-up and the safety profile was manageable.

Golcadomide is an orally administered cereblon E3 ligase modulator, that degrades target proteins to produce dual immunomodulatory and direct cell-destructing anti-tumour activity [1]. The phase 1b CC-220-DLBCL-001 trial (NCT04884035) investigated the safety and efficacy of golcadomide plus R-CHOP in participants with untreated aggressive BCL. Safety was the primary endpoint of this study. Dr Marc Hoffman (The University of Kansas Cancer Center, KS, USA) presented the 12-month follow-up results [2].

Participants received ≤ 6 x 21-day cycles of golcadomide plus R-CHOP therapy and were randomised to 0.2 mg or 0.4 mg golcadomide at days 1 to 7 of each treatment cycle during the dose expansion phase. Of the 78 included participants, most had Ann Arbor stage III–IV (83.3%), 82% had high-risk disease, and 82% had diffuse large BCL with a histological diagnosis of “not otherwise specified”.

Grade 3 or 4 treatment-emergent adverse events (TEAEs) were seen in 91% of the participants, predominantly neutropenia (87%) and thrombocytopenia (42%). Serious TEAEs were reported in 46% of the participants, of which febrile neutropenia (19%) was the most common AE.

In the highest dose group (n=33), the CMR rate was 88% at the end of therapy and all participants were progression-free. This result was consistent across risk and cell of origin subgroups. At 12 months follow-up, the progression-free survival rate was 85% in the high-dose group and 75% in the low-dose group, with similar rates in biologically distinct molecular subtypes germinal centre B-cell (GCB) and activated B-cell (ABC; see Figure, diffuse large BCL only).

Figure: Treatment response and treatment follow-up per patient participant receiving the high golcadomide dose (0.4 mg) [2]



ABC, activated B-cell diffuse large BCL; CMR, complete metabolic response; (non-)GCB, (non-) germinal centre B-cell diffuse large BCL; PD, progressive disease; PR, partial response; UNK, unknown.

These findings support the currently recruiting GOLSEEK-1 trial (NCT06356129), an upstarting phase 3 study comparing golcadomide plus R-CHOP to R-CHOP alone as first-line treatment for participants with high-risk large BCL.

1. Matyskiela ME, et al. J Med Chem. 2018;61(2):535–542.
2. Hoffman M, et al. Golcadomide, a potential first-in-class oral CELMOD agent, plus R-chop in patients with untreated aggressive B-cell lymphoma: safety and 12-month efficacy results. S235, EHA congress 2024, 13–16 June, Madrid, Spain.

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Posted on 12 August 202412 August 2024