Background Up to 75% of peripheral T-cell lymphoma (PTCL) patients (pts) treated with frontline CHOP-based therapy have relapsed/refractory (r/r) disease and subsequent lines of therapy offer response rates <30% with median progression-free survival (PFS) of 2-4 months. Golidocitinib, a selective JAK1 tyrosine-kinase inhibitor, has shown promising anti-tumor activity in pts with r/r PTCL with an objective response rate (ORR) of 44.3% (Song & Malpica et al, Lancet Oncology 2023). Herein, we report the updated 2-year follow-up of golidocitinib for r/r PTCL in a U.S. single-center.

Methods We included pts enrolled from a single-center in the JACKPOT8 part B trial, a single-arm, multinational, phase 2 study (NCT04105010). Eligible pts (≥18 years, r/r PTCL, performance status ECOG ≤2) were given golidocitinib 150 mg orally once daily in 21-day cycles until progression of disease (PD) or other discontinuation criteria were met. We evaluated baseline characteristics, ORR and the co-primary endpoints; 2-year PFS and 2-year overall survival (OS), assessed using the Kaplan-Meier method. Correlatives were analyzed between responders (complete [CR] and partial response [PR]) and non-responders (PD) using Fisher's exact test with a p< 0.05 for statistical significance, and included in-house next generation sequencing panel, molecular subtyping (TBX21 and GATA3), phosphorylated signal transducer and activator of transcription 1 (pSTAT1) and pSTAT3 and T-follicular helper (TFH) phenotyping by immunohistochemistry.

Results Thirteen pts were included, median age was 55.9 years (range 19.8-75.2), with 38.5% (n=5) >60 years, and 54% (n=7) female. Subtypes were ALK negative anaplastic large cell lymphoma (ALCL) (n=3), ALK+ ALCL (n=2), PTCL, not otherwise specified (NOS) (n=4), T-cell prolymphocytic leukemia (n=1), and angioimmunoblastic T-cell lymphoma (n=3). The majority were stage III-IV (84.6%, n=11).

Frontline regimens were BV-CHP in 76.9% (n=10) and CHOP in 23.1% (n=3), with 76.9% (n=10) having initial CR or PR and 15.4% (n=2) receiving consolidative autologous stem cell transplantation (SCT) prior to enrollment. Golidocitinib was started as second-, third- or fourth-line therapy in 53.8% (n=7), 30.8% (n=4) and 15.4% (n=2), respectively.

The ORR was 53.8% (n=7, 95%CI 25.8%-79.7%) with CR=46.1% and PR=7.7%. With a median follow-up of 24.9 months (IQR 14.9-32.9 months), median OS was not reached and 2-year OS was 76.9% (95%CI 44.2%-91.9%). Median and 2-year PFS were 37.9 months and 58.3%, respectively (95%CI 27%-80.1%). As of last follow up, except for one pt with CNS relapse (PFS 37.9 months) and one pt taken off study due to autologous SCT consolidation after CR, all other responders remain in CR (n=4) and PR (n=1); including 2 pts with ongoing CR while being off therapy (one pt opted for therapy break [PFS 15 months], and one pt developed squamous cell carcinoma of the neck related to smoking and therapy was held due to non-adherence [PFS 18 months]).

Among all pts, responders had TFH phenotype (n=3/3, 100%) vs. non-TFH (n=4/10, 40%), p=0.192; and among the PTCL, NOS and ALCL (n=9), responders had TBX21 phenotype (n=4/4, 100%) vs. non-TBX21 (n=0/5, 0%), p=0.008. pSTAT1 and pSTAT3 expression were not associated with response (p=0.29 and p=0.95, respectively). STAT3 mutation was present in only 2 out of 7 pts with response to therapy and none of those with no response (p=0.46).

Grade 3-4 treatment-related adverse events occurred in 30.8% (n=4) and included anemia (7.7%), neutropenia (15.4%), febrile neutropenia (7.7%), thrombocytopenia (7.7%), leukocytosis (7.7%), and disseminated zosters (7.7%). All were clinically manageable, with no grade 5 events. Three pts (23.1%) had dose reduction to 75 mg every other day (all >65 years) and there was no drug discontinuation.

Conclusion In this cohort of U.S. pts with r/r PTCL receiving golidocitinib, efficacy and tolerability were comparable with the overall cohort in the JACKPOT8 part B trial which included primarily Asian pts. With the longest follow-up for golidocitinib, responses were durable (longest responder 3.1 years) with 2 pts remaining in CR despite therapy break, suggesting a long-lasting effect. Responders had a TFH phenotype and expressed TBX21, which need to be confirmed in a larger cohort. Given the promising results and unmet need, the ongoing GOLDEN trial aims to evaluate the safety and efficacy of golidocitinib in the frontline management of PTCL (NCT06630091).

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2025
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