JAK inhibition with ruxolitinib in relapsed or refractory classical Hodgkin lymphoma: Final results of a phase II, open label, multicentre clinical trial (JeRiCHO)

• Published in: European journal of haematology 2022-12, Vol.109 (6), p.728-735
• Main Authors: Gillessen, Sarah, Pluetschow, Annette, Vucinic, Vladan, Ostermann, Helmut, Kobe, Carsten, Bröckelmann, Paul J., Böll, Boris, Eichenauer, Dennis A., Heger, Jan‐Michel, Borchmann, Sven, Fuchs, Michael, Borchmann, Peter, Engert, Andreas, Tresckow, Bastian
• Format: Article
• Language: English
• Subjects: Clinical trials; Hodgkin lymphoma; Hodgkin's lymphoma; JAK‐inhibition; JAK‐inhibitor; Lymphoma; Medical prognosis; Patients; refractory; relapsed; ruxolitinib; Toxicity; treatment
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.13859

Objectives Patients with classical Hodgkin lymphoma (cHL) relapsing after second‐line therapy have a dismal prognosis and novel approaches are required for this patient group. Based on promising (pre‐)clinical data and the favourable toxicity profile, we performed a phase II clinical trial with the JAK inhibitor ruxolitinib in patients with relapsed or refractory cHL (r/r cHL). Methods Patients ≥18 years with histologically confirmed r/r cHL who failed second‐line treatment were included. Ruxolitinib was given orally at a dose of 25 mg twice daily in continuous 28‐day cycles until progression or unacceptable toxicity. Primary endpoint was the PET/CT‐based overall response rate (ORR; complete response (CR) or partial response (PR)) after 2 cycles; secondary endpoints included progression‐free (PFS) and overall survival (OS) as well as feasibility. The Jericho Trial adopted a 2‐stage phase 2 design (Simon 1989). Results Among the 12 included patients in stage 1, 2 had a PR, 3 had a stable disease (SD) and 6 had progressive disease (PD) after two treatment cycles (ORR: 2/12 evaluable patients, 16.7%). Median PFS was 3.6 months, the 1‐year OS estimate was 50.6% (median not reached). The toxicity profile was favourable with only one grade IV adverse event (7.1%) reported. Conclusion Ruxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1.