Ruxolitinib shows activity against Hodgkin lymphoma but not primary mediastinal large B-cell lymphoma

Abstract

Background: The upregulated expression of the JAK/STAT pathway promotes tumor growth in Hodgkin lymphoma (HL) and primary mediastinal large B-cell lymphoma (PMBCL). Based on the hypothesis that JAK2 is a therapeutic target, we performed a prospective pilot study using ruxolitinib.

Methods: Relapsed or refractory patients with HL or PMBCL were eligible for this study, and JAK2 amplification was assessed by fluorescence in situ hybridization. Ruxolitinib was administered orally at a dose of 20 mg twice daily for a 28-day cycle. Treatment was continued for up to 16 cycles or until progressive disease or intolerability. The primary objective was to assess the overall disease control rate comprising complete response (CR), partial response (PR), or stable disease (SD).

Results: We analyzed 13 HL patients and six PMBCL patients. All responders (one CR, five PR, and one SD) had HL whereas all cases of PMBCL progressed after first or second cycle. The disease control rate for HL was 54% (7/13) with median response duration of 5.6 months. JAK2 amplification was present in six of nine patients tested (four HL, two PMBCL), and three of these HL patients showed PR (n = 2) or SD (n = 1). None of the three HL patients shown to not have JAK2 amplification responded to ruxolitinib. Most treatment-related adverse events were grade 1 or 2 and manageable.

Conclusions: Ruxolitinib has single-agent activity against HL but does not act against PMBCL with or without JAK2 amplification.

Trial registration: The study population was patients who had relapsed or refractory HL or PMBCL, and patients were registered for our pilot study after providing written informed consent between November 2013 and November 2015 (CilinicalTrials.gov: NCT01965119).

Keywords: Hodgkin lymphoma; JAK2; Mediastinal large B-cell lymphoma; Ruxolitinib.

Fig. 1

a Comparison of clinical characteristics of patients between Hodgkin lymphoma and primary mediastinal large B-cell lymphoma at the time of enrollment; b One case of Hodgkin lymphoma achieved complete response; c One patient with Hodgkin lymphoma achieving stable disease after the second cycle also showed improved disease status

Fig. 2

Summary of 19 patients receiving ruxolitinib treatment

Fig. 3

a Waterfall plot demonstrating percent change from baseline in target tumor dimensions (best response, n = 19); b A representative image of JAK2 amplification; c JAK2 amplification is present in six patients: four Hodgkin lymphoma and two primary mediastinal large B-cell lymphoma; d Three of six patients with JAK2 amplification achieved partial response or stable disease, whereas three Hodgkin lymphoma patients without JAK2 amplification showed disease progression

Fig. 4

a, b The progression-free survival and overall survival of Hodgkin lymphoma patients were significantly longer than those of primary mediastinal large B-cell lymphoma patients; c Summary of treatment-related adverse effects