A Phase 2 Study of Nivolumab Using a Fixed Dose of 40 mg (Nivo40) in Patients With Relapsed/Refractory Hodgkin Lymphoma

Kirill V Lepik, Liudmila V Fedorova, Elena V Kondakova, Yuri R Zalyalov, Elena V Babenko, Elena E Lepik, Polina V Kotselyabina, Anastasia V Beynarovich, Marina O Popova, Nikita P Volkov, Lilia V Stelmakh, Vadim V Baykov, Ivan S Moiseev, Natalia B Mikhailova, Alexander D Kulagin, Boris V Afanasyev, Kirill V Lepik, Liudmila V Fedorova, Elena V Kondakova, Yuri R Zalyalov, Elena V Babenko, Elena E Lepik, Polina V Kotselyabina, Anastasia V Beynarovich, Marina O Popova, Nikita P Volkov, Lilia V Stelmakh, Vadim V Baykov, Ivan S Moiseev, Natalia B Mikhailova, Alexander D Kulagin, Boris V Afanasyev

Abstract

The introduction of nivolumab has changed the landscape of relapsed/refractory classical Hodgkin lymphoma (r/r cHL) treatment. Despite its clinical importance, this therapy may remain inaccessible for a significant number of patients worldwide, especially in low-income countries, due to its high cost. The results of pharmacokinetic analysis and clinical observations suggest the potential efficacy of low dose nivolumab in r/r cHL patients. The aim of this trial was to assess the efficacy and safety of nivolumab at a fixed dose of 40 mg in patients with r/r cHL. The study included 30 patients with r/r cHL, treated with 40 mg nivolumab every 2 weeks. The median dose of nivolumab per kilogram bodyweight was 0.59 mg/kg (0.4-1 mg/kg). Median follow up was 19.2 months (range 12.7-25.4). The objective response rate was 70%, with 13 (43.3%) patients achieving a complete response. Median PFS was 18.4 months (95% CI, 11.3 to 18.5 months) with 18-month PFS of 53.6% (95% CI, 32%-71%). At the time of analysis, 96.7% of patients were alive with a median OS not reached. Severe (grade 3-5) adverse events were observed in 4 patients (13.3%). Nivolumab in a fixed dose of 40 mg was efficient in patients with r/r cHL, independent from dose per kg bodyweight. The results of this study are in good agreement with previously reported data and create a rationale for further studies aimed to define the optimal dosing regimen of nivolumab for the treatment of r/r cHL. Registered at www.clinicaltrials.gov (NCT03343665).

Conflict of interest statement

The authors have indicated they have no potential conflicts of interest to disclose.

Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.

Figures

Figure 1
Figure 1
Response characteristics among all patients and treatment outcomes. (A) Structure of best overall response (BOR) during nivolumab treatment. The colors represent the BOR during nivolumab treatment: blue complete response (CR),light blue partial response (PR), brown stable disease (SD), red progression (PD), tial indeterminate response type 2 (IR2), light tial indeterminate response type 2 (IR2). Numbers represent the percent of patients with particular response type. Response characteristics and outcomes in all patients. (B) Overall survival for the whole patient group according to nivolumab dosage. (C) Overall (blue) and progression-free survival (PFS) in whole patient group.
Figure 2
Figure 2
Progression-free survival regarding the presence of B-symptoms and PET(-) status at first restaging. A. Progression-free survival (PFS) in patients without B-symptoms vs. patients with B-symptoms at study start. B. Progression-free survival (PFS) in patients with early PET negative complete response at 3 months after the treatment initiation versus other patients.
Figure 3
Figure 3
Dynamics of CD3+PD1+ T cells proportion from peripheral blood lymphocytes. Box plots represent median values and ranges, p - significance level (Wilcoxon matched pair test).

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