Long-Term Outcomes of Nivolumab Therapy in Patients with Relapsed/Refractory Classic Hodgkin’s Lymphoma after High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Real Clinical Practice

AUTOIMMUNE THROMBOCYTOPENIA , ,

KV Lepik1, NP Volkov1, NB Mikhailova1, EV Kondakova1, LA Tsvetkova1, YuR Zalyalov1, EE Lepik1, LV Fedorova1, AV Beinarovich1, MV Demchenkova2, OG Smykova1, PV Kotselyabina1, IS Moiseev1, VV Baikov1, BV Afanasyev1

1 RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

2 Regional Oncologic Dispensary, 32 Frunze str., Irkutsk, Russian Federation, 664035

For correspondence: Kirill Viktorovich Lepik, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; е-mail: lepikkv@gmail.com

For citation: Lepik KV, Volkov NP, Mikhailova NB, et al. Long-Term Outcomes of Nivolumab Therapy in Patients with Relapsed/Refractory Classic Hodgkin’s Lymphoma after High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Real Clinical Practice. Clinical oncohematology. 2020;13(3):280–8 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-280-288

ABSTRACT

Aim. To assess prognostic factors and to analyze the outcomes of nivolumab therapy in patients with relapsed/refractory classic Hodgkin’s lymphoma (cHL) after autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The retrospective analysis included 42 patients treated with nivolumab 3 mg/kg after auto-HSCT in the period from 2016 to 2020. The response to nivolumab therapy was assessed every three months by whole-body PET/CT based on LYRIC criteria. Toxicity profile was assessed by establishing adverse events (AE) based on NCI CTCAE 4.03 criteria.

Results. The study included 42 patients with relapsed/refractory cHL: 21 (50 %) men and 21 (50 %) women. The median age was 32.5 years (range 22–43 years). At diagnosis the following cHL stages were identified: stage II in 14 pts (33.3 %), stage III in 12 pts (28.6 %), and stage IV in 16 pts (38.1 %). Primary chemoresistance after the first-line therapy was observed in 26 pts (61.9 %) and early relapse in 4 pts (9.52 %). The median follow-up was 38 months, 3-year overall survival was 97 % (95% confidence interval, 95% CI, 83.2–99.6 %), 3-year progression-free survival (PFS) was 34.8 % (95% CI 20.3–49.9 %; median 12.9 months). Objective response was reported in 69 % of patients, complete response (CR) in 33.3 %, partial response in 35.7 %, stable disease in 7.1 %, indeterminate response in 14.3 %, and progression in 9.5 % of patients. The analysis of factors affecting PFS revealed significant differences in patients who reached CR after 6 nivolumab cycles: 3-year PFS 56.2 % (95% CI 24.4–79.1 %) vs. 25.2 % (95% CI 10.46–43.1 %) in patients who did not reach CR (p = 0.054). If extranodal lesions were identified at nivolumab therapy onset, PFS was 29 % (95% CI 7.8–37.5 %) vs. 68 % (95% CI 35.9–86.8 %) in their absence (p = 0.0079). The overall rate of AEs on nivolumab therapy was 92.9 %, severe AEs of grade 3–4 were observed in 19.1 % of patients.

Conclusion. Nivolumab shows high efficacy in the treatment of patients with relapsed/refractory cHL after the failure of auto-HSCT and considerably improves prognosis compared with historical control. The efficacy of nivolumab is independent of brentuximab vedotin use and duration of prior therapy. Throughout the follow-up period the toxicity level of nivolumab was acceptable and controlled. Clinical factors that affect prognosis for patients on immunotherapy were identified.

Keywords: Hodgkin’s lymphoma, nivolumab, brentuximab vedotin, auto-HSCT, immunotherapy.

Received: March 24, 2020

Accepted: June 15, 2020

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