H Beköz1, N Karadurmuş2, S Paydaş3, A Türker4, T Toptaş5, T Fıratlı Tuğlular5, M Sönmez6, Z Gülbaş7, E Tekgündüz8, A H Kaya8, M Özbalak9, N Taştemir10, L Kaynar11, R Yıldırım12, I Karadoğan13, M Arat14, F Pepedil Tanrıkulu15, V Özkocaman16, H Abalı17, M Turgut18, M Kurt Yüksel19, M Özcan19, M H Doğu20, S Kabukçu Hacıoğlu21, I Barışta4, M Demirkaya22, F D Köseoğlu23, S K Toprak19, M Yılmaz24, H C Demirkürek25, O Demirkol26, B Ferhanoğlu27. 1. Division of Hematology, Department of Internal Medicine, Medical Faculty, Medipol University, Istanbul. 2. Division of Medical Oncology, Department of Internal Medicine, Gulhane Research and Training Hospital, Ankara. 3. Division of Medical Oncology, Department of Internal Medicine, Medical Faculty, Cukurova University, Adana. 4. Division of Medical Oncology, Department of Internal Medicine, Medical Faculty, Hacettepe University, Ankara. 5. Division of Hematology, Department of Internal Medicine, Medical Faculty, Marmara University, Istanbul. 6. Division of Hematology,Department of Internal Medicine, Medical Faculty, Karadeniz Technical University, Trabzon. 7. Division of Hematology, Anadolu Medical Center, Izmıt. 8. Division of Hematology, Dr Abdurrahman Yurtaslan Ankara Oncology Research and Training Hospital, Ankara. 9. Division of Internal Medicine, Bahçelievler State Hospital, İstanbul. 10. Division of Hematology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul. 11. Division of Hematology, Department of Internal Medicine, Medical Faculty, Erciyes University, Kayseri. 12. Division of Hematology, Department of Internal Medicine, Medical Faculty, Ataturk University, Erzurum. 13. Division of Hematology, Medstar Antalya Hospital, Antalya. 14. Division of Hematology, Florence Nighthingale Hospital, Istanbul. 15. Division of Hematology, Dr Turgut Noyan Research and Training Center, Baskent University, Adana. 16. Division of Hematology, Department of Internal Medicine, Medical Faculty, Uludag University, Bursa. 17. Division of Medical Oncology, Acıbadem University Medical Faculty Adana Hospital, Adana. 18. Division of Hematology, Department of Internal Medicine, Medical Faculty, Ondokuz Mayıs University, Samsun. 19. Division of Hematology, Department of Internal Medicine, Medical Faculty, Ankara University, Ankara. 20. Division of Hematology, Istanbul Research and Training Hospital, Istanbul. 21. Division of Hematology, Department of Internal Medicine, Medical Faculty, Pamukkale University, Denizli. 22. Division of Medical Oncology, Department of Pediatrics, Medical Faculty, Uludag University, Bursa. 23. Division of Hematology, Department of Internal Medicine, Medical Faculty, Ege University, Izmir. 24. Division of Hematology, Department of Internal Medicine, Medical Faculty, Gaziantep University, Gaziantep. 25. Division of Nuclear Medicine, V.K.V. American Hospital, Istanbul. 26. Department of Nuclear Medicine, Koc University School of Medicine, İstanbul. 27. Division of Hematology, V.K.V. American Hospital and Department of Internal Medicine, Division of Hematology, Koc University School of Medicine, Istanbul, Turkey. Electronic address: bferhan@gmail.com.
Abstract
BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.
BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.
Authors: Diede van Ens; Charlotte M Mousset; Tim J A Hutten; Anniek B van der Waart; Diana Campillo-Davo; Sanne van der Heijden; Denise Vodegel; Hanny Fredrix; Rob Woestenenk; Loreto Parga-Vidal; Joop H Jansen; Nicolaas P M Schaap; Eva Lion; Harry Dolstra; Willemijn Hobo Journal: Bone Marrow Transplant Date: 2020-06-11 Impact factor: 5.483
Authors: A Amraee; M R Evazi; M Shakeri; N Roozbeh; M Ghazanfarpour; M Ghorbani; J Ansari; L Darvish Journal: Clin Transl Oncol Date: 2019-02-09 Impact factor: 3.340
Authors: Francesco Merli; Filippo Ballerini; Barbara Botto; Manuel Gotti; Vincenzo Pavone; Alessandro Pulsoni; Pietro Maria Stefani; Fulvio Massaro; Simonetta Viviani Journal: Acta Biomed Date: 2020-05-25