Treatment and Prognosis of Relapsed or Refractory Hodgkin Lymphoma Patients Ineligible for Stem Cell Transplantation
Authors:
H. Mociková 1; A. Sýkorová 2; P. Štěpánková 2; J. Marková 1; J. Michalka 3; Z. Král 3; L. Burešová 4; D. Belada 2
Authors‘ workplace:
Interní hematologická klinika 3. LF UK a FN Královské Vinohrady, Praha
1; IV. interní hematologická klinika LF UK a FN Hradec Králové
2; Interní hematologická a onkologická klinika LF MU a FN Brno
3; DSC Services, s. r. o., Tišnov
4
Published in:
Klin Onkol 2014; 27(6): 424-428
Category:
Original Articles
doi:
https://doi.org/10.14735/amko2014424
Overview
Background:
Relapses occur in 20–30% of patients with Hodgkin lymphoma (HL). Currently, there is no widely accepted standard treatment strategy in relapsed/refractory HL patients ineligible for autologous stem cell transplantation (ASCT). This article retrospectively evaluates survival and prognosis of patients with relapsed/refractory HL who were not suitable for high-dose chemotherapy and ASCT. New drugs and their efficacy in this indication are also disscussed.
Patients and Methods:
A total of 17 patients treated with at least three lines of standard chemotherapy ± radiotherapy were analysed. High-dose chemotherapy and ASCT was not indicated due to advanced age (seven patients), chemorefractory disease (seven patients), cardiotoxicity (two patients) and insufficient stem cell collection of CD34+ cells (one patient).
Results:
Median follow-up of the whole group after establishing the diagnosis was 3.48 years. Overall response to the second-line treatment was achieved in eight patients (47.0%). Four patients (23,5%) were classified as primary refractory after the first-line treatment and three more chemorefractory patients (17,6%) were detected after the second-line treatment. Out of 17 patients four are still alive (23,5%) in remission and 13 have died (eight due to HL progressions, four due to toxicity of the treatment and one patient with unknown cause of death). The estimated 5-year overall survival from the time of initial diagnosis was 46.3% and 30.8% when counted from the diagnosis of the first relapse. The estimated 5-year overall survival of four primary chemorefractory patients was significantly worse when compared to the group of 13 relapsed patients: 0 vs. 60.6%, p < 0,001.
Conclusion:
Prognosis of relapsed/refractory HL patients ineligible for ASCT and treated with several lines of standard chemotherapy ± radiotherapy is poor. Brentuximab vedotin is indicated in primary refractory patients in the second-line settings and in other relapsed patients in the third-line treatment. This strategy would help to increase the number of remissions, hence achieving a higher survival rate.
Key words:
Hodgkin lymphoma – relapse – brentuximab vedotin
This study was supported by the research project P 27/2012, Third Faculty of Medicine, Charles University in Prague.
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
Submitted:
9. 9. 2014
Accepted:
28. 9. 2014
Sources
1. Gordon L, Hong F, Fisher R et al. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced‑stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol 2013; 31(6): 684– 691. doi: 10.1200/ JCO.2012.43.4803.
2. Engert A, Diehl V, Franklin J et al. Escalated‑dose BEACOPP in the treatment of patients with advanced‑stage Hodgkin‘s lymphoma: 10 years of follow‑up of the GHSG HD9 study. J Clin Oncol 2009; 27(27): 4548– 4554. doi: 10.1200/ JCO.2008.19.8820.
3. Carde P, Karrasch M, Fortpied C et al. ABVD (8 cycles) versus BEACOPP (4 escalated cycles => 4 baseline) in stage III– IV high‑risk Hodgkin lymphoma (HL): first results of EORTC 20012 Intergroup randomized phase III clinical trial. J Clin Oncol 2012; 30 (Suppl): 510.
4. Skoetz N, Trelle S, Rancea M et al. Effect of initial treatment strategy on survival of patients with advanced‑stage Hodgkin‘s lymphoma: a systematic review and network meta‑analysis. Lancet Oncol 2013; 14(10): 943– 952. doi: 10.1016/ S1470‑ 2045(13)70341‑ 3.
5. Linch DC, Winfield D, Goldstone AH et al. Dose intensification with autologous bone‑ marrow transplantation in relapsed and resistant Hodgkin‘s disease, results of a BNLI randomised trial. Lancet 1993; 341(8852): 1051– 1054.
6. Schmitz N, Pfistner B, Sextro M et al. Aggressive conventional chemotherapy compared with high‑dose chemotherapy with autologous haemopoietic stem‑ cell transplantation for relapsed chemosensitive Hodgkin’s disease: a randomised trial. Lancet 2002; 359(9323): 2065– 2071.
7. Mociková H, Pytlík R, Raida L et al. Léčba pacientů s relabovaným/ refrakterním Hodgkinovým lymfomem. Klin Onkol 2011; 24(2): 121– 125.
8. Josting A, Rueffer U, Franklin J et al. Prognostic factors and treatment outcome in primary progressive Hodgkin lymphoma: a report from the German Hodgkin Lymphoma Study Group. Blood 2000; 96(4): 1280– 1286.
9. Forero‑Torres A, Fanale M, Advani R et al. Brentuximab vedotin in transplant‑ naive patients with relapsed or refractory Hodgkin lymphoma: analysis of two phase I studies. Oncologist 2012; 17(8): 1073– 1080. doi: 10.1634/ theoncologist.2012‑ 0133.
10. Younes A, Gopal AK, Smith SE et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin‘s lymphoma. J Clin Oncol 2012; 30(18): 2183– 2189. doi: 10.1200/ JCO.2011.38.0410.
11. Sasse S, Rothe A, Goergen H et al. Brentuximab vedotin (SGN‑ 35) in patients with transplant‑ naive relapsed/ refractory Hodgkin lymphoma. Leuk Lymphoma 2013; 54(10): 2144– 2148. doi: 10.3109/ 10428194.2013.775434.
12. Corazzelli G, Angrilli F, D‘Arco A et al. Efficacy and safety of bendamustine for the treatment of patients with recurring Hodgkin lymphoma. Br J Haematol 2013; 160(2): 207– 215. doi: 10.1111/ bjh.12120.
13. Moskowitz AJ, Hamlin PA Jr, Perales MA et al. Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol 2013; 31(4): 456– 460. doi: 10.1200/ JCO.2012.45.3308.
14. Johnston PB, Inwards DJ, Colgan JP et al. A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol 2010; 85(5): 320– 324. doi: 10.1002/ ajh.21664.
15. Younes A, Sureda A, Ben‑ Yehuda D et al. Panobinostat in patients with relapsed/ refractory Hodgkin‘s lymphoma after autologous stem‑ cell transplantation: results of a phase II study. J Clin Oncol 2012; 30(18): 2197– 2203. doi: 10.1200/ JCO.2011.38.1350.
16. Younes A, Oki Y, Bociek RG et al. Mocetinostat for relapsed classical Hodgkin‘s lymphoma: an open‑ label, single‑arm, phase 2 trial. Lancet Oncol 2011; 12(13): 1222– 1228. doi: 10.1016/ S1470‑ 2045(11)70265‑ 0.
17. Fehniger TA, Larson S, Trinkaus K et al. A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma. Blood 2011; 118(19): 5119– 5125. doi: 10.1182/ blood‑ 2011‑ 07‑ 362475.
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