Classical Hodgkin lymphoma - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main Hodgkin lymphoma page for regimens that include active anticancer treatment.
=Untreated, early-stage favorable (ESF)=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Engert et al. 2007 (GHSG HD7)	1993-1998 	Phase 3 (C)	ABVD x 2 	Shorter FFTF
No anticancer treatment
====Subsequent treatment====
*EFRT consolidation
===References===
# GHSG HD7: Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Wit M, Paulus U, Hasenclever D, Loeffler M, Müller RP, Müller-Hermelink HK, Dühmke E, Diehl V. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol. 2007 Aug 10;25(23):3495-502. Epub 2007 Jul 2. link to original article EuroPMC
## Pooled update: Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. Epub 2017 Apr 18. link to original article EuroPMC
=Consolidation after upfront therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Young et al. 1973 	1967-1972 	Phase 3 (C) 	1. Intermittent BCNU	Did not meet efficacy endpoints
Young et al. 1973 	1967-1972 	Phase 3 (C) 	2. Intermittent MOPP	Did not meet efficacy endpoints
Aleman et al. 2003 (EORTC 20884) 	1989-2000 	Phase 3 (C) 	IFRT 	Did not meet primary endpoint of RFS36
Straus et al. 2004 	1990-2000 	Phase 3 (C) 	EFRT 	Might have shorter OS
Thomas et al. 2017 (EORTC-GELA H9-F)	1998-2004 	Phase 3 (E-de-esc)	1. IFRT x 2000 cGy 	Not reported
Thomas et al. 2017 (EORTC-GELA H9-F)	1998-2004 	Phase 3 (E-de-esc)	2. IFRT x 3600 cGy 	Shorter RFS
Borchmann et al. 2011 (GHSG HD12) 	1999-2003 	Phase 3 (C) 	ISRT x 3000 cGy 	Might have lower FFTF60
Radford et al. 2015 (UK NCRI RAPID) 	2003-2010 	Phase 3 (E-de-esc)	IFRT 	Inconclusive whether non-inferior PFS36 PFS: 90.8% vs 94.6% (rate ratio 0.64, 95% CI 0.34-1.19)
No further treatment.
====Preceding treatment====
*Young et al. 1973: Induction MOPP
*EORTC 20884: Induction MOPP-ABV x 6 to 8
*Straus et al. 2004: Induction ABVD x 6
*GHSG HD12: Induction eBEACOPP x 8 versus BEACOPP4+4
*UK NCRI RAPID: Induction ABVD x 3
*EORTC-GELA H9-F: Induction EBVP x 6
===References===
# Young RC, Canellos GP, Chabner BA, Schein PS, DeVita VT. Maintenance chemotherapy for advanced Hodgkin's disease in remission. Lancet. 1973 Jun 16;1(7816):1339-43. link to original article EuroPMC
# EORTC 20884: Aleman BM, Raemaekers JM, Tirelli U, Bortolus R, van 't Veer MB, Lybeert ML, Keuning JJ, Carde P, Girinsky T, van der Maazen RW, Tomsic R, Vovk M, van Hoof A, Demeestere G, Lugtenburg PJ, Thomas J, Schroyens W, De Boeck K, Baars JW, Kluin-Nelemans JC, Carrie C, Aoudjhane M, Bron D, Eghbali H, Smit WG, Meerwaldt JH, Hagenbeek A, Pinna A, Henry-Amar M; EORTC Lymphoma Group. Involved-field radiotherapy for advanced Hodgkin's lymphoma. N Engl J Med. 2003 Jun 12;348(24):2396-406. link to original article EuroPMC
# Straus DJ, Portlock CS, Qin J, Myers J, Zelenetz AD, Moskowitz C, Noy A, Goy A, Yahalom J. Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Blood. 2004 Dec 1;104(12):3483-9. Epub 2004 Aug 17. link to original article EuroPMC
# GHSG HD12: Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage Hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article EuroPMC NCT00265031
## Update: von Tresckow B, Kreissl S, Dipl-Math HG, Bröckelmann PJ, Pabst T, Fridrik M, Rummel M, Jung W, Thiemer J, Sasse S, Bürkle C, Baues C, Diehl V, Engert A, Borchmann P; German Hodgkin Study Group. Intensive treatment strategies in advanced-stage Hodgkin's lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol. 2018 Oct 01;5(10):e462-73. link to original article EuroPMC
# UK NCRI RAPID: Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. link to original article EuroPMC NCT00943423
# EORTC-GELA H9-F: Thomas J, Fermé C, Noordijk EM, Morschhauser F, Girinsky T, Gaillard I, Lugtenburg PJ, André M, Lybeert MLM, Stamatoullas A, Beijert M, Hélias P, Eghbali H, Gabarre J, van der Maazen RWM, Jaubert J, Bouabdallah K, Boulat O, Roesink JM, Christian B, Ong F, Bordessoule D, Tertian G, Gonzalez H, Vranovsky A, Quittet P, Tirelli U, de Jong D, Audouin J, Aleman BMP, Henry-Amar M. Comparison of 36 Gy, 20 Gy, or no radiation therapy after 6 cycles of EBVP chemotherapy and complete remission in early-stage Hodgkin lymphoma without risk factors: results of the EORTC-GELA H9-F intergroup randomized trial. Int J Radiat Oncol Biol Phys. 2018 Apr 1;100(5):1133-1145. Epub 2017 Oct 27. link to original article EuroPMC NCT00005584
=Maintenance after upfront therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Sokal et al. 1974	1965-1967 	Randomized, fewer than 20 pts in this subgroup (C)	BCG 	Shorter PFS
Note: this study was open to patients with "malignant lymphoma" but the majority had Hodgkin disease.
===References===
# Sokal JE, Aungst CW, Snyderman M. Delay in progression of malignant lymphoma after BCG vaccination. N Engl J Med. 1974 Dec 5;291(23):1226-30. link to original article EuroPMC
=Maintenance after salvage therapy=
==Placebo==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
von Treskckow et al. 2016 (PATH)	2010-06 to 2011-05 	Phase 3 (C)	Panobinostat 	Did not meet primary endpoint of DFS1
Moskowitz et al. 2015 (AETHERA) 	2010-2012 	Phase 3 (C)	Brentuximab vedotin	Shorter PFSMedian PFS: 24.1 vs 42.9 mo(HR 1.75, 95% CI 1.23-2.50)
1PATH had a very low accrual and was not powered to investigate the original primary endpoint (DFS).
No further active antineoplastic treatment after transplant.
====Preceding treatment====
*Autologous HSCT consolidation (preparative regimen not specified)
===References===
# AETHERA: Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9;385(9980):1853-62. Epub 2015 Mar 18. Erratum in: Lancet. 2015 Aug 8;386(9993):532. link to original article EuroPMC NCT01100502
## HRQoL analysis: Ramsey SD, Nademanee A, Masszi T, Holowiecki J, Abidi M, Chen A, Stiff P, Viviani S, Sweetenham JW, Radford J, Zhu Y, Bonthapally V, Thomas E, Richhariya A, Hunder NN, Walewski J, Moskowitz CH. Quality of life results from a phase 3 study of brentuximab vedotin consolidation following autologous haematopoietic stem cell transplant for persons with Hodgkin lymphoma. Br J Haematol. 2016 Dec;175(5):860-867. Epub 2016 Sep 21. link to original article link to PMC article EuroPMC
## Update: Moskowitz CH, Walewski J, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Viviani S, Bachanova V, Sureda A, McClendon T, Lee C, Lisano J, Sweetenham J. Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood. 2018 Dec 20;132(25):2639-2642. Epub 2018 Sep 28. link to original article EuroPMC
# PATH: von Tresckow B, Morschhauser F, Szer J, Eichenauer DA, Abramson JS, Sureda A, Engert A. Panobinostat consolidation in patients with Hodgkin lymphoma at risk for relapse after high dose chemotherapy and autologous stem cell transplant: final results after early trial discontinuation. Leuk Lymphoma. 2017 Jan;58(1):222-225. Epub 2016 May 17. link to original article EuroPMC NCT01034163
Category:Classical Hodgkin lymphoma regimens
Category:Null regimens
Category:Disease-specific pages
Category:Aggressive lymphomas