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Review

Optimizing salvage therapy for Hodgkin lymphoma: progress and future challenges

&
Pages 467-478 | Received 04 Feb 2024, Accepted 21 Jun 2024, Published online: 27 Jun 2024

References

  • Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the world health organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia. 2022 Jul;36(7):1720–1748. doi: 10.1038/s41375-022-01620-2
  • Chohan K, Ansell SM. Current salvage therapies in Hodgkin lymphoma. Leuk Lymphoma. 2022 Jun;63(6):1267–1280. doi: 10.1080/10428194.2021.2024819
  • Voorhees TJ, Beaven AW. Therapeutic updates for relapsed and refractory classical Hodgkin lymphoma. Cancers (Basel). 2020 Oct 8;12(10):2887. doi: 10.3390/cancers12102887
  • Driessen J, Tonino SH, Moskowitz AJ, et al. How to choose first salvage therapy in Hodgkin lymphoma: traditional chemotherapy vs novel agents. Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):240–246. doi: 10.1182/hematology.2021000311
  • Kuruvilla J, Keating A, Crump M. How I treat relapsed and refractory Hodgkin lymphoma. Blood. 2011 Apr 21;117(16):4208–4217. doi: 10.1182/blood-2010-09-288373
  • 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 Apr 24;341(8852):1051–1054. doi: 10.1016/0140-6736(93)92411-L
  • 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 Jun 15;359(9323):2065–2071. doi: 10.1016/S0140-6736(02)08938-9
  • Brockelmann PJ, Muller H, Gillessen S, et al. Clinical outcomes of relapsed and refractory Hodgkin lymphoma patients after contemporary first-line treatment: a German Hodgkin Study Group analysis. Leukemia. 2022 Mar;36(3):772–780. doi: 10.1038/s41375-021-01442-8
  • Moskowitz CH, Walewski J, Nademanee A, et al. 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. doi: 10.1182/blood-2018-07-861641
  • Sureda A, Andre M, Borchmann P, et al. Improving outcomes after autologous transplantation in relapsed/refractory Hodgkin lymphoma: a European expert perspective. BMC Cancer. 2020 Nov 10;20(1):1088. doi: 10.1186/s12885-020-07561-2
  • Wilke C, Cao Q, Dusenbery KE, et al. Role of consolidative radiation therapy after autologous hematopoietic cell transplantation for the treatment of relapsed or refractory Hodgkin lymphoma. Int J Radiat Oncol Biol Phys. 2017 Sep 1;99(1):94–102. doi: 10.1016/j.ijrobp.2017.05.007
  • Moskowitz CH, Matasar MJ, Zelenetz AD, et al. Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood. 2012 Feb 16;119(7):1665–1670. doi: 10.1182/blood-2011-10-388058
  • Sucak GT, Ozkurt ZN, Suyani E, et al. Early post-transplantation positron emission tomography in patients with Hodgkin lymphoma is an independent prognostic factor with an impact on overall survival. Ann Hematol. 2011 Nov;90(11):1329–1336. doi: 10.1007/s00277-011-1209-0
  • Yhim HY, Eshet Y, Metser U, et al. Risk stratification for relapsed/refractory classical Hodgkin lymphoma integrating pretransplant Deauville score and residual metabolic tumor volume. Am J Hematol. 2022 May;97(5):583–591. doi: 10.1002/ajh.26500
  • 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 Jun 20;30(18):2183–2189. doi: 10.1200/JCO.2011.38.0410
  • Arai S, Fanale M, DeVos S, et al. Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant. Leuk Lymphoma. 2013 Nov;54(11):2531–2533. doi: 10.3109/10428194.2013.798868
  • Ansell SM, Radford J, Connors JM, et al. Overall survival with brentuximab vedotin in stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2022 Jul 28;387(4):310–320. doi: 10.1056/NEJMoa2206125
  • Ansell SM, Brockelmann PJ, von Keudell G, et al. Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 205 study. Blood Adv. 2023 Oct 24;7(20):6266–6274. doi: 10.1182/bloodadvances.2023010334
  • Chen R, Zinzani PL, Lee HJ, et al. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019 Oct 3;134(14):1144–1153. doi: 10.1182/blood.2019000324
  • Kuruvilla J, Ramchandren R, Santoro A, et al. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021 Apr;22(4):512–524. doi: 10.1016/S1470-2045(21)00005-X
  • Herrera AF, LeBlanc ML, Castellino SM, et al. SWOG S1826, a randomized study of nivolumab(N)-AVD versus brentuximab vedotin(BV)-AVD in advanced stage (AS) classic Hodgkin lymphoma (HL). J Clin Oncol. 2023;41(17_suppl):LBA4–LBA4. doi: 10.1200/JCO.2023.41.17_suppl.LBA4
  • Armand P, Zinzani PL, Lee HJ, et al. Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma. Blood. 2023 Sep 7;142(10):878–886. doi: 10.1182/blood.2022019386
  • Bartlett NL, Niedzwiecki D, Johnson JL, et al. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin’s lymphoma: CALGB 59804. Ann Oncol. 2007 Jun;18(6):1071–1079. doi: 10.1093/annonc/mdm090
  • Moccia AA, Hitz F, Hoskins P, et al. Gemcitabine, dexamethasone, and cisplatin (GDP) is an effective and well-tolerated salvage therapy for relapsed/refractory diffuse large B-cell lymphoma and Hodgkin lymphoma. Leuk Lymphoma. 2017 Feb;58(2):324–332. doi: 10.1080/10428194.2016.1193852
  • Josting A, Rudolph C, Reiser M, et al. Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin’s disease. Ann Oncol. 2002 Oct;13(10):1628–1635. doi: 10.1093/annonc/mdf221
  • Aparicio J, Segura A, Garcera S, et al. ESHAP is an active regimen for relapsing Hodgkin’s disease. Ann Oncol. 1999 May;10(5):593–595. doi: 10.1023/A:1026454831340
  • Gutierrez A, Rodriguez J, Martinez-Serra J, et al. Gemcitabine and oxaliplatinum: an effective regimen in patients with refractory and relapsing Hodgkin lymphoma. Onco Targets Ther. 2014;7:2093–2100. doi: 10.2147/OTT.S70264
  • Moskowitz CH, Nimer SD, Zelenetz AD, et al. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001 Feb 1;97(3):616–623. doi: 10.1182/blood.V97.3.616
  • Proctor SJ, Jackson GH, Lennard A, et al. Strategic approach to the management of Hodgkin’s disease incorporating salvage therapy with high-dose ifosfamide, etoposide and epirubicin: a northern region lymphoma group study (UK). Ann Oncol. 2003;14 Suppl 1:i47–50. doi: 10.1093/annonc/mdg710
  • Ferme C, Mounier N, Divine M, et al. Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin’s disease in relapse or failure after initial chemotherapy: results of the Groupe d’Etudes des lymphomes de l’Adulte H89 trial. J Clin Oncol. 2002 Jan 15;20(2):467–475. doi: 10.1200/JCO.20.2.467
  • Bonfante V, Viviani S, Santoro A, et al. Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin’s disease. Br J Haematol. 1998 Nov;103(2):533–535. doi: 10.1046/j.1365-2141.1998.00989.x
  • Santoro A, Magagnoli M, Spina M, et al. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin’s lymphoma. Haematologica. 2007 Jan;92(1):35–41. doi: 10.3324/haematol.10661
  • Moskowitz CH, Yahalom J, Zelenetz AD, et al. High-dose chemo-radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre-transplant functional imaging. Br J Haematol. 2010 Mar;148(6):890–897. doi: 10.1111/j.1365-2141.2009.08037.x
  • Labrador J, Cabrero-Calvo M, Perez-Lopez E, et al. ESHAP as salvage therapy for relapsed or refractory Hodgkin’s lymphoma. Ann Hematol. 2014 Oct;93(10):1745–1753. doi: 10.1007/s00277-014-2114-0
  • Santoro A, Mazza R, Pulsoni A, et al. Five-year results of the BEGEV salvage regimen in relapsed/refractory classical Hodgkin lymphoma. Blood Adv. 2020 Jan 14;4(1):136–140. doi: 10.1182/bloodadvances.2019000984
  • Eyre TA, Phillips EH, Linton KM, et al. Results of a multicentre UK-wide retrospective study evaluating the efficacy of brentuximab vedotin in relapsed, refractory classical Hodgkin lymphoma in the transplant naive setting. Br J Haematol. 2017 Nov;179(3):471–479. doi: 10.1111/bjh.14898
  • Chen R, Palmer JM, Martin P, et al. Results of a multicenter phase II trial of brentuximab vedotin as second-line therapy before autologous transplantation in relapsed/refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2015 Dec;21(12):2136–2140. doi: 10.1016/j.bbmt.2015.07.018
  • Zinzani PL, Pellegrini C, Cantonetti M, et al. Brentuximab vedotin in transplant-naive relapsed/refractory Hodgkin lymphoma: experience in 30 patients. Oncology. 2015 Dec;20(12):1413–1416. doi: 10.1634/theoncologist.2015-0227
  • Merryman RW, Redd RA, Nishihori T, et al. Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma. Blood Adv. 2021 Mar 23;5(6):1648–1659. doi: 10.1182/bloodadvances.2020003556
  • Halahleh K, Al Sawajneh S, Saleh Y, et al. Pembrolizumab for the treatment of relapsed and refractory classical Hodgkin lymphoma after autologous transplant and in transplant-naive patients. Clin Lymphoma Myeloma Leuk. 2022 Aug;22(8):589–595. doi: 10.1016/j.clml.2022.02.009
  • Cole PD, McCarten KM, Pei Q, et al. Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin’s lymphoma (AHOD1221): a Children’s oncology group, multicentre single-arm, phase 1-2 trial. Lancet Oncol. 2018 Sep;19(9):1229–1238. doi: 10.1016/S1470-2045(18)30426-1
  • Broccoli A, Argnani L, Botto B, et al. First salvage treatment with bendamustine and brentuximab vedotin in Hodgkin lymphoma: a phase 2 study of the Fondazione Italiana Linfomi. Blood Cancer J. 2019 Dec 11;9(12):100. doi: 10.1038/s41408-019-0265-x
  • LaCasce AS, Bociek RG, Sawas A, et al. Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood. 2018 Jul 5;132(1):40–48. doi: 10.1182/blood-2017-11-815183
  • Garcia-Sanz R, Sureda A, de la Cruz F, et al. Brentuximab vedotin and ESHAP is highly effective as second-line therapy for Hodgkin lymphoma patients (long-term results of a trial by the Spanish GELTAMO group). Ann Oncol. 2019 Apr 1;30(4):612–620. doi: 10.1093/annonc/mdz009
  • Abuelgasim KA, Alzahrani M, Alsharhan Y, et al. Chemoimmunotherapy with brentuximab vedotin combined with ifosfamide, gemcitabine, and vinorelbine is highly active in relapsed or refractory classical Hodgkin lymphoma. Bone Marrow Transplant. 2019 Jul;54(7):1168–1172. doi: 10.1038/s41409-019-0454-z
  • Kersten MJ, Driessen J, Zijlstra JM, et al. Combining brentuximab vedotin with dexamethasone, high-dose cytarabine and cisplatin as salvage treatment in relapsed or refractory Hodgkin lymphoma: the phase II HOVON/LLPC Transplant BRaVE study. Haematologica. 2021 Apr 1;106(4):1129–1137. doi: 10.3324/haematol.2019.243238
  • Moskowitz AJ, Schoder H, Gavane S, et al. Prognostic significance of baseline metabolic tumor volume in relapsed and refractory Hodgkin lymphoma. Blood. 2017 Nov 16;130(20):2196–2203. doi: 10.1182/blood-2017-06-788877
  • Herrera AF, Palmer J, Martin P, et al. Autologous stem-cell transplantation after second-line brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Ann Oncol. 2018 Mar 1;29(3):724–730. doi: 10.1093/annonc/mdx791
  • Advani RH, Moskowitz AJ, Bartlett NL, et al. Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results. Blood. 2021 Aug 12;138(6):427–438. doi: 10.1182/blood.2020009178
  • Diefenbach CS, Hong F, Ambinder RF, et al. Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2020 Sep;7(9):e660–e670. doi: 10.1016/S2352-3026(20)30221-0
  • Diefenbach CS, Jegede O, Ansell SM, et al. Results from an intergroup randomized phase II study of the combinations of ipilimumab, nivolumab and brentuximab vedotin in patients with relapsed/refractory classic Hodgkin lymphoma: a trial of the ECOG-ACRIN research group (E4412). Blood. 2023;142(Supplement 1):607–607. doi: 10.1182/blood-2023-184531
  • O’Connor OA, Lue JK, Sawas A, et al. Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin’s lymphoma: an international, multicentre, single-arm, phase 1-2 trial. Lancet Oncol. 2018 Feb;19(2):257–266. doi: 10.1016/S1470-2045(17)30912-9
  • Bryan LJ, Casulo C, Allen PB, et al. Pembrolizumab added to ifosfamide, carboplatin, and etoposide chemotherapy for relapsed or refractory classic Hodgkin lymphoma: a multi-institutional phase 2 investigator-initiated nonrandomized clinical trial. JAMA Oncol. 2023 May 1;9(5):683–691. doi: 10.1001/jamaoncol.2022.7975
  • Moskowitz AJ, Shah G, Schoder H, et al. Phase II trial of pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin as second-line therapy for relapsed or refractory classical Hodgkin lymphoma. J Clin Oncol. 2021 Oct 1;39(28):3109–3117. doi: 10.1200/JCO.21.01056
  • Mei MG, Lee HJ, Palmer JM, et al. Response-adapted anti-PD-1-based salvage therapy for Hodgkin lymphoma with nivolumab alone or in combination with ICE. Blood. 2022 Jun 23;139(25):3605–3616. doi: 10.1182/blood.2022015423
  • Harker-Murray P, Mauz-Körholz C, Leblanc T, et al. Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults. Blood. 2023 Apr 27;141(17):2075–2084. doi: 10.1182/blood.2022017118
  • Sureda-Balari A, Terol MJ, Domingo-Domènech E, et al. T098: brentuximab vedotin plus ESHAP (BRESHAP) versus ESHAP in patients with relapsed or refractory classical Hodgkin’s lymphoma. interim results of the BRESELIBET prospective clinical trial. Hemasphere. 2022;6:45. doi: 10.1097/01.HS9.0000890960.29449.17
  • Desai SH, Spinner MA, David K, et al. Checkpoint inhibitor-based salvage regimens prior to autologous stem cell transplant improve event-free survival in relapsed/refractory classic Hodgkin lymphoma. Am J Hematol. 2023 Mar;98(3):464–471. doi: 10.1002/ajh.26827
  • Shotton R, Kirkwood AA, Northend M, et al. Real world outcomes and responses to second-line therapy in relapsed/refractory Hodgkin lymphoma: a multicentre UK study. Hematol Oncol. 2021;39(S2). doi: 10.1002/hon.106_2880
  • Driessen J, de Wit F, Herrera AF, et al. Brentuximab vedotin and chemotherapy in relapsed/refractory Hodgkin lymphoma: a propensity score–matched analysis. Blood Adv. 2024;8(11):2740–2752. doi: 10.1182/bloodadvances.2023012145
  • Svoboda J, Ballard HJ, Bair SM, et al. Current selection patterns, toxicities and outcomes of pre-transplant salvage treatment regimens in patients with relapsed/refractory Hodgkin lymphoma: results of a multicenter retrospective analysis. Blood. 2019;134(Supplement_1):2855–2855. doi: 10.1182/blood-2019-123741
  • Borchmann P, Moccia AA, Greil R, et al. BRECADD is non-inferior to EBEACOPP in patients with advanced stage classical Hodgkin lymphoma: efficacy results of the GHSG phase III HD21 trial. Hematol Oncol. 2023;41(S2):881–882. doi: 10.1002/hon.3196_LBA5
  • Borchmann P, Goergen H, Kobe C, et al. PET-guided treatment in patients with advanced-stage Hodgkin’s lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin study group. Lancet. 2017 Dec 23;390(10114):2790–2802. doi: 10.1016/S0140-6736(17)32134-7
  • Federico M, Fortpied C, Stepanishyna Y, et al. Long-term follow-up of the response-adapted intergroup EORTC/LYSA/FIL H10 trial for localized Hodgkin lymphoma. J Clin Oncol. 2024 Jan 1;42(1):19–25. doi: 10.1200/JCO.23.01745
  • Luminari S, Fossa A, Trotman J, et al. Long-term follow-up of the response-adjusted therapy for advanced Hodgkin lymphoma trial. J Clin Oncol. 2024 Jan 1;42(1):13–18. doi: 10.1200/JCO.23.01177
  • Daw S, Hasenclever D, Mascarin M, et al. Risk and response adapted treatment guidelines for managing first relapsed and refractory classical Hodgkin lymphoma in children and young people. Recommendations from the EuroNet pediatric Hodgkin lymphoma group. Hemasphere. 2020 Feb;4(1):e329. doi: 10.1097/HS9.0000000000000329
  • Alig SK, Shahrokh Esfahani M, Garofalo A, et al. Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling. Nature. 2024 Jan;625(7996):778–787. doi: 10.1038/s41586-023-06903-x
  • Maco M, Kupcova K, Herman V, et al. Circulating tumor DNA in Hodgkin lymphoma. Ann Hematol. 2022 Nov;101(11):2393–2403. doi: 10.1007/s00277-022-04949-x

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