Haematologica (May 2021)

Improved outcomes of high-risk relapsed Hodgkin lymphoma patients after high-dose chemotherapy: a 15-year analysis

  • Yago Nieto,
  • Stephen Gruschkus,
  • Benigno C. Valdez,
  • Roy B. Jones,
  • Paolo Anderlini,
  • Chitra Hosing,
  • Uday Popat,
  • Muzaffar Qazilbash,
  • Partow Kebriaei,
  • Amin Alousi,
  • Neeraj Saini,
  • Samer Srour,
  • Katayoun Rezvani,
  • Jeremy Ramdial,
  • Melissa Barnett,
  • Alison Gulbis,
  • Terri Lynn Shigle,
  • Sairah Ahmed,
  • Swaminathan Iyer,
  • Hun Lee,
  • Ranjit Nair,
  • Simrit Parmar,
  • Raphael Steiner,
  • Bouthaina Dabaja,
  • Chelsea Pinnix,
  • Jillian Gunther,
  • Branko Cuglievan,
  • Kris Mahadeo,
  • Sajad Khazal,
  • Hubert Chuang,
  • Richard Champlin,
  • Elizabeth J. Shpall,
  • Borje S. Andersson

DOI
https://doi.org/10.3324/haematol.2021.278311
Journal volume & issue
Vol. 107, no. 4

Abstract

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High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment for chemosensitive relapsed classical Hodgkin lymphoma, although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR classical Hodgkin lymphoma patients treated with HDC/ASCT at our institution between 01/01/2005 and 12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring more than one salvage line, or positron emission tomography (PET)-positive disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (n=146), busulphan/melphalan (BuMel) (n=38), gemcitabine( Gem)/BuMel (n=189) and vorinostat/Gem/BuMel (n=128). The Gem/BuMel and vorinostat/Gem/BuMel cohorts had more HRR criteria and more patients with PET-positive disease at ASCT. Treatment with brentuximab vedotin (BV) or anti-PD1 prior to ASCT, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). The median follow-up is 50 months (range, 6-186). Outcomes improved over time, with 2-year progressionfree survival (PFS)/overall survival (OS) rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016- 2019) (P<0.0001). Five-year PFS/OS rates were 72%/87% after vorinostat/ GemBuMel, 55%/75% after GemBuMel, 45%/61% after BEAM, and 39%/57% after BuMel (PFS: P=0.0003; OS: P<0.0001). These differences persisted within the PET-negative and PET-positive subgroups. Prior BV and vorinostat/GemBuMel were independent predictors of more favorable outcome, whereas primary refractory disease, ≥2 salvage lines, bulky relapse, B symptoms and PET-positivity at ASCT correlated independently with unfavorable outcomes. In conclusion, post-HDC/ASCT outcomes of patients with HRR classic Hodgkin lymphoma have improved over the last 15 years. Pre-ASCT BV treatment and optimized synergistic HDC (vorinostat/GemBuMel) were associated with this improvement.