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, 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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00427765 NCT00410982 NCT01200329.

Figures

Figure 1.
Figure 1.
Progression-free survival and overall survival of all patients. PFS: progression-free survival; OS: overall survival; ASCT: autologous stem-cell transplantation.
Figure 2.
Figure 2.
Outcomes by treatment year. (A) Progression-free survival, (B) overall survival.
Figure 3.
Figure 3.
Outcomes by high-dose chemotherapy regimen. (A) Progression-free survival, (B) overall survival. GemBuMel: gemcitabine/busulphan/melphalan; BEAM: carmustine/etoposide /cytarabine/melphalan; BuMel: busulphan/melphalan.
Figure 4.
Figure 4.
Progression-free survival by high-dose chemotherapy regimen according to positron emission tomography status. (A) Progression-free survival in patients with (A) positron emission tomography (PET)-negative disease and with (B) PET-positive disease.

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Source: PubMed

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