Improved outcomes for relapsed/refractory Hodgkin lymphoma after autologous transplantation in the era of novel agents

To the Editor,

We read with great interest the manuscript by Spinner et al. (1) reporting improved outcomes for relapsed/refractory (R/R) classical Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT) in the era of novel agents. We would like to congratulate the authors for this report confirming that brentuximab vedotin (BV) and checkpoint inhibitors (CPI) have changed the landscape of R/R HL (2). In this single institution study (1), the authors have clearly demonstrated that overall survival (OS) was superior in 183 patients with R/R HL who underwent ASCT between 2011-2020 as compared to that of 159 patients transplanted between 2001 and 2010 (4-year estimates: 89.1% vs 79.0%, p=0.011). Conversely, for 91 patients who progressed after ASCT, improvement in post progression survival in recent years did not reach statistical significance, likely reflecting the small sample size.
Salvage chemotherapy and ASCT results in the cure of around 50% of patients with HL failing first-line therapy (3). Historically, patients who progressed after ASCT had a poor outcome, with a median OS of around 1-2 years (4). To assess the most recent trends in survival after post-ASCT relapse, we conducted within the Lymphoma working party of the European Society of Blood and Marrow Transplantation (EBMT), a retrospective, registry-based, multicenter study that included 1781 adult patients with relapsed HL after ASCT, over a period of 12 years (from 2006 to 2017) (5). We found a significant improvement in the 4-year OS after relapse, which increased from 32% in patients who relapsed between 2006 and 2008 to 63% in those who relapsed between 2015 and 2017 (p=0.001) (5). Notably, the survival improvement over time was predominantly observed in patients who had an early relapse (within 12 months) after ASCT. This makes our findings even more impressive because, typically, shorter survival is associated with early relapse. This effect is likely due to the greater efficacy and novel mechanism of action of the new monoclonal antibodies (2). Our study represents the largest analysis to date assessing the outcomes and characteristics of patients with relapsed HL after ASCT, and our findings show that the survival of these patients has significantly improved over time. These large-scale real-world data can serve as a benchmark for future studies in this setting.

References

1- Spinner MA, Sica RA, Tamaresis JS, Lu Y, Chang C, Lowsky R, Frank MJ, Johnston LJ, Miklos DB, Muffly L, Negrin RS, Rezvani AR, Shiraz P, Shizuru JA, Weng WK, Binkley MS, Hoppe RT, Advani RH, Arai S. Improved outcomes for relapsed/refractory Hodgkin lymphoma after autologous transplantation in the era of novel agents. Blood. 2023 Mar 1:blood.2022018827.
2- Mohty R, Dulery R, Bazarbachi AH, Savani M, Hamed RA, Bazarbachi A, Mohty M. Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies. Blood Cancer J. 2021 Jul 9;11(7):126.
3- Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM, Haenel 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;359:2065-71.
4- Moskowitz AJ, Perales MA, Kewalramani T, Yahalom J, Castro-Malaspina H, Zhang Z, et al. Outcomes for patients who fail high dose chemoradiotherapy and autologous stem cell rescue for relapsed and primary refractory Hodgkin lymphoma. Br J Haematol. 2009;146:158-63.
5- Bazarbachi A, Boumendil A, Finel H, Khvedelidze I, Romejko-Jarosinska J, Tanase A, Akhtar S, Ben Othman T, Ma'koseh M, Afanasyev B, Cheikh J, Briones J, Gülbas Z, Hamladji RM, Elverdi T, Blaise D, Martínez C, Alma E, Halaburda K, Sousa AB, Glass B, Robinson S, Montoto S, Sureda A. The outcome of patients with Hodgkin lymphoma and early relapse after autologous stem cell transplant has improved in recent years. Leukemia. 2022 Jun;36(6):1646-1653.