Outcome Analysis of High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation in Patients with Hodgkin Lymphoma: A Francophone Society of Bone Marrow Transplantation and Cellular Therapy Study
Authors: Dulery Remy , Reman Oumedaly , Boumemdil Ariane , Bouabdallah Reda , Brice Pauline , Gastinne Thomas , Tabrizi Reza , Quittet Philippe , Huynh Anne , Salles Gilles , Monjanel Helene , Stamatoullas Aspasia , Bourhis Jean-Henri , Bonmati Caroline , Francois Sylvie , Nguyen Quoc Stephanie , Bay Jacques Olivier , Cahn Jean-Yves , Turlure Pascal , Dauriac Charles , Mohty Mohamad , Peffault De Latour Regis , Yakoub-Agha Ibrahim 
Published: October 2019

Abstract
Background
Many patients with relapsed or refractory Hodgkin's lymphoma (HL) undergo high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). However, most large reports include patients treated in the 90's. We aimed to analyze the outcome of a HL patients treated in the last decade with HDC and auto-SCT in a large cohort study.
Patients and methods
In the setting of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, we retrospectively analyzed 1987 consecutive adult patients (age < 65 years) with biopsy-proven HL who received a first auto-SCT between 2003 and 2014.
Results
Median age at auto-SCT was 33.7 years (range, 18-65) and 60% patients were male. Disease status at transplant was complete remission in 1040 patients (52%), partial response in 727 (37%) and progressive disease in 220 (11%). The main conditioning regimen was BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=1497). At one month, cumulative incidence of neutrophil engraftment was 97.6% (95% CI 96.8-98.2), whereas cumulative incidence of death without engraftment was 0.2% (95% CI 0.07-0.5). After a median follow-up of 16.4 months (IQR, 4.4-47.2), 3-year overall survival (OS), disease-free survival (DFS), cumulative incidences of relapse (IR) and non-relapse mortality (NRM) were 80.4% (95% CI 78.1-82.9), 59% (95% CI 56.1-62), 35.9% (95% CI 33.1-38.7) and 5% (95% CI 3.9-6.4), respectively. There was no significant difference in terms of outcome between patients treated during the time period 2003-2008 and 2009-2014. 3-year OS and DFS were 70.5% and 43.7% in patients with progressive disease at transplant, 75% and 52.1% in patients in partial response, 87.2% and 67.8% in patients in complete remission (p<0.0001 and p<0.0001, respectively). Male had a decreased 3-year OS compared to female (HR 1.46, 95% CI: 1.15-1.84; p=0.002). Age ≥ 35 years was associated with a higher NRM (HR 1.67, 95% CI: 1.06-2.65; p=0.029) but a better PFS (HR 0.77, 95% CI: 0.65-0.91; p=0.002). Overall, patient age did not significantly influence OS (p=0.19). Primary refractory or multiple relapsed patients had a worse outcome than the others. A number of previous treatment lines ≥ 3 negatively influenced OS (HR 1.91, 95% CI: 1.42-2.58; p<0.0001), PFS (HR 2.03, 95% CI: 1.60-2.56; p<0.0001), IR (HR 1.90, 95% CI: 1.48-2.45; p<0.0001) and NRM (HR 3.17, 95% CI: 1.69-5.96; p=0.0003). Cumulative incidence of NRM reached 9% at 3 years in these patients. Finally, patients who relapsed after auto-SCT (n=494) had a 3-year OS of 52.8% (95% CI 47.7-58.3).
Conclusion
In conclusion, HDC followed by auto-SCT is highly efficient in relapsed HL patients. However, relapse occurs in over 40% of patients < 35 years old or with partial response at transplant and in over 50% of patients with progressive disease at transplant or ≥ 3 previous treatment lines. Additional data are being collected to better identify which high-risk patients could benefit from post-transplant immunotherapy or tandem auto-allo transplant.

Disclosures
Brice: Roche: Honoraria; Bristol Myers-Squibb: Honoraria; Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Seattle Genetics: Research Funding; Gilead: Honoraria. Salles:Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Janssen: Honoraria. Peffault De Latour:PFIZER: Consultancy, Honoraria, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding; ALEXION: Consultancy, Honoraria, Research Funding.