Outcomes of Patients With Classic Hodgkin Lymphoma Who Relapsed After Autologous Stem Cell Transplant

Immune checkpoint inhibitors (ICIs) and brentuximab vedotin (BV) are novel agents for classic Hodgkin lymphoma, including relapse after autologous stem cell transplant (ASCT). However, their impact on survival post-ASCT relapse, in comparison with conventional therapy, is less known due to the lack of randomized controlled trials. Clinical characteristics and outcomes of 115 patients with relapse (or progression) after ASCT are studied. After a median follow-up of 8.59 years from post-ASCT relapse, the median progression-free survival (PFS) and overall survival (OS) were 0.91 and 5.07 years, respectively. Median lines of therapy after post-ASCT relapse was 2 (range, 1–12). The median PFS was not reached (NR) versus 1.11 versus 0.50 versus 0.85 versus 0.78 years (P = 0.006) and OS was NR versus 7.60 versus 3.08 versus 3.51 versus 3.17 years (P = 0.28) in patients first treated with ICIs versus BV versus investigational agents versus chemotherapy versus radiation therapy (RT). First-line treatment with novel agents (ie, ICIs and BV) was associated with superior outcomes compared with investigational agents and chemotherapy/RT with a median PFS of 1.65 versus 0.50 versus 0.79 years (P = 0.003) and a median OS of 7.60 versus 3.08 versus 3.32 years (P = 0.08). Regardless of lines of therapy, the treatment with ICIs had the most favorable outcome with a median PFS and OS of 3.98 and NR years, respectively. Allogeneic stem cell transplant (allo-SCT) was done in 23 patients (20%), and the median post-allo-SCT PFS and OS were 1.31 and 2.35 years, respectively. In conclusion, survival following post-ASCT relapse improves significantly when patients receive novel agents.

[1]  S. Ansell,et al.  SOHO State of the Art Updates and Next Questions | From Biology to Therapy: Progress in Hodgkin Lymphoma. , 2021, Clinical lymphoma, myeloma & leukemia.

[2]  N. Johnson,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. , 2021, The Lancet. Oncology.

[3]  R. Küppers,et al.  Molecular biology of Hodgkin lymphoma , 2021, Leukemia.

[4]  A. Jemal,et al.  Cancer Statistics, 2021 , 2021, CA: a cancer journal for clinicians.

[5]  I. Lossos,et al.  A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma. , 2020, Blood.

[6]  J. Serody,et al.  Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  R. Advani,et al.  Hodgkin Lymphoma, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. , 2020, Journal of the National Comprehensive Cancer Network : JNCCN.

[8]  S. Ansell Hodgkin lymphoma: A 2020 update on diagnosis, risk‐stratification, and management , 2020, American journal of hematology.

[9]  A. Szabo,et al.  Trends in postrelapse survival in classic Hodgkin lymphoma patients after experiencing therapy failure following auto-HCT. , 2020, Blood advances.

[10]  G. Heinze,et al.  An unjustified benefit: immortal time bias in the analysis of time‐dependent events , 2018, Transplant international : official journal of the European Society for Organ Transplantation.

[11]  J. Connors,et al.  Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma , 2017, The New England journal of medicine.

[12]  S. Schuster,et al.  Outcomes of patients with relapsed/refractory Hodgkin lymphoma progressing after autologous stem cell transplant in the current era of novel therapeutics: A retrospective analysis , 2017, American journal of hematology.

[13]  M. Shipp,et al.  Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  J. Raemaekers,et al.  Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  R. Bouabdallah,et al.  Haploidentical transplantation with post-infusion cyclophosphamide in advanced Hodgkin lymphoma , 2017, Bone Marrow Transplantation.

[16]  K. Savage,et al.  Nivolumab for classical Hodgkin lymphoma after autologous stem-cell transplantation and brentuximab vedotin failure: a prospective phase 2 multi-cohort study , 2016, The Lancet. Oncology.

[17]  F. d'Amore,et al.  Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. , 2016, The New England journal of medicine.

[18]  J. Radford,et al.  Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. , 2015, The New England journal of medicine.

[19]  M. Millenson,et al.  PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. , 2015, The New England journal of medicine.

[20]  M. Ravic,et al.  A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. , 2011, Blood.

[21]  J. Snowden,et al.  Identification of prognostic factors predicting outcome in Hodgkin's lymphoma patients relapsing after autologous stem cell transplantation. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[22]  S. Horning,et al.  Defining a Hodgkin lymphoma population for novel therapeutics after relapse from autologous hematopoietic cell transplant , 2013, Leukemia & lymphoma.

[23]  A. Zelenetz,et al.  Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Scott E Smith,et al.  Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  V. Diehl,et al.  Dose intensity of chemotherapy in patients with relapsed Hodgkin's lymphoma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  J. Garcia-conde,et al.  Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol. , 2006, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[27]  A. Zelenetz,et al.  Progressive disease following autologous transplantation in patients with chemosensitive relapsed or primary refractory Hodgkin's disease or aggressive non-Hodgkin's lymphoma , 2003, Bone Marrow Transplantation.

[28]  Dirk Hasenclever,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 , 2002, The Lancet.

[29]  V. Diehl,et al.  Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.