Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma

• Type of Material: Article
• Authors: Reid W Merryman, Division of Hematologic Malignancies; Robert A Redd, Dana-Farber Cancer Institute; Taiga Nishihori, Moffitt Cancer Center, Tampa; Julio Chavez, Moffitt Cancer Center, Tampa; Yago Nieto, The University of Texas MD Anderson Cancer Center; Justin M Darrah, City of Hope, Duarte; Uttam Rao, Vanderbilt University; Michael T Byrne, Vanderbilt University; David A Bond, The Ohio State University Hospital; Kami J Maddocks, The Ohio State University Hospital; Michael A Spinner, Stanford University; Ranjana H Advani, Stanford University; Hatcher J Ballard, Hospital of the University of Pennsylvania; Jakub Svoboda, Hospital of the University of Pennsylvania; Anurag K Singh, University of Kansas Medical Center; Joseph P McGuirk, University of Kansas Medical Center; Dipenkumar Modi, Wayne State University; Radhakrishnan Ramchandren, University of Tennessee; Jason Romancik, Emory University; Jonathon Cohen, Emory University; Matthew J Frigault, Massachusetts General Hospital; Yi-Bin Chen, Massachusetts General Hospital; Anthony Serritella, University of Chicago; Justine Kline, University of Chicago; Stephen Ansell, Mayo Clinic, Rochester; Sunita Nathan, Rush University; Maryam Rahimian, Beth Israel Deaconess Medical Center; Robin M Joyce, Beth Israel Deaconess Medical Center; Mansi Shah, Rutgers Cancer Institute of New Jersey; Kevin A David, Rutgers Cancer Institute of New Jersey; Steven Park, Levine Cancer Institute, Charlotte; Anne W Beaven, University of North Carolina; Alma Habib, University of Minnesota, Minneapolis; Veronika Bachanova, University of Minnesota, Minneapolis; Shazia Nakhoda, Fox Chase Cancer Center; Nadia Khan, Fox Chase Cancer Center; Ryan C Lynch, University of Washington; Stephen D Smith, University of Washington; Vincent T Ho, Division of Hematologic Malignancies; Ann LaCasce, Division of Hematologic Malignancies; Philippe Armand, Division of Hematologic Malignancies; Alex F Herrera, City of Hope, Duarte
• Language: English
• Date: 2021-03-12
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by The American Society of Hematology
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2020003556
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 5
• Issue: 6
• Start Page: 1648
• End Page: 1659
• Grant/Funding Information: A.F.H. is supported by the Emmet and Toni Stephenson Leukemia and Lymphoma Society Scholar Award and the Lymphoma Research Foundation Larry and Denise Mason Clinical Investigator Career Development Award.
• Keywords: Life Sciences & Biomedicine; Hematology; Science & Technology
• Research Categories: Biology, Biostatistics; Health Sciences, Oncology

Abstract

Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to $1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to $2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received $4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.