Durable remission for four pediatric patients with high-risk relapsed classical Hodgkin lymphoma treated with brentuximab vedotin plus gemcitabine but without autologous stem cell transplantation: A report from the Children's Oncology Group
Corresponding Author
Ilia N. Buhtoiarov
Department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Cleveland Clinic Children's, Cleveland, Ohio, USA
Correspondence
Ilia N. Buhtoiarov, Pediatric Hematology/Oncology and BMT, Cleveland Clinic Children's, 9500 Euclid Ave, R3-118, Cleveland, OH 44195, USA.
Email: [email protected]
Search for more papers by this authorNkechi I. Mba
Department of Pediatric Hematology and Oncology, Driscoll Children's Hospital, Corpus Christi, Texas, USA
Search for more papers by this authorCrystal D. L. Santos
Department of Pediatric Hematology and Oncology, Driscoll Children's Hospital, Corpus Christi, Texas, USA
Search for more papers by this authorKathleen M. McCarten
Imaging and Radiation Oncology Core Rhode Island, Lincoln, Rhode Island, USA
Search for more papers by this authorMonika L. Metzger
Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA
Search for more papers by this authorQinglin Pei
Children's Oncology Group, Department of Biostatistics, University of Florida, Gainesville, Florida, USA
Search for more papers by this authorKayla Baker
Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorKara M. Kelly
Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
Search for more papers by this authorPeter D. Cole
Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorCorresponding Author
Ilia N. Buhtoiarov
Department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Cleveland Clinic Children's, Cleveland, Ohio, USA
Correspondence
Ilia N. Buhtoiarov, Pediatric Hematology/Oncology and BMT, Cleveland Clinic Children's, 9500 Euclid Ave, R3-118, Cleveland, OH 44195, USA.
Email: [email protected]
Search for more papers by this authorNkechi I. Mba
Department of Pediatric Hematology and Oncology, Driscoll Children's Hospital, Corpus Christi, Texas, USA
Search for more papers by this authorCrystal D. L. Santos
Department of Pediatric Hematology and Oncology, Driscoll Children's Hospital, Corpus Christi, Texas, USA
Search for more papers by this authorKathleen M. McCarten
Imaging and Radiation Oncology Core Rhode Island, Lincoln, Rhode Island, USA
Search for more papers by this authorMonika L. Metzger
Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA
Search for more papers by this authorQinglin Pei
Children's Oncology Group, Department of Biostatistics, University of Florida, Gainesville, Florida, USA
Search for more papers by this authorKayla Baker
Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorKara M. Kelly
Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA
Search for more papers by this authorPeter D. Cole
Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
Search for more papers by this authorFunding information: NCTN Operations Center, Grant Number: U10CA180886; NCTN Statistics & Data Center, Grant Number: U10CA180899; St. Baldrick's Foundation
Abstract
Patients with therapy-refractory or high-risk relapsed classical Hodgkin lymphoma are typically treated with the high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) to consolidate the response to salvage therapy. The combination of brentuximab vedotin with gemcitabine has recently been shown to be an effective and safe salvage regimen. While the majority of patients with complete responses to this regimen ultimately underwent HDC/ASCT consolidation, four subjects, reported herein, achieved durable complete remissions lasting more than 4 years after the study treatment but without ASCT consolidation. Further investigation of treatment strategies incorporating targeted agents may allow omission of HDC/ASCT for select patients.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
REFERENCES
- 1Kelly KM. Hodgkin lymphoma in children and adolescents: improving the therapeutic index. Blood. 2015; 126(22): 2452-2458.
- 2Daw S, Hasenclever D, Mascarin M, et al. Risk and response adapted treatment guidelines for managing first relapsed and refractory classical Hodgkin lymphoma in children and young people. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group. Hemasphere. 2020; 4(1):e329.
- 3Moskowitz AJ, Herrera AF, Beaven AW. Relapsed and refractory classical Hodgkin lymphoma: keeping pace with novel agents and new options for salvage therapy. Am Soc Clin Oncol Educ Book. 2019; 39: 477-486.
- 4LaCasce AS. Treating Hodgkin lymphoma in the new millennium: relapsed and refractory disease. Hematol Oncol. 2019; 37: 87-91.
- 5Ansell SM. Hodgkin lymphoma: 2018 update on diagnosis, risk-stratification, and management. Am J Hematol. 2018; 93(5): 704-715.
- 6Flerlage JE. Improving care for all pediatric patients with Hodgkin lymphoma. J Natl Compr Canc Netw. 2021; 19(6): 771-772
- 7Hoppe RT, Advani RH, Ai WZ, et al. Hodgkin lymphoma, version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020; 18(6): 755-781.
- 8Perales MA, Ceberio I, Armand P, et al. Role of cytotoxic therapy with hematopoietic cell transplantation in the treatment of Hodgkin lymphoma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015; 21(6): 971-983.
- 9Linch DC, Winfield D, Goldstone AH, et al. Dose intensification with ABMT in relapsed and resistant Hodgkin's disease, results of a BNLI randomised trial. Lancet. 1993; 341: 1051-1054.
- 10Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with ASCT for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002; 325: 2065-2071.
- 11Harker-Murray PD, Drachtman RA, Hodgson DC, et al. Stratification of treatment intensity in relapsed pediatric Hodgkin lymphoma. Pediatr Blood Cancer. 2014; 61(4): 579-586.
- 12Rancea M, Monsef I, von Tresckow B, et al. High-dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma. Cochrane Database Syst Rev. 2013;(6):CD009411. https://doi.org/10.1002/14651858.cd009411.pub2
- 13Cole PD, McCarten KM, Pei Q, et al. Brentuximab vedotin with gemcitabine for paediatric and young adult patients with relapsed or refractory Hodgkin's lymphoma (AHOD1221): a Children's Oncology Group, multicentre single-arm, phase 1–2 trial. Lancet Oncol. 2018; 19(9): 1229-1238.
- 14Friedman DL, Chen L, Wolden S, et al. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014; 32(32): 3651-3658.
- 15Mauz-Körholz C, Hasenclever D, Dörffel W, et al. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010; 28(23): 3680-3686. PMID: 20625128
- 16Kelly KM, Cole PD, Pei Q, et al. Response-adapted therapy for the treatment of children with newly diagnosed high risk Hodgkin lymphoma (AHOD0831): a report from the Children's Oncology Group. Br J Haematol. 2019; 187(1): 39-48.
- 17Kelly KM, Hodgson D, Appel B, et al. Children's Oncology Group's 2013 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2013; 60(6): 972-978.
- 18LaCasce AS, Bociek RG, Ahmed Sawas A, et al. Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood 2018; 132(1): 40-48.
- 19Moskowitz CH, Nademanee A, Masszi T, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015; 385(9980): 1853-1862.
- 20Diefenbach CS, Hong F, Ambinder RF, et al. Ipilimumab, nivolumab, and brentuximab vedotin combination therapies in patients with relapsed or refractory Hodgkin lymphoma: phase 1 results of an open-label, multicentre, phase 1/2 trial. Lancet Haematol. 2020; 7(9): e660-e670.
