In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.

Academic Medical Center Amsterdam The Netherlands

Academic Medical Center University of Amsterdam Amsterdam The Netherlands

Biostatistics Memorial Sloan Kettering Cancer Center New York USA

British Columbia Cancer Agency Vancouver Canada

Celgene Summit

Children's National Health System Washington USA

Cleveland Clinic Cleveland USA

Columbia University College of Physicians and Surgeons and New York Presbyterian Hospital New York

Department of Diagnostic Medicine University of Modena Modena Italy

Department of Haemato Oncology Barts Cancer Institute London UK

Department of Hematology National Cancer Center Hospital Tokyo Japan

Department of Hematology Université de Lille 2 Lille France

Department of Hematology University Hospital Centre Zagreb Zagreb Croatia

Department of Hematology University of Bologna Bologna

Department of Hematology University of Copenhagen Denmark

Department of Internal Medicine Universität des Saarlandes Homburg Germany

Department of Internal Medicine University Hospital of Cologne Cologne Germany

Department of Oncology Stanford University Stanford

Department of Radiology Memorial Sloan Kettering Cancer Center New York

Division of Medical Oncology and Hematology Princess Margaret Cancer Centre Toronto Canada

Divisions of Cancer Treatment and Diagnosis National Cancer Institute National Institutes of Health Bethesda USA

Fox Chase Cancer Center Philadelphia USA

Fred Hutchinson Cancer Research Center Seattle USA

Genentech San Francisco USA

Haemato Oncology Hôpital Saint Louis Paris France

Haematology Department Plymouth University UK

Hematology Université Lyon 1 Lyon Sud Charles Mérieux Lyon France

Janssen Research and Development Spring House USA

John Theurer Cancer Center Hackensack University Medical Center Hackensack

Lymphoid Malignancies Branch National Cancer Institute Bethesda USA

Lymphoma and Stem Cell Transplantation Program Charles University Prague Czech Republic

Lymphoma Service

Massachusetts General Hospital Center for Lymphoma Boston

Mayo Clinic Rochester USA

Medicine Clinic 3 Ludwig Maximilian University Munich Germany

Nuclear Medicine Hôpitaux Universitaires Henri Mondor Créteil France

Oncology UCLA Los Angeles USA

Pediatrics Department Roswell Park Cancer Institute Buffalo USA

Peter MacCallum Cancer Centre and University of Melbourne Australia

Servier Neuilly sur Seine France

Statistics EORTC Brussels Belgium

U T M D Anderson Cancer Center Houston

University of Michigan Comprehensive Cancer Center Ann Arbor USA

University of Pennsylvania School of Medicine Philadelphia USA

Weill Cornell Medicine and and New York Presbyterian Hospital New York

Komentář v

Ann Oncol. 2017 Jul 1;28(7):1409-1411. doi: 10.1093/annonc/mdx209. PubMed

Komentář v

Nat Rev Clin Oncol. 2017 Sep;14(9):527-528. doi: 10.1038/nrclinonc.2017.81. PubMed

Zobrazit více v PubMed

Cheson BD. The International Harmonization Project for response criteria in lymphoma clinical trials. Hematol Oncol Clin North Am 2007; 21(5): 841–854. PubMed

Cheson BD, Horning SJ, Coiffier B. et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999; 17(4): 1244.. PubMed

Juweid ME, Stroobants S, Hoekstra OS. et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 2007; 25(5): 571–578. PubMed

Cheson BD, Fisher RI, Barrington SF. et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32(27): 3059–3068. PubMed PMC

Younes A, Ansell S, Fowler N. et al. The landscape of new drugs in lymphoma. Nat Rev Clin Oncol 2016. Dec 29 [Epub ahead of print], doi: 10.1038/nrclinonc.2016.205. PubMed PMC

Younes A, Hagenbeek A, Coiffier B.. Optimising the lymphoma response criteria in the era of targeted therapy. Lancet Oncol 2011; 12(7): 616–617. PubMed

Oxnard GR, Morris MJ, Hodi FS. et al. When progressive disease does not mean treatment failure: reconsidering the criteria for progression. J Natl Cancer Inst 2012; 104(20): 1534–1541. PubMed PMC

Fournier L, Ammari S, Thiam R, Cuenod CA.. Imaging criteria for assessing tumour response: RECIST, mRECIST, Cheson. Diagn Interv Imaging 2014; 95(7-8): 689–703. PubMed

Eisenhauer EA, Therasse P, Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45(2): 228–247. PubMed

Cheson BD, Pfistner B, Juweid ME. et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007; 25(5): 579–586. PubMed

Assouline S, Meyer RM, Infante-Rivard C. et al. Development of adapted RECIST criteria to assess response in lymphoma and their comparison to the International Workshop Criteria. Leuk Lymphoma 2007; 48(3): 513–520. PubMed

Schwartz LH, Bogaerts J, Ford R. et al. Evaluation of lymph nodes with RECIST 1.1. Eur J Cancer 2009; 45(2): 261–267. PubMed

Anderson JR, Cain KC, Gelber RD.. Analysis of survival by tumor response and other comparisons of time-to-event by outcome variables. J Clin Oncol 2008; 26(24): 3913–3915. PubMed

Bowman AW, Azzalini A, Applied Smoothing Techniques for Data Analysis: the Kernel Approach with S-Plus Illustrations. London: Oxford University Press; 1997.

Friedman 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. PubMed PMC

Aurer I, Eghbali H, Raemaekers J. et al. Gem-(R)CHOP versus (R)CHOP: a randomized phase II study of gemcitabine combined with (R)CHOP in untreated aggressive non-Hodgkin's lymphoma–EORTC lymphoma group protocol 20021 (EudraCT number 2004-004635-54). Eur J Haematol 2011; 86(2): 111–116. PubMed

Hagenbeek A, Eghbali H, Monfardini S. et al. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma. J Clin Oncol 2006; 24(10): 1590–1596. PubMed

Offner F, Samoilova O, Osmanov E. et al. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood 2015; 126(16): 1893–1901. PubMed PMC

Salles G, Seymour JF, Offner F. et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011; 377(9759): 42–51. PubMed

van Oers MH, Van Glabbeke M, Giurgea L. et al. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol 2010; 28(17): 2853–2858. PubMed PMC

Evens AM, Balasubramanian S, Vose JM. et al. A Phase I/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed/Refractory Lymphoma. Clin Cancer Res 2016; 22(5): 1059–1066. PubMed

Gopal AK, Kahl BS, de Vos S. et al. PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 2014; 370(11): 1008–1018. PubMed PMC

Coiffier B, Osmanov EA, Hong X. et al. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol 2011; 12(8): 773–784. PubMed

Bland JM, Altman DG.. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1(8476): 307–310. PubMed

Cleveland WS. Robust locally weighted regression and smoothing scatterplots. J Am Stat Assoc.1979; 74(368): 829–836.

Federico M, Bellei M, Marcheselli L. et al. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol 2009; 27(27): 4555–4562. PubMed

Barrington SF, Mikhaeel NG, Kostakoglu L. et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol 2014; 32(27): 3048–3058. PubMed PMC

Pelosi E, Penna D, Douroukas A. et al. Bone marrow disease detection with FDG-PET/CT and bone marrow biopsy during the staging of malignant lymphoma: results from a large multicentre study. Q J Nucl Med Mol Imaging 2011; 55(4): 469–475. PubMed

Adams HJ, Kwee TC, de Keizer B. et al. FDG PET/CT for the detection of bone marrow involvement in diffuse large B-cell lymphoma: systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2014; 41(3): 565–574. PubMed

El-Galaly TC, d'Amore F, Mylam KJ. et al. Routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography/computed tomography-staged treatment-naive patients with Hodgkin lymphoma. J Clin Oncol 2012; 30(36): 4508–4514. PubMed

Meignan M, Itti E, Gallamini A, Younes A.. FDG PET/CT imaging as a biomarker in lymphoma. Eur J Nucl Med Mol Imaging 2015; 42(4): 623–633. PubMed

Younes A, Sureda A, Ben-Yehuda D. et al. Panobinostat in Patients With Relapsed/Refractory Hodgkin's Lymphoma After Autologous Stem-Cell Transplantation: Results of a Phase II Study. J Clin Oncol 2012. Apr 30 [Epub ahead of print]. PubMed

Younes A, Gopal AK, Smith SE. et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol 2012; 30(18): 2183–2189. PubMed PMC

Younes A, Oki Y, Bociek RG. et al. Mocetinostat for relapsed classical Hodgkin's lymphoma: an open-label, single-arm, phase 2 trial. Lancet Oncol 2011; 12(13): 1222–1228. PubMed PMC

Advani RH, Buggy JJ, Sharman JP. et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 2013; 31(1): 88–94. PubMed PMC

Witzig TE, Wiernik PH, Moore T. et al. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin's lymphoma. J Clin Oncol 2009; 27(32): 5404–5409. PubMed

Chanan-Khan A, Miller KC, Lawrence D. et al. Tumor flare reaction associated with lenalidomide treatment in patients with chronic lymphocytic leukemia predicts clinical response. Cancer.117(10): 2127–2135. PubMed

Armand P, Shipp MA, Ribrag V. et al. Programmed death-1 blockade with pembrolizumab in patients with classical Hodgkin lymphoma after brentuximab vedotin failure. J Clin Oncol 2016; 34: 3733–3739. PubMed PMC

Zinzani PL, Ribrag V, Moskowitz CH. et al. Phase 1b Study of PD-1 Blockade with Pembrolizumab in Patients with Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma (PMBCL). Blood 2015; 126(23): 3986.

Younes A, Santoro A, Shipp M. et al. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol 2016; 17(9): 1283–1294. PubMed PMC

Goy A, Sinha R, Williams ME. et al. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol 2013; 31(29): 3688–3695. PubMed PMC

Witzig TE, Vose JM, Zinzani PL. et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol 2011; 22(7): 1622–1627. PubMed

Kochenderfer JN, Dudley ME, Kassim SH. et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 2015; 33(6): 540–549. PubMed PMC

Park JH, Brentjens RJ.. Adoptive immunotherapy for B-cell malignancies with autologous chimeric antigen receptor modified tumor targeted T cells. Discov Med 2010; 9(47): 277–288. PubMed PMC

Turtle CJ, Hanafi LA, Berger C. et al. Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med 2016; 8(355): 355ra116. PubMed PMC

Bollard CM, Gottschalk S, Torrano V. et al. Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins. J Clin Oncol 2014; 32(8): 798–808. PubMed PMC

Hodi FS, Hwu WJ, Kefford R. et al. Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with pembrolizumab. J Clin Oncol 2016; 34(13): 1510–1517. PubMed PMC

Hoos A, Wolchok JD, Humphrey RW, Hodi FS.. CCR 20th anniversary commentary: immune-related response criteria–capturing clinical activity in immuno-oncology. Clin Cancer Res 2015; 21(22): 4989–4991. PubMed

Wolchok JD, Hoos A, O'Day S. et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15(23): 7412–7420. PubMed

Cheson BD, Ansell S, Schwartz L. et al. Refinement of the Lugano classification response criteria for lymphoma in the era of immunomodulatory therapy. Blood 2016; 128: 2489–2496. PubMed

Byrd JC, Brown JR, O'Brien S. et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014; 371(3): 213–223. PubMed PMC

Dreyling M, Jurczak W, Jerkeman M. et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet 2016; 387(10020): 770–778. PubMed

Furtado M, Wang ML, Munneke B. et al. Ibrutinib-associated lymphocytosis corresponds to bone marrow involvement in mantle cell lymphoma. Br J Haematol 2015; 170(1): 131–134. PubMed

Herman SE, Niemann CU, Farooqui M. et al. Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study. Leukemia 2014; 28(11): 2188–2196. PubMed PMC

Rossi D, Gaidano G.. Lymphocytosis and ibrutinib treatment of CLL. Blood 2014; 123(12): 1772–1774. PubMed

Wang ML, Rule S, Martin P. et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013; 369(6): 507–516. PubMed PMC

Brown JR, Byrd JC, Coutre SE. et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood 2014; 123(22): 3390–3397. PubMed PMC

Fiorcari S, Brown WS, McIntyre BW. et al. The PI3-kinase delta inhibitor idelalisib (GS-1101) targets integrin-mediated adhesion of chronic lymphocytic leukemia (CLL) cell to endothelial and marrow stromal cells. PLoS One 2013; 8(12): e83830.. PubMed PMC

Panageas KS, Ben-Porat L, Dickler MN. et al. When you look matters: the effect of assessment schedule on progression-free survival. J Natl Cancer Inst 2007; 99(6): 428–432. PubMed

A comparison of the prognostic performance of the Lugano 2014 and RECIL 2017 response criteria in patients with NHL from the phase III GOYA and GALLIUM trials

Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial