Excellent outcomes of transformed lymphomas in the rituximab era without autologous stem cell transplantation: an Australian single-centre experience.
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Australia
/ epidemiology
Cyclophosphamide
Disease-Free Survival
Doxorubicin
Hematopoietic Stem Cell Transplantation
Humans
Lymphoma, Non-Hodgkin
Neoplasm Recurrence, Local
Prednisone
Rituximab
Transplantation, Autologous
Vincristine
diffuse large B-cell lymphoma
follicular lymphoma
histologic transformation
marginal zone lymphoma
rituximab
transformed lymphoma
Journal
Internal medicine journal
ISSN: 1445-5994
Titre abrégé: Intern Med J
Pays: Australia
ID NLM: 101092952
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
revised:
21
04
2020
received:
17
01
2020
accepted:
17
06
2020
pubmed:
2
7
2020
medline:
15
12
2021
entrez:
2
7
2020
Statut:
ppublish
Résumé
Histologic transformation (HT) is an important event with adverse prognosis in the natural history of indolent lymphomas. There are minimal data on HT in the Australian setting. To characterise patients with biopsy-proven HT and their outcomes identified at a tertiary Australian Hospital. All patients with biopsy-proven HT during a 15-year period (2002-2017) were included. Clinico-pathological data were systematically collected from review of patient records. Survival estimates were assessed using the Kaplan-Meier method and compared using the log-rank test. Associations between variables and clinical outcomes were evaluated using Cox's proportional hazards model. A cohort of 45 patients was identified with a median age of 66 years and the majority (59%) having high-risk disease (Revised-International Prognostic Index score ≥3). R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) induction was used in 69%, with an overall response rate of 82% (complete response (CR), 75%). Sixty-one percent of these induction responders received consolidation, with autologous stem cell transplant (ASCT) performed in only 17% and rituximab maintenance given to 31%. With a median follow up of 47 months (range: 4-136), the 5-year overall survival (OS) was 69% (95% CI: 52%, 81%). Chemotherapy-naivety at HT was associated with a superior rate of CR (84% vs 54%, P = 0.057) and 5-year OS (82% vs 46%, P = 0.012). Rituximab maintenance was associated with a durable progression-free survival in induction responders. Excellent OS was observed in this modern cohort of patients treated with rituximab-containing induction and low rate of consolidation by ASCT, particularly in those who were chemotherapy-naïve at HT.
Sections du résumé
BACKGROUND
BACKGROUND
Histologic transformation (HT) is an important event with adverse prognosis in the natural history of indolent lymphomas. There are minimal data on HT in the Australian setting.
AIMS
OBJECTIVE
To characterise patients with biopsy-proven HT and their outcomes identified at a tertiary Australian Hospital.
METHODS
METHODS
All patients with biopsy-proven HT during a 15-year period (2002-2017) were included. Clinico-pathological data were systematically collected from review of patient records. Survival estimates were assessed using the Kaplan-Meier method and compared using the log-rank test. Associations between variables and clinical outcomes were evaluated using Cox's proportional hazards model.
RESULTS
RESULTS
A cohort of 45 patients was identified with a median age of 66 years and the majority (59%) having high-risk disease (Revised-International Prognostic Index score ≥3). R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) induction was used in 69%, with an overall response rate of 82% (complete response (CR), 75%). Sixty-one percent of these induction responders received consolidation, with autologous stem cell transplant (ASCT) performed in only 17% and rituximab maintenance given to 31%. With a median follow up of 47 months (range: 4-136), the 5-year overall survival (OS) was 69% (95% CI: 52%, 81%). Chemotherapy-naivety at HT was associated with a superior rate of CR (84% vs 54%, P = 0.057) and 5-year OS (82% vs 46%, P = 0.012). Rituximab maintenance was associated with a durable progression-free survival in induction responders.
CONCLUSIONS
CONCLUSIONS
Excellent OS was observed in this modern cohort of patients treated with rituximab-containing induction and low rate of consolidation by ASCT, particularly in those who were chemotherapy-naïve at HT.
Substances chimiques
Rituximab
4F4X42SYQ6
Vincristine
5J49Q6B70F
Doxorubicin
80168379AG
Cyclophosphamide
8N3DW7272P
Prednisone
VB0R961HZT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1825-1834Subventions
Organisme : Medical Research Future Fund Next Generation Clinician Researcher Fellowship
Informations de copyright
© 2020 Royal Australasian College of Physicians.
Références
Montoto S. Treatment of patients with transformed lymphoma. Hematol Am Soc Hematol Educ Progr 2015; 2015: 625-30.
Noy A, Schoder H, Gonen M, Weissler M, Ertelt K, Cohler C et al. The majority of transformed lymphomas have high standardized uptake values (SUVs) on positron emission tomography (PET) scanning similar to diffuse large B-cell lymphoma (DLBCL). Ann Oncol 2009; 20: 508-12.
Bodet-Milin C, Kraeber-Bodere F, Moreau P, Campion L, Dupas B, Le Gouill S. Investigation of FDG-PET/CT imaging to guide biopsies in the detection of histological transformation of indolent lymphoma. Haematologica 2008; 93: 471-2.
Strati P, Ahmed MA, Fowler NH, Hagemeister FB, Fayad L, Rodriguez MA et al. Prognostic value of baseline SUVmax in patients with advanced stage follicular lymphoma receiving frontline rituximab-based therapy. J Clin Oncol 2019; 37: 7540.
Mir F, Barrington SF, Brown H, Nielsen T, Sahin D, Meignan M et al. Baseline SUVmax did not predict histological transformation in follicular lymphoma in the phase 3 GALLIUM study. Blood 2020; 135: 1214-18.
Casulo C, Burack WR, Friedberg JW. Transformed follicular non-Hodgkin lymphoma. Blood 2015; 125: 40-7.
Pasqualucci L, Khiabanian H, Fangazio M, Vasishtha M, Messina M, Holmes AB et al. Genetics of follicular lymphoma transformation. Cell Rep 2014; 6: 130-40.
Okosun J, Bodor C, Wang J, Araf S, Yang C-Y, Pan C et al. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet 2014; 46: 176-81.
Gonzalez-Rincon J, Mendez M, Gomez S, Garcia JF, Martin P, Bellas C, et al. Unraveling transformation of follicular lymphoma to diffuse large B-cell lymphoma. PLoS One 2019; 14: e0212813.
Federico M, Caballero Barrigón MD, Marcheselli L, Tarantino V, Manni M, Sarkozy C et al. Rituximab and the risk of transformation of follicular lymphoma: a retrospective pooled analysis. Lancet Haematol 2018; 5: e359-e67.
Montoto S, Davies AJ, Matthews J, Calaminici M, Norton AJ, Amess J et al. Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol 2007; 25: 2426-33.
Al-Tourah AJ, Gill KK, Chhanabhai M, Hoskins PJ, Klasa RJ, Savage KJ et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma. J Clin Oncol 2008; 26: 5165-9.
Ban-Hoefen M, Vanderplas A, Crosby-Thompson AL, Abel GA, Czuczman MS, Gordon LI et al. Transformed non-Hodgkin lymphoma in the rituximab era: analysis of the NCCN outcomes database. Br J Haematol 2013; 163: 487-95.
Link BK, Maurer MJ, Nowakowski GS, Ansell SM, Macon WR, Syrbu SI et al. Rates and outcomes of follicular lymphoma transformation in the Immunochemotherapy era: a report from the University of Iowa/Mayo Clinic specialized program of research excellence molecular epidemiology resource. J Clin Oncol 2013; 31: 3272-8.
Sarkozy C, Trneny M, Xerri L, Wickham N, Feugier P, Leppa S et al. Risk factors and outcomes for patients with follicular lymphoma who had histologic transformation after response to first-line Immunochemotherapy in the PRIMA trial. J Clin Oncol 2016; 34: 2575-82.
Wagner-Johnston ND, Link BK, Byrtek M, Dawson KL, Hainsworth J, Flowers CR et al. Outcomes of transformed follicular lymphoma in the modern era: a report from the National LymphoCare Study (NLCS). Blood 2015; 126: 851-7.
Alonso-Alvarez S, Magnano L, Alcoceba M, Andrade-Campos M, Espinosa-Lara N, Rodriguez G et al. Risk of, and survival following, histological transformation in follicular lymphoma in the rituximab era. A retrospective multicentre study by the Spanish GELTAMO group. Br J Haematol 2017; 178: 699-708.
Link BK. Will a better understanding of the problem with transformed follicular lymphoma lead to better outcomes? J Clin Oncol 2016; 34: 2566-7.
Trotman J, Cheah CY, Marlton P, Opat S. Front-line management of non-Hodgkin lymphoma in Australia. Part 1: follicular lymphoma. Intern Med J 2019; 49: 422-33.
Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L 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: 42-51.
Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C et al. Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med 2017; 377: 1331-44.
Rusconi C, Anastasia A, Chiarenza A, Marcheselli L, Cavallo F, Rattotti S et al. Outcome of transformed follicular lymphoma worsens according to the timing of transformation and to the number of previous therapies. A retrospective multicenter study on behalf of Fondazione Italiana Linfomi (FIL). Br J Haematol 2019; 185: 713-17.
Kahl BS. An iatrogenic orphan? Blood 2019; 134: 1273-4.
Anderson MA, Blombery P, Seymour JF. Transformed lymphoma. Hematol Oncol Clin North Am 2016; 30: 1317-32.
Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P et al. The Revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 2007; 109: 1857-61.
eviQ. Non-Hodgkin lymphoma R-CHOP21 (rituximab CYCLOPHOSPHamide DOXOrubicin vinCRISTine prednisolone). 2019 [cited 2020 Jan 6]. Available from: https://www.eviq.org.au/haematology-and-bmt/lymphoma/non-hodgkin-lymphoma/70-r-chop21-rituximab-cyclophosphamide-doxorubici
eviQ. Non-Hodgkin lymphoma R-CVP (rituximab CYCLOPHOSPHamide vinCRISTine prednisolone). 2019 [cited 2020 Jan 6]. Available from: https://www.eviq.org.au/haematology-and-bmt/lymphoma/non-hodgkin-lymphoma/168-r-cvp-rituximab-cyclophosphamide-vincristine
Cheah CY, Herbert KE, O'Rourke K, Kennedy GA, George A, Fedele PL et al. A multicentre retrospective comparison of central nervous system prophylaxis strategies among patients with high-risk diffuse large B-cell lymphoma. Br J Cancer 2014; 111: 1072-9.
eviQ. Autologous conditioning protocol BEAM (carmustine etoposide cytarabine melphalan). 2016 [cited 2019 Oct 30]. Available from: https://www.eviq.org.au/haematology-and-bmt/blood-and-marrow-transplant/autologous/405-autologous-conditioning-protocol-beam-carmust
eviQ. Autologous conditioning protocol LACE (lomustine cytarabine cyclophosphamide etoposide). 2017 [cited 2019 Oct 30]. Available from: https://www.eviq.org.au/haematology-and-bmt/blood-and-marrow-transplant/autologous/1467-autologous-conditioning-protocol-lace-lomust
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 2014; 32: 3059-68.
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM 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: 1244.
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007; 25: 579-86.
Mendez M, Torrente M, Sanchez-Beato M, Gonzalez-Rincon J, Royuela A, Gomez-Codina J et al. Transformed follicular lymphoma in the rituximab era: a report from the Spanish lymphoma oncology group. Hematol Oncol 2019; 37: 143-50.
Guirguis HR, Cheung MC, Piliotis E, Spaner D, Berinstein NL, Imrie K et al. Survival of patients with transformed lymphoma in the rituximab era. Ann Hematol 2014; 93: 1007-14.
Morschhauser F, Fowler NH, Feugier P, Bouabdallah R, Tilly H, Palomba ML et al. Rituximab plus Lenalidomide in advanced untreated follicular lymphoma. N Engl J Med 2018; 379: 934-47.
Morschhauser F, Le Gouill S, Feugier P, Bailly S, Nicolas-Virelizier E, Bijou F et al. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. Lancet Haematol 2019; 6: e429-e37.
Zucca E, Rondeau S, Vanazzi A, Østenstad B, Mey UJM, Rauch D et al. Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy. Blood 2019; 134: 353-62.
Andorsky DJ, Coleman M, Yacoub A, Melear JM, Fanning SR, Kolibaba K et al. MAGNIFY: phase IIIb interim analysis of induction R2 followed by maintenance in relapsed/refractory indolent non-Hodgkin lymphoma. J Clin Oncol 2019; 37: 7513-13.
Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity. Blood 2015; 125: 22-32.