TREATMENT OUTCOMES AND CLINICAL RELEVANCE IN PATIENTS WITH DOUBLE EXPRESSOR DLBCL Sirapat Rungwittayatiwat1, Paisarn Boonsakan2, Pichika Chantrathammachart1, Teeraya Puavilai1, Sulada Pukiat1, Sithakom Phusanti1,3, Kochawan Boonyawat1, Pathawut Wacharapornin1, Pantep Angchaisuksiri1, Artit Ungkanont1,3, Suporn Chuncharunee1 Pimjai Niparuck1

Main Article Content

PIMJAI NIPARUCK

Keywords

diffuse large B cell lymphoma, double expressor lymphoma, GCB, non GCB, survival

Abstract

Background: Double-expressor lymphoma (DEL) was found accounting for 20- 30% of DLBCL. We conducted this study to analyze the survival, the clinical presentation and the factors associated with treatment outcomes in DEL-DLBCL.


MethodsA retrospective study of 291 patients diagnosed with DLBCL during January 2015 - December 2018.


Results: Of the 291 patients, median age was 63 years, germinal center B cell like DLBCL (GCB) and non-GCB subtypes were found in 32% and 68%, respectively. DEL was found in 46% of 264 patients with available immunohistochemistry staining for MYC protein. Patients with DEL was significantly more common in elderly patients (p= 0.017) and non-GCB subtype (p= 0.006). High serum lactate dehydrogenase (LDH) levels and high Ki-67 index were significantly found in DEL patients than those in non-DEL patients (p= 0.024 and p= 0.04, respectively).  3y-OS and 3y-DFS in DEL patients were shorter than those in non-DEL group, 58.7% versus 78.9% (p=0.026) and 58.4% versus 67.7% (p=0.343), respectively. Independent factors affecting both OS and DFS in DEL patients were ECOG 3-4, high LDH level, extranodal involvement> 1 site, DHL, high IPI and stage III-IV.


Conclusions: High incidence of DEL was observed in this study, especially in patients aged 60 years or older and non-GCB subtype. Patients with DEL showed dismal DFS and OS.

Downloads

Download data is not yet available.
Abstract 98 | PDF Downloads 32 HTML Downloads 1

References

1. Bunworasate U, Siritanaratanakul N, Khuhapinant A, Lekhakula A, Rujirojindakul P, Sirijerachai C, Chansung K, Suwanban T, Chuncharunee S, Niparuck P, Nawarawong W, Norasetthada L, Kanitsap N, Mongkonsritragoon W, Numbenjapon T, Prayongratana K, Pornvipavee R, Intragumtornchai T. A nationwide prospective multicenter study of clinical features and outcomes of non-Hodgkin lymphoma in Thailand: an analysis of 939 cases. 2011:2064-64.
2. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Müller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275-82.
3. Aggarwal A, Rafei H, Alakeel F, NafezFinianos A, LingLiu M, Bahesh E, LAscensao J, Mobarek D. Outcome of Patients with Double-Expressor Lymphomas (DELs) Treated with R-CHOP or R-EPOCH. Blood. 2016;128:5396.
4. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375-90.
5. Nowakowski GS, Laplant BR, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE. Lenalidomide Combined with R-CHOP (R2CHOP) overcomes negative prognostic impact of ABC molecular subtype in newly diagnosed diffuse large B-cell lymphoma. Blood. 2016;128:3035.
6. Dodero A, Guidetti A, Tucci A, Barretta F, Novo M, Devizzi L, Re A, Passi A, Pellegrinelli A, Pruneri G, Miceli R, Testi A, Pennisi M, Di Chio MC, Matteucci P, Carniti C, Facchetti F, Rossi G, Corradini P. Dose-adjusted EPOCH plus rituximab improves the clinical outcome of young patients affected by double expressor diffuse large B-cell lymphoma. Leukemia. 2019;33(4):1047-51.
7. Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Müller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immuno-histochemistry using a tissue microarray. Blood. 2004;103:275-82.
8. Choi WW, Weisenburger DD, Greiner TC, Piris MA, Banham AH, Delabie J, Braziel RM, Geng H, Iqbal J, Lenz G, Vose JM, Hans CP, Fu K, Smith LM, Li M, Liu Z, Gascoyne RD, Rosenwald A, Ott G, Rimsza LM, Campo E, Jaffe ES, Jaye DL, Staudt LM, Chan WC. A new immuno-stain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin Cancer Res. 2009;15(17): 5494-502.
9. Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, Scott DW, Tan KL, Steidl C, Sehn LH, Chan WC, Iqbal J, Meyer PN, Lenz G, Wright G, Rimsza LM, Valentino C, Brunhoeber P, Grogan TM, Braziel RM, Cook JR, Tubbs RR, Weisenburger DD, Campo E, Rosenwald A, Ott G, Delabie J, Holcroft C, Jaffe ES, Staudt LM, Gascoyne RD. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30:3452-9.
10. Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A, Liu WM, Visco C, Li Y, Miranda RN, Montes-Moreno S, Dybkaer K, Chiu A, Orazi A, Zu Y, Bhagat G, Richards KL, Hsi ED, Choi WW, Zhao X, van Krieken JH, Huang Q, Huh J, Ai W, Ponzoni M, Ferreri AJ, Zhou F, Slack GW, Gascoyne RD, Tu M, Variakojis D, Chen W, Go RS, Piris MA, Møller MB, Medeiros LJ, Young KH. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates highrisk gene expression signatures: a report from the International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013;121:4021-31.
11. Riedell PA, Smith SMJC. Double hit and double expressors in lymphoma: definition and treatment. 2018;124(24):4622-32.
12. Liu Y, Barta SK. Diffuse large B-cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2019;94:604-16.
13. Green TM, Young KH, Visco C, Xu-Monette ZY, Orazi A, Go RS, Nielsen O, Gadeberg OV, Mourits-Andersen T, Frederiksen M, Pedersen LM, Møller MB. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28): 3460-7.
14. Sathyanarayanan V, Oki Y, Issa AK, AminAhmed M, Noorani M, AFanale M, B.Hagemeister F, S.Neelapu S, J.Nastoupil L, Fowler N, Turturro F, Davis R, Rodriguez A, Wang M, FengMS L,
H.Young K, J.McDonnell T, CPinnix C, Westin JR. High risk diffuse large B cell lymphoma: a comparison of aggressive subtypes treated with dose adjusted chemotherapy-the University of Texas MD Anderson Experience. American Society of Hematology. Washington, DC; 2016.
15. Kawashima I, Inamoto Y, Maeshima AM, Nomoto J, Tajima K, Honda T, Shichijo T, Kawajiri A, Takemura T, Onishi A, Ito A, Tanaka T, Fuji S, Kurosawa S, Kim SW, Maruyama D, Tobinai K, Kobayashi Y, Fukuda T. Double-Expressor Lymphoma is associated with poor outcomes after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2018;24:294-300.
16. Zhang Y, Wang H, Ren C, Yu H, Fang W, Zhang N, Gao S, Hou Q. Correlation Between C-MYC, BCL-2, and BCL-6 protein expression and gene translocation as biomarkers in diagnosis and prognosis of diffuse large B-cell lymphoma. Front Pharmacol. 2019;9:1497.
17. Kluk MJ, Chapuy B, Sinha P, Roy A, Dal Cin P, Neuberg DS, Monti S, Pinkus GS, Shipp MA, Rodig SJ. Immunohistochemical detection of MYC-driven diffuse large B-cell lymphomas. PLoS ONE. 2012;7:e33813.