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Long-term follow-up of abbreviated R-CHOP chemoimmunotherapy for completely resected limited-stage diffuse large B cell lymphoma (CISL 12-09)

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Abstract

The standard of treatment for completely resected limited-stage diffuse large B cell lymphoma (DLBCL) in patients without residual lesions has not yet been established. Previously, we designed a phase II trial to evaluate the safety and efficacy of three cycles of abbreviated R-CHOP in patients with completely resected limited-stage DLBCL and reported favorable survival outcomes. We present the long-term follow-up results to taking into account the importance of delayed relapse in patients with limited-stage DLBCL. With a median follow-up duration of 62.7 months (range, 60.2–75.5 months), the 5-year OS and DFS rates were both 95.0% (95% confidence interval, 85.59–104.11%). Only one patient experienced disease progression which was confirmed at 12.3 months, and one patient with primary intestinal DLBCL developed non-small cell lung cancer 6 years after treatment. The long-term results of our data support the use of three cycles of abbreviated R-CHOP for patients with completely resected limited-stage DLBCL. The study was reviewed and approved by the review boards of the participating institutes and registered at ClinicalTrials.gov, number NCT01279902, in August 3, 2010.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Pfreundschuh M, Kuhnt E, Trümper L, Österborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani P-L, Shpilberg O, Kvaloy S, Brown PN, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N, Group ftMIT (2011) CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 12(11):1013–1022. https://doi.org/10.1016/s1470-2045(11)70235-2

    Article  CAS  PubMed  Google Scholar 

  2. Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Du KL, Benchalal M, Moles M-P, Gouill SL, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V (2018) R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood 131(2):174–181. https://doi.org/10.1182/blood-2017-07-793984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP (2008) Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group Study 0014. J Clin Oncol 26(14):2258–2263. https://doi.org/10.1200/jco.2007.13.6929

    Article  CAS  PubMed  Google Scholar 

  4. Sehn LH (2012) Chemotherapy alone for localized diffuse large B-cell lymphoma. Cancer J 18(5):421–426. https://doi.org/10.1097/ppo.0b013e31826c5907

    Article  CAS  PubMed  Google Scholar 

  5. Sehn LH, Savage KJ, Hoskins P, Klasa R, Shenkier T, Voss N, Wilson D, Connors JM (2007) Limited-stage diffuse large B-cell lymphoma (DLBCL) patients with a negative pet scan following three cycles of R-CHOP can be effectively treated with abbreviated chemoimmunotherapy alone. Blood 110(11):787–787. https://doi.org/10.1182/blood.v110.11.787.787

    Article  Google Scholar 

  6. Kim SJ, Kang HJ, Kim JS, Oh SY, Choi CW, Lee SI, Won JH, Kim MK, Kwon JH, Mun Y-C, Kwak J-Y, Kwon JM, Hwang IG, Kim HJ, Park J, Oh S, Huh J, Ko YH, Suh C, Kim WS (2011) Comparison of treatment strategies for patients with intestinal diffuse large B-cell lymphoma: surgical resection followed by chemotherapy versus chemotherapy alone. Blood 117(6):1958–1965. https://doi.org/10.1182/blood-2010-06-288480

    Article  CAS  PubMed  Google Scholar 

  7. Weledji EP, Orock GE (2015) Surgery for non-Hodgkin’s lymphoma. Oncol Rev 9(1):274. https://doi.org/10.4081/oncol.2015.274

    Article  PubMed  PubMed Central  Google Scholar 

  8. Yoon DH, Sohn BS, Oh SY, Lee WS, Lee SM, Yang DH, Huh J, Suh C (2017) Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09). Oncotarget 8(8):13367–13374. https://doi.org/10.18632/oncotarget.14531

    Article  PubMed  PubMed Central  Google Scholar 

  9. Larouche J-F, Berger F, Chassagne-Clément C, Ffrench M, Callet-Bauchu E, Sebban C, Ghesquières H, Broussais-Guillaumot F, Salles G, Coiffier B (2010) Lymphoma recurrence 5 years or later following diffuse large B-cell lymphoma: clinical characteristics and outcome. J Clin Oncol 28(12):2094–2100. https://doi.org/10.1200/jco.2009.24.5860

    Article  PubMed  Google Scholar 

  10. 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 (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282. https://doi.org/10.1182/blood-2003-05-1545

    Article  CAS  PubMed  Google Scholar 

  11. Younes A, Hilden P, Coiffier B, Hagenbeek A, Salles G, Wilson W, Seymour JF, Kelly K, Gribben J, Pfreunschuh M, Morschhauser F, Schoder H, Zelenetz AD, Rademaker J, Advani R, Valente N, Fortpied C, Witzig TE, Sehn LH, Engert A, Fisher RI, Zinzani PL, Federico M, Hutchings M, Bollard C, Trneny M, Elsayed YA, Tobinai K, Abramson JS, Fowler N, Goy A, Smith M, Ansell S, Kuruvilla J, Dreyling M, Thieblemont C, Little RF, Aurer I, Oers MHJV, Takeshita K, Gopal A, Rule S, Sd V, Kloos I, Kaminski MS, Meignan M, Schwartz LH, Leonard JP, Schuster SJ, Seshan VE (2017) International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann Oncol 28(7):1436–1447. https://doi.org/10.1093/annonc/mdx097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kumar A, Lunning MA, Zhang Z, Migliacci JC, Moskowitz CH, Zelenetz AD (2015) Excellent outcomes and lack of prognostic impact of cell of origin for localized diffuse large B-cell lymphoma in the rituximab era. Br J Haematol 171(5):776–783. https://doi.org/10.1111/bjh.13766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sehn LH, Scott DW, Villa D, Gerrie AS, Freeman CL, Parsons CA, Pickles T, Lo A, Farinha P, Slack GW, Wilson D, Tonseth RP, Connors JM, Savage KJ (2019) Long-term follow-up of a PET-guided approach to treatment of limited-stage diffuse large B-cell lymphoma (DLBCL) in British Columbia (BC). Blood 134(Supplement_1):401. https://doi.org/10.1182/blood-2019-128722

    Article  Google Scholar 

  14. Persky DO, Li H, Stephens DM, Park SI, Bartlett NL, Swinnen LJ, Barr PM, Winegarden JD, Constine LS, Fitzgerald TJ, Leonard JP, Kahl BS, Leblanc ML, Song JY, Fisher RI, Rimsza LM, Smith SM, Friedberg JW (2019) PET-directed therapy for patients with limited-stage diffuse large B-cell lymphoma - results of intergroup NCTN study S1001. Blood 134(Supplement_1):349–349. https://doi.org/10.1182/blood-2019-123871

    Article  Google Scholar 

  15. Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes H-G, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, Brown PN, Federico M, Lengfelder E, Ad R, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M, Investigators FT, Alliance GL (2020) Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet 394(10216):2271–2281. https://doi.org/10.1016/s0140-6736(19)33008-9

    Article  CAS  Google Scholar 

  16. Offner F, Samoilova O, Osmanov E, Eom H-S, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, Hvd V, Enny C, Rizo A, Ferhanoglu B (2015) Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood 126(16):1893–1901. https://doi.org/10.1182/blood-2015-03-632430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D (2013) Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet 381(9880):1817–1826. https://doi.org/10.1016/s0140-6736(13)60313-x

    Article  CAS  PubMed  Google Scholar 

  18. Hüttmann A, Rekowski J, Müller SP, Hertenstein B, Franzius C, Mesters R, Weckesser M, Kroschinsky F, Kotzerke J, Ganser A, Bengel FM, Rosée PL, Freesmeyer M, Höffkes H-G, Hertel A, Behringer D, Prange-Krex G, Griesshammer M, Holzinger J, Wilop S, Krohn T, Raghavachar A, Maschmeyer G, Brink I, Schroers R, Gaska T, Bernhard H, Giagounidis A, Schütte J, Dienst A, Hautzel H, Naumann R, Klein A, Hahn D, Pöpperl G, Grube M, Marienhagen J, Schwarzer A, Kurch L, Höhler T, Steiniger H, Nückel H, Südhoff T, Römer W, Brinkmann M, Ose C, Alashkar F, Schmitz C, Dürig J, Hoelzer D, Jöckel K-H, Klapper W, Dührsen U (2019) Six versus eight doses of rituximab in patients with aggressive B cell lymphoma receiving six cycles of CHOP: results from the “positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas” (PETAL) trial. Ann Hematol 98(4):897–907. https://doi.org/10.1007/s00277-018-3578-0

    Article  CAS  PubMed  Google Scholar 

  19. Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH (2004) Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin’s lymphoma: eastern cooperative oncology group study 1484. J Clin Oncol 22(15):3032–3038. https://doi.org/10.1200/jco.2004.06.088

    Article  CAS  PubMed  Google Scholar 

  20. Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thieblemont C, Ferme C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F, Groupe d'Etude des Lymphomes de lA (2007) CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 25(7):787–792. https://doi.org/10.1200/JCO.2006.07.0722

    Article  CAS  PubMed  Google Scholar 

  21. Lee HS, Park LC, Lee EM, Shin SH, Ye BJ, Oh SY, Song MK, Lee SM, Lee WS, Kang BW, Chang MH, Cho SG, Yahng SA, Yoon SS, Kwon JH, Kim YS (2014) Comparison of therapeutic outcomes between surgical resection followed by R-CHOP and R-CHOP alone for localized primary intestinal diffuse large B-cell lymphoma. Am J Clin Oncol 37(2):182–187. https://doi.org/10.1097/COC.0b013e318271b125

    Article  CAS  PubMed  Google Scholar 

  22. Kang J, Chae H, Hong JY, Yoon DH, Kim S, Park JS, Lee SW, Park CS, Ryu J-S, Huh J, Suh C (2020) Distinct clinical characteristics at diagnosis in patients with late relapses compared with early relapses of diffuse large B-cell lymphoma treated with R-CHOP. Leuk Lymphoma 61(5):1–7. https://doi.org/10.1080/10428194.2019.1709831

    Article  CAS  Google Scholar 

  23. Coiffier B, Thieblemont C, Neste EVD, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H (2010) Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood 116(12):2040–2045. https://doi.org/10.1182/blood-2010-03-276246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Stephens DM, Li H, LeBlanc ML, Puvvada SD, Persky D, Friedberg JW, Smith SM (2016) Continued risk of relapse independent of treatment modality in limited-stage diffuse large B-cell lymphoma: final and long-term analysis of Southwest Oncology Group Study S8736. J Clin Oncol 34(25):2997–3004. https://doi.org/10.1200/jco.2015.65.4582

    Article  PubMed  PubMed Central  Google Scholar 

  25. Morton LM, Curtis RE, Linet MS, Bluhm EC, Tucker MA, Caporaso N, Ries LA, Fraumeni JF Jr (2010) Second malignancy risks after non-Hodgkin’s lymphoma and chronic lymphocytic leukemia: differences by lymphoma subtype. J Clin Oncol 28(33):4935–4944. https://doi.org/10.1200/jco.2010.29.1112

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by grants (2017-198) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.

Author information

Author notes

  1. Sora Kang and Hyungwoo Cho these authors contributed equally contributed as first authors.

    Dok Hyun Yoon and Cheolwon Suh these authors are designated as joint corresponding authors.

Authors and Affiliations

  1. Department of Internal Medicine, Asan Medical Center, Seoul, South Korea

    Sora Kang

  2. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea

    Hyungwoo Cho, Dok Hyun Yoon & Cheolwon Suh

  3. Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea

    Byeong Seok Sohn

  4. Department of Internal Medicine, Dong-A University Hospital, Busan, South Korea

    Sung Yong Oh

  5. Department of Hemato-Oncology, Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea

    Won-Sik Lee & Sang Min Lee

  6. Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, South Korea

    Deok-Hwan Yang

  7. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Jooryung Huh

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  1. Sora Kang
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Contributions

SR Kang and HW Cho participated in the writing and editing of the manuscript; DH Yoon, BS Sohn, and C Suh participated in trial development; JR Huh reviewed all the pathological findings; DH Yoon, SY Oh, WS Lee, SM Lee, DH Yang, and C Suh enrolled patients for the trial; SR Kang and HW Cho performed all the statistical analysis; and DH Yoon and C Suh administered the trial.

Corresponding authors

Correspondence to Dok Hyun Yoon or Cheolwon Suh.

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Conflict of interest

DH Yoon, SY Oh, and C Suh have received research funding from Roche. None of the other authors have relevant conflicts of interest to declare.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was reviewed and approved by the review boards of the participating institutes.

Consent to participate

Informed consent was obtained from all patients for being included in the study.

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All statistical analyses were performed using SPSS version 23 and R statistical software version 3.6.3.

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Kang, S., Cho, H., Sohn, B. et al. Long-term follow-up of abbreviated R-CHOP chemoimmunotherapy for completely resected limited-stage diffuse large B cell lymphoma (CISL 12-09). Ann Hematol 99, 2831–2836 (2020). https://doi.org/10.1007/s00277-020-04284-z

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