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Treating Diffuse Large B Cell Lymphoma in the Very Old or Frail Patients

  • Lymphoma (DO Persky, Section Editor)
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Opinion statement

R-CHOP has been the standard of care for diffuse large B cell lymphoma (DLBCL), curing approximately 60% of patients for more than 2 decades. However, the optimal treatment of patients who are too frail to tolerate this regimen and/or are not candidates for anthracycline therapy continues to be debated. MInT and GELA trials established addition of rituximab to CHOP in DLBCL but excluded patients older than 80 years. Multiple regimens have been tried with varying success in the very elderly, including R-mini-CHOP, R-mini CEOP, R-split CHOP, pre-phase strategies, and R-GCVP. However, there has not been a randomized trial among these strategies. Although addition of novel agents including ibrutinib, brentuximab vedotin, lenalidomide, and many others on the horizon holds promise in this population, none have been tested in a randomized setting or have results awaited. There is also a lack of a validated and easy to use clinical tool in this population to predict patients who will not tolerate R-CHOP. Identifying patients who will not tolerate R-CHOP early with the help of tools like CGA, along with integrating biology-based treatment (ibrutinib, lenalidomide in activated B cell type DLBCL) is being investigated in this population.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.

    Article  PubMed  Google Scholar 

  2. Flowers CR, Sinha R, Vose JM. Improving outcomes for patients with diffuse large B-cell lymphoma. CA Cancer J Clin. 2010;60(6):393–408.

    PubMed  Google Scholar 

  3. Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016;66(6):443–59.

    Article  Google Scholar 

  4. Smith A, Howell D, Patmore R, Jack A, Roman E. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer. 2011;105(11):1684–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Peyrade F, Gastaud L, Re D, Pacquelet-Cheli S, Thyss A. Treatment decisions for elderly patients with haematological malignancies: a dilemma. Lancet Oncol. 2012;13(8):e344–52.

    Article  PubMed  Google Scholar 

  6. Scher KS, Hurria A. Under-representation of older adults in cancer registration trials: known problem, little progress. J Clin Oncol. 2012;30(17):2036–8.

    Article  PubMed  Google Scholar 

  7. Fisher RI, Miller TP, O'Connor OA. Diffuse aggressive lymphoma. ASH Education Program Book 2004;2004(1):221–36.

  8. Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937–47.

    Article  PubMed  Google Scholar 

  9. Nowakowski GS, Czuczman MS. ABC, GCB, and double-hit diffuse large B-cell lymphoma: does subtype make a difference in therapy selection? Am Soc Clin Oncol Educ Book. 2015;35:e449–57.

    Article  Google Scholar 

  10. Mareschal S, Lanic H, Ruminy P, Bastard C, Tilly H, Jardin F. The proportion of activated B-cell like subtype among de novo diffuse large B-cell lymphoma increases with age. Haematologica. 2011;96(12):1888–90.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Klapper W, Kreuz M, Kohler CW, Burkhardt B, Szczepanowski M, Salaverria I, et al. Patient age at diagnosis is associated with the molecular characteristics of diffuse large B-cell lymphoma. Blood. 2012;119(8):1882–7.

    Article  PubMed  CAS  Google Scholar 

  12. Paul U, Richter J, Stuhlmann-Laiesz C, Kreuz M, Nagel I, Horn H, et al. Advanced patient age at diagnosis of diffuse large B-cell lymphoma is associated with molecular characteristics including ABC-subtype and high expression of MYC. Leuk Lymphoma. 2018;59(5):1213–21.

    Article  PubMed  Google Scholar 

  13. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. Editorial. N Engl J Med. 2002;346(4):280–2.

    Article  Google Scholar 

  14. Boslooper K, Kibbelaar R, Storm H, Veeger NJ, Hovenga S, Woolthuis G, et al. Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone is beneficial but toxic in very elderly patients with diffuse large B-cell lymphoma: a population-based cohort study on treatment, toxicity and outcome. Leuk Lymphoma. 2014;55(3):526–32.

    Article  PubMed  CAS  Google Scholar 

  15. Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2005;23(18):4117–26.

    Article  PubMed  CAS  Google Scholar 

  16. Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005;23(22):5027–33.

    Article  PubMed  CAS  Google Scholar 

  17. Pfreundschuh M, Trümper L, Österborg A, Pettengell R, Trneny M, Imrie K, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7(5):379–91.

    Article  PubMed  CAS  Google Scholar 

  18. Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, et al. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013;14(6):525–33.

    Article  PubMed  CAS  Google Scholar 

  19. Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile J-F, Castaigne S, et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011;12(5):460–8.

    Article  PubMed  CAS  Google Scholar 

  20. Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, et al. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly “fit” patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012;53(4):581–8.

    Article  PubMed  CAS  Google Scholar 

  21. Moccia AA, Schaff K, Hoskins P, Klasa R, Savage KJ, Shenkier T, et al. R-CHOP with etoposide substituted for doxorubicin (R-CEOP): excellent outcome in diffuse large B Cell lymphoma for patients with a contraindication to anthracyclines. Blood. 2009;114(22):40.

  22. Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, et al. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute Trial. J Clin Oncol. 2014;32(4):282–7.

    Article  PubMed  CAS  Google Scholar 

  23. Thieblemont C, Grossoeuvre A, Houot R, Broussais-Guillaumont F, Salles G, Traulle C, et al. Non-Hodgkin’s lymphoma in very elderly patients over 80 years. A descriptive analysis of clinical presentation and outcome. Ann Oncol. 2008;19(4):774–9.

    Article  PubMed  CAS  Google Scholar 

  24. Delafuente JC. Understanding and preventing drug interactions in elderly patients. Crit Rev Oncol Hematol. 2003;48(2):133–43.

    Article  PubMed  Google Scholar 

  25. Laribi K, Denizon N, Bolle D, Truong C, Besançon A, Sandrini J, et al. R-CVP regimen is active in frail elderly patients aged 80 or over with diffuse large B cell lymphoma. Ann Hematol. 2016;95(10):1705–14.

    Article  PubMed  CAS  Google Scholar 

  26. Aapro M, Bernard-Marty C, Brain EG, Batist G, Erdkamp F, Krzemieniecki K, et al. Anthracycline cardiotoxicity in the elderly cancer patient: a SIOG expert position paper. Ann Oncol. 2011;22(2):257–67.

    Article  PubMed  CAS  Google Scholar 

  27. Davis CC, Cohen JB, Shah KS, Hutcherson DA, Surati MJ, Valla K, et al. Efficacy and tolerability of anthracycline-based therapy in elderly patients with diffuse large B-cell lymphoma. Clinical Lymphoma, Myeloma and Leukemia. 2015;15(5):270–7.

    Article  PubMed  Google Scholar 

  28. Zeeneldin AA, Sallam YA, Gaber AA, Shaheen AA. Non-anthracycline chemotherapy associated with a poor outcome in elderly Egyptian patients with diffuse large B-cell non-Hodgkin lymphoma. JCMT 2015;1(2):76.

    Article  CAS  Google Scholar 

  29. Extermann M, Hurria A, et al. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25(14):1824–31.

  30. Kreher S, Lammer F, Augustin D, Pezzutto A, Baldus CD. R-split-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma. Eur J Haematol. 2014;93(1):70–6.

    Article  PubMed  CAS  Google Scholar 

  31. Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008;9(2):105–16.

    Article  PubMed  CAS  Google Scholar 

  32. Pfreundschuh M, Müller C, Zeynalova S, Kuhnt E, Wiesen MHJ, Held G, et al. Suboptimal dosing of rituximab in male and female patients with DLBCL. Blood. 2014;123(5):640–6.

    Article  PubMed  CAS  Google Scholar 

  33. Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, et al. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group. J Clin Oncol. 2014;32(36):4127–33.

    Article  PubMed  CAS  Google Scholar 

  34. Pfreundschuh M, Murawski N, Zeynalova S, Ziepert M, Loeffler M, Hanel M, et al. Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients. Br J Haematol. 2017;179(3):410–20.

    Article  PubMed  CAS  Google Scholar 

  35. Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rube C, et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004;104(3):634–41.

    Article  PubMed  CAS  Google Scholar 

  36. •• Svoboda J, Landsburg DJ, Dwivedy Nasta S, Barta SK, Khan N, Fung HC, et al. Brentuximab vedotin with R-CHP chemotherapy as frontline treatment for patients with CD30 positive primary mediastinal large B-cell, diffuse large B-cell, and grey zone lymphomas: results of a phase I/II multisite trial. Blood. 2017;130(Suppl 1):191. Use of brentuximab vedotin in CD 30 positive aggressive B cell lymphomas as anthracycline free option. Phase III trials are awaited.

    Google Scholar 

  37. Younes A, Zinzani PL, Sehn LH, Johnson PWM, Gascoyne RD, Ahmadi T, et al. A randomized, double-blind, placebo-controlled phase 3 study of ibrutinib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in subjects with newly diagnosed nongerminal center B-cell subtype of diffuse large B-cell lymphoma (DLBCL). J Clin Oncol. 2014;32(15_suppl):TPS8615-TPS.

    Google Scholar 

  38. •• Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study. J Clin Oncol. 2015;33(3):251–7. Lenalidomide is effective in non-GCB DLBCL in a non-randomized study.

    Article  PubMed  CAS  Google Scholar 

  39. • Nowakowski GS, Chiappella A, Witzig TE, Spina M, Zhang L, Flament J, et al. Randomized, phase III trial of the efficacy and safety of lenalidomide plus R-CHOP vs R-CHOP in patients with untreated ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2015;33(15_suppl):TPS8600-TPS. Use of lenalidomide as a novel agent in a biology based treatment.

    Google Scholar 

  40. Westin JR, Oki Y, Fayad L, Nastoupil LJ, Turturro F, Hagemeister FB, et al. Rituximab, lenalidomide, and ibrutinib alone and combined with dose adjusted chemotherapy for patients with high risk diffuse large B-cell lymphoma. J Clin Oncol. 2016;34(15_suppl):TPS7575-TPS.

    Article  Google Scholar 

  41. •• Reddy NM, Greer JP, Morgan DS, Chen H, Park SI, Richards KL. A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high-intermediate risk diffuse large B-cell lymphoma. Leukemia. 2017;31(1):241–4. Lenalidomide maintenence in elderly patients to prevent relapse.

    Article  PubMed  CAS  Google Scholar 

  42. Stefoni V, Casadei B, Bottelli C, Gaidano G, Ciochetto C, Cabras M, et al. Short-course R-CHOP followed by (90)y-ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients: 7-year long-term results. Blood Cancer J. 2016;6(5):e425.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Trebouet A, Marchand T, Lemal R, Gyan E, Broussais-Guillaumot F, Guillermin Y, et al. Lymphoma occurring in patients over 90 years of age: characteristics, outcomes, and prognostic factors. A retrospective analysis of 234 cases from the LYSA. Ann Oncol. 2013;24(10):2612–8.

    Article  PubMed  CAS  Google Scholar 

  44. Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz J-P, Lichtman S, et al. Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol. 2005;55(3):241–52.

    Article  PubMed  Google Scholar 

  45. •• Tucci A, Martelli M, Rigacci L, Riccomagno P, Cabras MG, Salvi F, et al. Comprehensive geriatric assessment is an essential tool to support treatment decisions in elderly patients with diffuse large B-cell lymphoma: a prospective multicenter evaluation in 173 patients by the Lymphoma Italian Foundation (FIL). Leuk Lymphoma. 2015;56(4):921–6. Study using CGA in elderly DLBCL patients as a method to stratify for treatment choice.

    Article  PubMed  CAS  Google Scholar 

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Financial disclosure statement

This work was supported in part by grant P30 CA023074 from the National Cancer Institute, National Institutes of Health, and Bethesda, MD.

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Authors and Affiliations

  1. College of Medicine, Hematology/Oncology, University of Arizona Cancer Center, 1515 N. Campbell Avenue, Tucson, AZ, 85724, USA

    Abhijeet Kumar MD

  2. Department of Medicine, Hematology/Oncology, Blood and Marrow Transplantation, University of Arizona, Tucson, AZ, 85724, USA

    Muhammad Asad Fraz MD, Muhammad Usman MD, Saad Ullah Malik MD, Awais Ijaz MD, Ceren Durer MD, Seren Durer MD, Muhammad Junaid Tariq MD, Ali Younas Khan MD, Anum Qureshi MD, Warda Faridi MD & Faiz Anwer MD

  3. Department of Geriatrics, Tri-City Medical Center, 4002 Vista way, Oceanside, CA, 92056, USA

    Aboo Nasar MD

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Correspondence to Abhijeet Kumar MD.

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Conflict of Interest

Abhijeet Kumar declares that he has no conflict of interest.

Muhammad Asad Fraz declares that he has no conflict of interest.

Muhammad Usman declares that he has no conflict of interest.

Saad Ullah Malik declares that he has no conflict of interest.

Awais Ijaz declares that he has no conflict of interest.

Ceren Durer declares that he has no conflict of interest.

Seren Durer declares that he has no conflict of interest.

Muhammad Junaid Tariq declares that he has no conflict of interest.

Ali Younas Khan declares that he has no conflict of interest.

Anum Qureshi declares that he has no conflict of interest.

Warda Faridi declares that he has no conflict of interest.

Aboo Nasar declares that he has no conflict of interest.

Faiz Anwer has received speaker’s honoraria from InCyte and has received compensation from Seattle Genetics for service on an advisory board.

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Kumar, A., Fraz, M.A., Usman, M. et al. Treating Diffuse Large B Cell Lymphoma in the Very Old or Frail Patients. Curr. Treat. Options in Oncol. 19, 50 (2018). https://doi.org/10.1007/s11864-018-0565-6

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