Keywords
lymphoma, elderly patient, comorbidities
How to Cite
Riva, E. (2019). Aggresive B cell Non Hodgkin Lymphoma in elderly population: diagnostic and therapeutic approach. Journal of Hematology, 22(Extraordin), 38–45. Retrieved from https://revistahematologia.com.ar/index.php/Revista/article/view/54
Abstract
Diagnostic and therapeutic approach in aggressive B-cell lymphomas in elderly patients is extremely relevant in clinical practice, as most patients are older than 65 years. These patients are usually underrepresented in clinical trials, and present particular challenges, because they are more frail and at greater treatment-related toxicity and mortality. In this article we review current evidence regarding diagnosis and treatment of diffuse large B-cell lymphoma. We highlight geriatric comprehensive evaluation is of utmost importance for taking rational, patient-oriented decisions.
References
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4. Extermann M, Albrand G, Chen H et al. Are older French patients as willing as older American patients to undertake chemotherapy? J Clin Oncol. 2003; 21(17):3214-3219.
5. Yellen SB, Cella DF, Leslie WT. Age and clinical decision making in oncology patients. J Natl Cancer Inst. 1994; 86(23): 1766-1770.
6. Chouliara Z, Miller M, Stott D et al. Older people with cancer: perceptions and feelings about information, decision-making and treatment—a pilot study. Eur J Oncol Nurs. 2004; 8(3): 257-261.
7. Meropol NJ, Egleston BL, Buzaglo JS et al. Cancer patient preferences for quality and length of life. Cancer. 2008; 113(12): 3459-3466.
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9. Murawski N, Pfreundschuh M, Zeynalova S et al. Optimization of rituximab for the treatment of DLBCL (I): dose-dense rituximab in the DENSER-CHOP-14 trial of the DSHNHL. Ann Oncol. 2014; 25: 1800-1806.
10. Reeve BB, Mitchell SA, Dueck AC et al. Recommended patient-reported core set of symptoms to measure in adult cancer treatment trials. J Natl Cancer Inst. 2014; 106: pii: dju129.
11. Advani RH, Chen H, Habermann TM et al. Comparison of conventional prognostic índices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). Br J Haematol. 2010; 151(2):143-151.
12. Zhou Z, Sehn LH, Rademaker AW et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014; 123: 837-842.
13. Wildiers H, Heeren P, Puts M et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014; 32: 2595-2603.
14. kshop on clinical trial methodology in older individuals with a diagnosis of solid tumors. Ann Oncol. 2011; 22: 1922-1926.
15. for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study. PLoS One. 2014; 9: e115060.
16. Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc. 1968;16, 622-626.
17. C. Buske, M. Hutchings, M. Ladetto, V. Goede, U. Mey, P. Soubeyran, M. Spina, R. Stauder, M. Trneny, U. Wedding, P. Fields & The ESMO Lymphoma Consensus Conference Panel Members. ESMO Guidelines. ESMO Consensus Conference on malignant lymphoma: general perspectives and recommendations for the clinical management of the elderly patient with malignant lymphoma. Annals of Oncology. 29: 544-562, 2018 doi:10.1093/annonc/mdx413.
18. Bellera C, Praud D, Petit-Monéger A et al. Barriers to inclusion of older adults in randomised controlled clinical trials on NonHodgkin’s lymphoma: a systematic review. Cancer Treat Rev. 2013;39: 812-817. 33.
19. Quinten C, Coens C, Mauer M et al. Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials. Lancet Oncol. 2009; 10: 865-871.
20. Yancik R, Ries LA. Cancer in older persons: an international issue in an aging world. Semin Oncol. 2004; 31: 128-136.
21. Maartense E, Kluin-Nelemans HC, le Cessie S et al. Different age limits for elderly patients with indolent and aggressive non-Hodgkin lymphoma and the role of relative survival with increasing age. Cancer. 2000; 89: 2667-2676. 112.
22. Pfreundschuh M, Schubert J, Ziepert M 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 randomized controlled trial (RICOVER-60). Lancet Oncol. 2008; 9: 105-116.
23. Coiffier B, Lepage E, Briere J et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-42.
24. Habermann TM, Weller EA, Morrison VA et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:3121-7.
25. Griffiths RI, Gleeson ML, Mikhael J et al. Comparative effectiveness and cost of adding rituximab to first-line chemotherapy for elderly patients diagnosed with diffuse large B-cell lymphoma. Cancer. 2012;118:6079-88.
26. Delarue L, Tilly H, Salles G et al. R-CHOP 14 compared to R-CHOP21 in elderly patients with diffuse large B cell lymphoma: results of the interim analysis of the LNH03-68 GELA study. Blood. 2009; 114:169 abs406.
27. Cunningham D, Smith P, Mouncey P et al. CHOP 14 vs RCHOP 21: result of a randomized phase III trial of patients with diffuse large B cell NHL. J Clin Oncol. 2011; 29(supl) abs 8000.
28. Merli F, Luminari S, Rossi G 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. LeukLymphoma. 2012;53(4):581-588.
29. Odejide OO, Cronin AM, Davidoff AJ et al. Limited stage diffuse large B cell lymphoma: comparative effectiveness of treatment strategies in a large cohort of elderly patients. Leuk Lymphoma. 2015; 56(3):716-724.
30. Olszewski AJ, Mantripragada KC, Castillo JJ. Risk factors for early death after rituximab-based immunochemotherapy in older patients with diffuse large B-celllymphoma. J Natl Compr Canc Netw. 2016; 14: 1121-1129.
31. Peyrade F, Jardin F, Thieblemont C et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80years with diffuse large B-cell lymphoma: a multicenter, single-arm, phase 2 trial. Lancet Oncol. 2011; 12: 460-468.
32. Peyrade F, Bologna S, Delwail V et al. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80years or older: an open-label, multicenter, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017; 4: e46-e55.
33. Fields PA, Townsend W, Webb A 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: 282-287.
34. Luminari S, Montanini A, Caballero D et al. Nonpegylated liposomal doxorubicin (MyocetTM) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial. Ann Oncol. 2010; 21: 1492-1499.
35. Held G, Murawski N, Ziepert M et al. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014; 32: 1112-1118.
36. Bittenbring JT, Neumann F, Altmann B et al. Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab. J Clin Oncol. 2014; 32: 3242-3248.
37. Gisselbrecht C, Glass B, Mounier N et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010; 28: 4184-4190. 130.
38. Mounier N, El Gnaoui T, Tilly H et al. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial. Haematologica 2013; 98: 1726-1731.
39. Arcari A, Chiappella A, Spina M et al. Safety and efficacy of rituximab plus bendamustine in relapsed or refractory diffuse large B-cell lymphoma patients: an Italian retrospective multicenter study. Leuk Lymphoma. 2016; 57: 1823-1830.
40. Pettengell R, Coiffier B, Narayanan G et al. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicenter, open-label, randomised trial. Lancet Oncol. 2012; 13: 696-706.
41. Ferreri AJ, Sassone M, Zaja F et al. Lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for autologous stem cell transplantation: an open label, single-arm, multicentre phase 2 trial. Lancet Haematol. 2017; 4: e137-e146.
2. 2015; http://europa. eu/epc/sites/epc/files/docs/pages/ageing_report_2015_en.pdf (8 July 2016, date last accessed).
3. Hamaker ME, Stauder R, van Munster BC. Ongoing clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points? Ann Oncol. 2014; 25: 675-681.
4. Extermann M, Albrand G, Chen H et al. Are older French patients as willing as older American patients to undertake chemotherapy? J Clin Oncol. 2003; 21(17):3214-3219.
5. Yellen SB, Cella DF, Leslie WT. Age and clinical decision making in oncology patients. J Natl Cancer Inst. 1994; 86(23): 1766-1770.
6. Chouliara Z, Miller M, Stott D et al. Older people with cancer: perceptions and feelings about information, decision-making and treatment—a pilot study. Eur J Oncol Nurs. 2004; 8(3): 257-261.
7. Meropol NJ, Egleston BL, Buzaglo JS et al. Cancer patient preferences for quality and length of life. Cancer. 2008; 113(12): 3459-3466.
8. Wildiers H, Mauer M, Pallis A et al. End points and trial design in geriatric oncology research: a Joint European Organisation for Research and Treatment of CancerAlliance for Clinical Trials in Oncology-International Society of Geriatric Oncology Position Article. J Clin Oncol. 2013; 31(29): 3711-3718.
9. Murawski N, Pfreundschuh M, Zeynalova S et al. Optimization of rituximab for the treatment of DLBCL (I): dose-dense rituximab in the DENSER-CHOP-14 trial of the DSHNHL. Ann Oncol. 2014; 25: 1800-1806.
10. Reeve BB, Mitchell SA, Dueck AC et al. Recommended patient-reported core set of symptoms to measure in adult cancer treatment trials. J Natl Cancer Inst. 2014; 106: pii: dju129.
11. Advani RH, Chen H, Habermann TM et al. Comparison of conventional prognostic índices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). Br J Haematol. 2010; 151(2):143-151.
12. Zhou Z, Sehn LH, Rademaker AW et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood. 2014; 123: 837-842.
13. Wildiers H, Heeren P, Puts M et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 2014; 32: 2595-2603.
14. kshop on clinical trial methodology in older individuals with a diagnosis of solid tumors. Ann Oncol. 2011; 22: 1922-1926.
15. for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study. PLoS One. 2014; 9: e115060.
16. Linn BS, Linn MW, Gurel L. Cumulative illness rating scale. J Am Geriatr Soc. 1968;16, 622-626.
17. C. Buske, M. Hutchings, M. Ladetto, V. Goede, U. Mey, P. Soubeyran, M. Spina, R. Stauder, M. Trneny, U. Wedding, P. Fields & The ESMO Lymphoma Consensus Conference Panel Members. ESMO Guidelines. ESMO Consensus Conference on malignant lymphoma: general perspectives and recommendations for the clinical management of the elderly patient with malignant lymphoma. Annals of Oncology. 29: 544-562, 2018 doi:10.1093/annonc/mdx413.
18. Bellera C, Praud D, Petit-Monéger A et al. Barriers to inclusion of older adults in randomised controlled clinical trials on NonHodgkin’s lymphoma: a systematic review. Cancer Treat Rev. 2013;39: 812-817. 33.
19. Quinten C, Coens C, Mauer M et al. Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials. Lancet Oncol. 2009; 10: 865-871.
20. Yancik R, Ries LA. Cancer in older persons: an international issue in an aging world. Semin Oncol. 2004; 31: 128-136.
21. Maartense E, Kluin-Nelemans HC, le Cessie S et al. Different age limits for elderly patients with indolent and aggressive non-Hodgkin lymphoma and the role of relative survival with increasing age. Cancer. 2000; 89: 2667-2676. 112.
22. Pfreundschuh M, Schubert J, Ziepert M 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 randomized controlled trial (RICOVER-60). Lancet Oncol. 2008; 9: 105-116.
23. Coiffier B, Lepage E, Briere J et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-42.
24. Habermann TM, Weller EA, Morrison VA et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:3121-7.
25. Griffiths RI, Gleeson ML, Mikhael J et al. Comparative effectiveness and cost of adding rituximab to first-line chemotherapy for elderly patients diagnosed with diffuse large B-cell lymphoma. Cancer. 2012;118:6079-88.
26. Delarue L, Tilly H, Salles G et al. R-CHOP 14 compared to R-CHOP21 in elderly patients with diffuse large B cell lymphoma: results of the interim analysis of the LNH03-68 GELA study. Blood. 2009; 114:169 abs406.
27. Cunningham D, Smith P, Mouncey P et al. CHOP 14 vs RCHOP 21: result of a randomized phase III trial of patients with diffuse large B cell NHL. J Clin Oncol. 2011; 29(supl) abs 8000.
28. Merli F, Luminari S, Rossi G 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. LeukLymphoma. 2012;53(4):581-588.
29. Odejide OO, Cronin AM, Davidoff AJ et al. Limited stage diffuse large B cell lymphoma: comparative effectiveness of treatment strategies in a large cohort of elderly patients. Leuk Lymphoma. 2015; 56(3):716-724.
30. Olszewski AJ, Mantripragada KC, Castillo JJ. Risk factors for early death after rituximab-based immunochemotherapy in older patients with diffuse large B-celllymphoma. J Natl Compr Canc Netw. 2016; 14: 1121-1129.
31. Peyrade F, Jardin F, Thieblemont C et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80years with diffuse large B-cell lymphoma: a multicenter, single-arm, phase 2 trial. Lancet Oncol. 2011; 12: 460-468.
32. Peyrade F, Bologna S, Delwail V et al. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80years or older: an open-label, multicenter, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017; 4: e46-e55.
33. Fields PA, Townsend W, Webb A 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: 282-287.
34. Luminari S, Montanini A, Caballero D et al. Nonpegylated liposomal doxorubicin (MyocetTM) combination (R-COMP) chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL): results from the phase II EUR018 trial. Ann Oncol. 2010; 21: 1492-1499.
35. Held G, Murawski N, Ziepert M et al. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014; 32: 1112-1118.
36. Bittenbring JT, Neumann F, Altmann B et al. Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab. J Clin Oncol. 2014; 32: 3242-3248.
37. Gisselbrecht C, Glass B, Mounier N et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010; 28: 4184-4190. 130.
38. Mounier N, El Gnaoui T, Tilly H et al. Rituximab plus gemcitabine and oxaliplatin in patients with refractory/relapsed diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial. Haematologica 2013; 98: 1726-1731.
39. Arcari A, Chiappella A, Spina M et al. Safety and efficacy of rituximab plus bendamustine in relapsed or refractory diffuse large B-cell lymphoma patients: an Italian retrospective multicenter study. Leuk Lymphoma. 2016; 57: 1823-1830.
40. Pettengell R, Coiffier B, Narayanan G et al. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicenter, open-label, randomised trial. Lancet Oncol. 2012; 13: 696-706.
41. Ferreri AJ, Sassone M, Zaja F et al. Lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for autologous stem cell transplantation: an open label, single-arm, multicentre phase 2 trial. Lancet Haematol. 2017; 4: e137-e146.
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