Management Considerations and Challenges in Older Individuals with Diffuse Large B-cell Lymphoma
Main Article Content
Abstract
Diffuse Large B-cell Lymphoma (DLBCL) is classically a disease of older individuals. However, varying definitions of “older” age, underrepresentation in clinical trials, and significant patient heterogeneity requires a highly personalized treatment approach. Older patients often have comorbidities leading to decreased tolerance with standard of care therapies; however, predictive tools such as the simplified Comprehensive Geriatric Assessment may help tailor treatments accordingly. Several approaches have been introduced to augment therapeutic tolerance in the front-line setting, including prephase therapies, attenuation of current standard of care chemoimmunotherapy dosing, or alternative chemotherapeutic agents when prohibitive comorbidities such as cardiovascular disease are present. In the relapsed and refractory disease setting antibody-based therapies have improved outcomes and demonstrated therapeutic tolerance in older patients. Cellular therapies and bone marrow transplantation remain options for fit patients who are eligible and should be considered. The aim of this review is to focus on patient assessment and treatment recommendations in older patients with DLBCL.
Keywords:
Large B-cell Lymphoma, Older Individuals with Diffuse Large B-cell Lymphoma
Article Details
How to Cite
GIESE, Noah et al.
Management Considerations and Challenges in Older Individuals with Diffuse Large B-cell Lymphoma.
Medical Research Archives, [S.l.], v. 12, n. 5, may 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5435>. Date accessed: 04 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i5.5435.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. National Cancer Institute. SEER Cancer Stat Facts: Diffuse Large B-Cell Lymphoma. Published 2023. Accessed March 20, 2024. https://seer.cancer.gov/statfacts/html/dlbcl.html
2. Kanas G, Ge W, Quek RGW, Keeven K, Nersesyan K, Jon E. Arnason. Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020–2025. Leuk Lymphoma. 2022;63(1):54-63. doi:10.1080/10428194.2021.1975188
3. Wang Y, Ren X, Huang K, et al. Comparison of first-line treatments for elderly patients with diffuse large B-cell lymphoma: A systematic review and network meta-analysis. Front Immunol. 2023;13. doi:10.3389/fimmu. 2022.1082293
4. Coiffier B, Lepage E, Brière J, et al. CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma. New England Journal of Medicine. 2002;346(4):235 -242. doi:10.1056/NEJMoa011795
5. U.S. Census Bureau. 2020 Census Demographic and Housing Characteristics File (DHC). https://www.census.gov/data/tables/2023/dec/2020-census-dhc.html
6. Leukemia and Lymphoma Society. NHL SUBTYPES. https://www.lls.org/lymphoma/non-hodgkin-lymphoma/nhl-subtypes
7. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2017. Published online April 2020.
8. Wang SS. Epidemiology and etiology of diffuse large B-cell lymphoma. Semin Hematol. Published online November 2023. doi:10.1053/j.seminhematol.2023.11.004
9. Arcari A, Cavallo F, Puccini B, Vallisa D. New treatment options in elderly patients with Diffuse Large B-cell Lymphoma. Front Oncol. 2023;13. doi:10.3389/fonc.2023.1214026
10. Al Armashi AR, Al Zubaidi A, Mahmood O, Thierheimer M, Alkrekshi A, Abdulhaq H. Trends in Diffuse Large B-Cell Lymphoma Mortality in the United States: A Comprehensive Review from 2000 to 2020. Blood. 2023;142(Supplement 1):1765-1765. doi:10.1182/blood-2023-180270
11. Ulu BU, Yiğenoğlu TN, Başcı S, et al. Factors affecting survival in elderly patients with diffuse large B-Cell lymphoma. Leuk Res. 2021;110:106700. doi:10.1016/j.leukres.2021.106700
12. Hounsome L, Eyre TA, Ireland R, et al. Diffuse large B cell lymphoma (DLBCL) in patients older than 65 years: analysis of 3 year Real World data of practice patterns and outcomes in England. Br J Cancer. 2022;126(1 ):134-143. doi:10.1038/s41416-021-01525-4
13. Abu Sabaa A, Mörth C, Hasselblom S, et al. Age is the most important predictor of survival in diffuse large B‐cell lymphoma patients achieving event‐free survival at 24 months: a Swedish population‐based study. Br J Haematol. 2021;193(5):906-914. doi:10.1 111/bjh.17206
14. Ekberg S, Crowther M, Harrysson S, Jerkeman M, E. Smedby K, Eloranta S. Patient trajectories after diagnosis of diffuse large B-cell lymphoma—a multistate modelling approach to estimate the chance of lasting remission. Br J Cancer. 2022;127(9):1642-1649. doi:10.1038/s41416-022-01931-2
15. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800 -1808. doi:10.1182/blood-2017-03-769620
16. Shimkus G, Nonaka T. Molecular classification and therapeutics in diffuse large B-cell lymphoma. Front Mol Biosci. 2023;10. doi:10.3389/fmolb.2023.1124360
17. Roschewski M, Phelan JD, Wilson WH. Molecular Classification and Treatment of Diffuse Large B-Cell Lymphoma and Primary Mediastinal B-Cell Lymphoma. The Cancer Journal. 2020;26(3):195-205. doi:10.1097/PP O.0000000000000450
18. 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):1888-1890. doi:10.3324/haematol.2011.050617
19. Rosenwald A, Bens S, Advani R, et al. Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma: A Study by the Lunenburg Lymphoma Biomarker Consortium. Journal of Clinical Oncology. 2019;37(35):3359-3368. doi:10.1200/JCO.19.00743
20. Hurria A, Togawa K, Mohile SG, et al. Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter Study. Journal of Clinical Oncology. 2011;29(25):3457-3465. doi:10.12 00/JCO.2011.34.7625
21. Mohile SG, Dale W, Somerfield MR, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. Journal of Clinical Oncology. 2018; 36(22):2326-2347. doi:10.1200/JCO.2018.78.8687
22. Li D, Sun CL, Kim H, et al. Geriatric Assessment–Driven Intervention (GAIN) on Chemotherapy-Related Toxic Effects in Older Adults With Cancer. JAMA Oncol. 2021;7(11): e214158. doi:10.1001/jamaoncol.2021.4158
23. Mohile SG, Mohamed MR, Xu H, et al. Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study. The Lancet. 2021;398(10314):1894-1904. doi:10.1016/S0140-6736(21)01789-X
24. Williams GR, Hopkins JO, Klepin HD, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Questions and Answers. JCO Oncol Pract. 2023;19(9):718-723. doi:10.1200/OP.23.00263
25. Merli F, Luminari S, Tucci A, et al. Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi. Journal of Clinical Oncology. 2021;39(11):1214-1222. doi:10.1200/JCO.20.02465
26. Tucci A, Martelli M, Rigacci L, 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):921-926. doi:10.3109/10428194.2014.953142
27. Lugtenburg PJ, Mutsaers PGNJ. How I treat Elderly Patients with DLBCL in the frontline setting. Blood. Published online November 22, 2022. doi:10.1182/blood.2020 008239
28. Rudresha AH, Hassan SA, Sreevalli A, et al. Pre-phase strategy to mitigate first cycle effect in diffuse large B cell lymphoma. J Egypt Natl Canc Inst. 2022;34(1):20. doi:10.11 86/s43046-022-00116-5
29. Lugtenburg PJ, Mutsaers PGNJ. How I treat Elderly Patients with DLBCL in the frontline setting. Blood. Published online November 22, 2022. doi:10.1182/blood.2020 008239
30. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. Eur Heart J. 2016;37(36):2768-2801. doi:10.1093/eurhe artj/ehw211
31. Ganatra S, Nohria A, Shah S, et al. Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series. Cardio-Oncology. 2019;5(1):1. doi:10.1186/s40959-019-0036-7
32. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology. 2015;33(28):319 9-3212. doi:10.1200/JCO.2015.62.3488
33. Morita Y, Kanemasa Y, Sasaki Y, et al. Impact of pegfilgrastim approval on relative dose intensity and outcomes of R-CHOP for diffuse large B-cell lymphoma. Medicine. 2022;101(10):e29028. doi:10.1097/MD.0000000000029028
34. Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP. Journal of Clinical Oncology. 2016;3 4(26):3150-3156. doi:10.1200/JCO.2015.65.6520
35. Schmitz N, Frontzek F. CNS prophylaxis in DLBCL: time to say goodbye? Blood. 2022;139(3):315-317. doi:10.1182/blood.2021014043
36. Burns EA, Wilson JJ, Mathur S, et al. Long-term outcomes in patients with Burkitt lymphoma older than 65 years: an analysis of the Texas Cancer Registry. Ann Hematol. 2023;102(10):2753-2763. doi:10.1007/s00277-023-05328-w
37. Eyre TA, Kirkwood AA, Wolf J, et al. Stand‐alone intrathecal central nervous system (CNS) prophylaxis provide unclear benefit in reducing CNS relapse risk in elderly DLBCL patients treated with R‐CHOP and is associated increased infection‐related toxicity. Br J Haematol. 2019;187(2):185-194. doi:10.1111/bjh.16070
38. Feugier P, Van Hoof A, Sebban 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. Journal of Clinical Oncology. 2005;23(18):411 7-4126. doi:10.1200/JCO.2005.09.131
39. Coiffier B, Thieblemont C, Van Den Neste E, et al. 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. 2010;116(12): 2040-2045. doi:10.1182/blood-2010-03-276246
40. 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 randomised controlled trial (RICOVER-60). Lancet Oncol. 2008;9(2):105-116. doi:10.1016/S1470-2045(08)70002-0
41. Cunningham D, Hawkes EA, Jack A, et al. 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. The Lancet. 2013;381(9880):1817-1826. doi:10.1016/S0140-6736(13)60313-X
42. Delarue R, Tilly H, Mounier N, 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):525-533. doi:10.101 6/S1470-2045(13)70122-0
43. Zhang WH, Li GY, Ma YJ, et al. Reduced-dose EPOCH-R chemotherapy for elderly patients with advanced stage diffuse large B cell lymphoma. Ann Hematol. 2018;97(10):18 09-1816. doi:10.1007/s00277-018-3369-7
44. Bartlett NL, Wilson WH, Jung SH, et al. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. Journal of Clinical Oncology. 2019;37( 21):1790-1799. doi:10.1200/JCO.18.01994
45. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2022;386(4):351 -363. doi:10.1056/NEJMoa2115304
46. Peyrade F, Jardin F, Thieblemont C, 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):460-468. doi:10.1016/S147 0-2045(11)70069-9
47. Shin HJ, Chung JS, Song MK, Kim SK, Choe S, Cho GJ. Addition of rituximab to reduced-dose CHOP chemotherapy is feasible for elderly patients with diffuse large B-cell lymphoma. Cancer Chemother Pharmacol. 2012;69(5):1165-1172. doi:10.100 7/s00280-011-1814-6
48. Nowakowski GS, Hong F, Scott DW, et al. Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412. Journal of Clinical Oncology. 2021;39(12):1329-1338. doi:10.12 00/JCO.20.01375
49. Moccia AA, Schaff K, Freeman C, et al. Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines. Blood Adv. 2021;5(5):1483-1489. doi:10.1182/bloo dadvances.2020002982
50. 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. Leuk Lymphoma. 2012;53(4):581-588. doi:10.3109/ 10428194.2011.621565
51. Chan JY, Somasundaram N, Grigoropoulos N, et al. Evolving therapeutic landscape of diffuse large B-cell lymphoma: challenges and aspirations. Discover Oncology. 2023;14(1):132. doi:10.1007/s126 72-023-00754-8
52. Di M, Huntington SF, Olszewski AJ. Challenges and Opportunities in the Management of Diffuse Large B-Cell Lymphoma in Older Patients. Oncologist. 2021;26(2):120-132. doi:10.1002/onco.13610
53. Feugier P, Van Hoof A, Sebban 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. Journal of Clinical Oncology. 2005;23(18):411 7-4126. doi:10.1200/JCO.2005.09.131
54. 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. Journal of Clinical Oncology. 2006;24(19):3121-3127. doi:10.1200/JCO.2005.05.1003
55. Eyre TA, Martinez‐Calle N, Hildyard C, et al. Impact of intended and relative dose intensity of R‐CHOP in a large, consecutive cohort of elderly diffuse large B‐cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age. J Intern Med. 2019;285(6):681-692. doi:10.1111/joim. 12889
56. Sehn LH, Congiu AG, Culligan DJ, et al. No Added Benefit of Eight Versus Six Cycles of CHOP When Combined with Rituximab in Previously Untreated Diffuse Large B-Cell Lymphoma Patients: Results from the International Phase III GOYA Study. Blood. 2018;132(Supplement 1):783-783. doi:10.118 2/blood-2018-99-116845
57. Wästerlid T, Biccler JL, Brown PN, et al. Six cycles of R-CHOP-21 are not inferior to eight cycles for treatment of diffuse large B-cell lymphoma: a Nordic Lymphoma Group Population-based Study. Annals of Oncology. 2018;29(8):1882-1883. doi:10.1093/annonc/mdy184
58. Tilly H, Morschhauser F, Bartlett NL, et al. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b–2 study. Lancet Oncol. 2019;20(7):9 98-1010. doi:10.1016/S1470-2045(19)30091-9
59. Tilly H, Gomes da Silva M, Vitolo U, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2015;26:v116-v125. doi:10.1093/a nnonc/mdv304
60. Hu B, Reagan PM, Sehn LH, et al. Subgroup analysis of elderly patients (pts) with diffuse large B‐cell lymphoma (DLBCL) in the Phase 3 POLARIX study. Hematol Oncol. 2023;41(S2):416-418. doi:10.1002/hon.3164_306
61. Nowakowski GS, Chiappella A, Gascoyne RD, et al. ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology. 2021;39(12):1317-1328. doi:10.1200/JCO.20.01366
62. Martine E.D. Chamuleau, Coreline N. Burggraaff, Marcel Nijland, et al. Treatment of patients with MYC rearrangement positive large B-cell lymphoma with R-CHOP plus lenalidomide: results of a multicenter HOVON phase II trial. Haematologica. 2019;105(12):28 05-2812. doi:10.3324/haematol.2019.238162
63. de Jonge AV, van Werkhoven ED, Dinmohamed AG, et al. A Propensity Score-Adjusted Comparison of Lenalidomide + R-CHOP Versus R-CHOP for MYC -Rearranged DLBCL Patients. Blood. 2022;140(Supplemen t 1):2059-2060. doi:10.1182/blood-2022-163204
64. Chihara D, Westin JR, Oki Y, et al. Management strategies and outcomes for very elderly patients with diffuse large B‐cell lymphoma. Cancer. 2016;122(20):3145-3151. doi:10.1002/cncr.30173
65. Owens CN, Migliacci JC, Horwitz SM, et al. Dose-Adjusted EPOCH +/- Rituximab in Older Patients with High Grade Diffuse Large B-Cell Lymphoma, Burkitt and T-Cell Lymphoma: An Effective Regimen with Acceptable Toxicity Profile. Blood. 2014;124( 21):4450-4450. doi:10.1182/blood.V124.21.4450.4450
66. Hershman DL, McBride RB, Eisenberger A, Tsai WY, Grann VR, Jacobson JS. Doxorubicin, Cardiac Risk Factors, and Cardiac Toxicity in Elderly Patients With Diffuse B-Cell Non-Hodgkin’s Lymphoma. Journal of Clinical Oncology. 2008;26(19):315 9-3165. doi:10.1200/JCO.2007.14.1242
67. Peyrade F, Jardin F, Thieblemont C, 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):460-468. doi:10.1016/S147 0-2045(11)70069-9
68. Juul MB, Jensen PH, Engberg H, et al. Treatment strategies and outcomes in diffuse large B-cell lymphoma among 1011 patients aged 75 years or older: A Danish population-based cohort study. Eur J Cancer. 2018;99:86-96. doi:10.1016/j.ejca.2018.05.006
69. Mats Jerkeman. A Randomized, Multicenter, Phase III Trial Comparing Treatment With R-mini-CHOP With R-mini-CHP + Polatuzumab Vedotin in Patients With Diffuse Large Cell B Cell Lymphoma (POLAR BEAR). https://clinicaltrials.gov/study/NCT04332822
70. Di M, Huntington SF, Olszewski AJ. Challenges and Opportunities in the Management of Diffuse Large B-Cell Lymphoma in Older Patients. Oncologist. 2021;26(2):120-132. doi:10.1002/onco.13610
71. Storti S, Spina M, Pesce EA, et al. Rituximab plus bendamustine as front-line treatment in frail elderly (>70 years) patients with diffuse large B-cell non-Hodgkin lymphoma: a phase II multicenter study of the Fondazione Italiana Linfomi. Haematologica. 2018;103(8):1345-1350. doi:10.3324/haematol.2017.186569
72. Braulke F, Zettl F, Ziepert M, et al. First-line Treatment With Bendamustine and Rituximab for Old and Frail Patients With Aggressive Lymphoma: Results of the B-R-ENDA Trial. Hemasphere. 2022;6(12):e808. doi:10.1097/HS9.0000000000000808
73. Wang M, Fowler N, Wagner-Bartak N, et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013;27(9):1902-1909. doi:10.1038/leu.2013.95
74. Thieblemont C, Howlett S, Casasnovas R, et al. Lenalidomide maintenance for diffuse large B‐cell lymphoma patients responding to R‐CHOP: quality of life, dosing, and safety results from the randomised controlled REMARC study. Br J Haematol. 2020;189(1):84-96. doi:10.1111/bjh.16300
75. Xu PP, Shi ZY, Qian Y, et al. Ibrutinib, rituximab, and lenalidomide in unfit or frail patients aged 75 years or older with de novo diffuse large B-cell lymphoma: a phase 2, single-arm study. Lancet Healthy Longev. 2022;3(7):e481-e490. doi:10.1016/S2666-756 8(22)00123-4
76. Jones G, Plastaras J, Ng A, Kelsey C. The Evolving Role of Radiation Therapy in DLBCL: From Early-Stage to Refractory Disease. Oncology. 2022;(3612):718-727. doi:10.4688 3/2022.25920980
77. Wong J, Pickles T, Connors J, et al. Efficacy of Palliative Radiation Therapy (RT) for Chemotherapy Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Population-Based Retrospective Review. Pract Radiat Oncol. 2021;11(2):e203-e209. doi:10.1016/j.prro.2020.11.003
78. Kuczynski EA, Sargent DJ, Grothey A, Kerbel RS. Drug rechallenge and treatment beyond progression—implications for drug resistance. Nat Rev Clin Oncol. 2013;10(10):5 71-587. doi:10.1038/nrclinonc.2013.158
79. Jurczak W, Zinzani PL, Gaidano G, et al. Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Annals of Oncology. 2018;29(5):1266-1272. doi:10.1093/annonc/mdy056
80. Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7): 978-988. doi:10.1016/S1470-2045(20)30225-4
81. Qualls DA, Lambert N, Caimi PF, et al. Tafasitamab and lenalidomide in large B-cell lymphoma: real-world outcomes in a multicenter retrospective study. Blood. 2023;142(26):2327-2331. doi:10.1182/blood.2023021274
82. Zammarchi F, Corbett S, Adams L, et al. ADCT-402, a PBD dimer–containing antibody drug conjugate targeting CD19-expressing malignancies. Blood. 2018;131(10):1094-1105. doi:10.1182/blood-2017-10-813493
83. Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):7 90-800. doi:10.1016/S1470-2045(21)00139-X
84. Caimi PF, Ardeshna KM, Reid E, et al. The AntiCD19 Antibody Drug Immunoconjugate Loncastuximab Achieves Responses in DLBCL Relapsing After AntiCD19 CAR-T Cell Therapy. Clin Lymphoma Myeloma Leuk. 2022;22(5):e335-e339. doi:10.1016/j.clml.2021.11.005
85. Alderuccio JP, Ai WZ, Radford J, et al. Loncastuximab tesirine in relapsed/refractory high-grade B-cell lymphoma: a subgroup analysis from the LOTIS-2 study. Blood Adv. 2022;6(16):4736-4739. doi:10.1182/bloodadvances.2022007782
86. Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology. 2020;38(2):155-165. doi:10.1200/JCO.19.00172
87. Budde LE, Olszewski AJ, Assouline S, et al. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Nat Med. 2024;30(1):229-239. doi:10.1038/s41591-023 -02726-5
88. Westin J, Olszewski AJ, Fogliatto L, et al. SUNMO: A phase III trial evaluating the efficacy and safety of mosunetuzumab in combination with polatuzumab vedotin vs rituximab plus gemcitabine and oxaliplatin in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Journal of Clinical Oncology. 2023;41(16_suppl):TPS758 6-TPS7586. doi:10.1200/JCO.2023.41.16_suppl.TPS7586
89. Bartlett NL, Assouline S, Giri P, et al. Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2023;7(17):4926-4935. doi:10.1182/bloodadvances.2022009260
90. Olszewski AJ, Phillips TJ, Hoffmann MS, et al. Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study. Blood Adv. 2023;7(20):6055-6065. doi:10.11 82/bloodadvances.2023010840
91. Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell–Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. Journal of Clinical Oncology. 2023;41 (12):2238-2247. doi:10.1200/JCO.22.01725
92. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2022;387(24):2220-2231. doi:10.10 56/NEJMoa2206913
93. Shipp M, Harrington D, Anderson J, Armitage J. A Predictive Model for Aggressive Non-Hodgkin’s Lymphoma. New England Journal of Medicine. 1993;329(14):987-994. doi:10.1056/NEJM199309303291402
94. Neelapu SS, Jacobson CA, Oluwole OO, et al. Outcomes of older patients in ZUMA-1, a pivotal study of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2020;135(23):2106-2109. doi:10.1182/blood.2019004162
95. Muffly L, Pasquini MC, Martens M, et al. Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States. Blood. 2017;130(9):1156-1164. doi:10.1182/blood-2017-03-772368
96. Greenwell IB, Dahi PB. Transplant and chimeric antigen receptor T-cell therapies in elderly patients with lymphoma, a narrative review. Ann Lymphoma. 2022;6:8-8. doi:10.2 1037/aol-22-7
97. Burns EA, Gentille C, Trachtenberg B, Pingali SR, Anand K. Cardiotoxicity Associated with Anti-CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Recognition, Risk Factors, and Management. Diseases. 2021;9(1):20. doi:10.3390/diseases9010020
98. Roberts ZJ, Better M, Bot A, Roberts MR, Ribas A. Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma. 2018;59(8):1785-1796. doi:10.1080/10428194.2017.1387905
99. Ghosh AK, Chen DH, Guha A, Mackenzie S, Walker JM, Roddie C. CAR T Cell Therapy–Related Cardiovascular Outcomes and Management. JACC CardioOncol. 2020;2(1): 97-109. doi:10.1016/j.jaccao.2020.02.011
100. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2019;380( 1):45-56. doi:10.1056/NEJMoa1804980
101. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. The Lancet. 2020;396( 10254):839-852. doi:10.1016/S0140-6736(20) 31366-0
102. Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91-103. doi:10. 1016/S1470-2045(21)00591-X
103. Ram R, Grisariu S, Shargian-Alon L, et al. Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study. Haematologica. 2021;107(5):1111-1118. doi: 10.3324/haematol.2021.278288
104. Sano D, Lekakis L, Feng L, et al. SAFETY AND EFFICACY OF AXICABTAGENE CILOLEUCEL (AXI‐CEL) IN OLDER PATIENTS: RESULTS FROM THE US LYMPHOMA CAR‐T CONSORTIUM. Hematol Oncol. 2019;37(S2): 304-305. doi:10.1002/hon.113_2630
105. Nastoupil LJ, Jain MD, Feng L, et al. Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. Journal of Clinical Oncology. 2020;38(27):3119-3128. doi:10.12 00/JCO.19.02104
106. Dreger P, Holtick U, Subklewe M, et al. Impact of age on outcome of CAR-T cell therapies for large B-cell lymphoma: the GLA/DRST experience. Bone Marrow Transplant. 2023;58(2):229-232. doi:10.1038/ s41409-022-01867-4
107. Chihara D, Liao L, Tkacz J, et al. Real-world experience of CAR T-cell therapy in older patients with relapsed/refractory diffuse large B-cell lymphoma. Blood. 2023;142(12):1 047-1055. doi:10.1182/blood.2023020197
108. Bishop MR. The benefit of CAR T cells in older patients. Blood. 2020;135(23):2020-2021. doi:10.1182/blood.2020005592
109. Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23(8):1066-1077. doi:10.1016/S1 470-2045(22)00339-4
110. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin’s Lymphoma. New England Journal of Medicine. 1995;333(23):1540-1545. doi:10. 1056/NEJM199512073332305
111. Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology. 2020;38(2):155-165. doi:10.1200/JCO.19.00172
112. Sweetenham JW, Pearce R, Philip T, et al. High-dose therapy and autologous bone marrow transplantation for intermediate and high grade non-Hodgkin’s lymphoma in patients aged 55 years and over: results from the European Group for Bone Marrow Transplantation. The EBMT Lymphoma Working Party. Bone Marrow Transplant. 1994;14(6):981-987.
113. Dahi PB, Lee J, Devlin SM, et al. Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma. Blood Adv. 2021;5(1 2):2608-2618. doi:10.1182/bloodadvances.2020004167
114. Andorsky DJ, Cohen M, Naeim A, Pinter-Brown L. Outcomes of auto-SCT for lymphoma in subjects aged 70 years and over. Bone Marrow Transplant. 2011; 46(9):1219-1225. doi:10.1038/bmt.2010.289
115. Munshi PN, Chen Y, Ahn KW, et al. Outcomes of Autologous Hematopoietic Cell Transplantation in Older Patients with Diffuse Large B-Cell Lymphoma. Transplant Cell Ther. 2022;28(8):487.e1-487.e7. doi:10.1016/j.jtct.2022.05.029
116. Sun L, Li S, El-Jawahri A, et al. Autologous Stem Cell Transplantation in Elderly Lymphoma Patients in Their 70s: Outcomes and Analysis. Oncologist. 2018;23(5):624-630. doi:10.1634/theoncologist.2017-0499
117. Jantunen E, Canals C, Rambaldi A, et al. Autologous stem cell transplantation in elderly patients (>=60 years) with diffuse large B-cell lymphoma: an analysis based on data in the European Blood and Marrow Transplantation registry. Haematologica. 2008;93(12):1837-1842. doi:10.3324/haematol.13273
118. Hermet E, Cabrespine A, Guièze R, et al. Autologous hematopoietic stem cell transplantation in elderly patients (≥70years) with non-Hodgkin’s lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study. J Geriatr Oncol. 2015;6(5):346-352. doi:10.1016/j.jgo. 2015.04.005
119. Davison K, Chen BE, Kukreti V, et al. Treatment outcomes for older patients with relapsed/refractory aggressive lymphoma receiving salvage chemotherapy and autologous stem cell transplantation are similar to younger patients: a subgroup analysis from the phase III CCTG LY.12 trial. Annals of Oncology. 2017;28(3):622-627. doi:10.1093/annonc/mdw653
120. Chihara D, Izutsu K, Kondo E, et al. High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Elderly Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma: A Nationwide Retrospective Study. Biology of Blood and Marrow Transplantation. 2014;20(5):684-689. doi:10. 1016/j.bbmt.2014.01.025
121. Chopra R, Goldstone AH, Pearce R, et al. Autologous versus allogeneic bone marrow transplantation for non-Hodgkin’s lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data. Journal of Clinical Oncology. 1992;10(11):169 0-1695. doi:10.1200/JCO.1992.10.11.1690
122. Shah NN, Ahn KW, Litovich C, et al. Allogeneic transplantation in elderly patients ≥65 years with non-Hodgkin lymphoma: a time-trend analysis. Blood Cancer J. 2019;9(1 2):97. doi:10.1038/s41408-019-0261-1
2. Kanas G, Ge W, Quek RGW, Keeven K, Nersesyan K, Jon E. Arnason. Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020–2025. Leuk Lymphoma. 2022;63(1):54-63. doi:10.1080/10428194.2021.1975188
3. Wang Y, Ren X, Huang K, et al. Comparison of first-line treatments for elderly patients with diffuse large B-cell lymphoma: A systematic review and network meta-analysis. Front Immunol. 2023;13. doi:10.3389/fimmu. 2022.1082293
4. Coiffier B, Lepage E, Brière J, et al. CHOP Chemotherapy plus Rituximab Compared with CHOP Alone in Elderly Patients with Diffuse Large-B-Cell Lymphoma. New England Journal of Medicine. 2002;346(4):235 -242. doi:10.1056/NEJMoa011795
5. U.S. Census Bureau. 2020 Census Demographic and Housing Characteristics File (DHC). https://www.census.gov/data/tables/2023/dec/2020-census-dhc.html
6. Leukemia and Lymphoma Society. NHL SUBTYPES. https://www.lls.org/lymphoma/non-hodgkin-lymphoma/nhl-subtypes
7. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2017. Published online April 2020.
8. Wang SS. Epidemiology and etiology of diffuse large B-cell lymphoma. Semin Hematol. Published online November 2023. doi:10.1053/j.seminhematol.2023.11.004
9. Arcari A, Cavallo F, Puccini B, Vallisa D. New treatment options in elderly patients with Diffuse Large B-cell Lymphoma. Front Oncol. 2023;13. doi:10.3389/fonc.2023.1214026
10. Al Armashi AR, Al Zubaidi A, Mahmood O, Thierheimer M, Alkrekshi A, Abdulhaq H. Trends in Diffuse Large B-Cell Lymphoma Mortality in the United States: A Comprehensive Review from 2000 to 2020. Blood. 2023;142(Supplement 1):1765-1765. doi:10.1182/blood-2023-180270
11. Ulu BU, Yiğenoğlu TN, Başcı S, et al. Factors affecting survival in elderly patients with diffuse large B-Cell lymphoma. Leuk Res. 2021;110:106700. doi:10.1016/j.leukres.2021.106700
12. Hounsome L, Eyre TA, Ireland R, et al. Diffuse large B cell lymphoma (DLBCL) in patients older than 65 years: analysis of 3 year Real World data of practice patterns and outcomes in England. Br J Cancer. 2022;126(1 ):134-143. doi:10.1038/s41416-021-01525-4
13. Abu Sabaa A, Mörth C, Hasselblom S, et al. Age is the most important predictor of survival in diffuse large B‐cell lymphoma patients achieving event‐free survival at 24 months: a Swedish population‐based study. Br J Haematol. 2021;193(5):906-914. doi:10.1 111/bjh.17206
14. Ekberg S, Crowther M, Harrysson S, Jerkeman M, E. Smedby K, Eloranta S. Patient trajectories after diagnosis of diffuse large B-cell lymphoma—a multistate modelling approach to estimate the chance of lasting remission. Br J Cancer. 2022;127(9):1642-1649. doi:10.1038/s41416-022-01931-2
15. Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800 -1808. doi:10.1182/blood-2017-03-769620
16. Shimkus G, Nonaka T. Molecular classification and therapeutics in diffuse large B-cell lymphoma. Front Mol Biosci. 2023;10. doi:10.3389/fmolb.2023.1124360
17. Roschewski M, Phelan JD, Wilson WH. Molecular Classification and Treatment of Diffuse Large B-Cell Lymphoma and Primary Mediastinal B-Cell Lymphoma. The Cancer Journal. 2020;26(3):195-205. doi:10.1097/PP O.0000000000000450
18. 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):1888-1890. doi:10.3324/haematol.2011.050617
19. Rosenwald A, Bens S, Advani R, et al. Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma: A Study by the Lunenburg Lymphoma Biomarker Consortium. Journal of Clinical Oncology. 2019;37(35):3359-3368. doi:10.1200/JCO.19.00743
20. Hurria A, Togawa K, Mohile SG, et al. Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter Study. Journal of Clinical Oncology. 2011;29(25):3457-3465. doi:10.12 00/JCO.2011.34.7625
21. Mohile SG, Dale W, Somerfield MR, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology. Journal of Clinical Oncology. 2018; 36(22):2326-2347. doi:10.1200/JCO.2018.78.8687
22. Li D, Sun CL, Kim H, et al. Geriatric Assessment–Driven Intervention (GAIN) on Chemotherapy-Related Toxic Effects in Older Adults With Cancer. JAMA Oncol. 2021;7(11): e214158. doi:10.1001/jamaoncol.2021.4158
23. Mohile SG, Mohamed MR, Xu H, et al. Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study. The Lancet. 2021;398(10314):1894-1904. doi:10.1016/S0140-6736(21)01789-X
24. Williams GR, Hopkins JO, Klepin HD, et al. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Questions and Answers. JCO Oncol Pract. 2023;19(9):718-723. doi:10.1200/OP.23.00263
25. Merli F, Luminari S, Tucci A, et al. Simplified Geriatric Assessment in Older Patients With Diffuse Large B-Cell Lymphoma: The Prospective Elderly Project of the Fondazione Italiana Linfomi. Journal of Clinical Oncology. 2021;39(11):1214-1222. doi:10.1200/JCO.20.02465
26. Tucci A, Martelli M, Rigacci L, 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):921-926. doi:10.3109/10428194.2014.953142
27. Lugtenburg PJ, Mutsaers PGNJ. How I treat Elderly Patients with DLBCL in the frontline setting. Blood. Published online November 22, 2022. doi:10.1182/blood.2020 008239
28. Rudresha AH, Hassan SA, Sreevalli A, et al. Pre-phase strategy to mitigate first cycle effect in diffuse large B cell lymphoma. J Egypt Natl Canc Inst. 2022;34(1):20. doi:10.11 86/s43046-022-00116-5
29. Lugtenburg PJ, Mutsaers PGNJ. How I treat Elderly Patients with DLBCL in the frontline setting. Blood. Published online November 22, 2022. doi:10.1182/blood.2020 008239
30. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. Eur Heart J. 2016;37(36):2768-2801. doi:10.1093/eurhe artj/ehw211
31. Ganatra S, Nohria A, Shah S, et al. Upfront dexrazoxane for the reduction of anthracycline-induced cardiotoxicity in adults with preexisting cardiomyopathy and cancer: a consecutive case series. Cardio-Oncology. 2019;5(1):1. doi:10.1186/s40959-019-0036-7
32. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. Journal of Clinical Oncology. 2015;33(28):319 9-3212. doi:10.1200/JCO.2015.62.3488
33. Morita Y, Kanemasa Y, Sasaki Y, et al. Impact of pegfilgrastim approval on relative dose intensity and outcomes of R-CHOP for diffuse large B-cell lymphoma. Medicine. 2022;101(10):e29028. doi:10.1097/MD.0000000000029028
34. Schmitz N, Zeynalova S, Nickelsen M, et al. CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP. Journal of Clinical Oncology. 2016;3 4(26):3150-3156. doi:10.1200/JCO.2015.65.6520
35. Schmitz N, Frontzek F. CNS prophylaxis in DLBCL: time to say goodbye? Blood. 2022;139(3):315-317. doi:10.1182/blood.2021014043
36. Burns EA, Wilson JJ, Mathur S, et al. Long-term outcomes in patients with Burkitt lymphoma older than 65 years: an analysis of the Texas Cancer Registry. Ann Hematol. 2023;102(10):2753-2763. doi:10.1007/s00277-023-05328-w
37. Eyre TA, Kirkwood AA, Wolf J, et al. Stand‐alone intrathecal central nervous system (CNS) prophylaxis provide unclear benefit in reducing CNS relapse risk in elderly DLBCL patients treated with R‐CHOP and is associated increased infection‐related toxicity. Br J Haematol. 2019;187(2):185-194. doi:10.1111/bjh.16070
38. Feugier P, Van Hoof A, Sebban 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. Journal of Clinical Oncology. 2005;23(18):411 7-4126. doi:10.1200/JCO.2005.09.131
39. Coiffier B, Thieblemont C, Van Den Neste E, et al. 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. 2010;116(12): 2040-2045. doi:10.1182/blood-2010-03-276246
40. 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 randomised controlled trial (RICOVER-60). Lancet Oncol. 2008;9(2):105-116. doi:10.1016/S1470-2045(08)70002-0
41. Cunningham D, Hawkes EA, Jack A, et al. 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. The Lancet. 2013;381(9880):1817-1826. doi:10.1016/S0140-6736(13)60313-X
42. Delarue R, Tilly H, Mounier N, 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):525-533. doi:10.101 6/S1470-2045(13)70122-0
43. Zhang WH, Li GY, Ma YJ, et al. Reduced-dose EPOCH-R chemotherapy for elderly patients with advanced stage diffuse large B cell lymphoma. Ann Hematol. 2018;97(10):18 09-1816. doi:10.1007/s00277-018-3369-7
44. Bartlett NL, Wilson WH, Jung SH, et al. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. Journal of Clinical Oncology. 2019;37( 21):1790-1799. doi:10.1200/JCO.18.01994
45. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2022;386(4):351 -363. doi:10.1056/NEJMoa2115304
46. Peyrade F, Jardin F, Thieblemont C, 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):460-468. doi:10.1016/S147 0-2045(11)70069-9
47. Shin HJ, Chung JS, Song MK, Kim SK, Choe S, Cho GJ. Addition of rituximab to reduced-dose CHOP chemotherapy is feasible for elderly patients with diffuse large B-cell lymphoma. Cancer Chemother Pharmacol. 2012;69(5):1165-1172. doi:10.100 7/s00280-011-1814-6
48. Nowakowski GS, Hong F, Scott DW, et al. Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412. Journal of Clinical Oncology. 2021;39(12):1329-1338. doi:10.12 00/JCO.20.01375
49. Moccia AA, Schaff K, Freeman C, et al. Long-term outcomes of R-CEOP show curative potential in patients with DLBCL and a contraindication to anthracyclines. Blood Adv. 2021;5(5):1483-1489. doi:10.1182/bloo dadvances.2020002982
50. 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. Leuk Lymphoma. 2012;53(4):581-588. doi:10.3109/ 10428194.2011.621565
51. Chan JY, Somasundaram N, Grigoropoulos N, et al. Evolving therapeutic landscape of diffuse large B-cell lymphoma: challenges and aspirations. Discover Oncology. 2023;14(1):132. doi:10.1007/s126 72-023-00754-8
52. Di M, Huntington SF, Olszewski AJ. Challenges and Opportunities in the Management of Diffuse Large B-Cell Lymphoma in Older Patients. Oncologist. 2021;26(2):120-132. doi:10.1002/onco.13610
53. Feugier P, Van Hoof A, Sebban 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. Journal of Clinical Oncology. 2005;23(18):411 7-4126. doi:10.1200/JCO.2005.09.131
54. 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. Journal of Clinical Oncology. 2006;24(19):3121-3127. doi:10.1200/JCO.2005.05.1003
55. Eyre TA, Martinez‐Calle N, Hildyard C, et al. Impact of intended and relative dose intensity of R‐CHOP in a large, consecutive cohort of elderly diffuse large B‐cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age. J Intern Med. 2019;285(6):681-692. doi:10.1111/joim. 12889
56. Sehn LH, Congiu AG, Culligan DJ, et al. No Added Benefit of Eight Versus Six Cycles of CHOP When Combined with Rituximab in Previously Untreated Diffuse Large B-Cell Lymphoma Patients: Results from the International Phase III GOYA Study. Blood. 2018;132(Supplement 1):783-783. doi:10.118 2/blood-2018-99-116845
57. Wästerlid T, Biccler JL, Brown PN, et al. Six cycles of R-CHOP-21 are not inferior to eight cycles for treatment of diffuse large B-cell lymphoma: a Nordic Lymphoma Group Population-based Study. Annals of Oncology. 2018;29(8):1882-1883. doi:10.1093/annonc/mdy184
58. Tilly H, Morschhauser F, Bartlett NL, et al. Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b–2 study. Lancet Oncol. 2019;20(7):9 98-1010. doi:10.1016/S1470-2045(19)30091-9
59. Tilly H, Gomes da Silva M, Vitolo U, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2015;26:v116-v125. doi:10.1093/a nnonc/mdv304
60. Hu B, Reagan PM, Sehn LH, et al. Subgroup analysis of elderly patients (pts) with diffuse large B‐cell lymphoma (DLBCL) in the Phase 3 POLARIX study. Hematol Oncol. 2023;41(S2):416-418. doi:10.1002/hon.3164_306
61. Nowakowski GS, Chiappella A, Gascoyne RD, et al. ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology. 2021;39(12):1317-1328. doi:10.1200/JCO.20.01366
62. Martine E.D. Chamuleau, Coreline N. Burggraaff, Marcel Nijland, et al. Treatment of patients with MYC rearrangement positive large B-cell lymphoma with R-CHOP plus lenalidomide: results of a multicenter HOVON phase II trial. Haematologica. 2019;105(12):28 05-2812. doi:10.3324/haematol.2019.238162
63. de Jonge AV, van Werkhoven ED, Dinmohamed AG, et al. A Propensity Score-Adjusted Comparison of Lenalidomide + R-CHOP Versus R-CHOP for MYC -Rearranged DLBCL Patients. Blood. 2022;140(Supplemen t 1):2059-2060. doi:10.1182/blood-2022-163204
64. Chihara D, Westin JR, Oki Y, et al. Management strategies and outcomes for very elderly patients with diffuse large B‐cell lymphoma. Cancer. 2016;122(20):3145-3151. doi:10.1002/cncr.30173
65. Owens CN, Migliacci JC, Horwitz SM, et al. Dose-Adjusted EPOCH +/- Rituximab in Older Patients with High Grade Diffuse Large B-Cell Lymphoma, Burkitt and T-Cell Lymphoma: An Effective Regimen with Acceptable Toxicity Profile. Blood. 2014;124( 21):4450-4450. doi:10.1182/blood.V124.21.4450.4450
66. Hershman DL, McBride RB, Eisenberger A, Tsai WY, Grann VR, Jacobson JS. Doxorubicin, Cardiac Risk Factors, and Cardiac Toxicity in Elderly Patients With Diffuse B-Cell Non-Hodgkin’s Lymphoma. Journal of Clinical Oncology. 2008;26(19):315 9-3165. doi:10.1200/JCO.2007.14.1242
67. Peyrade F, Jardin F, Thieblemont C, 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):460-468. doi:10.1016/S147 0-2045(11)70069-9
68. Juul MB, Jensen PH, Engberg H, et al. Treatment strategies and outcomes in diffuse large B-cell lymphoma among 1011 patients aged 75 years or older: A Danish population-based cohort study. Eur J Cancer. 2018;99:86-96. doi:10.1016/j.ejca.2018.05.006
69. Mats Jerkeman. A Randomized, Multicenter, Phase III Trial Comparing Treatment With R-mini-CHOP With R-mini-CHP + Polatuzumab Vedotin in Patients With Diffuse Large Cell B Cell Lymphoma (POLAR BEAR). https://clinicaltrials.gov/study/NCT04332822
70. Di M, Huntington SF, Olszewski AJ. Challenges and Opportunities in the Management of Diffuse Large B-Cell Lymphoma in Older Patients. Oncologist. 2021;26(2):120-132. doi:10.1002/onco.13610
71. Storti S, Spina M, Pesce EA, et al. Rituximab plus bendamustine as front-line treatment in frail elderly (>70 years) patients with diffuse large B-cell non-Hodgkin lymphoma: a phase II multicenter study of the Fondazione Italiana Linfomi. Haematologica. 2018;103(8):1345-1350. doi:10.3324/haematol.2017.186569
72. Braulke F, Zettl F, Ziepert M, et al. First-line Treatment With Bendamustine and Rituximab for Old and Frail Patients With Aggressive Lymphoma: Results of the B-R-ENDA Trial. Hemasphere. 2022;6(12):e808. doi:10.1097/HS9.0000000000000808
73. Wang M, Fowler N, Wagner-Bartak N, et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013;27(9):1902-1909. doi:10.1038/leu.2013.95
74. Thieblemont C, Howlett S, Casasnovas R, et al. Lenalidomide maintenance for diffuse large B‐cell lymphoma patients responding to R‐CHOP: quality of life, dosing, and safety results from the randomised controlled REMARC study. Br J Haematol. 2020;189(1):84-96. doi:10.1111/bjh.16300
75. Xu PP, Shi ZY, Qian Y, et al. Ibrutinib, rituximab, and lenalidomide in unfit or frail patients aged 75 years or older with de novo diffuse large B-cell lymphoma: a phase 2, single-arm study. Lancet Healthy Longev. 2022;3(7):e481-e490. doi:10.1016/S2666-756 8(22)00123-4
76. Jones G, Plastaras J, Ng A, Kelsey C. The Evolving Role of Radiation Therapy in DLBCL: From Early-Stage to Refractory Disease. Oncology. 2022;(3612):718-727. doi:10.4688 3/2022.25920980
77. Wong J, Pickles T, Connors J, et al. Efficacy of Palliative Radiation Therapy (RT) for Chemotherapy Relapsed or Refractory Diffuse Large B-Cell Lymphoma: A Population-Based Retrospective Review. Pract Radiat Oncol. 2021;11(2):e203-e209. doi:10.1016/j.prro.2020.11.003
78. Kuczynski EA, Sargent DJ, Grothey A, Kerbel RS. Drug rechallenge and treatment beyond progression—implications for drug resistance. Nat Rev Clin Oncol. 2013;10(10):5 71-587. doi:10.1038/nrclinonc.2013.158
79. Jurczak W, Zinzani PL, Gaidano G, et al. Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Annals of Oncology. 2018;29(5):1266-1272. doi:10.1093/annonc/mdy056
80. Salles G, Duell J, González Barca E, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7): 978-988. doi:10.1016/S1470-2045(20)30225-4
81. Qualls DA, Lambert N, Caimi PF, et al. Tafasitamab and lenalidomide in large B-cell lymphoma: real-world outcomes in a multicenter retrospective study. Blood. 2023;142(26):2327-2331. doi:10.1182/blood.2023021274
82. Zammarchi F, Corbett S, Adams L, et al. ADCT-402, a PBD dimer–containing antibody drug conjugate targeting CD19-expressing malignancies. Blood. 2018;131(10):1094-1105. doi:10.1182/blood-2017-10-813493
83. Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):7 90-800. doi:10.1016/S1470-2045(21)00139-X
84. Caimi PF, Ardeshna KM, Reid E, et al. The AntiCD19 Antibody Drug Immunoconjugate Loncastuximab Achieves Responses in DLBCL Relapsing After AntiCD19 CAR-T Cell Therapy. Clin Lymphoma Myeloma Leuk. 2022;22(5):e335-e339. doi:10.1016/j.clml.2021.11.005
85. Alderuccio JP, Ai WZ, Radford J, et al. Loncastuximab tesirine in relapsed/refractory high-grade B-cell lymphoma: a subgroup analysis from the LOTIS-2 study. Blood Adv. 2022;6(16):4736-4739. doi:10.1182/bloodadvances.2022007782
86. Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology. 2020;38(2):155-165. doi:10.1200/JCO.19.00172
87. Budde LE, Olszewski AJ, Assouline S, et al. Mosunetuzumab with polatuzumab vedotin in relapsed or refractory aggressive large B cell lymphoma: a phase 1b/2 trial. Nat Med. 2024;30(1):229-239. doi:10.1038/s41591-023 -02726-5
88. Westin J, Olszewski AJ, Fogliatto L, et al. SUNMO: A phase III trial evaluating the efficacy and safety of mosunetuzumab in combination with polatuzumab vedotin vs rituximab plus gemcitabine and oxaliplatin in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Journal of Clinical Oncology. 2023;41(16_suppl):TPS758 6-TPS7586. doi:10.1200/JCO.2023.41.16_suppl.TPS7586
89. Bartlett NL, Assouline S, Giri P, et al. Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2023;7(17):4926-4935. doi:10.1182/bloodadvances.2022009260
90. Olszewski AJ, Phillips TJ, Hoffmann MS, et al. Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study. Blood Adv. 2023;7(20):6055-6065. doi:10.11 82/bloodadvances.2023010840
91. Thieblemont C, Phillips T, Ghesquieres H, et al. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell–Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. Journal of Clinical Oncology. 2023;41 (12):2238-2247. doi:10.1200/JCO.22.01725
92. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2022;387(24):2220-2231. doi:10.10 56/NEJMoa2206913
93. Shipp M, Harrington D, Anderson J, Armitage J. A Predictive Model for Aggressive Non-Hodgkin’s Lymphoma. New England Journal of Medicine. 1993;329(14):987-994. doi:10.1056/NEJM199309303291402
94. Neelapu SS, Jacobson CA, Oluwole OO, et al. Outcomes of older patients in ZUMA-1, a pivotal study of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2020;135(23):2106-2109. doi:10.1182/blood.2019004162
95. Muffly L, Pasquini MC, Martens M, et al. Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States. Blood. 2017;130(9):1156-1164. doi:10.1182/blood-2017-03-772368
96. Greenwell IB, Dahi PB. Transplant and chimeric antigen receptor T-cell therapies in elderly patients with lymphoma, a narrative review. Ann Lymphoma. 2022;6:8-8. doi:10.2 1037/aol-22-7
97. Burns EA, Gentille C, Trachtenberg B, Pingali SR, Anand K. Cardiotoxicity Associated with Anti-CD19 Chimeric Antigen Receptor T-Cell (CAR-T) Therapy: Recognition, Risk Factors, and Management. Diseases. 2021;9(1):20. doi:10.3390/diseases9010020
98. Roberts ZJ, Better M, Bot A, Roberts MR, Ribas A. Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma. 2018;59(8):1785-1796. doi:10.1080/10428194.2017.1387905
99. Ghosh AK, Chen DH, Guha A, Mackenzie S, Walker JM, Roddie C. CAR T Cell Therapy–Related Cardiovascular Outcomes and Management. JACC CardioOncol. 2020;2(1): 97-109. doi:10.1016/j.jaccao.2020.02.011
100. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2019;380( 1):45-56. doi:10.1056/NEJMoa1804980
101. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. The Lancet. 2020;396( 10254):839-852. doi:10.1016/S0140-6736(20) 31366-0
102. Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91-103. doi:10. 1016/S1470-2045(21)00591-X
103. Ram R, Grisariu S, Shargian-Alon L, et al. Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study. Haematologica. 2021;107(5):1111-1118. doi: 10.3324/haematol.2021.278288
104. Sano D, Lekakis L, Feng L, et al. SAFETY AND EFFICACY OF AXICABTAGENE CILOLEUCEL (AXI‐CEL) IN OLDER PATIENTS: RESULTS FROM THE US LYMPHOMA CAR‐T CONSORTIUM. Hematol Oncol. 2019;37(S2): 304-305. doi:10.1002/hon.113_2630
105. Nastoupil LJ, Jain MD, Feng L, et al. Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. Journal of Clinical Oncology. 2020;38(27):3119-3128. doi:10.12 00/JCO.19.02104
106. Dreger P, Holtick U, Subklewe M, et al. Impact of age on outcome of CAR-T cell therapies for large B-cell lymphoma: the GLA/DRST experience. Bone Marrow Transplant. 2023;58(2):229-232. doi:10.1038/ s41409-022-01867-4
107. Chihara D, Liao L, Tkacz J, et al. Real-world experience of CAR T-cell therapy in older patients with relapsed/refractory diffuse large B-cell lymphoma. Blood. 2023;142(12):1 047-1055. doi:10.1182/blood.2023020197
108. Bishop MR. The benefit of CAR T cells in older patients. Blood. 2020;135(23):2020-2021. doi:10.1182/blood.2020005592
109. Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23(8):1066-1077. doi:10.1016/S1 470-2045(22)00339-4
110. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous Bone Marrow Transplantation as Compared with Salvage Chemotherapy in Relapses of Chemotherapy-Sensitive Non-Hodgkin’s Lymphoma. New England Journal of Medicine. 1995;333(23):1540-1545. doi:10. 1056/NEJM199512073332305
111. Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Journal of Clinical Oncology. 2020;38(2):155-165. doi:10.1200/JCO.19.00172
112. Sweetenham JW, Pearce R, Philip T, et al. High-dose therapy and autologous bone marrow transplantation for intermediate and high grade non-Hodgkin’s lymphoma in patients aged 55 years and over: results from the European Group for Bone Marrow Transplantation. The EBMT Lymphoma Working Party. Bone Marrow Transplant. 1994;14(6):981-987.
113. Dahi PB, Lee J, Devlin SM, et al. Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma. Blood Adv. 2021;5(1 2):2608-2618. doi:10.1182/bloodadvances.2020004167
114. Andorsky DJ, Cohen M, Naeim A, Pinter-Brown L. Outcomes of auto-SCT for lymphoma in subjects aged 70 years and over. Bone Marrow Transplant. 2011; 46(9):1219-1225. doi:10.1038/bmt.2010.289
115. Munshi PN, Chen Y, Ahn KW, et al. Outcomes of Autologous Hematopoietic Cell Transplantation in Older Patients with Diffuse Large B-Cell Lymphoma. Transplant Cell Ther. 2022;28(8):487.e1-487.e7. doi:10.1016/j.jtct.2022.05.029
116. Sun L, Li S, El-Jawahri A, et al. Autologous Stem Cell Transplantation in Elderly Lymphoma Patients in Their 70s: Outcomes and Analysis. Oncologist. 2018;23(5):624-630. doi:10.1634/theoncologist.2017-0499
117. Jantunen E, Canals C, Rambaldi A, et al. Autologous stem cell transplantation in elderly patients (>=60 years) with diffuse large B-cell lymphoma: an analysis based on data in the European Blood and Marrow Transplantation registry. Haematologica. 2008;93(12):1837-1842. doi:10.3324/haematol.13273
118. Hermet E, Cabrespine A, Guièze R, et al. Autologous hematopoietic stem cell transplantation in elderly patients (≥70years) with non-Hodgkin’s lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study. J Geriatr Oncol. 2015;6(5):346-352. doi:10.1016/j.jgo. 2015.04.005
119. Davison K, Chen BE, Kukreti V, et al. Treatment outcomes for older patients with relapsed/refractory aggressive lymphoma receiving salvage chemotherapy and autologous stem cell transplantation are similar to younger patients: a subgroup analysis from the phase III CCTG LY.12 trial. Annals of Oncology. 2017;28(3):622-627. doi:10.1093/annonc/mdw653
120. Chihara D, Izutsu K, Kondo E, et al. High-Dose Chemotherapy with Autologous Stem Cell Transplantation for Elderly Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma: A Nationwide Retrospective Study. Biology of Blood and Marrow Transplantation. 2014;20(5):684-689. doi:10. 1016/j.bbmt.2014.01.025
121. Chopra R, Goldstone AH, Pearce R, et al. Autologous versus allogeneic bone marrow transplantation for non-Hodgkin’s lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data. Journal of Clinical Oncology. 1992;10(11):169 0-1695. doi:10.1200/JCO.1992.10.11.1690
122. Shah NN, Ahn KW, Litovich C, et al. Allogeneic transplantation in elderly patients ≥65 years with non-Hodgkin lymphoma: a time-trend analysis. Blood Cancer J. 2019;9(1 2):97. doi:10.1038/s41408-019-0261-1