Diffuse Large B-Cell Lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), representing approximately one-third of cases of NHL. DLBCL is an aggressive blood cancer that can be rapidly fatal if left untreated.¹ Without medical attention, the average lifespan of a patient with a diagnosis of DLBCL is less than 1 year.²

DLBCL Life Expectancy Relative to Treatment Response

Survival has improved with the advent and addition of anti-CD20 antibody therapy.³ Between 50% to 70% of patients with DLBCL undergoing immunochemotherapy with Rituxan® (rituximab) combined with cyclophosphamide, hydroxydaunorubicin (sold as Lipodox® or Doxil®), Oncovin® (vincristine), and prednisone (R-CHOP) achieve complete remission. However, 20% of patients with DLBCL have refractory disease that progresses despite first-line R-CHOP treatment, and relapse may occur in 30% of patients who achieve complete remission after initial treatment. A small subgroup of patients (5%) with DLBCL have a partial rather than a complete response to R-CHOP treatment.⁴

Death due to R-CHOP-induced toxicities is rare in younger patients with DLBCL, but the mortality rate is 5% in patients older than 70 years who experience chemotherapy-induced toxicity, which usually correlates with lack of a treatment response.⁴ 

Read more about DLBCL treatment

DLBCL Life Expectancy According to Age

Because of the comorbidities and frailty that usually accompany old age, it is anticipated that the life expectancy of older patients with DLBCL will be shorter. According to one study, patients past the age of 80 with DLBCL are less likely to receive standard R-CHOP treatment, but of the patients in this age group, those who do receive R-CHOP therapy have the longest survival.⁵

Similarly, a study that analyzed 87 patients with DLBCL from 2000 to 2016 suggested that the ability to complete the standard R-CHOP chemotherapy is critical to improve the survival rates of patients over 80 years old. In this study, the researchers observed no statistical difference between younger and older patients with DLBCL who completed R-CHOP treatment.²

A study of 7114 patients with DLBCL whose data was obtained from the Swedish Lymphoma Registry reported that the median age of patients at DLBCL diagnosis was approximately 70 years. When patients between 50 and 60 years old were compared with age-matched, healthy individuals from the general population, those with an age-adjusted International Prognostic Index (aa-IPI) score of 2 or higher had the greatest reduction in loss of life expectancy, or number of life-years lost because of cancer. Although the overall loss of life expectancy decreased from 8 to 4.6 years during the 13-year study period (2000-2013), patients in the 50- to 60-year age group, especially men, were still estimated to have lost more than 8 years of life as a consequence of DLBCL in 2013.³ 

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DLBCL Life Expectancy Corresponding to SEER Staging

The American Cancer Society has published 5-year relative survival rates for patients with DLBCL according to stage in the Surveillance, Epidemiology, and End Results (SEER) database. Approximately 74% of patients with a localized stage of DLBCL survive 5 years, whereas 73% of those with a regional stage and 57% of those with a distant stage survive 5 years. For all SEER stages combined, the 5-year survival rate is 64%.⁶ 

Read more about DLBCL diagnosis

DLBCL Life Expectancy According to Subtype and Pathogenesis

Correct identification of the DLBCL subtype and understanding of DLBCL pathogenesis are critical to determining the most effective treatment at the outset and improving the life expectancy of patients with DLBCL.

The Effects of DLBCL Subtype on Life Expectancy

DLBCL can be classified into 2 major molecular subgroups — germinal center B-cell (GCB) and activated B-cell (ABC) — although some forms of DLBCL cannot be specified. These subtypes have vast differences in clinical outcome, and overall survival is typically worse among patients with the ABC subtype of DLBCL treated with standard chemotherapy than in patients with the GCB subtype similarly treated.⁸ 

Advances in molecular classification, specifically the clonic B-cell receptor pathway, have provided a new means of targeted therapy to address these problems. Patients with ABC DLBCL responded better than patients with GCB DLBCL (response rates of 83% vs 13%; P <.001) to treatment with bortezomib, a proteasome inhibitor that targets and suppresses nuclear factor kappa B (NF-κB) plus dose-adjusted etoposide, prednisone, Oncovin, cyclophosphamide, and hydroxydaunorubicin with rituximab (DA-EPOCH-R) rather than standard R-CHOP therapy. The patients with ABC DLBCL who received bortezomib plus DA-EPOCH-R had a median overall survival of 10.8 months, whereas the median overall survival was 3.4 months in the patients with GCB DLBCL (P =.003).^8,9

Read more about DLBCL types

The Effects of DLBCL Pathogenesis on Life Expectancy

Some patients are resistant to the standard R-CHOP chemotherapy treatment. A large proportion of refractory patients present with double-protein expression lymphoma (DPL), double-hit lymphoma (DHL), or triple-hit lymphoma (THL). DPL involves high expression of MYC and BCL2 proteins, while DHL and THL involve chromosomal translocations of MYC, BCL2, and/or BCL6 genes. Patients with these refractory subtypes typically have a poor prognosis. Their overall survival and progression-free survival is lower compared to late-relapsing patients who respond better to salvage chemotherapy.⁴

Additionally, clinical outcomes are poor in patients who have DLBCL with high expression of MYC and BCL2 proteins (double-expressor lymphoma), although the outcomes are slightly better than those in patients with double-hit lymphoma. BCL2 hyperexpression alone predicts shorter progression-free survival and overall survival in patients with DLBCL.⁴ 

JUN and CYCS signaling strongly correlated with DLBCL progression in older patients and male patients. Compared with younger patients, JUN was the only commonly unregulated, specific key gene in both older female and male patients with DLBCL.⁷

References

1. Gandhi S. Diffuse large B-cell lymphoma (DLBCL): practice essentials. Medscape. Updated May 6, 2021. Accessed August 19, 2022.
2. Adıyaman SC, Alacacıoğlu İ, Ersen Danyeli A, et al. Prognostic factors in elderly patients with diffuse large B-cell lymphoma and their treatment results. Turk J Haematol. 2019;36(2):81-87. doi:10.4274/tjh.galenos.2019.2018.0219
3. Ekberg S, Jerkeman M, Andersson PO, et al. Long-term survival and loss in expectancy of life in a population-based cohort of 7114 patients with diffuse large B-cell lymphoma. Am J Hematol. 2018;93(8):1020-1028. doi:10.1002/ajh.25147
4. Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure—what to do? Hematology Am Soc Hematol Educ Program. 2016;2016(1):366-378. doi:10.1182/asheducation-2016.1.366 
5. Williams JN, Rai A, Lipscomb J, Koff JL, Nastoupil LJ, Flowers CR. Disease characteristics, patterns of care, and survival in very elderly patients with diffuse large B-cell lymphoma. Cancer. 2015;121(11):1800-1808. doi:10.1002/cncr.29290
6.  Survival rates and factors that affect prognosis (outlook) for non-Hodgkin lymphoma. American Cancer Society. Accessed August 19, 2022.
7. Beheshti A, Neuberg D, McDonald JT, Vanderburg CR, Evens AM. The impact of age and sex in DLBCL: systems biology analyses identify distinct molecular changes and signaling networks. Cancer Inform. 2015;14:141-148. doi:10.4137/CIN.S34144
8. 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-e457. doi:10.14694/EdBook_AM.2015.35.e449
9. Dunleavy K, Pittaluga S, Czuczman MS, et al. Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood. 2009;113(24):6069-6076. doi:10.1182/blood-2009-01-199679

Reviewed by Debjyoti Talukdar, MD, on 8/30/2022.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.