Diffuse Large B-Cell Lymphoma (DLBCL)


Diffuse large B-cell lymphoma (DLBCL) is the most commonly occurring non-Hodgkin lymphoma, accounting for at least 30% of cases. It is caused by various genetic and environmental factors that result in the development of abnormally large B-cells, which in turn affect the lymphatic system. DLBCL may aggressively spread to extranodal sites if left untreated and is associated with high morbidity and mortality.1,2 

Comorbidities affect prognosis and decisions regarding appropriate, safe treatment, especially in older patients with DLBCL.

Associated Comorbidities

The most common comorbid conditions associated with patients diagnosed with DLBCL include cardiovascular, respiratory, and endocrine disorders.

A retrospective study in the United States analyzed comorbidities among 4074 patients with DLBCL. Patients with an ICD-10-CM diagnosis code for DLBCL after October 1st, 2015 (index date) were divided into two groups: incident (patients with no prior ICD-9-CM code for unspecified DLBCL), and prevalent (patients with an ICD-9-CM code for unspecified DLBCL before the index date). Incidence patients reported hypertension (68.4%), diabetes (31.1%), and cardiac arrhythmias (25.3%) as common comorbidities, while prevalence patients reported hypertension (62.5%), diabetes (28.3%), and chronic pulmonary disease (20.6%) as common comorbidities.2

Impact of Comorbidities on DLBCL Prognosis

A multicenter real-world evidence study analyzed the impact of comorbidities on prognosis and toxicity in patients diagnosed with DLBCL. The most frequent comorbidities involved the vasculature (51%), endocrine organs (45%), and hypertension (43%). Any comorbidities associated with the renal, hepatic, gastrointestinal, or respiratory systems were independently correlated with worse progression-free survival and overall survival.3

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Effect of Comorbidities on DLBCL Treatment

Several clinical studies have been conducted to assess the effect of comorbidities on DLBCL treatment. This research helps illuminate how concurrent diseases and conditions may affect prognosis.

Swedish Lymphoma Register Study

Wästerlid and colleagues identified 3905 adults with DLBCL from 2007 to 2013 through the Swedish Lymphoma Register and assessed the effects of 17 comorbidities on treatment intent and outcomes using the Charlson Comorbidity Index (CCI). The most common comorbidities included cardiovascular disease (14%), solid cancer (13%), and diabetes (10%).4 

Patients with at least 1 comorbidity demonstrated an increased likelihood of scoring 2 or higher on the ECOG performance status scale than patients without comorbidities (31% vs 18%, respectively). Patients presenting with metastatic cancer, cerebrovascular disease, dementia, and psychiatric disorders demonstrated worse performance status at the time of DLBCL diagnosis. Consequently, the presence of comorbidities also correlated with International Prognostic Index (IPI) scoring secondary to its assessment of risk factors such as age and performance status.4 

Patients with comorbid DLBCL and peptic ulcers, dementia, psychiatric disorders, solid cancers, and diseases of the cardiovascular system, liver, peripheral vascular system, and renal system  were less likely to receive treatment with curative intent, affecting outcomes.4

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Kocher’s Study of DLBCL Treated With R-CHOP

A recent study by Kocher and colleagues used the CCI and the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) to examine the impact of comorbidities on 181 patients with DLBCL receiving R-CHOP (Rituxan® [rituximab] combined with cyclophosphamide, hydroxydaunorubicin [sold as Lipodox® or Doxil®], Oncovin® [vincristine], and prednisone) chemotherapy. Similar to other studies, they found that comorbidities adversely affected prognosis in patients receiving curative R-CHOP treatment.5

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Alternative Treatments to Reduce the Risk of Comorbidities

Patients aged 80 years and over with DLBCL demonstrate an increased risk of comorbidities, which correlates with increased rates of severe adverse events, premature treatment discontinuation, and toxicity with chemotherapy. Alternative treatment regimens include R-miniCHOP and R-CEOP treatment.6

Read more about DLBCL epidemiology

R-CEOP substitutes etoposide for hydroxydaunorubicin for patients with cardiovascular comorbidities who have absolute contraindications to anthracycline-based chemotherapy. Substitution with etoposide results in inferior long-term outcomes for these patients compared to R-CHOP therapy; however, anthracycline derivatives increase the risk of cardiotoxicity in patients with already compromised cardiovascular systems.7,8 The increased cardiotoxic risk of R-CHOP therapy explains the requirement of multigated acquisition scans (MUGA) and echocardiography to assess ejection fraction prior to the initiation of chemotherapy.

Read more about DLBCL experimental therapies

References

  1. Gandhi S. Diffuse large B-cell lymphoma: practice essentials. Medscape. Updated May 6, 2021. Accessed August 19, 2022.
  2. Yang X, Laliberté F, Germain G, et al. Real-world demographic and clinical characteristics of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in the United States (US). J Clin Oncol. 2019;37(15_suppl):e18347. doi:10.1200/JCO.2019.37.15_suppl.e18347
  3. Shouse G, Kaempf A, Yashar D, et al. Impact of comorbidities on outcomes and toxicity in patients treated with CAR T-cell therapy for diffuse large B cell lymphoma (DLBCL): a multicenter RWE study. Blood. 2021;138(Supplement 1):529. doi:10.1182/blood-2021-149735
  4. Wästerlid T, Mohammadi M, Smedby KE, et al. Impact of comorbidity on disease characteristics, treatment intent and outcome in diffuse large B-cell lymphoma: a Swedish Lymphoma Register study. J Intern Med. 2019;285(4):455-468. doi:10.1111/joim.12849
  5. Kocher F, Mian M, Seeber A, Fiegl M, Stauder R. The prognostic impact of comorbidities in patients with de-novo diffuse large B-cell lymphoma treated with R-CHOP immunochemotherapy in curative intent. J Clin Med. 2020;9(4):1005. doi:10.3390/jcm9041005
  6. Wästerlid T, Murphy S, Villa D, El-Galaly TC. Diffuse large B-cell lymphoma among the elderly: a narrative review of current knowledge and future perspectives. Ann Lymphoma. 2022;6:6. doi:10.21037/aol-22-2
  7. Puckrin R, Ghosh S, Peters A, Stewart D. Inferior outcomes with R-CEOP for patients with diffuse large B-cell lymphoma and cardiovascular comorbidities. Leuk Lymphoma. 2022;63(3):583-590. doi:10.1080/10428194.2021.1992762
  8. 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/bloodadvances.2020002982

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

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