SAN ANTONIO—Diffuse large B-cell lymphoma (DLBCL) becomes much more difficult to treat in older patients, according to a new study suggesting that more adults of advanced age be included in clinical trials for new agents.
Researchers from the South Texas Veterans Health Care System, the University of Texas Health Science Center and UT’s MD Anderson Cancer Center, all in San Antonio, pointed out that the median age for DLBCL diagnosis is 66 years.
The study presented at the recent American Society of Hematology’s 65 Annual Meeting and Exposition in San Diego noted that incidence increases with age, and about 30% of patients diagnosed are older than 75 years old.1
“In the context of an aging population, unfit or frail individuals pose a unique challenge due to their limited tolerance for combination chemotherapy and are often excluded from clinical trials,” the authors explained. “The VHA is one of the largest integrated providers of cancer care in the United States catering to an older population, making it ideal to study real-world outcomes in this geriatric population.”
Their study sought to present the final analysis of our large cohort of geriatric patients (≥ 65 years old) diagnosed with DLBCL treated within the VHA.
This study reviewed 6,266 randomly selected patients with an ICD code for DLBCL within the VHA between Jan. 1, 2011, and Dec. 31, 2021. Data abstractors collected baseline patient and disease characteristics and treatment responses.
The researchers determined fall and delirium rates, Charlson Comorbidity Index and survival rates using electronic health record query. The patient population was divided into three age groups: 65 to 74 years, 75 to 84 years, and 85 years or older, represented by A, B, and C, respectively.
Of the total population 3,178, 2,124 (66.8%) qualified for data analysis due to the age limit of 65 or older. The distribution of age was 61.0%, 28.8%, and 10.2% in A, B, and C, respectively.
The researchers reported that 18.3% of patients in C had an ECOG score 3-4 compared to 16.4% in B and 9.0% in A. “With increasing age, patients had an increased incidence of repeated falls and delirium within the six months prior to and following diagnosis (5.9% in A vs 8.0% in B vs 10.1% in C),” they add.
Across all age groups, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) remained the most common first-line regimen. The utilization of R-CHOP decreased significantly, however, from A to C (69.7% versus 53.5% versus 27.5% in A, B, and C, respectively).
“In comparison to the other age groups, patients in group C were more likely to receive R-mini-CHOP (1.5% in A vs 9.8% in B vs 19.7% in C),” the study pointed out. At the same time, the percentage of patients that did not receive any chemotherapy increased with age (5.3% versus 11.8% versus 30.7% in A, B, and C, respectively, p=<0.001).
“Of those who received chemotherapy, 23.2% in A, 32.7% in B, and 39.7% in C did not complete the intended number of treatment cycles,” the authors wrote. “693 (32.6%) patients did not receive any treatment or were not able to complete the intended number of cycles. Among patients who received treatment, older patients were more likely to have primary refractory disease or die before completing the first line of treatment (21.8% versus 24.4% vs 34.8% for A, B, and C, respectively, p=0.001). Additionally, geriatric patients with primary refractory disease were less likely to receive salvage therapy.”
The study noted that the median overall survival was 71, 42, and 14 months in A, B and C, respectively. The 12-month survival rate was 77% in A, 69% in B, and 51% in C. Only 1.3% of the total population were enrolled in a clinical trial.
Advising that their study is one of the largest to examine disease patterns, treatment approaches and outcomes in a geriatric cohort diagnosed with DLBCL within the VHA, the researchers noted that the rate of treatment initiation is low and completion rates decline significantly with age above 65 years. The reasons so many of the very elderly fail to complete the intended number of chemotherapy cycles? Poor performance status and increased incidence of delirium and falls.
“Our study suggests that approximately one-third of patients are unable to receive first line treatment or are unable to complete first line intended treatment,” the authors noted. “The outcomes are dismal for patients with relapse or refractory disease, which further contributes to very low long-term survivals.”
They suggested that novel therapies, such as antibody drug conjugates, bispecific T-cell engagers and chimeric antigen receptor T-cell therapy offer different toxicity profiles and could be better tolerated by the very elderly.
“Nonchemotherapy-based novel agents in upfront approaches should include geriatric patients in clinical trials to ensure that the benefits of medical advancements extend to this population, addressing the unique challenges they face,” the study team emphasized.
DLBCL is the most common non-Hodgkin lymphoma and accounts for 30% of all non-Hodgkin lymphoma cases, according to a previous VA study. It has an incidence of 5.6 per 100,000 persons per year in the United States.
The article in Future Oncology pointed out that a majority of patients are cured with first-line (1L) therapy that typically includes rituximab and an anthracycline-containing chemotherapy. Still, as many as 40% of patients are refractory to or relapse (R/R) after responding to initial treatment.2
Patients with R/R disease after 1L treatment who are eligible for bone marrow transplantation (BMT) receive an aggressive chemotherapy or chemoimmunotherapy (CT/CIT) regimen and, if responsive to CT/CIT, proceed to consolidative BMT, according to the authors from the George E. Wahlen VAMC and the University of Utah, both in Salt Lake City.
Some of those patients achieve long-term remissions, but those who do not respond, or who relapse after transplant, might receive further treatments of varying intensity.
- Kaur S, Mader M, Franklin K, Williams M, cl. (2023, Dec. 9-12) Retrospective Analysis of Treatment Patterns and Outcomes in Geriatric Patients with Diffuse Large B-Cell Lymphoma (DLBCL) in the Veterans Health Administration (VHA). 65th American Society of Hematology Annual Meeting and Exposition, San Diego, California.
- Chien HC, Morreall D, Patil V, Rasmussen KM, et. al. i Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma. Future Oncol. 2021 Feb;17(4):411-422. doi: 10.2217/fon-2020-0522. Epub 2020 Oct 29. PMID: 33115291.
