Investigating Trends in Survival Outcomes Among the Oldest Patients with DLBCL

The probability of developing non-Hodgkin lymphoma (NHL) increases with age. Thus, as the U.S. population ages, a greater number of patients are at risk for acquiring NHL. This includes diffuse large B-cell lymphoma (DLBCL) – a disease with a mean age at diagnosis of 70 years. People >80 years old now comprise more than one-quarter of those ≥65 years old, but, because of their multiple comorbidities, poor performance status, and concerns about chemotherapy-induced toxicities, are rarely included in clinical trials of DLBCL.

Unfortunately, that has led to a lack of consensus regarding treatment in this population, according to Upama Giri, MD, and Michael G. Martin, MD, both from the University of Tennessee Health Science Center in Memphis, who published a research letter in Blood Advances analyzing survival outcomes in patients who were ≥80 years old at the time of DLBCL diagnosis.

Drs. Giri and Martin conducted a population-based study of data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, identifying 14,386 cases diagnosed with DLBCL between 1983 and 2013.

The data were split into three cohorts:

  • cohort 1: cases diagnosed between 1983 and 1996 (n=2,578)
  • cohort 2: cases diagnosed between 1997 and 2005 (n=5,131)
  • cohort 3: cases diagnosed between 2006 and 2013 (n=6,677)

“These study periods were selected since rituximab was approved for treatment of relapsed or refractory, low‐grade or follicular, B‐cell NHL in 1997, and its approval was extended to treatment of DLBCL in 2006,” the authors explained.

Each cohort was further divided into two groups: Group A included patients 80-89 years old and group B included patients ≥90 years old.

The authors measured overall survival (OS; calculated as the time from diagnosis until death from any cause or date of last follow‐up) and disease-specific survival (DSS; calculated as the time from diagnosis until death from DLBCL or date of last follow‐up) at 24 months.

OS and DSS for both groups and for all survival periods increased over time; this survival increase was markedly higher for patients in group A than in group B. In group A, rates of 6-, 12-, and 24-month OS and DSS increased significantly over time (p<0.005 and p=0.04). In group B, rates of 12- and 24-month OS increased significantly over time, but there was no significant difference in DSS over time (p value not provided). See the TABLE for rates of OS and DSS at various timepoints.

Multivariate analyses identified several factors associated with survival:

  • hazard ratio (HR) for year of diagnosis = 0.87 for cohort 2 vs. cohort 1 (95% CI 0.811‐0.926; p<0.005) and 0.76 for cohort 3 vs. cohort 1 (95% CI 0.710‐0.808; p<0.005), meaning survival improved in latter years.
  • HR for increasing age at diagnosis = 1.43 for group B vs. group A (95% CI 1.334‐1.529; p<0.005), meaning survival was better for younger patients.
  • HR for Ann Arbor stage = 1.27 (95% CI 1.241‐1.292; p<0.005), indicating worse survival for higher-stage disease.

Drs. Giri and Martin provided several possible explanations for this improved survival, including the introduction of rituximab, better control of comorbidities, and improved performance status in older patients. All of these factors “could have contributed to more physicians and patients willing to proceed with treatment and this improvement in survival,” they noted. “More prospective studies are needed in the very old patient population, taking into consideration the comorbidities associated with these age groups to clearly define guidelines for management of DLBCL in this population,” the authors concluded.

The study’s findings were limited by the nature of SEER data, since information regarding comorbidities and modalities of treatment are not available.


Reference
Giri U, Martin MG. Survival outcomes in the very elderly with DLBCL prior to and after the introduction of rituximab: a US population-based study. Blood Adv. 2017;1:615-8.

TABLE. Rates of Overall and Disease-Specific Survival
Overall Survival
Cohort 1 (n=2,578) Cohort 2 (n=5,131) Cohort 3 (n=6,677)
Group A (n=2,239) Group B (n=339) Group A (n=4,436) Group B (n=695) Group A (n=5,740) Group B (n=937)
3-month 67.1% 54.0% 67.2% 58.4% 68.5% 58.1%
6-month 51.6% 38.5% 55.9% 42.4% 57.5% 44.9%
12-month 37.0% 25.3% 42.4% 30.5% 47.2% 34.2%
24-month 25.0% 16.2% 32.3% 19.6% 39.0% 23.3%
Disease-Specific Survival
Cohort 1 (n=2,578) Cohort 2 (n=5,131) Cohort 3 (n=6,677)
Group A (n=2,239) Group B (n=339) Group A (n=4,436) Group B (n=695) Group A (n=5,740) Group B (n=937)
3-month 72.0% 59.0% 71.8% 64.5% 72.6% 64.4%
6-month 59.0% 46.7% 62.0% 51.5% 62.9% 52.1%
12-month 45.0% 35.8% 49.3% 41.2% 53.6% 43.0%
24-month 33.5% 29.2% 40.6% 32.5% 46.9% 33.7%

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