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Older Age Alone Should Not Rule Out Intensive Treatment of Aggressive Non-Hodgkin's Lymphoma

Key findings

  • This retrospective study examined outcomes for 295 consecutive patients ≥65 years old (median age, 73; range, 65–100) who received chemotherapy or chemo-immunotherapy for newly diagnosed aggressive non-Hodgkin's lymphoma
  • 74% of patients were alive five years after diagnosis; furthermore, rates of five-year survival exceeded 65% in all age brackets
  • However, 42% of patients had grade 3–5 nonhematologic toxicity, 41% experienced an unplanned hospital admission within six months of therapy initiation and 15% required dose reduction and/or interruption of therapy
  • Patients ≥80 years old had particularly high rates of grade 4–5 nonhematologic toxicity (more than fourfold higher than patients ages 65–69) and ICU admission (more than threefold higher)
  • Detailed information presented here about outcomes and complications by age bracket can help clinicians counsel patients about the ramifications of treating aggressive non-Hodgkin's lymphoma

In 2019, adults ages 65 and older represented about a quarter of new cases of aggressive non-Hodgkin's lymphoma (NHL). This malignancy is highly problematic for older adults since it often requires intensive therapy, which is potentially curative but can result in substantial toxicities in this population. Yet older adults have been underrepresented in clinical trials of lymphoma therapies.

Now, P. Connor Johnson, MD, attending oncologist in the Center for Lymphoma at the Massachusetts General Hospital Cancer CenterAreej El-Jawahri, MD, an oncologist in the Division of Hematology and Oncology at the Mass General Cancer Center, and Christine Seel Ritchie, MD, MSPH, director of research in the Division of Palliative Care and Geriatric Medicine and director of the Mongan Institute Center for Aging and Serious Illness at Mass General, and colleagues have gathered retrospective evidence that intensive therapy for aggressive NHL has survival benefits across all age brackets of older adults. In The Oncologist, they also identify risk factors for treatment toxicity and unplanned hospitalization.

Study Cohort

The retrospective study involved 295 consecutive patients ≥65 years old who received chemotherapy or chemo-immunotherapy at Mass General between April 2000 and July 2020 for a new diagnosis of aggressive NHL. The median age was 73 (range, 65–100). 83% of patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and the median Charlson comorbidity index score was 0 (range, 0–6), emphasizing this was a relatively fit cohort of patients.

A broad set of aggressive NHL subtypes was represented, led by diffuse large B-cell lymphoma (69%). 59.5% of patients had advanced disease.

Clinical Outcomes and Health Care Utilization

  • Overall response rate—87% of patients
  • Complete response rate—84%
  • 5-year overall survival—74%
  • Grade 3–5 nonhematologic toxicities—42%
  • Grade 4–5 nonhematologic toxicities—8%
  • Grade 5 (fatal) toxicity—3.4%
  • Dose reduction and/or interruption—15%
  • Unplanned hospital admission within six months of therapy initiation—41%
  • ICU admission within six months—6%

Key Results by Age Bracket

  • 5-year overall survival—82% among the 96 patients ages 65–69, 72% among the 77 patients ages 70–74, 74% among the 59 patients ages 75–79, and 66% among the 63 patients ages 80+
  • Grade 3–5 nonhematologic toxicity—35%, 47%, 51%, 40%
  • Grade 4–5 nonhematologic toxicity—3%, 9%, 8.5%, 14%
  • Unplanned hospitalization—34%, 45.5%, 47.5%, 40%
  • ICU admission—3%, 5%, 7%, 11%

Risk Factors for Complications

  • Albumin <3.5 g/dL: Patients had a greater likelihood of grade 3–5 nonhematologic toxicity (adjusted OR (aOR), 4.29; P<0.001) and unplanned hospitalization (aOR, 2.83; P=0.003)
  • Charlson comorbidity index ≥2: Patients had a greater likelihood of grade 3–5 nonhematologic toxicity (aOR, 4.22; P<0.001) and unplanned hospitalization (aOR, 3.93; P=0.001)
  • Treatment with EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) with or without rituximab: Patients has a greater likelihood of unplanned hospitalization (aOR, 5.45; P=0.012)

Guidance for Shared Decision-making and Supportive Care

These findings can help clinicians communicate important information to patients about the ramifications of treating aggressive NHL. Across age brackets, intensive therapy had substantial survival benefits, so age alone should not be a criterion when selecting therapy.

However, patients must be informed that the burden of treatment toxicity and health care use may also be considerable. Comprehensive geriatric assessment (e.g., nutritional status, cognitive status, mood and frailty) can help identify older adults who are candidates for intensive therapy, and targeted supportive care interventions are recommended throughout the illness course.

74%
rate of 5-year overall survival among patients ages 65–100 treated intensively for aggressive non-Hodgkin's lymphoma

42%
rate of grade 3–5 nonhematologic toxicities among patients ages 65–100 treated intensively for aggressive non-Hodgkin's lymphoma

4x
greater odds of grade 3–5 nonhematologic toxicities in older patients treated intensively for aggressive non-Hodgkin's lymphoma who had albumin

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