PIANCENZA, ITALY — Nearly one-half (49%) of all veterans in the United States are 65 years or older. Most of those older veterans (5.5 million) served during the Vietnam era, while 183,000 were World War II veterans, according to the 2021 American Community Survey (ACS).
That presents a challenge for VHA clinicians who treat complex cancers, such as diffuse large B-cell lymphoma (DCBL), where most of the patients are older than 65 and their numbers are expected to increase in coming years.
“A simplified geriatric assessment based on a careful evaluation of the fitness status and comorbidities is essential to choose the correct intensity of treatment,” according to a recent report in Frontiers in Oncology. “Fit older patients can benefit from a standard immunochemotherapy, while unfit/frail patients frequently need reduced doses or substitution of particular agents with less toxic ones.”1
Italian authors reviewed new therapies, including polatuzumab vedotin, tafasitamab, bispecific antibodies, that have indicated promising results in relapsed/refractory patients, especially in cases not eligible to transplant.
“Some of these new drugs have been tested as single agents or in combinations as first-line treatment, aiming to improve the outcome of the traditional chemotherapy. If preliminary efficacy and safety data are confirmed in future clinical trials, a chemo-free immunotherapic approach could become an alternative option to offer a curative treatment even in frail patients,” the researchers advised.
DLBCL is the most frequent lymphoma subtype with a median age at diagnosis of 66 years, according to background information in the article. “ With the aging of the general population in Western countries, the number of old patients with lymphoma will continually increase, requiring specific considerations. Common issues in the treatment of geriatric patients are related to comorbidities and limited organ reserve (e.g., bone marrow, liver, and kidney) with a higher risk of toxicity.”
The authors further advised clinicians to consider issues related to impaired physical and/or cognitive functions that might affect the patient’s ability to get to the hospital or to manage therapies at home, especially if no caregiver is available.
“Besides factors regarding patients’ fitness status, an unfavorable biology of the disease may also contribute to an inferior outcome,” they pointed out. “DLBCLs in older patients are characterized by a higher prevalence of activated B-cell (ABC) subtypes and EBV-positive cases (3). The global prognosis of older DLBCL patients has certainly improved in the last few years thanks to immunochemotherapy combinations but is still poorer than in younger patients. Older patients are under-represented in clinical studies, particularly in clinical trials leading to marketing authorization of new cancer therapies.”
Essentially, the study emphasized that treating elderly patients with aggressive lymphoma “poses the clinical dilemma of balancing a potential cure while minimizing toxicity. Age per se is not a contraindication to a full-dose curative treatment, but comorbid conditions and impaired functional status may often suggest a reduced dose and/or drug substitution to improve tolerance.”
It added that traditional measures of performance status might not be accurate enough to define treatment goals and tailor treatment intensity. That is especially the case, according to the authors, because today’s elderly patients are so heterogeneous.
The European Society for Medical Oncology recommends the use of geriatric assessment to avoid the risk of undertreatment or overtreatment, and the authors advised that The Fondazione Italiana Linfomi (FIL) has recently validated in a large prospective series of DLBCL patients older than 64 years –the Elderly Project- a simplified geriatric assessment (sGA) based on age—older or younger than 80 – Cumulative Illness Rating Scale for Geriatrics (CIRS-G), activities of daily living (ADL), and instrumental activities of daily living (IADL).
“This sGA is an objective, reproducible tool that can be easily managed by onco-hematologists (in less than 10 minutes) and permits to classify older patients as fit (55%), unfit (28%) or frail (18%), with significantly different outcomes,” they wrote.
The review pointed out that the POLARIX study is the only randomized phase III trial in DLBCL that has shown a significant improvement so far in the progression-free survival (PFS). “In this trial, polatuzumab vedotin, an antibody-drug-conjugated targeting CD79b, replaced vincristine in the R-CHOP scheme,” according to the authors. “The new pola-R-CHP regimen showed a 2-year PFS of 76.7% compared to 70.2% of standard R-CHOP in intermediate-risk or high-risk DLBCL patients aged 18-80 years, with similar safety profiles. The overall survival (OS) rate at 2 years did not differ significantly (88.7% in the pola-R-CHP group versus 88.6% in the R-CHOP group). An exploratory subgroup analysis highlighted a stronger benefit in patients > 60 years, non-GCB types, double expressors, and high IPI.”
The review noted that the management of elderly patients with aggressive lymphoma continues to be a challenge, ‘but a new era has been opened.”
It added that objective parameters “that define the fitness status of the patient are fundamental to establish the correct treatment intensity and should be included in future clinical trials. A quality-of-life assessment and patient-reported outcomes should also be considered as crucial end points. New drugs, with immunological mechanisms of action, could help improve the outcome of patients relapsed or refractory after standard chemotherapy or those not eligible to standard chemotherapy because of comorbidities.”
- Arcari A, Cavallo F, Puccini B, Vallisa D. New treatment options in elderly patients with Diffuse Large B-cell Lymphoma. Front Oncol. 2023 Jul 3;13:1214026. doi: 10.3389/fonc.2023.1214026. PMID: 37465115; PMCID: PMC10351275.
