Editor’s Note: From October 18 to 20, 2024, the “2024 Jiangsu Provincial Association of Hematology Physicians Annual Meeting,” hosted by the Jiangsu Provincial Association of Hematology Physicians and organized by Taizhou People's Hospital and the First Affiliated Hospital of Nanjing Medical University, took place in Taizhou, Jiangsu. This event focused on standardized diagnosis and treatment of hematological diseases, providing a high-level academic exchange platform for professionals in hematology. We invited Dr. Wenyu Shi, the executive chairman from Affiliated Hospital of Nantong University, to share his insights with Hematology Frontier.

Hematology Frontier: Elderly patients with diffuse large B-cell lymphoma (DLBCL) often present with multiple comorbidities and poor physical status, posing significant challenges in diagnosis and treatment. Could you elaborate on the unique difficulties these patients face and how these challenges impact treatment choices and outcomes?

Dr. Wenyu Shi: Elderly DLBCL patients face several distinct challenges in diagnosis and treatment, including:

1. Comorbidities

Older patients frequently have underlying health issues such as cardiovascular disease and diabetes, which can limit treatment options. For instance, those with heart conditions may not tolerate anthracyclines (like doxorubicin in the R-CHOP regimen), requiring dose adjustments or alternative therapies. Special attention must also be paid to liver and kidney function for proper drug metabolism and toxicity management.

2. Biological Differences

Studies show that elderly DLBCL patients often have more adverse prognostic factors. For example, they have a higher proportion of the non-GCB (non-germinal center B-cell-like) subtype, which is associated with poorer outcomes.

3. Poor Physical Condition

Many elderly patients experience physical decline and malnutrition, making it challenging to tolerate standard chemotherapy doses. Physical performance, often assessed using performance scores like the ECOG scale, is crucial in treatment selection. Patients with lower physical function may not withstand the standard R-CHOP regimen, requiring reduced doses or alternative options, such as targeted therapies or low-dose chemotherapy.

4. Lower Tolerance to Chemotherapy Toxicity

Older patients are more susceptible to chemotherapy-related side effects, including bone marrow suppression, infections, and gastrointestinal issues, which can lead to treatment interruption or dose reduction, impacting treatment efficacy. They are also at a higher risk of post-treatment complications, necessitating enhanced monitoring and supportive care.

5. Cognitive Function and Adherence Issues

Cognitive impairments and compliance issues are common among elderly patients, potentially affecting their ability to adhere to treatment schedules and medications. This can result in delayed or suboptimal treatment, impacting overall outcomes. Family support is essential to help elderly patients follow treatment plans.

Impact on Treatment Choices and Outcomes:

In light of these unique challenges, we have established clinical pathways specifically for elderly, newly diagnosed DLBCL patients within the Jiangsu Lymphoma Collaboration Group to guide clinical practice and optimize treatment outcomes. Balancing standardization and personalization is crucial for elderly DLBCL treatment. Treatment strategies should maximize efficacy while minimizing adverse reactions. By comprehensively evaluating patients’ health status and tumor characteristics, physicians can tailor treatment plans, improving both treatment efficacy and survival rates.

Hematology Frontier: Elderly DLBCL patients often struggle with standard chemotherapy regimens, facing reduced efficacy and increased adverse drug reactions. What limitations exist in the current standard treatment for elderly DLBCL, and what recent advancements have been made in treating these patients?

Dr. Wenyu Shi: The limitations for elderly DLBCL patients receiving standard treatments include:

1. Poor Tolerance to Chemotherapy

Standard regimens like R-CHOP cause significant toxicity in elderly patients, leading to adverse reactions and treatment discontinuation, impacting overall effectiveness.

2. Insufficient Personalization

Current treatment plans often do not adequately consider patients’ age, functional status, or comorbidities, resulting in suboptimal outcomes.

3. Drug Interactions

Elderly patients frequently take multiple medications for comorbidities, increasing the risk of drug interactions, potentially affecting both treatment safety and efficacy.

Recent Advances for Elderly DLBCL Treatment:

1. Antibody-Drug Conjugates (ADCs)

Combinations like polatuzumab vedotin with R-miniCHP have demonstrated good tolerance and efficacy, particularly for elderly patients. Drugs like brentuximab vedotin offer options for patients with high CD30 expression, enhancing therapeutic outcomes when combined with chemotherapy.

2. Bispecific Antibodies

Agents like mosunetuzumab and glofitamab have shown significant efficacy and safety, offering promising options for elderly patients.

3. Small Molecule Targeted Therapies

BTK inhibitors provide new options, particularly for MCD-subtype DLBCL patients.

4. Immunomodulatory Drugs (IMiDs)

Lenalidomide has shown potential benefits in DLBCL patients, especially when combined with other therapies.

5. HDAC Inhibitors

Drugs like chidamide have potential efficacy in dual-expressing DLBCL.

These newer therapies provide safer, effective options for elderly DLBCL patients, significantly improving prognosis and quality of life. Moving toward low-chemotherapy or even chemotherapy-free approaches may represent the future of elderly DLBCL treatment.

Hematology Frontier: To further optimize treatment pathways for elderly DLBCL patients, what specific efforts or improvements would you suggest?

Dr. Wenyu Shi: To optimize treatment pathways for elderly DLBCL patients, the following measures may be considered:

1. Comprehensive Assessment Tools

Develop and promote more practical assessment tools, such as Comprehensive Geriatric Assessment (CGA), to evaluate patients’ physical, psychological, and social support needs, enabling more personalized treatment plans. Focus on all health and functional aspects, including medical, cognitive, and social support. Patients can be categorized into “fit,” “unfit,” and “frail” groups to customize treatment plans and improve survival rates. For instance, standard treatment might suit fit patients, while reduced chemotherapy or targeted therapies like BTK inhibitors may better serve unfit and frail patients.

2. Multidisciplinary Collaboration

Establish multidisciplinary teams, including specialists in hematology, oncology, geriatrics, nutrition, and mental health, to address the diverse needs of elderly patients throughout treatment.

3. Personalized Treatment Strategies

Base treatment on biomarkers, genomic characteristics, and performance status, creating individualized treatment regimens to maximize efficacy and minimize adverse events.

4. Enhanced Supportive Care

Provide comprehensive supportive care, including nutritional interventions, pain management, and psychological support, to improve treatment tolerance and overall quality of life.

5. Clinical Trials

Encourage elderly patients to participate in clinical trials to access innovative treatments. For instance, Professor Li Jianyong from Jiangsu Provincial People’s Hospital and I, along with multiple domestic centers, have launched a prospective, single-arm, multicenter study investigating the combination of polatuzumab vedotin, rituximab, and orelabrutinib for newly diagnosed, frail, non-GCB subtype elderly DLBCL patients. So far, 10 patients have been enrolled, with promising efficacy and manageable safety. We invite eligible patients to join, and medical professionals to engage in discussions to help advance lymphoma treatment.

These efforts can improve treatment pathways for elderly DLBCL patients, enhancing outcomes and patient satisfaction.