Educational theme | Treatment considerations for elderly patients with lymphoma

Introduction

Despite a number of recent advances in the management and treatment of lymphoma, there remains a significant unmet need in the elderly population. Elderly patients are often underrepresented in clinical trials and typically have a worse prognosis compared to younger patients in the same setting. They can be less able to tolerate certain treatment protocols, limiting the therapeutic options available to them, and they are likely to present with comorbidities which can further complicate treatment.

Our educational theme series this quarter is focused on treatment considerations for older patients with lymphoma and chronic lymphocytic leukemia (CLL).

Treatment

Standard of care for many older patients with lymphoma has traditionally been conventional chemotherapy, such as the cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) regimens, followed by autologous stem cell transplantation. While the R-CHOP chemotherapy protocol is effective for many patients, it has limited utility in older patient populations. As part of the LNH03-6B trial (NCT00144755), Camus, et al., demonstrated that while the beneficial effects of R-CHOP treatment can be sustained for up to 10 years in patients aged 60­–80 years with diffuse large B-cell lymphoma, relapse or progression in this same patient group leads to dismal outcomes.¹ This underscores the importance of developing alternate treatment strategies for this difficult to treat patient population. Recent advances in several therapeutic areas may help to close this treatment gap.

CAR T-cell therapy

Chimeric antigen receptor (CAR) T-cell therapy has transformed the landscape of lymphoma treatment in recent years. A number of CAR-T cell therapies are currently approved for the treatment of elderly patients with varying subtypes of these conditions, including lisocabtagene maraleucel, axicabtagene ciloleucel, brexucabtagene autoleucel, and tisagenlecleucel. Read more about these approvals below:

• Lisocabtagene maraleucel receives FDA approval for the second-line treatment of large B-cell lymphoma
• Axicabtagene ciloleucel receives US FDA approval as second-line treatment for large B-cell lymphoma
• Tisagenlecleucel receives FDA approval for the treatment of relapsed or refractory follicular lymphoma
• Brexucabtagene autoleucel receives FDA approval for the treatment of relapsed/refractory mantle cell lymphoma

Take a look at the video below for some of the key considerations for CAR T-cell therapy in elderly patients with lymphoma.

• [EMBED: What are the key considerations for CAR T-cell therapy in elderly patients with lymphoma? ]

Antibody-based therapy

Improvements to antibody-based therapy approaches have improved outcomes for elderly lymphoma patient populations. These therapies can provide a more targeted treatment approach than traditional chemotherapy regimens, often with less severe side-effects. For example, the monoclonal antibody therapy loncastuximab tesirine was shown to be well-tolerated and efficacious in elderly patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), as part of the LOTIS-2 trial (NCT03589469). Please see our detailed analysis below for more information.

• Treatment with loncastuximab tesirine in patients with R/R DLBCL: Health-related QoL, symptoms, and tolerability data

The Lymphoma Hub previously spoke with Adam Olszewski regarding the safety and efficacy of mosunetuzumab in elderly patients with previously untreated DLBCL—check out the video below.

• Is mosunetuzumab safe and effective for elderly patients with untreated DLBCL? – video

Kinase inhibitors/targeted therapy

A deeper understanding of the pathophysiological drivers of lymphoma has led to the development of targeted therapies, including a number of kinase-specific inhibitors. Ibrutinib has demonstrated significantly improved progression-free survival (PFS) in elderly patients in comparison to other chemotherapy; however, the data also raised questions on adverse events associated with this therapy. Read more about this below.

• Efficacy and safety of ibrutinib + BR in the treatment of elderly patients with MCL: Primary analysis from SHINE III

Another kinase inhibitor, zanubrutinib, and the novel PI3Kδ inhibitor parsaclisib have also shown significant clinical benefit in treating elderly patients with R/R marginal zone lymphoma. Read our article detailing clinical benefits of both therapies below for more information.

• Novel targeted therapies for R/R marginal zone lymphoma

Novel combinations

Novel combination therapies have proved more effective than monotherapy for elderly patients in a variety of settings. Have a look at a selection of our articles below for up-to-date information on a number of novel combinations.

• Chemo-free combination of lenalidomide + rituximab in elderly/frail patients with MCL and DLBCL
• Practice patterns and outcomes in older patients with DLBCL in England: A real-world data analysis
• Educational theme | R-miniCHOP plus lenalidomide for elderly patients with DLBCL: Results from the phase III SENIOR trial

Socioeconomic influence

Socioeconomic setting is an important consideration when selecting appropriate treatment protocols for older patients with lymphoma. It can influence both access to treatment and patient outcomes. Read more about this aspect of treatment selection below.

• Outcomes of elderly patients with primary CNS lymphoma in different socioeconomic settings; a 12-year population-based analysis of combined modality treatment
• Geriatric hematology in low-resource settings: Improving care for older people through the implementation of geriatric hematology programs

Conclusion

While there have been significant advances in the treatment of older patients with lymphoma in recent years, more progress is needed to address this unmet need. With no standard approach to treating this patient population, there are multiple factors to consider when selecting appropriate treatment protocols.