Prospective geriatric assessment and geriatric consultation in CAR T-cell therapy for older patients with lymphoma

The therapeutic landscape of lymphoma is rapidly advancing, with intense cellular immunotherapy now being considered in older patients (≥65 years). Given the effectiveness of a geriatric assessment (GA) to guide treatment intensity, the American Society of Clinical Oncology recommends this cohort receive a GA prior to and during cancer therapy.

A recent article by Lin, et al. evaluated the effectiveness of a multi-dimensional GA and consultation for patients with relapsed/refractory (R/R) large B cell lymphoma (LBCL) undergoing chimeric antigen receptor (CAR) T-cell therapy. The aim was to understand whether frailty and vulnerability contribute to the outcomes of CAR T-cell therapy.

Study design

This trial included 75 patients diagnosed with R/R LBCL after two or more lines of therapy. GAs included the Cumulative Illness Rating Scale-Geriatric, to assess comorbidity burden; Montreal Cognitive Assessment, to assess cognition; and Timed Up and Go test, to assess mobility.

Patients aged 65–86 years were included in assessment. Overall, 35 patients received axicabtagene ciloleucel and 40 patients received tisagenlecleucel. Overall, 48 patients (64%) had formal geriatric consultation with GA prior to lymphodepletion conditioning (geriatric consult group) and 27 patients (36%) did not (usual care group). The study endpoints included overall survival (OS), progression-free survival and safety.

Results

• At a median follow-up of 22 months, OS and progression-free survival rates were similar in both patient subgroups; this is consistent with previous data for cohorts in this age group.
  • Median overall survival was 23 months (interquartile range [IQR], 12–not reached)
  • Median progression-free survival was 6 months (IQR, 2.9–15)
• The odds of cytokine release syndrome and immune effector cell-associated neurotoxicity (ICANS) were lower in the group that had a formal geriatrics consultation compared with the group that did not (Figure 1).
  • The authors suggest this is related to an increased awareness of identified GA deficits and the efforts to remedy this.
• Polypharmacy (>5) was significantly associated with the development of ICANS after adjusting for lactate dehydrogenase and CAR T-cell product (p < 0.002).
• Cognitive impairment (defined by Montreal Cognitive Assessment score <26) was significantly associated with worse OS (p = 0.035) and the emergence of ICANS (p = 0.014), whereas mobility impairment was linked to the emergence of cytokine release syndrome (p = 0.031).

Figure 1. Odds ratio of CRS and ICANS in geriatric consult group versus usual care group* 

CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity.
*Adapted from Lin, et al.

Safety

• Overall, 36 (48%) patients died due to relapse or progression (n = 30), toxicities (n = 3), and infections related to COVID-19 (n = 2).

Conclusion

GA deficits, such as cognitive and mobility impairment, polypharmacy, and multi-morbidity, are associated with survival and toxicities in a non-chemotherapy-based cellular immunotherapy setting. Therefore, integration of GA into the standard management of CAR T-cell therapy could be beneficial for healthcare professionals and provide guidance when selecting patients for intensive treatments.