CAR T-cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma aged ≥65 years

Despite the advancements of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), real-world evidence suggests a limit in the number of older patients (≥65 years) receiving this treatment.¹ Close to 30% of patients with DLBCL are diagnosed at ≥75 years; therefore, there is an unmet need for accessible, effective, and tolerable treatment options for patients in this cohort.¹

Here, we summarize a review by Chirara et al.¹ in Blood, covering the clinical characteristics and use of CAR T-cell therapy in older patients, the cost-effectiveness of treating older patients with R/R DLBCL with CAR T-cell therapy, and the implications of these results.

Study design

In this US-based real-world evidence study, patients were analyzed from the Medicare fee-for-service database and analyzed according to age split 65–69 years, 70–74 years, and ≥75 years. Overall, data were collected from 78,839 patients with R/R DLBCL; however, fewer met the inclusion and exclusion criteria (Table 1).

Table 1. Baseline characteristics*

CAR, chimeric antigen receptor. *Adapted from Chihara D, et al.1 †Total of 516 patients are included in baseline Charlson Comorbidity Index calculation. ‡Presence of therapy in the 28-day period before CAR T-cell treatment, excluding therapies administered on the same day as CAR T-cell therapy. Cyclophosphamide and fludarabine administered in the period 10 days before CAR T-cell therapy are also excluded. §Value withheld to comply with the Centers for Medicare & Medicaid Services policy of minimizing the risk to identify patients. ‖The Centers for Medicare & Medicaid Services cell size suppression policy sets minimum thresholds for the display of Centers for Medicare & Medicaid Services data, in which no cell (e.g., admissions, discharges, patients, and services) containing a value of one to ten can be reported directly.
Characteristics, % (unless otherwise specified)	65–69 years, n = 202	70–74 years, n = 176	≥75 years, n = 173
Age, median, years	67	72	78.6
Urban/suburban	79.2	80.7	82.1
Male	53.5	52.8	56.6
Baseline Charlson Comorbidity Index, mean†	5	5	5
Bridging therapies‡
Any therapy	50.5	39.2	52.6
Chemotherapy or targeted therapy	31.7	23.3	31.8
Corticosteroids	~§	~§	13.3
Radiotherapy	~§,‖	~§,‖	7.5
CAR T-cell administration setting
Inpatient	84.7	88.1	75.1
Length of stay, mean, days	12.36	21.15	13.09
Outpatient	15.3	11.9	24.9

Results

At 11.9 months post CAR T-cell therapy (including axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel):

• 34% of patients aged ≥65 years received a next treatment for DLBCL
• 57% of patients aged ≥65 years died.

Endpoints according to age varied: patients aged 70–74 years had the most efficacious effects post CAR-T cell therapy compared with patients aged 65–69 and ≥75 years (Table 2). Patients aged ≥75 years showed significantly shorter event-free survival compared with patients aged 65–74 years (p = 0.002) but there was no significant difference in overall survival between age groups (p = 0.130).

Table 2. Median EFS and OS according to age subgroup*

EFS, event-free survival; NA, not applicable; OS, overall survival. *Adapted from Chihara D, et al.1
Endpoint	All patients	Patients aged 65–69 years	Patients aged 70–74 years	Patients aged ≥75 years
Median EFS, months	7.2	6.5	12.6	5.3
12-month EFS, %	NA	43	52	34
Median OS, months	17.1	NA	NA	NA
12-month OS estimate, %	NA	57	64	54

Cost-effectiveness analysis

Patients who had more than 90 days’ follow-up post CAR T-cell therapy had healthcare costs measured as healthcare resource use including inpatient, outpatient, and emergency department use. Out of 445 patients assessed:

• In the inpatient setting, 29% had ≥1 rehospitalization after discharge and 30% had ≥1 emergency department visit ≤90 days after CAR T-cell treatment.
• Readmission rate was highest in patients aged 65–69 years and lowest in patients aged 70–74 years:
  • 34%, 22%, and 29% in patients aged 65–69, 70–74, and ≥75 years, respectively.
• In the outpatient setting, 42% had ≥1 rehospitalization after discharge and 32% had ≥1 emergency department visit ≤90 days after CAR T-cell treatment.
• Readmission rate was highest in patients aged 65–69 years and lowest in patients aged ≥75 years
  • 54%, 50%, and 30% in patients aged 65–69, 70–74 and ≥75 years, respectively.

Overall, the median total healthcare cost in all patients ≥90 days follow-up post CAR T-cell therapy was $352,572. According to age, the mean cost was $311,699, $296,192, and $271,767 in patients aged 65–69, 70–74, and ≥75 years, respectively. Cost-effectiveness was balanced across age groups but still considered substantial, even when recorded as lower due to Medicare reimbursement rates being lower than other payment types.

Conclusion

This study has shown the success of CAR T-cell therapy in older patients with R/R DLBCL, providing long-term remission comparable to younger patients. However, this study also highlights the continued lack of use of CAR T-cell therapy in older patients. This may be due to comorbidities and quality of life associated with patients in this cohort, and it is suggested comprehensive geriatric tests assessing activities in the day-to-day life of patients ≥65 years could reduce the risk of complications from treatment.

This study also highlights an unmet need for studies investigating the toxicity and efficacy of CAR T-cell therapy compared with other treatment options for patients ≥65 years with R/R DLBCL. For example, long-term remission recorded in patients who received CAR T-cell therapy could alter the cost-effectiveness of this treatment by lowering healthcare costs and resources. There continues to be a need for future treatments to be more accessible, cost-effective, and tolerable in patients, especially those aged ≥75 years.