Abstract and Introduction

Abstract

The emergence of chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape for diffuse large B-cell lymphoma (DLBCL); however, real-world experience reporting outcomes among older patients treated with CAR T-cell therapy is limited. We leveraged the 100% Medicare fee-for-service claims database and analyzed outcomes and cost associated with CAR T-cell therapy in 551 older patients (aged ≥65 years) with DLBCL who received CAR T-cell therapy between 2018 and 2020. CAR T-cell therapy was used in third line and beyond in 19% of patients aged 65 to 69 years and 22% among those aged 70 to 74 years, compared with 13% of patients aged ≥75 years. Most patients received CAR T-cell therapy in an inpatient setting (83%), with an average length of stay of 21 days. The median event-free survival (EFS) following CAR T-cell therapy was 7.2 months. Patients aged ≥75 years had significantly shorter EFS compared with patients aged 65 to 69 and 70 to 74 years, with 12-month EFS estimates of 34%, 43%, and 52%, respectively (P = .002). The median overall survival was 17.1 months, and there was no significant difference by age groups. The median total health care cost during the 90-day follow-up was $352 572 and was similar across all age groups. CAR T-cell therapy was associated with favorable effectiveness, but the CAR T-cell therapy use in older patients was low, especially in patients aged ≥75 years, and this age group had a lower rate of EFS, which illustrates the unmet need for more accessible, effective, and tolerable therapy in older patients, especially those aged ≥75 years.

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma, with annual estimated new cases of ≈25 000 in the United States.^[1] The median age of onset of DLBCL is 66 years, and close to 30% of patients are diagnosed at age ≥75 years.^[2] The percentage of the population aged ≥65 years is projected to increase from 15% in 2016 to 21% in 2030, according to the US census, and thus the prevalence of older patients with DLBCL is expected to grow with the aging population.^[3] Treatment of this geriatric patient population can be challenging because of multiple factors, such as comorbidities, poor performance status (PS), and potentially higher-risk DLBCL biology.^[4]

The treatment landscape for relapsed/refractory DLBCL has dramatically evolved in recent years. Historically, platinum-based chemotherapy, followed by high-dose therapy/autologous stem cell transplant (auto-SCT), was the only option for long-term remission for relapsed/refractory DLBCL;^[5,6] however, older patients are frequently considered ineligible for this treatment, except fit patients,^[7] and survival outcomes for those who did not receive auto-SCT following recurrence were dismal.^[8] Development of CD19-directed autologous chimeric antigen receptor (CAR) T-cell therapy has resulted in a paradigm shift in the treatment of relapsed/refractory DLBCL,^[9–11] providing an effective treatment option for older patients who are not necessarily candidates for auto-SCT. CAR T-cell therapy can achieve long-term remissions for a portion of patients experiencing a recurrence of DLBCL often independent of characteristics, such as age.^[9,11–14] The US Food and Drug Administration first approved axicabtagene ciloleucel (axi-cel) in late 2017, soon followed by tisagenlecleucel in 2018, and then lisocabtagene maraleucel in 2021 for patients with DLBCL or high-grade B-cell lymphomas who are relapsed or refractory to ≥2 prior lines of therapy based on single-arm phase 2 trials.^[9,11,13]

Since the approval, multiple studies have reported on the realworld experience (RWE) of CAR T-cell therapy, confirming the effectiveness of this treatment, depending on various risk factors, such as serum lactate dehydrogenase, PS, and tumor burden before CAR T-cell infusion.^[15–22] The outcomes of CAR T-cell therapy in older patients also have been evaluated in both clinical trials and RWE studies.^[23–25] In the ZUMA-1 study, 27 patients aged ≥65 years and treated with axi-cel showed a 92% overall response rate and 42% of patients achieved ongoing response with a minimum of 24 months of follow-up at the time of the report.^[24] Jacobson et al analyzed 1297 patients who received commercial axi-cel and showed that response rate was higher among patients aged ≥65 years.^[16] Ram et al summarized the outcomes of 41 patients with DLBCL aged ≥70 years who received CAR T-cell therapy, most of them with tisagenlecleucel (81%), and reported that there was no significant difference in the rate of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), overall response rate, and progression-free survival in older patients compared with younger patients.^[23] However, studies had limited data, particularly among patients aged >70 years, evaluating how age or other factors affect survival outcomes among older patients who received CAR T-cell therapy. Moreover, no study has described health care use and cost associated with CAR T-cell therapy in older patients. Therefore, we evaluated the clinical outcomes and economic impact associated with CAR T-cell therapy in older patients with DLBCL by leveraging a Medicare claims database.