YESCARTA® safety profile in DLBCL | GileadPro

YESCARTA® safety outcomes in the ZUMA-7 study

Safety outcomes with YESCARTA® in ZUMA-7 were broadly consistent with other studies of intensive treatment for patients with R/R DLBCL, with toxicity rates being as expected and adverse events generally manageable^1–3

Median follow-up: 47.2 months
Adapted from Westin JR, et al. 2023.¹

* Includes tremor, confusional state, aphasia, encephalopathy, paresthesia, and delirium; ^† Includes bacterial, opportunistic, viral, COVID-19, and unspecified infections; ^‡ One patient died of AML and one died of lung adenocarcinoma, both deemed unrelated to study treatment per investigator assessment; ^‡ Includes fatal AEs that occured outside of the protocol-specified AE reporting window; ^§ Includes COVID-19, sepsis, acute respiratory distress syndrome, cardiac arrest, hepatitis B reactivation, myocardial infarction, pneumonia, and progressive multifocal leukoencephalopathy; ^II YESCARTA®-treated: Hepatitis B reactivation (n=1); ^¶ ASCT-treated; Cardiac arrest and acute respiratory distress syndrome (n=1 each).^1,3

YESCARTA® treatment led to generally manageable rates of CRS and neurologic toxicities in ZUMA-7, with all events resolved during the study^1,2

Study overview and baseline characteristics

ZUMA-7 was a phase 3, randomised, open-label, multicentre, pivotal study in 359 adult patients with 2L R/R DLBCL. Patients were randomised 1:1 to YESCARTA® (n=180) or salvage CIT +/- HDT-ASCT (n=179)^1,2

Study design and baseline characteristics

• Patients were stratified by response to 1L therapy and 2L adjusted IPI. Key patient eligibility criteria included being aged ≥18 years, R/R within ≤12 months of 1L therapy, and intended for salvage CIT +/- HDT-ASCT^1,2
• The primary endpoint was EFS. Key secondary endpoints included response and OS^1,2
• Patient characteristics at baseline were balanced between the two treatment groups and consistent with those expected in persons with R/R DLBCL^1,2
• Median age was 59 years (range, 21–81); 30% of patients were aged ≥65 years. 74% patients had primary refractory disease, 45% had a high 2L age-adjusted IPI (2 or 3 risk factors), 54% had elevated LDH, 79% had stage III or IV disease, and 19% had HGBCL (including double- or triple-hit lymphomas) according to the investigator’s assessment^1,2

YESCARTA® safety outcomes in the ZUMA-1 study

The safety profile of YESCARTA® was shown to be generally manageable based on the primary analyses of ZUMA-1 (median follow-up: 15.4 months) and remained consistent over five years of follow-up^4–6

• The most common adverse events of any grade were pyrexia (85%), neutropenia (84%), and anaemia (66%)⁶
• The most common adverse events of grade 3 or higher were neutropenia (78%), anaemia (43%), and thrombocytopenia (38%)⁶
• Over five years of follow-up, only two YESCARTA®-related grade 5 AEs were observed (one brain injury due to cardiac arrest and one haemophagocytic lymphohistocytosis)^4–6

YESCARTA® treatment led to generally manageable rates of CRS and neurologic toxicities in ZUMA-1, with most events resolved during the study period. Rates of CRS and ICANS decreased over the course of the study^4–6

Study overview and baseline characteristics

ZUMA-1 is a phase 1/2, single-arm, multicentre study in 101 adult patients with 3L R/R DLBCL assessing the safety and efficacy of YESCARTA®^4-6

Study design and baseline characteristics

• Key patient eligibility criteria included being aged ≥18 years with refractory disease defined as either progressive or stable disease as best response to the most recent prior therapy, or having relapsed within 12 months of auto-SCT^4–6
• The primary endpoint was ORR. Key secondary endpoints included OS, safety, and biomarker assessments^4–6
• Median age was 58 years (range, 23–76). Most patients (85%) had stage III or IV disease; 77% had disease that was resistant to 2L or later therapies, 21% had disease relapse after transplantation, 69% had received ≥3 previous therapies, and 26% had a history of primary refractory disease^4–6

YESCARTA® safety outcomes in the real world

Real-world analyses with YESCARTA® have demonstrated safety outcomes comparable to those seen in key clinical studies in a broader patient population, in both the 2L and 3L+ settings^1,5,7,8

* No grade 5 CRS or neurological events were reported in the YESCARTA® arm of ZUMA-7;^1,2† Includes YESCARTA®-infused patients with available data across both Era 1 (2018–2019, n=171) and Era 2 (2020–2022, n=407).⁸

The evolution and increased use of adverse event management strategies has resulted in reduced rates of high-grade CRS and ICANS, compared with those reported in ZUMA-1 and ZUMA-7^1,5,7,8

Real-world survival outcomes with YESCARTA® are similar to those in ZUMA-7 even though a broader patient population were treated. In the real-world setting, patients had:^1,2,7

• Greater median age
• Pre-apheresis therapy and post-apheresis bridging therapy
• Broader disease characteristics

Study overview and baseline characteristics

UK 2024 real-world evidence: a multicentre, real-world study of 2L YESCARTA® in 195 patients with R/R LBCL⁷
UK 2023 real-world evidence: a multicentre, real-world study of ≥3L YESCARTA® or tisagenlecleucel in 726 patients with R/R LBCL across 12 UK CAR T centres⁸

Baseline characteristics

• Baseline characteristics were broader in patients receiving YESCARTA® in UK real-world analyses than those seen in pivotal key clinical trials, in both the 2L and 3L+ setting^1–8