TOPLINE:

In patients with relapsed or refractory large B-cell lymphoma (LBCL), anti-CD19-directed chimeric antigen receptor (CAR) T-cell therapy administered after at least two prior lines of systemic therapy was associated with superior 3-year overall survival and progression-free survival compared with historical standard of care, according to findings from a propensity-weighted real-world study. Patients who received CAR T-cell therapy also had lower rates of hospital admissions, emergency department visits, and infection-related hospitalizations.

METHODOLOGY:

• Patients with relapsed or refractory LBCL have historically had poor outcomes with salvage therapies. Although multiple studies support the efficacy of anti-CD19-directed CAR T-cell therapies after two lines of systemic therapy, real-world evidence comparing their safety and effectiveness with previous standard-of-care options remains limited.
• Researchers conducted a retrospective, single-center cohort study comparing patients with relapsed or refractory LBCL who received CAR T-cell therapy (n = 85; median age, 61 years) from 2020 to 2022 vs historical control individuals (n = 150; median age, 57 years) who received standard of care from 2012 to 2017.
• Patients in the CAR T-cell therapy group received either axicabtagene ciloleucel (67%) or tisagenlecleucel (33%) as part of routine care after two or more lines of systemic therapy, whereas historical control individuals received standard-of-care management, including chemotherapy, clinical trial treatment, radiotherapy, targeted therapy, or best supportive care.
• The study outcomes included 3-year estimates for overall survival and progression-free survival, healthcare resource utilization, and hospitalization events. The median follow-up duration was 15 months for the CAR T-cell therapy group and 4 months for the historical control group.
• Overall, patients who received CAR T-cell therapy were more heavily treated than historical control individuals (mean number of lines of therapy, 3.49 vs 2.46; P < .001); 59.1% of control individuals received only the best supportive care beyond second-line therapy, whereas most CAR T-cell recipients received therapy in the third line (63.5%).

TAKEAWAY:

• At 3 years, the estimated overall survival was 59% vs 9% in the CAR T-cell group vs the historical control group. Median overall survival was not reached in CAR T-cell groups and was 4.4 months for control individuals (adjusted hazard ratio [aHR] for all-cause death, 0.21; P < .001).
• Similarly, the estimated 3-year progression-free survival was significantly better in the CAR T-cell group: 48% vs 6% for historical controls; the median progression-free survival was 14.4 months and 3.6 months, respectively (aHR, 0.28; P < .001).
• Patients who received CAR T-cell therapy had a significantly lower rate of healthcare resource utilization per 1000 person-days at risk than historical control individuals: hospital admissions (5.32 vs 9.10), emergency department visits (2.33 vs 4.81), ICU admissions (0.53 vs 1.25), and total number of days hospitalized (72.47 vs 89.06; P < .001 for all).
• Moreover, hospitalization rates for common complications were significantly lower in the CAR T-cell therapy group than in the historical control group: fever (0.93 vs 1.63), infection (1.48 vs 3.08), and neutropenia (0.66 vs 1.97; P < .001 for all).

IN PRACTICE:

“Our cohort data demonstrate a significant survival benefit associated with [third‑line or later] CAR-T compared with historical care management, with fewer hospitalizations and infections,” the study authors wrote. The findings “are consistent with the comparison of outcomes from the phase 2 trial of [axicabtagene ciloleucel] with those of a much more strictly defined [historical control] population.”

SOURCE:

The study, led by Tiana Kordbacheh, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada, was published online in Blood Advances.

LIMITATIONS:

As a retrospective study, certain baseline characteristics such as Eastern Cooperative Oncology Group performance status, double- or triple-hit disease status, and disease bulk status could not be included in propensity models. The lower unweighted lactate dehydrogenase in CAR T- cell therapy recipients likely reflected timing bias because lactate dehydrogenase was measured within a fixed window that often followed bridging therapy. Additionally, the historical control cohort did not represent today’s standard-of-care regimens, which increasingly include polatuzumab, tafasitamab, loncastuximab, or access to bispecific antibodies.

DISCLOSURES:

The research received support from the Canadian Cancer Society and the Institute for Clinical Evaluative Sciences, which receives annual funding from the Ontario Ministry of Health and the Ministry of Long-Term Care. Some authors reported receiving research funding or honoraria and having other ties with various sources including Gilead Sciences, Novartis, AbbVie, AstraZeneca, Bristol Myers Squibb, and others. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.