GLOFITAMAB EFFICACY, TOLERABILITY, and PRACTICAL IMPLICATIONS in the REAL WORLD: A UK MULTICENTRE, RETROSPECTIVE ANALYSIS.
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All Authors
Ediriwickrema, K.
Haynes, E.
El-Sharkawi, D.
Foldes, D.
Kanfer, E.
Kuhnl, A.
Linton, K.
Qasim, J.
Collins, G.
Lawless, S.
LTHT Author
Owen, Mary
LTHT Department
Leeds Cancer Centre
Oncology
Haematology
Oncology
Haematology
Non Medic
Publication Date
2024
Item Type
Conference Abstract
Language
Subject
ADULT , AGED , IMMUNOTHERAPY , CYTOKINES , LYMPHOMA, LARGE B-CELL, DIFFUSE , DRUG DOSAGE CALCULATIONS , DRUG THERAPY , WOMEN , LYMPHOMA, FOLLICULAR , FOLLOW-UP-STUDIES , CLINICAL PROTOCOLS , HISTOLOGY , INCIDENCE , INTENSIVE CARE UNITS , MEN , MIDDLE AGED , MULTICENTRE STUDIES AS TOPIC , NEUROTOXINS , NEUTROPHILS , LYMPHOMA, NON-HODGKIN , SURVIVAL RATE , DISEASE-FREE SURVIVAL , RECURRENCE , RETROSPECTIVE STUDIES , SEPSIS , ANTINEOPLASTIC AGENTS , HYPERTENSION , BIOLOGICAL PRODUCTS
Subject Headings
Abstract
Background: CAR-T cell therapy (CAR-T) has revolutionised the treatment landscape of relapsed/refractory diffuse large B-cell lymphoma (RR DLBCL). Unfortunately, the prognosis remains dismal for patients who are unsuitable for, or relapse following CAR-T. Glofitamab, a CD3:CD20 bispecific monoclonal antibody, in the registration trial demonstrated complete response rates (CRR) of 39%. The CRs have proven durable in 78% of patients with median follow up of 9 months, including prior CART treated patients. Consequently, glofitamab received UK licensing in 2023 for third line RR DLBCL. Aim(s): Real-world glofitamab experience is limited; we provide insights into efficacy, tolerability, and UK practical implications of delivering glofitamab. Method(s): A multicentre, retrospective analysis was performed on anonymised patient data treated with glofitamab accessed by both the UK compassionate/early access schemes and NICE licensed approval Results: 59 patients (pts.) were approved for glofitamab at 17 UK centres: median age 66 years (range 27-87), 61% male and 95% with a 0-3 performance status. Histological diagnoses included DLBCL(NOS) (58%), transformed follicular lymphoma (14%), other B-non-Hodgkin lymphomas (29%). IPI score >=3 in 46% (n=27), bulky disease in 19% (n=11) and a median of 3 prior treatment lines with 44% pts. having received >=4 prior lines. 81% (n=48) were refractory to their most recent line of therapy and 69% (n=41) had received prior CAR-T. Two pts. did not commence treatment due to progressive disease. A median of 3 cycles were administered with delays in 25% (n=15), primarily due to infections. One pt required dose reduction. 28% (n=17) experienced cytokine-release syndrome (CRS) (maximum grade 3 (n=1;) grade 2 (n=6)). Only 6 patients required treatment with tocilizumab. Two pts experienced immune effector cell-associated neurotoxicity syndrome (ICANS); (max grade 2 (n=1), grade 1 (n=1). 31% (n=18) experienced >=grade 3 neutropenia and 39% (n=23) experienced infection (maximum grade 3). One patient required intensive care unit (ICU) admission for vasopressor support for treatment of CRS and sepsis. The median follow-up was 3 months (IQR 2-4.25), complete metabolic response (CMR) was 22% (95% CI 12-36), overall response rate (ORR) was 49% (95% CI 35-65). Median duration of response was not reached, median progression free survival was 3 months (95% CI 2.3-N/A) and 6-month overall survival was 24% (95% CI 13-41). Response according to prior CAR-T treatment as well as extended follow up and further patient data will be updated at presentation. Summary/Conclusion: Glofitamab demonstrated CMR rates of 22% in an intention to treat analysis, which is encouraging in a heavily pre-treated population with use as median 4th line treatment, with 44% of patients receiving this in a 5th line setting. The low burden of ICU admissions and low incidence of CRS and ICANS, predominantly low grade, supports delivery in a range of hospital settings. Glofitamab, may provide a safe, viable CAR-T alternative with the potential for further improvement in outcomes when used in 3rd line settings.
Journal
HemaSphere