Real-World Management Patterns of Acute Toxicity Following Bispecific Antibody Therapy for Patients with B-Cell Lymphoma - the Geltamo (Spanish Lymphoma Group) Experience
Authors: Bastos-Oreiro Mariana , Iacoboni Gloria , Navarro Garces Víctor , Luzardo Henríquez Hugo Daniel , Rodriguez Salazar Maria Jose , Fernández Caldas-González Paula , Fernández Caldas-González Paula , Medina Irene , Manresa Pablo , González De Villambrosia Sonia , Gutierrez Antonio , Donato Eva , Busnego Barreto Maria Teresa , Gutierrez Norma C. , López Javier , Martín Moro Fernando , García-Noblejas Ana , Gómez Pilar , Romero Samuel , Jiménez Ubieto Ana , Perez Ceballos Elena , Navarro Belen , Villalon Blanco Lucia , Goñi Herranz María Angeles , Rodríguez Gil Miguel Ángel , Dourdil Victoria , Ormazabal Vélez Irati , Sanchez Anton Piva , Garcia-Sanz Ramon , Abrisqueta Costa Pau , Martín García-Sancho Alejandro 
Published: December 2024

Introduction:
The advent of T-cell engaging strategies for relapsed/refractory (r/r) non-Hodgkin lymphoma patients has completely changed the prognosis of this patient population. Bispecific antibodies (BsAbs) have shown impressive response rates and a favourable toxicity profile in the pivotal clinical trials, but real-world data to illustrate outcomes and management patterns outside of the trial setting are lacking. The aim of this study was to assess acute toxicities after BsAb administration, paying special attention to mitigation strategies and hospital resource utilization.
Materials and methods
In this retrospective, multicentre study, all GELTAMO (Spanish Lymphoma Group) sites who had treated NHL patients with CD20/CD3 BsAbs outside of the clinical trial setting were invited to participate. Given the lack of any fully reimbursed BsAb until June 2024, this use was in the setting of an early access program. Grading of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) followed the ASTCT criteria and management of these acute adverse events was carried out according to label recommendations and local guidelines. Response assessment followed Lugano criteria.
Results:
We included 51 patients treated with BsAbs in 23 Spanish centres. In terms of disease type, 44% had a follicular lymphoma (FL), 36% diffuse large B cell lymphoma (DLBCL) and 20% high-grade B cell lymphoma (HGBCL) (80% double hit [DH]). Considering the full cohort, 27 (53%) patients received epcoritamab (12 DLBCL, 7 HGBCL and 8 FL), 9 (18%) glofitamab (7 DLBCL, 2 HGBCL) and 15 (29%) mosunetuzumab (all FL).
Regarding patient characteristics, median age was 61 (range 39-82), 66% were male and 67% had ECOG-PS ≥1. Thirty-two percent of patients (n=16) had 4 or more previous treatment lines. Forty-four percent had received previous chimeric antigen receptor T-cell therapy (77% in the aggressive non-Hodgkin lymphoma [aNHL] cohort) and 57% had been exposed to bendamustine (86% for FL). Of the aNHL subset, 74% were primary refractory; 67% of the FL patients were early progressors (POD24).
In terms of efficacy outcomes, overall (complete) response rate for aNHL and FL was 50% (20%) and 77% (54%), respectively. With a median follow-up of 6.4 months for the full cohort (95%CI 4.2-14), median PFS and OS was 3.1 months (2.1-not reached [NR]) and 5.7 months (3.9-NR) for aNHL, 9.5 months (6.2-NR) and NR (88% at 15 months) for FL.
Focusing on safety, hospitalization was scheduled for early toxicity monitoring in 80% of patients. The patients not hospitalized on a scheduled basis all belonged to CAR-T centers (2 mosunetuzumab, 4 glofitamab, 4 epcoritamab). In the remaining 20% without a scheduled hospital stay, 24% required urgent admission after treatment due to CRS. The median hospitalization period was 5 days (range 1-44) including both scheduled and urgent episodes. In terms of acute adverse events, 43% developed CRS (10 [21%] grade 1 and 10 [21%] grade 2) and 3 patients (6.5%) developed ICANS (all grade 1). Tocilizumab was administered in 20% of patients (1 dose in 90% of cases) and 34% required steroids (median 3 days (IRQ 2-10)); 1 patient was admitted to intensive care with a complete heart block, requiring a pacemaker. Regarding infections, 15 patients (25%) developed any grade of infections (3/15 grade 3-5), almost all respiratory infections, with only one cutaneous infection. Cytopenias were reported in 20 patients (26%), 17/20 grade 3-4. During study follow-up, 13 patients died, in most cases (86%) due to disease progression; non-relapse mortality was 4% (2 patients), 1 with a respiratory bacterial infection and 1 with bacteriemia.
Conclusions:
In our cohort, early toxicity associated with the use of BsAbs was similar to that reported in the pivotal clinical trials. Considering the favourable toxicity profile, a lower rate of scheduled hospital admission could be explored. Additional follow-up is necessary to consolidate these safety data and obtain long-term efficacy results.