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3109 Real-World Management Patterns of Acute Toxicity Following Bispecific Antibody Therapy for Patients with B-Cell Lymphoma - the Geltamo (Spanish Lymphoma Group) Experience

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Poster II
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Supportive Care, Treatment Considerations, Adverse Events
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Mariana Bastos-Oreiro1*, Gloria Iacoboni, MD2*, Víctor Navarro Garces3*, Hugo Daniel Luzardo Henríquez4*, Maria Jose Rodriguez Salazar5*, Paula Fernández Caldas-González6*, Paula Fernández Caldas-González6*, Irene Medina7*, Pablo Manresa8*, Sonia González De Villambrosia9*, Antonio Gutierrez, MD, PhD10*, Eva Donato11*, Maria Teresa Busnego Barreto12*, Norma C. Gutierrez13,14*, Javier López15*, Fernando Martín Moro16*, Ana García-Noblejas17*, Pilar Gómez18*, Samuel Romero, MD19*, Ana Jiménez Ubieto20*, Elena Perez Ceballos21*, Belen Navarro22*, Lucia Villalon Blanco23*, María Angeles Goñi Herranz24*, Miguel Ángel Rodríguez Gil25*, Victoria Dourdil26*, Irati Ormazabal Vélez27*, Piva Sanchez Anton28*, Ramon Garcia-Sanz, MD, PhD29,30, Pau Abrisqueta Costa31* and Alejandro Martín García-Sancho32*

1Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
2Hospital Universitari Vall d’Hebron-Universitat Autónoma de Barcelona, SEATTLE, WA
3Oncology Data Science (odyssey) Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Universitari, Barcelona, Spain
4Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
5Hematology, Hospital Universitario de Tenerife, La Laguna, ESP
6Hematology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
7Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain, BARCELONA, Spain
8Hospital Universitario Dr. Balmis, ALICANTE, Spain
9Hematology Department, Hospital Universitario Marqués de Valdecilla (IDIVAL), Santander, Spain
10Hematology Department, Son Espases University Hospital, IdISBa, Palma, Spain
11Hematology Department, Hospital Universitario Doctor Peset, Valencia, Spain
12Hospital Universitario de la Candelaria, Santa Cruz De Tenerife, ESP
13Hospital Universitario De Salamanca, IBSAL, Salamanca, Spain
14Institute of Biomedical Research of Salamanca (IBSAL), University Hospital, Salamanca, Spain
15Hematology, Hospital Universitario Ramón y Cajal, Madrid, Spain
16Hematology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain
17Hospital Universitario de La Princesa, Madrid, Spain
18Hospital La Paz, Madrid, Spain
19Hematology Research Group, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
20Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
21Hospital Universitario Morales Meseguer, MURCIA, ESP
22Hospital Puerta De Hierro, Madrid, ESP
23Hospital Universitario Fundación Alcorcón, Alcorc N, Madrid, ESP
24Complejo Hospitalario de Navarra, Pamplona, Spain
25Hospital Universitario Virgen de las Nieves, Granada, Spain
26Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
27Hospital Universitario de Navarra, Pamplona, Spain
28Hospital Universitario de Navarra, Pamplona, ESP
29General University Hospital Gregorio Marañón, Madrid, Spain
30Health Research Institute Gregorio Marañón, Madrid, Spain
31University Hospital Vall d’Hebron, Barcelona, Spain
32Hematology Department, Hospital Universitario de Salamanca, IBSAL, CIBERONC, University of Salamanca, Salamanca, Spain

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.

Disclosures: Bastos-Oreiro: Gilead: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Astrazeneca: Honoraria; Sobi: Honoraria; Genmab: Honoraria; Lilly: Honoraria; Incyte: Honoraria; Kite: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Honoraria; BMS: Honoraria; Roche: Honoraria, Research Funding. Iacoboni: Novartis: Honoraria; AbbVie, AstraZeneca, Autolus, Bristol-Myers Squibb, Kite/Gilead, Miltenyi, Novartis, Lilly and Sandoz: Honoraria; Autolus, Bristol-Myers Squibb, Kite/Gilead, Miltenyi, Novartis: Consultancy; Miltenyi: Consultancy, Honoraria; Autolus: Consultancy; BMS: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; AstraZeneca: Honoraria, Other: Travel support; AbbVie: Honoraria, Other: Travel Support; AbbVie, AstraZeneca, Kite/Gilead, Miltenyi: Other: Travel support. Gutierrez: Amgen, Sanofi: Honoraria; University Hospital of Salamanca: Current Employment. Romero: Roche: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Jiménez Ubieto: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; Roche: Consultancy, Speakers Bureau; Regeneron Pharmaceuticals, Inc.: Consultancy; Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Speakers Bureau; Novartis: Speakers Bureau; Incyte: Speakers Bureau; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Garcia-Sanz: Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; MSD: Honoraria; Janssen: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Takeda Pharmaceutical: Consultancy, Honoraria. Martín García-Sancho: AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Kyowa Kirin: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel and Accommodation Support; Novartis: Consultancy; Roche: Honoraria, Other: Travel and Accommodation Support; Sobi: Consultancy, Honoraria; Takeda: Honoraria; Incyte: Consultancy, Honoraria; IDEOGEN: Consultancy, Honoraria; Miltenyi Biotec: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Genmab: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria, Other: Travel and Accommodation Support; EUSA Pharma: Honoraria; Bristol Myers Squibb: Consultancy, Honoraria, Other: Travel and Accommodation Support; BeiGene: Consultancy, Honoraria.

*signifies non-member of ASH