Safety and efficacy of CD3xCD20 bispecific antibody for the treatment of primary and secondary central nervous system lymphoma patients: A multicentric retrospective study
Year: 2025
Type: conference-abstract
Abstract: Introduction: Relapsed/refractory (R/R) central nervous system involvement (CNS) of aggressive B cell lymphoma presents a dismal prognosis with an unmet medical need. CD3xCD20 bispecific antibody (BsAbs) has recently provided a major improvement in the context of R/R aggressive B cell lymphoma with response rates of 50 to 80%. Patients with primary or secondary CNS lymphoma (P/SCNSL) were excluded from trials with CD3xCD20 BsABs, because of concerns regarding their bioavailability in the CNS and the increased risk of neurologic toxicities (ICANS). However, one previous report showed that glofitamab could be measured at an effective concentration in the CSF of 3 patients with SCNSL. The aim of our study is to evaluate the safety and clinical efficacy of CD3xCD20 bispecific antibody in daily practice of R/R P/SCNSL. Methods: Adult patients were eligible for this retrospective study if they presented with a R/R PCNSL, or a R/R aggressive B cell SCNSL with CNS involvement at the start of the treatment with CD3xCD20 BsAbs. Patients and disease characteristics were collected from medical records. Other concomitant anti-lymphoma treatments were authorized. Descriptive statistics and Kaplan-Meier estimates were used for survival analysis. Patients responding to CD3xCD20 BsAbs and subsequently consolidated by intensive chemotherapy and autologous stem cell transplantation (IC + ASCT) or chimeric antigen receptor (CAR) T cell therapy were censored for the progression-free survival (PFS) at time of ASCT or CAR-T cell infusion. Results: 55 patients within 22 French and Belgium institutions were identified. We first present results from 41 patients from 13 institutions for whom sufficient data were collected. Median age was 57 years (range, 34 to 77 years), with 56.1% males. 37 patients had SCNSL and 4 patients had PCNSL. Among patients with SCNSL, 15 patients (40.5%) had isolated CNS relapse when starting BsAbs and 22 patients (59.5%) had simultaneous CNS and systemic relapse. Patients had received a median of 3 previous lines of therapy (range, 2 to 5). Nineteen (46.5%) patients received previous treatment with CAR-T cells and 10 (24.3%) patients received previous ASCT. Thirty (73.2%) and eleven (26.8%) patients received epcoritamab and glofitamab respectively. Seven (23.3%) patients received epcoritamab as monotherapy. Twenty-three (76.7%) patients received epcoritamab in combination with lenalidomide (n=14, 46.7%), ibrutinib (n=5, 16.7%), pomalidomide (n=5, 16.7%), rituximab (n=4, 13.2%) or with polychemotherapies (n=3, 10.7%). One (9.1%) patient received glofitamab as monotherapy. Ten (90.9%) patients received glofitamab in combination with ibrutinib (n=7, 63.6%), lenalidomide (n=6, 54.5%) or pomalidomide (n=2, 18.1%). Patients received a median of 3 cycles of BsAbs (range, 1 to 12). Overall response (ORR) and complete response (CR) rates were 65.9% (27/41) and 36.6% (15/41), respectively. Twelve patients achieved partial response (PR) and 14 patients had progressive disease (PD). CR rate after BsAbs monotherapy and combination was 25% (2/8) and 39.4% (13/33), respectively. Nine responder patients received a subsequent treatment, with axicabtagene ciloleucel CAR-T cell therapy (n = 7 including 3 CR and 4 PR), thiotepa based IC + ASCT (n = 1 PR) and allogenic stem cell transplant (n = 1 CR). With a median follow-up of 6.7 months (range, 0.5 to 17.1), median PFS was 8.5 months and median OS was not reach. The median duration of response (DOR) was not reached. Among the 18 responder patients who continued BsAbs, 2 (7.4%) patients relapsed. One patient relapsed after CAR-T cell therapy. The patient who underwent allogenic transplant relapsed and achieved a 2nd CR after restarting BsAbs. Cytokine release syndrome (CRS) developed in 19 (46.3%) patients including 4 grade 3/4 events. Nine (22.0%) patients experienced neurotoxicities including 3 grade 3/4 events. There were no grade 5 neurotoxicity event. Conclusions: CD3xCD20 BsAbs resulted in encouraging response rates with expected toxicities in heavily pretreated R/R P/SCNSL patients including patients treated with prior CAR-T cell therapy. BsAbs is an option to be considered for R/R SCNSL and these encouraging results highlight the need for prospective trials testing their role in this setting. A prospective trial testing epcoritamab in R/R PCNSL began in France (NCT06931652).
Source: Blood
Authors: Adrien Gilbert, Inès Boussen, Hippolyte Bardet, Sandy Amorim, Florence Lachenal, François Lemonnier, Guillaume Dachy, Sarah Bailly, Marie Blonski, Steeve Chevreux, Adrien Chauchet, Clemence Loiseau, Valerie Vidal, Jean-Baptiste Bossard, Caterina Cristinelli, Driss Chaoui, Julie Abraham, Sophie Bernard, Herve Ghesquieres, Morgane Nudel Ortmans, Lise Willems, Celia Salanoubat, Caroline Houillier, Choquet Sylvain, Baptiste Delapierre, Carole Soussain
Institutions: Institut Curie, Pitié-Salpêtrière Hospital, Centre Hospitalier Universitaire de Caen Normandie, Assistance Publique – Hôpitaux de Paris, Centre Hospitalier Universitaire Henri-Mondor, Hôpitaux Universitaires Henri-Mondor, Cliniques Universitaires Saint-Luc, Centre Hospitalier Régional et Universitaire de Nancy, CHU Dijon Bourgogne, Centre Hospitalier Universitaire de Besançon, Hôpital Necker-Enfants Malades, Hôpital André Mignot, Centre Hospitalier de Lens, Hôpital Saint-Louis, Centre Hospitalier Universitaire de Limoges, Centre Hospitalier de la Côte Basque, Hospices Civils de Lyon, Hôpital Lyon Sud, Centre Hospitalier Universitaire de Lille, Hôpital Cochin, Laboratoire d'hématologie, Centre Hospitalier Sud Francilien
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4417004924