Real-world outcomes of glofitamab therapy in CAR-T naive patients with relapsed/refractory B-cell lymphoma
Abstract
Abstract Background The bispecific antibody (BsAb) glofitamab (G) has demonstrated high efficacy and acceptable feasibility in patients with aggressive relapsed/refractory (r/r) B-cell lymphoma in clinical trials. However, real-world evidence on its use remains limited, particularly in the context of evolving immunotherapy options and their sequencing. Here we report outcomes of glofitamab in CAR-T naive patients from a compassionate use program (CUP) and routine clinical practice. Materials and methods This multicenter retrospective study included CAR-T naive patients with r/r B-cell lymphoma who were treated with G within CUP or routine clinical practice in 22 Russian centers. Glofitamab was administered according to the approval study. The analysis included evaluation of overall response (ORR) and complete response (CR) rate, overall survival (OS), progression-free survival (PFS). We assessed the impact of clinical factors on CR achievement and PFS, along with characterization of adverse events (AEs). Results As of July 2025, 152 patients were enrolled. Median age at G initiation was 51 (19-83), male/female ratio - 72/80 (47/53%). The study population included patients with diffuse large B-cell lymphoma, both de novo and transformed (n=88, 58%), high-grade B-cell lymphoma (n=17, 11%), primary mediastinal large B-cell lymphoma (n=20, 13%), follicular large B-cell lymphoma (n=9, 6%) and other lymphomas (n=18, 12%). Median number of therapy lines before G was 3 (3-9). Overall, 122 patients (80%) had primary refractory/early relapsed disease, and 56 (37%) presented with Bulky disease (>7.5 cm) at G initiation. Twenty-four patients (16%) underwent auto-HCT, and 2 (1%) allo-HCT previously. The ORR, available for 150 of 152 patients, was 58% (n=87), comprising 45% CR and 13% partial remission (PR). Median follow up was 9.3 months (0.6-51.9). At the last follow-up, 143 (94%) pts discontinued therapy due to: end of treatment after 12 cycles (n=46, 32%), disease progression (n=69, 48%), infections (n=18, 12%, including COVID19 in 15 pts, 10%) or other reason (n=10, 7%). Median PFS was 5.8 months (CI 95%: 3.8-10.7), 1-year PFS 39.4% (CI 95%: 32.1-48.4); median OS was 17.9 months (CI 95%: 12.4-NA), 1-year OS was 59% (CI 95%: 51.2-67.9). Median OS and PFS in patients with CR were not reached; with median follow up 15.6 months (3.2-52), estimated 2-year PFS and OS were 72.8% (CI 95%: 61.3-86.5) and 81.3% (CI 95%: 70.9-93.1) respectively. In contrast, patients with PR demonstrated significantly worse outcomes, with median PFS of 5.5 months (CI 95%: 3.7-NA) and OS of 14.2 months (CI 95%: 8.4-NA). Recent bendamustine administration (≤3 months) prior to G initiation was associated with lower rate of CR (OR 0.31, 95% CI 0.14-0.66, p=0.003) and shorter PFS (3.6 vs 8.8 months, 95% CI 1.13-2.63, HR=1.72, p=0.01). Other risk factors for CR achievement and PFS duration included: ECOG PS >1 (CR: OR 0.41, 95% CI 0.20-0.83, p=0.016; PFS: HR 2.13, 95% CI 1.41–3.22, p=0.004), B symptoms (CR: OR 0.38, 95% CI 0.16-0.84, p=0.021; PFS: HR 2.06, 95% CI 1.32–3.21, p=0.001), and Bulky disease >7.5 cm (CR: OR 0.40, 95% CI 0.20-0.80, p=0.010; PFS: HR 1.91, 95% CI 1.26–2.90, p=0.002). Any grade AEs were observed in 132 patients (87%) including grade ≥3 AEs in 57 patients (38%). Grade 5 AEs were reported in 10 patients (7%). Any grade cytokine release syndrome (CRS) was observed in 63 (41%) pts with only 3 patients (2%) experiencing grade 3 CRS. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were documented. Infectious AEs occurred in 68 patients (45%), including grade ≥3 AEs in 20 patients (13%; with COVID-19 grade 5 AEs in 10 pts, 7%). Conclusion Glofitamab demonstrates high efficacy in CAR-T naive r/r B-cell lymphoma patients with CR rates comparable to the approval study in a real-world scenario. Notably, ECOG PS, B symptoms, Bulky disease and bendamustine exposure within 3 months prior to G initiation were associated with reduced incidence of CR and worse PFS.
Article Details
Authors (62)
Liudmila Fedorova
1RM Gorbacheva Research Institute, Saint Petersburg, Russian Federation
Nataliia Mikhailova
1RM Gorbacheva Research Institute, Saint Petersburg, Russian Federation
Kirill Lepik
1RM Gorbacheva Research Institute, Saint Petersburg, Russian Federation
Vladislav Markelov
1RM Gorbacheva Research Institute, Saint Petersburg, Russian Federation
Andrey Chekalov
1RM Gorbacheva Research Institute, Saint Petersburg, Russian Federation
Olesya Smykova
1RM Gorbacheva Research Institute, Saint Petersburg, Russian Federation
Gayane Tumyan
2National Medical Research Center of Oncology named after N.N. Blokhin, Moscow, Russian Federation
Anastasia Semenova
2National Medical Research Center of Oncology named after N.N. Blokhin, Moscow, Russian Federation
Arman Arakelyan
2National Medical Research Center of Oncology named after N.N. Blokhin, Moscow, Russian Federation
Lev Butaev
3Moscow Multidisciplinary Scientific and Clinical Center named after S.P. Botkin, Moscow, Russian Federation
Iuliia Oleinik
1Moscow multidisciplinary scientific and clinical center named after S.P. Botkin (Moscow, Russia), Bone marrow transplantation department №56, Moscow, Russian Federation
Evgeny Nikitin
3Moscow Multidisciplinary Scientific and Clinical Center named after S.P. Botkin, Moscow, Russian Federation
Vadim Ptushkin
1Moscow multidisciplinary scientific and clinical center named after S.P. Botkin (Moscow, Russia), Bone marrow transplantation department №56, Moscow, Russian Federation
Yana Mangasarova
4National Medical Research Center for Hematology, Moscow, Russian Federation
Aminat Magomedova
4National Medical Research Center for Hematology, Moscow, Russian Federation
Ekaterina Gitelzon
4National Medical Research Center for Hematology, Moscow, Russian Federation
Nelly Gabeeva
4National Medical Research Center for Hematology, Moscow, Russian Federation
Daria Koroleva
2National Medical Research Center for Hematology, Moscow, Russian Federation
Anna Smolyaninova
2National Medical Research Center for Hematology, Moscow, Russian Federation
Eugene Zvonkov
2National Medical Research Center for Hematology, Moscow, Russian Federation
Iurii Osipov
5V. A. Almazov National Medical Research Centre, Saint Petersburg, Russian Federation
Natalia Stepanova
5V. A. Almazov National Medical Research Centre, Saint Petersburg, Russian Federation
Tatiana Krinitsina
5V. A. Almazov National Medical Research Centre, Saint Petersburg, Russian Federation
Yulia Ryabukhina
6Clinical Hospital “Lapino 2” of the “Mother and Child” Group of companies, Moscow, Russian Federation
Gulnara Khusainova
7Republican Clinical Oncological dispensary MZ RT named after Professor M.Z. Sigal, Kazan, Russian Federation
Leisan Mukharliamova
7Republican Clinical Oncological dispensary MZ RT named after Professor M.Z. Sigal, Kazan, Russian Federation
Olga Smirnova
Irina Ishmatova
8National medical research cancer center n.a Petrov N.N, Saint Petersburg, Russian Federation
Anna Zverkova
8National medical research cancer center n.a Petrov N.N, Saint Petersburg, Russian Federation
Svetlana Elkhova
8National medical research cancer center n.a Petrov N.N, Saint Petersburg, Russian Federation
Stanislav Volchenkov
8National medical research cancer center n.a Petrov N.N, Saint Petersburg, Russian Federation
Ilya Ziuzgin
8National medical research cancer center n.a Petrov N.N, Saint Petersburg, Russian Federation
Diana Ivanova
9Moscow Clinical Research Center Hospital 52 of the Moscow City Health Department, Moscow, Russian Federation
Elena Baryakh
9Moscow Clinical Research Center Hospital 52 of the Moscow City Health Department, Moscow, Russian Federation
Elena Misyurina
9Moscow Clinical Research Center Hospital 52 of the Moscow City Health Department, Moscow, Russian Federation
Pervin Zeynalova
6Clinical Hospital “Lapino 2” of the “Mother and Child” Group of companies, Moscow, Russian Federation
Firusa Abbasbeyli
6Clinical Hospital “Lapino 2” of the “Mother and Child” Group of companies, Moscow, Russian Federation
Olga Timofeeva
6Clinical Hospital “Lapino 2” of the “Mother and Child” Group of companies, Moscow, Russian Federation
Iulia Podmankova
5V. A. Almazov National Medical Research Centre, Saint Petersburg, Russian Federation
Margarita Ulianova
12State budgetary institution of healthcare Leningrad regional clinical hospital, Saint Petersburg, Russian Federation
Victoria Basmanova
12State budgetary institution of healthcare Leningrad regional clinical hospital, Saint Petersburg, Russian Federation
Tatiana Tsyganok
13Sakhalin regional Clinical Hospital, Sakhalin, Russian Federation
Svetlana Samarina
14Kirov Research Institute of Hematology and Blood Transfusion of the Federal Medical and Biological Agency, Kirov, Russian Federation
Valeria Kimaikina
13Sakhalin regional Clinical Hospital, Sakhalin, Russian Federation
Ekaterina Zubkova
15Irkutsk region cancer center, Irkutsk, Russian Federation
Svetlana Ovanesian
15Irkutsk region cancer center, Irkutsk, Russian Federation
Alsou Iskhakova
16Republican clinical oncology dispensary of Ministry of Healthcare of the Republic of Bashkortostan, Ufa, Russian Federation
Aleksei Kuvshinov
17Russian Research Institute of Hematology and Transfusiology, Saint Petersburg, Russian Federation
Anastasiya Kuzyaeva
17Russian Research Institute of Hematology and Transfusiology, Saint Petersburg, Russian Federation
Galiya Isaeva
18Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine, Chelyabinsk, Russian Federation
Maria Andrievskih
18Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine, Chelyabinsk, Russian Federation
Olga Arzhanukhina
19Saratov State Medical University named after V. I. Razumovsky, Saratov, Russian Federation
Polina Makarovskaya
20Nizhniy Novgorod Region Clinical Hospital n.a.Semashko, Nizhniy Novgorod, Russian Federation
Olga Samoylova
20Nizhniy Novgorod Region Clinical Hospital n.a.Semashko, Nizhniy Novgorod, Russian Federation
Irina Vasileva
21State Budgetary Healthcare Institution of the Sverdlovsk Region “Central City Hospital No. 7, Yekaterinburg, Russian Federation
Alena Terekhova
22A.Tsyb Medical Radiological Research Center (MRRC) is the branch of the Federal State Budgetary Institution “National Medical Research Radiological Centre” of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
Natalia Falaleeva
22A.Tsyb Medical Radiological Research Center (MRRC) is the branch of the Federal State Budgetary Institution “National Medical Research Radiological Centre” of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
Vasily Shuvaev
22A.Tsyb Medical Radiological Research Center (MRRC) is the branch of the Federal State Budgetary Institution “National Medical Research Radiological Centre” of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
Sabina Vlasova
23Yaroslavl Regional Clinical Hospital, Yaroslavl, Russian Federation
Valery Lapin
3State Budgetary Healthcare Institution of the Yaroslavl Region “Regional Clinical Hospital”, Yaroslavl, Russian Federation
Varvara Bakhtina
24Krasnoyarsk Regional Clinical Hospital, Krasnoyarsk, Russian Federation
Alexander Kulagin
1RM Gorbacheva Research Institute, Saint Petersburg, Russian Federation