AUTHORS
Theodora Agnes Maria Claushuis, MD, PhD, Anca Prica2, Mary Gleeson3, Satyen Gohil, MD, PhD, MRCP, FRCPath4, Fulvio Massaro, MD, PhD5, Royston Ponraj, MBBS6, Krisha Mehta, MD7, Jeanette Doorduijn, MD8, Astrid MP Demandt, MD9, Marten Nijziel, MD, PhD10, Rita Varga, MD11, Giulia Magno, MD12, Marion Subklewe I, MD13, Maike Stegemann14, Mariana Bastos-Oreiro, MD, PhD15, wivine bernard16, Kristie Blum, MD17, Fabrizio Marino18, Ida Hude, MD19, Jan-Michel Heger, MD20, Rebecca Wurm-Kuczera, MD21, Juan Pablo Alderuccio, MD22, Thomas Melchardt, MD23, Ola Linden24, Wendy Osborne, MBBS (Hons), MRCP, FRCPath25, Soo Park, MD26, Jacinta Perram, MBBS, BSc, BA, FRACP, FRCPA, MPH27, Robert Kridel, MD28, Nazarii Shokun29, Wolfram Klapper30, Ann LaCasce, MD, MMSc31, Adam J. Olszewski, MD32, Mark Roschewski, MD33, Martine E.D. Chamuleau, MD PhD34
AFFILIATIONS
1 Amsterdam UMC, Amsterdam, Amsterdam, Netherlands
2 Princess Margaret Cancer Centre - University Health Network, Toronto, Canada
3 Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
4 University College London Hospitals NHS Foundation Trust, London, United Kingdom
5 Institut Jules Bordet, Hôpital Universitaire de Bruxelles,, Brussels, Belgium
6 Nepean Hospital, Nepean Blue Mountains Local Health District, Kingswood, Australia
7 Rutgers Robert Wood Johnson Medical School and Rutgers Cancer Institute, New Brunswick, United States
8 Erasmus MC Cancer Institute, University Medical Center Rotterdam, rotterdam, Netherlands
9 Maastricht University Medical Center+, maastricht, Netherlands
10 Catharina hospital, Eindhoven, Netherlands
11 Klinikum Oldenburg AöR, University Hospital of Carl von Ossietzky University, Oldenburg, Germany
12 LMU University Hospital, LMU Munich, Munich, Germany
13 LMU University Hospital, LMU Munich, Munich, Germany
14 Stegemann Kepler University Hospital, Johannes Kepler University Linz, Linz, Austria
15 Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
16 CHU UCL Namur, Yvoir, Belgium
17 Winship Cancer Institute, Emory University School of Medicine, Atlanta, United States
18 IRCCS San Raffaele Scientific Institute, Milan, Italy
19 University Hospital Centre Zagreb, Zagreb, Croatia
20 University of Cologne, Cologne, Germany
21 Charité–Universitätsmedizin Berlin, berlin, Germany
22 University of Miami Miller School of Medicine, Miami, United States
23 Paracelsus Medical University, Salzburg, Austria
24 Lund University, lund, Sweden
25 The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
26 University of California San Diego, La Jolla, United States
27 St Vincent’s Hospital Sydney, St Vincent’s Health Network, Darlinghurst, Australia
28 Princess Margaret Cancer Centre - University Health Network, Toronto, Canada
29 University of Salento, Lecce, Italy
30 University Hospital Schleswig-Holstein, Kiel, Germany
31 Dana-Farber Cancer Institute, Boston, United States
32 Brown University, Olszewski Rhode Island, United States
33 Memorial Sloan Kettering Cancer Center, New york, United States
34 Amsterdam UMC, Amsterdam, Amsterdam, Netherlands
ABSTRACT
Background:
Burkitt lymphoma (BL) is a highly aggressive B-cell malignancy associated with poor outcomes in patients with relapsed or refractory disease (median overall survival [OS] <3 months). CD19-directed CAR-T-cell therapy has shown limited efficacy in this setting [Samples et al, Blood 2025]. In a recent report, three patients with R/R BL treated with glofitamab (Glofit; CD20xCD3 bispecific antibody) and polatuzumab vedotin (Pola; anti-CD79B antibody–drug conjugate) achieved a complete response (CR) and were successfully bridged to consolidation, suggesting potential activity of this combination [Prica et al, NEJM 2025]. However, its efficacy has not yet been evaluated in a larger cohort.
Methods:
This international, multicenter, retrospective study evaluated real-world outcomes of 38 R/R BL patients treated with Glofit +/- Pola. As neither agent is approved for BL, treatment was given via compassionate use programs or on an individual-patient basis. Patients were identified through a survey conducted within the International BL Network. After ethics approval, clinical, pathology, and imaging data were collected from the treating centers. Pathology reports were reviewed by an independent pathologist with expertise in BL.
Outcomes
In total, 30 patients received Glofit + Pola after a median of 2 previous therapies (range 1-5). Median age was 42 years (range 21–70). First-line treatment consisted of DA-EPOCH-R (40%), R-CODOX-M/R-IVAC (33.3%), BFM/GMALL (10%) or other (16.7%). Most (87%) patients had sporadic BL, and 13% immune-deficiency associated BL. All cases had morphology consistent with BL, CD10 expression, and a MYC translocation. Independent pathology review has been performed until now on 25 patients, and identified 21 as definitive and 4 as likely BL (due to missing BCL2 or BCL6 rearrangement testing).
At start of Pola + Glofit, all patients had stage III/IV disease, 80% extranodal disease, 27% bulky disease, 13% bone marrow involvement and 33% central nervous system involvement. CNS disease was isolated in 50% and synchronous with systemic disease in 50%. 86% had refractory disease to the last line of therapy, and Pola + Glofit was started a median of 7 months after diagnosis (range 3-15).
Patients received a median of 3 cycles (range 2-12). Cytokine release syndrome occurred in 24% (grade (gr) 1: 7%, gr 2: 17%) and immune effector cell-associated neurotoxicity syndrome in 10% (gr 1: 7%, gr 2: 3%).
The overall response rate (ORR) in all patients was 63% (19/30), with a complete remission (CR) rate of 57% (17/30). In patients treated in second line, the ORR rate was 69% (9/13) and the CR rate was 62% (8/13), and in 3rd line and beyond the ORR was 59%(10/17) and CR 53% (9/17). In patients with CNS involvement, the ORR rate was 90% (9/10) and the CR rate was 80% (8/10). Response was assessed after 3 cycles or earlier in case of progression.
Consolidative treatment was administered to 41% of patients (24% allogeneic stem cell transplant (SCT)), 3% autologous SCT, 14% CAR-T). Of patients responding to treatment, 58% received consolidation therapy.
With a median follow up time of 8 months (range 3-40), the median progression-free survival (PFS) was 5.8 months (95% CI, 3.6-8.0) and the median OS was 11.0 months (95% CI, 0.5–21.5).
Among the 17 patients who achieved a CR to Glofit + Pola, median PFS and OS were not reached. Two patients (12%) had subsequent relapse at 5 and 11 months, respectively after consolidative allogeneic SCT in one patient and CAR T-cell therapy in the other. One patient died from infectious encephalitis 6 months after treatment initiation. The remaining 14 patients (82%) were alive and in ongoing remission at a median follow-up of 6 months (range 3-36).
Eight patients were treated with Glofit monotherapy after a median of 2 (range 1-4) prior treatment lines. Median age was 42 years (range 20–61). Median number of treatment cycles was 11 (range 1–12) and one patient received consolidative treatment (allogenic SCT). CR rate after Glofit monotherapy was 63% (5/8), whereas 38% (3/8) had progressive disease. Median PFS and OS after Glofit monotherapy were not reached.
Conclusion
Based on these real-world data, Glofit +/- Pola appears to be highly active in refractory BL, including in patients with CNS involvement. The complete response rate to Glofit + Pola in second-line is higher than that reported with chemotherapy. Additional follow up (and 1-year PFS results) will be presented at the meeting.
DISCLOSURES
Theodora Agnes Maria Claushuis, MD, PhD: No relevant conflicts of interest to declare.