C045 | Allogeneic Transplantation After Failure of Car-t Cells and Exposure to Bispecific Antibodies: Feasibility, Safety and Survival Outcomes
Year: 2025
Type: article
Abstract: Clinical outcome after Chimeric Antigen Receptor (CAR)T-cell failure in large B-cell lymphoma (LBCL) is dismal. Allogeneic stem cell transplantation (alloSCT) represents a potential curative salvage for relapsed/refractory LBCL, although concerns remain regarding its feasibility and safety in patients (pts) exposed to CAR-T and bispecific antibodies (BsAb). Between 2019 and 2025, within the prospective observational CAR-T SIE study, 83 disease progression were documented among 170 LBCL pts treated with CAR-T in two academic centers; 69 started salvage treatment, the most frequent being glofitamab in 38; among those, we retrospectively analysed outcomes of 35 who were also candidates to alloSCT consolidation. In 35 alloSCT candidates receiving BsAb, median progression-free-survival was 8.8 months; overall response rate was 63%, while 34% were refractory to BsAb. Ultimately, 13 (37%) underwent transplantation after achieving complete (n=11) or partial response (n=2), after either glofitamab (n=8) or subsequent treatments (n=5). The reasons for not proceeding to alloSCT in 22 pts were disease progression (n=15), patient’s choice (n=4), lack of donor (n=1), SARS-CoV-2-related death (n=1) and ongoing BsAb treatment (n=1). Compared to non-transplanted pts, allografted pts were younger (median age 48 vs 61 years, p=0.006), while histology, disease burden, CAR-T product, refractoriness to CAR-T or BsAb, time to CAR-T failure and number of previous treatments were similar between the two groups (p > 0.05). In 13 allografted pts, median number of previous therapies was 5 (range [r] 3-9); median time from last glofitamab to alloSCT was 66 days (r 34-369) (Table 1). Comorbidity score index (HCT-CI) was low in 69% (9) pts. All pts received reduced intensity conditioning regimens; all engrafted, and full donor chimerism was documented in all pts at +30 and +90. Acute and chronic graft-versus-host-disease occurred in 46% and 30% pts, respectively. Non-relapse mortality was 0%. At median follow-up of 18.4 months (IQR 14.5-38), all allografted pts are alive in complete remission (CR). Conversely, outcomes of 22 non-allografted pts were poor, with a median overall survival of 11.3 months after CAR-T failure and 13 (59%) disease-related deaths. In conclusion, although in a small cohort of patients, our data highlight the potential benefit of alloSCT consolidation in selected responders to salvage regimens despite extensive prior treatments with T-cell redirecting therapies.
Authors: A. Barone, C. De Philippis, F. Stella, A. Dodero, M. Pennisi, A. Santoro, C. Carlo-Stella, A. Guidetti, S. Bramanti, and P. Corradini
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093122431
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