The efficacy of targeted and immune‐based therapies in adults with <scp>TP53</scp>‐mutated acute lymphoblastic leukaemia
We retrospectively evaluated the treatment outcomes of 47 adult patients with TP53-mutated acute lymphoblastic leukaemia (ALL) treated with either blinatumomab, inotuzumab or/and CD19 CAR T-cell therapy. The complete remission with or without count recovery (CR/CRi) (negative minimal residual disease (MRD-) rate) following treatment with blinatumomab (n = 46), inotuzumab (n = 26) and CD19 CAR T cells (n = 6) was 58.7% (96.3%), 61.5% (60%) and 66.7% (75%) respectively. The median OS was 13.6 months (95% CI: 9.6-17.2) for all patients, and it was not significantly different based on the individual novel salvage therapy (p = 0.40). The 12-month leukaemia-free survival (LFS) for responders to blinatumomab, InO and CAR T cells was 20%, 11% and 0% (p = 0.743) respectively. Patients who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) post-response had improved 12-month LFS compared to those who did not (35% vs. 9%, p = 0.014). Among relapsed patients following blinatumomab, 11 (61%) presented with CD19-negative disease. Hence, targeted and immune-based therapies are effective in inducing high MRD-negative remission rates in adults with B-cell ALL harbouring TP53 mutations. Nonetheless, the durability of remission is short in the absence of allogeneic HCT consolidation and relapse frequently manifested as CD19-negative disease following blinatumomab.
Authors
- Ryan S. Jackson (ORCID: https://orcid.org/0000-0003-4626-2324)
- Vaibhav Agrawal (ORCID: https://orcid.org/0000-0002-6383-3777)
- Anthony S. Stein (ORCID: https://orcid.org/0000-0002-1786-1398)
- Vinod A. Pullarkat (ORCID: https://orcid.org/0000-0001-9129-3424)
- Amanda Blackmon (ORCID: https://orcid.org/0000-0003-0732-0800)
- Jose Tinajero (ORCID: https://orcid.org/0000-0002-1175-3564)
- Ahmed Aribi (ORCID: https://orcid.org/0000-0003-2497-3176)
- Stephen J. Forman (ORCID: https://orcid.org/0000-0002-2803-4152)
- Ibrahim Taha Aldoss (ORCID: https://orcid.org/0000-0001-9564-4498)
- Guido Marcucci
- Dat Ngo (ORCID: https://orcid.org/0009-0002-8848-2851)
- Monzr M. Al Malki (ORCID: https://orcid.org/0000-0001-8226-471X)
- Pamela S. Becker (ORCID: https://orcid.org/0000-0001-6235-9463)
- Andrew Artz (ORCID: https://orcid.org/0000-0003-0803-9607)
- Brian Ball (ORCID: https://orcid.org/0000-0001-8625-7023)
- Amandeep Salhotra (ORCID: https://orcid.org/0000-0002-9302-5041)
- Paul Koller (ORCID: https://orcid.org/0000-0003-3830-5320)
- Hoda Pourhassan (ORCID: https://orcid.org/0000-0003-3862-4612)
- Raju Pillai (ORCID: https://orcid.org/0000-0001-8553-4252)
- Salman Otoukesh (ORCID: https://orcid.org/0000-0002-7782-8805)
- Ryotaro Nakamura (ORCID: https://orcid.org/0000-0002-9082-0680)
- Huiyan Ma (ORCID: https://orcid.org/0000-0002-3335-4775)
Institutions
- City Of Hope National Medical Center (US)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1111/bjh.20260
- Citations
- 1
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 1.05