https://orcid.org/0000-0003-1217-4385
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ABSTRACT
Introduction Bispecific antibodies (BsAbs) represent a novel and potentially effective approach in cancer immunotherapy. These antibodies feature two unique binding domains, enabling them to simultaneously attach to two antigens or two epitopes of a single antigen. Recently, a variety of BsAbs targeting distinct B-cell antigens and myeloid lineage-specific surface markers—such as CD19xCD3, CD38xCD3, and CD123xCD3—have demonstrated promising results in heavily pretreated relapsed/refractory acute lymphoblastic leukemia (R/R ALL) and relapsed/refractory acute myeloid leukemia (R/R AML) patients. Areas covered New trail results were reported by different research groups at the 65th annual meeting of the American Society of Hematology (ASH). We provide a summary of the latest progress in BsAbs for immunotherapy in adult acute leukemia. Expert opinion B-ALL is the most favored leukemia for treatment with BsAbs, unlike T-ALL and AML, which are limited in constructs and results. The clinical application of blinatumomab in the first-line setting, combined with other therapies, has clearly benefited these B-ALL patients, especially older adults, due to its lower toxicity. In the B-ALL relapsed/refractory setting, new combinations with blinatumomab are under investigation, such as PD-1 or CTLA-4 inhibitors. We believe that with more clinical trial results, it is possible that blinatumomab will be used in new clinical indications soon. No novel BsAbs developed for B-ALL have yielded better results.
Article highlights
New trial results were reported at the 65th ASH annual meeting.
B-ALL is the most favored leukemia for treatment with BsAbs.
Blinatumomab combined with other therapies, has clearly benefited the B-ALL patients in the first line setting, especially older adults, due to its lower toxicity.
In the B-ALL relapsed/refractory setting, blinatumomab combined with D-1 or CTLA-4 inhibitors are under investigation.
There are limited results for BsAbs treatment in T-ALL and AML patients.
Abbreviations
| ALL | = | acute lymphoblastic leukemia |
| AlloHCT | = | allogeneic hematopoietic cell transplantation |
| AML | = | acute lymphoblastic leukemia |
| ASH | = | American Society of Hematology |
| BsAbs | = | bispecific antibodies |
| CMML | = | chronic myelomonocytic leukemia |
| CMR | = | complete molecular response |
| CR | = | complete response |
| mCR | = | marrow complete remission |
| MDS | = | myelodysplastic syndrome |
| MRD | = | minimal residual disease |
| OS | = | overall survival |
| R/R | = | relapsed or refractory |
| HR | = | hazard ratio |
| CRi | = | incomplete count recovery |
| INO | = | inotuzumab ozogamicin |
| HCT | = | hematopoietic cell transplantation |
| T-ALL | = | T-cell acute lymphoblastic leukemia |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Author contribution statement
J Yu designed and directed the manuscript. L Han, H Xing and W Cao wrote the manuscript draft. J Yu revised the manuscript. Y Song and Z Jiang provided resources. All authors reviewed and approved the final manuscript.
Acknowledgments
The authors would like to thank all the patients and their families for participating in clinical trials testing the drugs mentioned in this review.