Recent updates for antibody therapy for acute lymphoblastic leukemia
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xperimental Hematology & Oncology Open Access
REVIEW
Recent updates for antibody therapy for acute lymphoblastic leukemia Le Li and Ying Wang*
Abstract Acute lymphoblastic leukemia (ALL) is a hematologic malignancy arising from precursors of the lymphoid lineage. Conventional cytotoxic chemotherapies have resulted in high cure rates of up to 90% in pediatric ALL, but the outcomes for adult patients remain suboptimal with 5-year survival rates of only 30%-40%. Current immunotherapies exploit the performance of antibodies through several different mechanisms, including naked antibodies, antibodies linked to cytotoxic agents, and T-cell re-directing antibodies. Compared with chemotherapy, the application of an antibody–drug conjugates (ADC) called inotuzumab ozogamicin in relapsed or refractory (R/R) C D22+. ALL resulted in a complete remission (CR) rate of 81% and an overall median survival of 7.7 months with reduced toxicity. Similarly, blinatumomab, the first FDA-approved bispecific antibody (BsAb), produced a 44% complete response rate and an overall median survival of 7.7 months in a widely treated ALL population. In addition, approximately 80% of patients getting complete remission with evidence of minimal residual disease (MRD) achieved a complete MRD response with the use of blinatumomab. These results highlight the great promise of antibody-based therapy for ALL. How to reasonably determine the place of antibody drugs in the treatment of ALL remains a major problem to be solved for ongoing and future researches. Meanwhile the combination of antibody-based therapy with traditional standard of care (SOC) chemotherapy, chimeric antigen receptor (CAR) T-cell therapy and HSCT is also a challenge. Here, we will review some important milestones of antibody-based therapies, including combinational strategies, and antibodies under clinical development for ALL. Keywords: Acute lymphoblastic leukemia, Antibody–drug conjugates, T-cell redirecting antibodies, BiTE, Bispecific T cell engager, Blinatumomab, Bispecific antibody, Trispecific antibody Background The application of classical multi-agent chemotherapy in patients with ALL results in CR in more than 80% of patients. About 50% of newly diagnosed patients can achieve long-term disease control with further intensification or maintenance therapy. However 10% have initial refractory disease [1, 2]. What’s more, many patients with ALL will subsequently relapse after remission from initial chemotherapy. Due to practical constraints, prognosis of *Correspondence: [email protected] State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
R/R ALL remains grim. Treatment options are limited previously [3, 4]. Only 20–30% of these patients achieve a second complete remission with standard salvage chemotherapy [5]. Over 100 years ago, Paul Ehrlich, a German physician and scientist
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