Novel Immunotherapy Agents for Acute Lymphoblastic Leukaemia
Acute lymphoblastic leukaemia (ALL) in adults has a survival rate of 40–50% at 5 years, with a high relapse rate after first-line chemotherapy. After relapse, results with salvage therapy are currently unsatisfactory. Therefore, both the optimisation of front-line therapy to reduce relapse incidence...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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European Medical Journal
2017-08-01
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| Series: | European Medical Journal |
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| Online Access: | https://www.emjreviews.com/hematology/article/novel-immunotherapy-agents-for-acute-lymphoblastic-leukaemia/ |
| _version_ | 1818261963160944640 |
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| author | David Pesántez Adela Rodriguez Aina Oliver-Caldés Pablo Mozas Jordi Esteve |
| author_facet | David Pesántez Adela Rodriguez Aina Oliver-Caldés Pablo Mozas Jordi Esteve |
| author_sort | David Pesántez |
| collection | DOAJ |
| description | Acute lymphoblastic leukaemia (ALL) in adults has a survival rate of 40–50% at 5 years, with a high relapse rate after first-line chemotherapy. After relapse, results with salvage therapy are currently unsatisfactory. Therefore, both the optimisation of front-line therapy to reduce relapse incidence and the search for effective salvage therapies for relapsed/refractory (r/r) ALL have been of great interest to the medical community in recent years. The well-characterised expression of well-defined cell-surface antigens in B cell ALL (B)-ALL and T cell (T)-ALL, such as CD19, CD20, CD22, and CD52, has led to the development of several immunotherapy strategies, comprising ‘nude’ monoclonal antibodies (moAbs), conjugated moAbs, bispeciphic, or highly sophisticated chimeric antigen receptor (CAR)-T cell therapy.
Recently, both the bispecific moAb blinatumomab (anti-CD19 coupled with a CD3 recognition subunit) and the conjugated anti-CD22 moAb inotuzumab-ozogamicin have resulted in higher remission rates (44% versus 25%, and 80.7% versus 29.4%, respectively) and survival advantages (median overall survival [OS]: 7.7 months versus 4 months, and 7.7 months versus 6.7 months, respectively) in patients with r/r B-ALL when compared to standard salvage chemotherapy-based regimens. On the other hand, preliminary reports show feasibility and unprecedented response rates of ≤90% in highly refractory children and adults treated with CAR-modified T cells targeting the B cell specific CD19 antigen, which seem to be durable in a significant proportion of patients. Furthermore, the addition of anti-CD20 moAb rituximab to front-line standard chemotherapy in patients with CD20+ B-ALL has resulted in a clinical benefit, with prolongation of response duration and survival (3-year leukaemia-free survival and OS: 70% versus 38%; p<0.001, and 75% versus 47%; p=0.003).
In conclusion, immunotherapy is currently providing additional options for high-risk ALL patients both in front-line or advanced phase. Nonetheless, the optimal positioning of these novel agents, specially in relation to allogeneic haematopoietic stem-cell transplantion, needs to be clarified. This article aims to review several of these new therapeutic immunotherapy options available for patients with adult ALL, as well as their specific toxicity profile. |
| first_indexed | 2024-12-12T18:55:34Z |
| format | Article |
| id | doaj.art-59ea131376a04796baae56f50cf4f93d |
| institution | Directory Open Access Journal |
| issn | 2397-6764 |
| language | English |
| last_indexed | 2024-12-12T18:55:34Z |
| publishDate | 2017-08-01 |
| publisher | European Medical Journal |
| record_format | Article |
| series | European Medical Journal |
| spelling | doaj.art-59ea131376a04796baae56f50cf4f93d2022-12-22T00:15:15ZengEuropean Medical JournalEuropean Medical Journal2397-67642017-08-0123121127Novel Immunotherapy Agents for Acute Lymphoblastic LeukaemiaDavid Pesántez0Adela Rodriguez1Aina Oliver-Caldés2Pablo Mozas3Jordi Esteve4Medical Oncology Department, Hospital Clínic of Barcelona, Barcelona, SpainMedical Oncology Department, Hospital Clínic of Barcelona, Barcelona, SpainHematology Department, Hospital Clínic of Barcelona, Barcelona, SpainHematology Department, Hospital Clínic of Barcelona, Barcelona, SpainHematology Department, Hospital Clínic of Barcelona, Barcelona, Spain; Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; University of Barcelona, Barcelona, SpainAcute lymphoblastic leukaemia (ALL) in adults has a survival rate of 40–50% at 5 years, with a high relapse rate after first-line chemotherapy. After relapse, results with salvage therapy are currently unsatisfactory. Therefore, both the optimisation of front-line therapy to reduce relapse incidence and the search for effective salvage therapies for relapsed/refractory (r/r) ALL have been of great interest to the medical community in recent years. The well-characterised expression of well-defined cell-surface antigens in B cell ALL (B)-ALL and T cell (T)-ALL, such as CD19, CD20, CD22, and CD52, has led to the development of several immunotherapy strategies, comprising ‘nude’ monoclonal antibodies (moAbs), conjugated moAbs, bispeciphic, or highly sophisticated chimeric antigen receptor (CAR)-T cell therapy. Recently, both the bispecific moAb blinatumomab (anti-CD19 coupled with a CD3 recognition subunit) and the conjugated anti-CD22 moAb inotuzumab-ozogamicin have resulted in higher remission rates (44% versus 25%, and 80.7% versus 29.4%, respectively) and survival advantages (median overall survival [OS]: 7.7 months versus 4 months, and 7.7 months versus 6.7 months, respectively) in patients with r/r B-ALL when compared to standard salvage chemotherapy-based regimens. On the other hand, preliminary reports show feasibility and unprecedented response rates of ≤90% in highly refractory children and adults treated with CAR-modified T cells targeting the B cell specific CD19 antigen, which seem to be durable in a significant proportion of patients. Furthermore, the addition of anti-CD20 moAb rituximab to front-line standard chemotherapy in patients with CD20+ B-ALL has resulted in a clinical benefit, with prolongation of response duration and survival (3-year leukaemia-free survival and OS: 70% versus 38%; p<0.001, and 75% versus 47%; p=0.003). In conclusion, immunotherapy is currently providing additional options for high-risk ALL patients both in front-line or advanced phase. Nonetheless, the optimal positioning of these novel agents, specially in relation to allogeneic haematopoietic stem-cell transplantion, needs to be clarified. This article aims to review several of these new therapeutic immunotherapy options available for patients with adult ALL, as well as their specific toxicity profile.https://www.emjreviews.com/hematology/article/novel-immunotherapy-agents-for-acute-lymphoblastic-leukaemia/acute lymphoblastic leukaemia (all)immunotherapyblinatumomabinotuzumab-ozogamicin (io)chimeric antigen receptor (car) t-cellsrituximab |
| spellingShingle | David Pesántez Adela Rodriguez Aina Oliver-Caldés Pablo Mozas Jordi Esteve Novel Immunotherapy Agents for Acute Lymphoblastic Leukaemia European Medical Journal acute lymphoblastic leukaemia (all) immunotherapy blinatumomab inotuzumab-ozogamicin (io) chimeric antigen receptor (car) t-cells rituximab |
| title | Novel Immunotherapy Agents for Acute Lymphoblastic Leukaemia |
| title_full | Novel Immunotherapy Agents for Acute Lymphoblastic Leukaemia |
| title_fullStr | Novel Immunotherapy Agents for Acute Lymphoblastic Leukaemia |
| title_full_unstemmed | Novel Immunotherapy Agents for Acute Lymphoblastic Leukaemia |
| title_short | Novel Immunotherapy Agents for Acute Lymphoblastic Leukaemia |
| title_sort | novel immunotherapy agents for acute lymphoblastic leukaemia |
| topic | acute lymphoblastic leukaemia (all) immunotherapy blinatumomab inotuzumab-ozogamicin (io) chimeric antigen receptor (car) t-cells rituximab |
| url | https://www.emjreviews.com/hematology/article/novel-immunotherapy-agents-for-acute-lymphoblastic-leukaemia/ |
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