Acute Lymphocytic Leukemia (ALL)
Considering the gravity of acute lymphocytic leukemia (ALL) and the potential harm, researchers and pharma companies have actively engaged in investigating and formulating medications to combat this ailment. If you are interested in exploring drug development for ALL, Alfa Cytology recommends exploring the services we provide.
Introduction to ALL
ALL is a form of cancer that impacts both the blood and bone marrow. In ALL, these abnormal lymphoblasts, which are immature and incapable of functioning properly, rapidly proliferate and displace healthy cells in the bone marrow.
Types of ALL
ALL primarily impacts children, although it can manifest in adults as well. Approximately 6,000 cases of ALL are diagnosed annually in the United States, with over half of them occurring in children. Consequently, this hematological malignancy exhibits various classifications based on diverse cellular phenotypes and genetic attributes.
| B-cell ALL | The most prevalent subtype, accounts for approximately 80-85% of ALL cases. In this particular classification, there is a rapid proliferation and accumulation of abnormal lymphoblasts, which serve as precursor cells for B lymphocytes, within the bone marrow. |
| T-cell ALL | It comprises roughly 15-20% of ALL cases. Abnormal lymphoblasts in T-cell ALL originate as precursor cells for T lymphocytes and exhibit aberrant proliferation, thereby substituting normal cells. |
Therapeutic Market for ALL
In 2022, the therapeutic market for ALL was valued at $3.7942 billion. The market is growing due to an increase in the incidence of ALL and a surge in global bone marrow biopsies. Furthermore, increased investment in leukemia research and improving awareness of targeted therapies are driving market expansion. Currently, pharmaceutical companies such as Pfizer, Novartis, Bristol Myers Squibb, and Amgen hold a prominent position in the acute lymphoblastic leukemia market.
Therapeutic Therapies
The prognosis for ALL has significantly improved due to the introduction of tyrosine kinase inhibitors that target BCR-ABL1, monoclonal antibodies that target CD20, antibody-drug conjugates that target CD22, bispecific antibodies, and T-cell therapies utilizing CD19 chimeric antigen receptor. The emergence of these novel medications provides diverse therapy options for ALL.
- Chemotherapy
- Targeted therapy
- Immunotherapy
- Radiation therapy
- Allogeneic stem cell (bone marrow) transplantation
Fig. 1. New targeted therapy for acute lymphoblastic leukemia. (Malard, F.; Mohty, M., 2020)
Therapeutic antibodies have received significant attention in the development of drugs for ALL. Blinatumomab, constructed using antibody technology, is a bispecific CD19-directed CD3 T-cell engager. Inotuzumab ozogamicin represents a novel approach, utilizing a monoclonal antibody targeting CD22 conjugated to the toxin calicheamicin.
Drugs in Development
Despite the availability of some drugs for ALL therapy, challenges such as drug resistance, low efficacy, and the presence of side effects persist. Clinical trials are currently underway to test whether combinations of these therapy modalities can replace chemotherapy. Additionally, numerous researchers are actively seeking novel therapeutic approaches for ALL, including difficult-to-treat subtypes. The following section outlines several clinical trials investigating drug therapies for ALL.
| Drug | Study (phase) | Mechanism of action | Approved indication | Reference |
|---|---|---|---|---|
| Inotuzomab ozogamicin | III | ADC anti-CD22 | R/R B cell ALL | Kantarjian, H.M. et al., 2016 |
| Inotuzomab ozogamicin | I/II | ADC anti-CD2 | R/R ALL | DeAngelo, D.J. et al., 2017 |
| Inotuzomab ozogamicin | II | ADC anti-CD2/chemotherapy | R/R ALL | Jabbour, E. et al., 2018 |
| Blinatumomab | III | Anti CD3/CD19 | R/R B cell ALL | Kantarjian, H. et al., 2017 |
| Blinatumomab | II | Anti CD3/CD19 | Refractory MRD B-cell ALL | Gokbuget, N. et al., 2018 |
| Blinatumomab | II | Anti CD3/CD19 | R/R B-cell ALL | Martinelli, G. et al., 20117 |
| Tisagenlecleucel | II | Anti-CD19 CAR T cells | CD19+ B cell ALL that is refractory or in second or later relapse in patients up to 25 years of age | Maude, S.L. et al., 2018 |
As a leading service provider committed to delivering high-quality products and services, Alfa Cytology is dedicated to creating a significant impact on the lives of ALL through our innovative drug development endeavors. Contact us today to learn more about our services and how we can support your ALL drug development endeavors.
References
- Malard, F.; Mohty, M. Acute lymphoblastic leukaemia. The Lancet. 2020, 395(10230): 1146-1162.
- Kantarjian, H.M.; et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016, 375(8):740-53.
- DeAngelo, D.J.; et al. Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study. Blood Adv. 2017, 1: 1167-1180.
- Jabbour, E.; et al. Salvage chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD for patients with relapsed or refractory Philadelphia chromosomenegative acute lymphoblastic leukemia: a phase 2 clinical trial. JAMA Oncol. 2018, 4: 230-234.