By Jennifer Burke Elliott, Senior Scientific Director, Global Medical Affairs Oncology, Takeda
This article originally appeared on LinkedIn on November 16, 2020
Working in medical affairs at Takeda Oncology for more than a decade, I’ve had the opportunity to work across different disease areas with passionate, driven and inspiring colleagues who are dedicated to finding ground-breaking ways to meet the needs of people living with cancer, especially those in need of new treatment options. In my current role, I am a part of a team focused on research and development in higher-risk myelodysplastic syndromes (MDS) – for which there have been no novel advances in treatment in over ten years. People with higher-risk MDS have limited therapeutic options and poor outcomes, and only a minority are eligible for stem cell transplant, the only curative treatment.1
Takeda Oncology has a comprehensive clinical trial program evaluating investigational treatments for blood cancers, which we hope will contribute to improving outcomes for people living with cancer.
The Significant Gaps in MDS Treatment
MDS occurs when the blood-forming cells in a person’s bone marrow become abnormal, or dysplastic, and are unable to correctly make new blood cells. As a result, a person with MDS does not have enough normal blood cells, resulting in symptoms like fatigue, easy bruising, and frequent infection.2 MDS is classified into five categories – from very low-risk to very high-risk – based on blood counts, blast counts, mutations and cytogenetics. Higher-risk MDS is defined as intermediate, high or very high-risk on the International Prognostic Scoring System – Revised (IPSS-R), and these patients have a poorer prognosis.3 MDS can be fatal and approximately 40% of patients with higher-risk MDS transform into another aggressive cancer, acute myeloid leukemia (AML), which needs to be treated with urgency as the prognosis is even worse.4-6 Patients with higher-risk MDS often have low quality of life due to symptoms and the requirement for intrusive procedures, such as transfusions. Even with treatment, the survival for higher-risk MDS is approximately 15 months.7, 8
It is estimated that there are approximately 14,000 new cases of MDS reported every year in the U.S., with most cases diagnosed in people aged 70 or older.9 Patients with MDS are typically frail and have comorbid conditions, underscoring the need for new, effective therapies with a favorable safety profile. Hypomethylating agents (HMAs) are the current standard of care for higher-risk MDS, but response to these treatments is limited, and even with treatment, outcomes remain poor. Patients are urgently in need of new treatment options that extend survival, delay transformation to AML, and improve quality of life.
The Critical Need for Further Research
Conducting clinical trials that are designed to assess meaningful clinical endpoints can help address this need. One such measurement is event-free survival (EFS), which may be defined in clinical trials investigating MDS as death or the time to transformation to AML. While overall survival (OS) is the gold standard for clinical trial outcomes, it is important in investigations of higher-risk MDS to include specific measures that capture the two key outcomes for these patients – death and transformation to AML. Delaying these events is a critical goal of higher-risk MDS treatment.
Clinical trials investigating treatments for higher-risk MDS patients may also address other quality of life endpoints, such as reduced dependence on transfusions, reduced time in the hospital and reduced fatigue. As people with higher-risk MDS often have low blood cell counts, a treatment option that improves quality of life without being myelosuppressive – further decreasing blood counts – for example, is important. Fortunately, there are novel treatments on the horizon, that aim to help people with higher-risk MDS improve survival, delay transformation to AML, and maintain their quality of life.
Looking Forward: Takeda’s Continued Commitment
Takeda Oncology’s commitment to patients and history of investigating rare cancers provides us with the expertise to take the next leap forward and address the unique and urgent treatment needs of people living with cancer around the world.
We must continue to commit to research and clinical trials that investigate a range of outcome measures in order to truly improve treatment options. I am honored to be a part of a team that puts patients first in all that we do.
1 Bewersdorf, J.P. and Zeidan, A.M., Following in the footsteps of acute myeloid leukemia: are we witnessing the start of a therapeutic revolution for higher-risk myelodysplastic syndromes?, Leukemia & Lymphoma, 2020: 1-19
2 American Cancer Society. What Are Myelodysplastic Syndromes? https://www.cancer.org/cancer/myelodysplastic-syndrome/about/what-is-mds.html. Accessed November 2020.
3 Leukemia & Lymphoma Society. The International Prognostic Scoring System. https://www.lls.org/disease-information/myelodysplastic-syndromes/diagnosis/the-international-prognostic-scoring-system. Accessed November 2020.
4 Pfeilstocker, M., Tuechler, H., Sanz, G., et al. Time-dependent changes in mortality and transformation risk in MDS. Blood. 2016;128(7):902-910
5 Pfeilstocker, M., Tuechler, H., Sanz, G., et al. Time-dependent changes in mortality and transformation risk in MDS, supplemental material. Blood. 2016;128(7):1-28
6 Lene, S., Østgård, G., Medeiros, B. C., Epidemiology and impact of preceding or underlying disease in secondary acute myeloid leukemia. HemaSphere 2018; 2 | 153-155
7 Zeidan, A.M., Davidoff, A.J, Long, J.B., et al., Comparative clinical effectiveness of azacitidine versus decitabine in older patients with myelodysplastic syndromes British Journal of Haematology 2016: 175: 829-40
8 Bernal, T., Martinez-Camblor, P., Sanchez-Garcia, J., et al., Effectiveness of azacitidine in unselected high-risk myelodysplastic syndromes: results from the Spanish registry. Leukemia (2015) 29, 1875–1881
9 National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Myelodysplastic Syndromes, Chronic Myeloproliferative Disorders, and Chronic Myelomonocytic Leukemia. https://seer.cancer.gov/csr/1975_2016/browse_csr.php?sectionSEL=30&pageSEL=sect_30_table.02. Accessed November 2020.
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