TKI resistant- Chronic Myeloid Leukemia (CML) | Primary Research (KOL's Insight) | Market Intelligence | Epidemiology & Market Forecast-2035

The region of the BCR-ABL gene that codes for the BCR-ABL protein has undergone changes that result in TKI resistance in CML. Because of the mutations, some TKIs are unable to bind to the BCR-ABL protein efficiently. TKI may cease to function as a result. One TKI can overcome mutational resistance while other TKIs cannot be due to the slightly different ways that each TKI functions. Between 0 and 2.8 cases of chronic myelogenous leukemia are diagnosed annually. Men outnumber women by a factor of 100,000, and this difference gets larger as people get older. The observed differences may be caused by geographic and/or racial disparities as well as diagnostic precision. About 10% of newly diagnosed cases of leukemia are caused by the myeloproliferative disorder chronic myeloid leukemia (CML). The incidence of CML is rising as a result of the development of tyrosine kinase inhibitors (TKIs), which have decreased mortality.

Description

Changes in mutations of the region of the BCR-ABL gene that codes for the BCR-ABL protein lead to TKI resistance in CML. Some TKIs are unable to effectively bind to the BCR-ABL protein as a result of the mutations, which alter its shape. TKI might stop functioning as a result of this. Due to the slight variations in how each TKI functions, some TKIs are able to overcome mutational resistance while others are not. When CML is no longer responding to treatment or has become resistant to one TKI, switching to a different TKI may still produce a response. In order to achieve a macromolecular response and stop the progression of the disease into an accelerated or blast phase, TKI therapy must be fully effective within 12 months of starting treatment. The majority of patients receiving TKIs will experience a full hematologic recovery within three months of starting their treatment and a full cytogenetic recovery within six, twelve, or eighteen months. A full cellular response follows, and then BCR-ABL levels typically start to decline gradually. A test called BCR-ABL gene mutation analysis checks for BCR-ABL gene mutations that alter the BCR-ABL protein's shape in order to determine how well approved TKIs work. If the initial response to treatment is less than the response target or the follow-up period for a specific follow-up period, this test is advised. According to the findings of a multicenter study, next-generation sequencing (NGS) provided a more accurate indication of the BCR-ABL1 mutational status in CML patients who were not responding to TKI therapy than Sanger sequencing did. A myeloproliferative tumor called chronic myeloid leukemia (CML) is linked to molecular changes in the BCR-ABL1 fusion gene, which codes for the oncoprotein tyrosine kinase BCR-ABL1. Imatinib was the first TKI to receive approval, and this prompted the creation of tyrosine kinase inhibitors (TKIs). Although imatinib is effective for the majority of CML patients, resistance to this medication can result in treatment failure and relapse. The evolving picture of immune dysfunction and immune surveillance in chronic myelogenous leukemia emphasizes how important the immune system is for enhancing response to therapy in this type of leukemia. IFN-, the gold standard of early maintenance therapy, was interestingly used repeatedly to enhance TKIs during the TKI era because it had nonspecific, off-target effects on the immune system. To combat TKI resistance and/or intolerance, new micro-oncology strategies have emerged that target the immune system. These strategies include vaccines, ICI, and CAR-T cell therapy.

TKI resistant- Chronic Myeloid Leukemia (CML) (Epidemiology)

An annual incidence of 0-2-0,6 cases of chronic myelogenous leukemia. Men outnumber women by a factor of 100,000, and this difference grows steadily with age. The differences that have been observed may be a result of geographic and/or racial disparities as well as diagnostic precision. High doses of ionizing radiation or exposure to chemicals like benzene can both lead to CML. Because tyrosine kinase inhibitors (TKIs) are so commonly used, the incidence increased from 3.9 per 100,000 in 1985 to 11.9 per 100,000 in 2012. The program's most recent 8-year overall survival (OS) implementation rate was 89%. By 2022, 5,120 men and 3,740 women are expected to receive a new CML diagnosis, according to the American Cancer Society (ACS). According to the Emergency Management Association of America, 670 men and 550 women will die from CML in 2022, totaling 1,220 fatalities. The incidence and mortality of CML did not change significantly from 2009 to 2019. Based on data from 2015 to 2019, the age-adjusted rate of new cases was 1.9 per 100,000 person-years, and the death rate was 0.3 per 100,000 person-years.

TKI resistant- Chronic Myeloid Leukemia (CML) -Current Market Size & Forecast Trends

The market for TKI-resistant chronic myeloid leukemia (CML) is expected to grow significantly, driven by the increasing prevalence of CML and the need for effective treatments for patients who develop resistance to tyrosine kinase inhibitors (TKIs). As of 2023, the global CML treatment market was valued at approximately USD 7.51 billion and is projected to reach around USD 12.91 billion by 2032, with a CAGR of 6.20% during this period.

The emergence of new therapies specifically targeting TKI-resistant mutations, such as the T315I mutation, is a key driver of market growth. Drugs like ponatinib and asciminib have shown effectiveness against resistant cases, expanding treatment options for patients. Additionally, ongoing research into immunotherapies and novel agents aimed at overcoming resistance will likely contribute to market expansion through 2035.

North America is anticipated to dominate the market due to advanced healthcare infrastructure and significant investment in oncology research. However, challenges such as patent expirations of existing TKIs and cost-consciousness in treatment choices may impact growth rates in certain regions. Overall, the market for TKI-resistant CML is well-positioned for substantial growth as new therapeutic options continue to emerge.

About 10% of newly diagnosed cases of leukemia are caused by chronic myeloid leukemia (CML), a myeloproliferative disorder. Tyrosine kinase inhibitors (TKIs) were developed to reduce mortality, and as a result, the incidence of CML is rising. The majority of CML patients have chronic disease, of which approximately. If imatinib resistance is defined specifically, between 15 and 30% of people fit the bill. Imatinib resistance rates are significantly higher in more severe disease stages. The National Comprehensive Cancer Network's (NCCN's) and the European Leukemia Network's (ELN's) recommendations place a strong emphasis on patient monitoring to ensure they meet treatment milestones. Acquired resistance kinase domain point mutations in BCR-ABL1 have the strongest correlation with response loss. Dasatinib, Nilotinib, Bosutinib, Ponatinib, and the non-TKI omatinib mesuccinate are a few of the treatment options available for patients with imatinib-resistant CML. The patient's comorbidity status, prior treatments, comorbidities, treatment toxicity, and treatment objectives are just a few examples of the variables that influence the treatment modality selection. The preferred medications for the initial management of CML are tyrosine kinase inhibitors (TKIs). The first oral TKI to be approved for the treatment of CML was imatinib in May 2001. Second- and third-generation TKIs (such as dasatinib and nilotinib) were subsequently approved for use as first-line medications. In patients with chronic myeloid leukemia, TKI treatment significantly lowers mortality. Long-term TKI therapy decreased leukemic stem cells in a subset of patients, according to a Tang et al. study, Imatinib is outperformed by second-generation TKIs in terms of efficacy and has higher rates of CCyR and MMR. Also noted was a lower late conversion rate. Protein translation inhibitor Oacetaxin (Synribo) is used to treat chronic or refractory patients who have developed resistance to two or more TKIs (such as dasatinib, nilotinib, or imatinib) that cause CML.

Report Highlights

TKI resistant- Chronic Myeloid Leukemia (CML) - Current Market Trends

TKI resistant- Chronic Myeloid Leukemia (CML) - Current & Forecasted Cases across the G8 Countries

TKI resistant- Chronic Myeloid Leukemia (CML) - Market Opportunities and Sales Potential for Agents

TKI resistant- Chronic Myeloid Leukemia (CML) - Patient-based Market Forecast to 2035

TKI resistant- Chronic Myeloid Leukemia (CML) - Untapped Business Opportunities

TKI resistant- Chronic Myeloid Leukemia (CML) - Product Positioning Vis-a-vis Competitors' Products

TKI resistant- Chronic Myeloid Leukemia (CML) - KOLs Insight