TP53 Mutated Acute Myeloid Leukemia | Primary Research (KOL's Insight) | Market Intelligence | Epidemiology & Market Forecast-2035

For many fundamental processes, such as DNA repair, aging, senescence, and cancer, the TP53 protein is crucial. This has attracted a lot of interest. Acute myeloid leukemia (AML) is not well understood to be impacted by TP53. Contrary to many other types of human cancer, the majority of AMLs do not have genomic TP53 alterations. About 10% of patients with de novo acute myeloid leukemia (AML) have TP53 mutations. Despite the fact that TP53 mutations are significantly less common in AML than in other human cancers, they are associated with a poor response to chemotherapy and poor outcomes. For a long time, high-intensity chemotherapy, typically involving a combination of cytarabine and an anthracycline, was thought to be the standard of care for healthy patients. However, the most recent NCCN recommendations advise taking into account alternative induction methods in TP53-mutated disease.

Description

In addition to DNA repair, aging, senescence, and cancer, the TP53 protein is crucial for a number of fundamental processes. There has been a lot of interest in this. However, it is not known how TP53 affects acute myeloid leukemia (AML). Contrary to many other forms of human cancer, most AMLs do not have genomic TP53 alterations. It is becoming increasingly clear that the unaltered TP53 status of tumor cells can be used for therapeutic purposes. Because the TP53 gene is found in the majority of AMLs, its physiological tumor-suppressive functions may be used. Thus, clinical benefit from the use of pharmacological activators of the TP53 pathway in AML is possible. On the other hand, TP53 mutations are connected to chemoresistance and a high risk of relapse even though their frequency in AML is significantly lower than that of other human cancers. These alterations in TP53-mutant patients could lead to brand-new, focused vulnerabilities, opening the door for therapeutic targeting of TP53 mutant AML. The mutational status of TP53 presents opportunities and challenges for developing effective treatment approaches for AML. Despite being comparatively rare, TP53-mutated AML has been acknowledged as a significant molecular subgroup with arguably the worst prognosis of any. TP53 mutations are associated with complex cytogenetic abnormalities, advanced age, chemoresistance, and poor outcomes.

TP53 Mutated Acute Myeloid Leukemia (Epidemiology)

About 10% of patients with de novo acute myeloid leukemia (AML) have TP53 mutations. Even though TP53 mutations are more uncommon in AML than other human cancers, they are still associated with poor outcomes and a poor response to chemotherapy. Therefore, it is crucial to assess TP53 status in clinical procedures and academic research. TP53 mutations are present in about 5-15% of cases of AML. In 75% of these cases, it has been discovered to be the only mutated gene on NGS. Alterations to TP53, which are linked to older age, occur in up to 25% of elderly AML cases. Acute erythroblastic leukemia, therapy-related AML (t-AML), and these subtypes of AML are where TP53 mutations are most frequently found, despite the fact that they can be discovered in up to a third of cases of AML that has progressed from an underlying myeloproliferative neoplasm. A condition known as Li-Fraumeni syndrome, where there is a propensity for the development of additional solid tumor malignancies, may occur if the mutation is germline. Additionally, sporadic mutations are seen, which are frequently linked to exposure to carcinogens. The higher frequency of TP53 mutations in t-AML does not appear to be directly related to the development of chemotherapy-resistant hematopoietic stem cell clones with age-related TP53 mutations. With a potential growth rate of 1.9% over the forecast period, there will be 119,247 new cases of AML worldwide between 105,842 cases in 2019 and 2030. In the United States, there will be 21,530 cases of diagnosed acute myelogenous leukemia (AML) by 2030. Similar to this, 17,139 cases of AML will be diagnosed in the EU by 2030. With a potential growth rate of 1.9% over the forecast period, the global incidence of AML will rise from 105,842 cases in 2019 to 119,247 cases in 2030.

TP53 Mutated Acute Myeloid Leukemia -Current Market Size & Forecast Trends

The market for TP53-mutated acute myeloid leukemia (AML) is anticipated to grow significantly, with the overall AML treatment market valued at approximately USD 3.41 billion in 2024 and projected to reach around USD 12.63 billion by 2037, reflecting a compound annual growth rate (CAGR) of 10.6% during this period. TP53 mutations are associated with a more aggressive disease and resistance to standard therapies, which drives the demand for targeted treatments specifically addressing this mutation. The increasing incidence of AML, particularly in older populations, alongside advancements in personalized medicine and novel therapies, is expected to further boost market growth. North America is likely to dominate the market due to its advanced healthcare infrastructure and ongoing research efforts focused on improving outcomes for patients with TP53 mutations. Overall, the market for TP53-mutated AML is well-positioned for substantial expansion through 2035 as new treatment strategies continue to emerge.

For a long time, high-intensity chemotherapy, typically involving a combination of cytarabine and an anthracycline, was thought to be the standard of care for healthy patients. However, the most recent NCCN recommendations advise taking into account alternative induction methods in TP53-mutated disease. The discouraging outcomes following treatment with aggressive chemotherapy are reflected in the inclusion of TP53 mutations in the adverse-risk category by the ELN risk-stratification system. Patient outcomes from Phase 3 clinical trials that used mitoxantrone- or cytarabine-based induction or doxorubicin plus cytarabine as the induction were analyzed to develop this scoring system. Other studies have demonstrated that response rates after induction chemotherapy ranged from 20% to 42% with a median overall survival of 4-9 months. In addition, CPX-351, a more recent liposomal formulation of cytarabine and daunorubicin approved for the treatment of t-AML and AML with MRC, has been found to be less effective than expected when treated with it when the TP53 mutation is present. Hopes that TP53 mutations can be used therapeutically have been boosted by new therapeutic mechanisms used in the development of treatments. The two ways that immunotherapeutics have been improved are by bispecific DARTs and targeting new receptors. The mutated p53 protein is directly targeted by Eprenetapopt's, with some initial success. Even though these therapies have demonstrated encouraging results in early phase clinical trials, combining them may ultimately be necessary to achieve adequate responses that are also durable. Larger randomized trials are still needed to prove that these therapies are superior to those that are currently advised. Due to their similar biological traits and prognosis, recent research suggests that TP53-mutated AML and MDS with excessive blasts (MDS-EB) should be treated as a single disease entity. Given the relative rarity of TP53-mutated AML, this adaptation may simplify future clinical trial planning and eliminate existing drug approval hurdles, facilitating quicker access to TP53 targeted therapy. As treatments for AML and other myeloid disorders are created, it will be necessary to continue paying attention to the outcomes in the TP53-mutated population in order to find additional drugs that have activity in this environment. More effective treatments are still required for the challenging AML subgroup known as TP53-mutated disease.

Report Highlights

TP53 Mutated Acute Myeloid Leukemia - Current Market Trends

TP53 Mutated Acute Myeloid Leukemia - Current & Forecasted Cases across the G8 Countries

TP53 Mutated Acute Myeloid Leukemia - Market Opportunities and Sales Potential for Agents

TP53 Mutated Acute Myeloid Leukemia - Patient-based Market Forecast to 2035

TP53 Mutated Acute Myeloid Leukemia - Untapped Business Opportunities

TP53 Mutated Acute Myeloid Leukemia - Product Positioning Vis-a-vis Competitors' Products

TP53 Mutated Acute Myeloid Leukemia - KOLs Insight