Navigating Advances in AML Treatment
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The European Hematology Association (EHA) Congress is a crucial event for oncologists and researchers to convene and discuss the latest breakthroughs in cancer treatment. EHA offers a platform to present new clinical data, debate treatment paradigms, and share innovative approaches. The 2024 Congress featured numerous abstracts on AML, providing fresh insights into therapeutic strategies and patient management. This e-newsletter highlights summaries of key abstracts, with additional information available on The Practical Hematologist website. These summaries emphasize the importance of staying updated on the latest research to enhance clinical practice and patient care. |
Highlighted Abstract Summaries
FLAG Regimen, Combined with Gemtuzumab (FLAG-GO) Results in Better Optimal Molecular Response and Outcomes, Compared to Combination with Idarubicin (FLAG-IDA) in Untreated Core Binding Factor AML
Authors: Gautam Borthakur, Farhad Ravandi, Tapan Kadia, Courtney DiNardo, et al
Background: Optimal molecular response (OMR) is a critical parameter impacting outcomes in core-binding factor (CBF) AML. The addition of gemtuzumab ozogamicin (GO) to the FLAG regimen (fludarabine, GCSF, cytarabine) has been associated with improved molecular and clinical outcomes compared to FLAG combined with idarubicin (IDA).
Overview & Results: This phase 2 trial monitored OMR and survival outcomes in newly diagnosed CBF-AML patients treated with FLAG-GO versus FLAG-IDA. A total of 179 patients were treated, with 85 receiving FLAG-GO and 94 receiving FLAG-IDA. The study found that OMR at the end of induction and consolidation was significantly higher in the FLAG-GO cohort (61% and 83%) compared to the FLAG-IDA cohort (41% and 56%). Overall survival at six years was 80% for FLAG-GO and 70% for FLAG-IDA, while relapse-free survival at six years was 76% for FLAG-GO and 58% for FLAG-IDA.
Relevance: These findings suggest that the FLAG-GO regimen leads to higher optimal molecular response rates and improved long-term outcomes in patients with de novo CBF AML compared to FLAG-IDA. This supports the use of FLAG-GO as a preferred induction/consolidation regimen for better patient outcomes.
Link to Abstract: Abstract P565
Pre-Induction with Four Weekly High-Dose Cytarabine Reduces Mortality Rate and Prolongs Progression-Free Survival in Acute Myelogenous Leukemia (AML): A Comparative Study
Authors: Maher Salamoon, Mehdi Balti
Background: AML remains one of the most challenging and lethal diseases, regardless of morphologic subtype and risk category. Traditional induction therapy, such as the standard (3+7) regimen, has limited success, prompting the need for innovative approaches to improve response and survival rates.
Overview & Results: This study aimed to evaluate the role of pre-induction with weekly high-dose cytarabine on response rate and relapse-free survival. The study involved 100 AML patients. Group I (50 patients) received the standard (3+7) regimen, while Group II (50 patients) received pre-induction with 3 grams of cytarabine on days 1, 8, 15, and 28, followed by the standard (3+7) regimen. Both groups underwent consolidation chemotherapy. Results showed that the response rate was significantly higher in Group II (62% vs. 45%, p=0.05). Group II also exhibited a lower mortality rate (15% decrease, p=0.03), better PFS (89 months vs. 13 months, p=0.05), and a better toxicity profile with shorter hospital stays post-induction (18 days vs. 25 days, median).
Relevance: This study demonstrates that pre-induction with high-dose cytarabine can significantly improve outcomes in AML patients by enhancing response rates, reducing mortality, and prolonging progression-free survival. This suggests a viable strategy to improve patient management and survival outcomes in AML. Implementing this pre-induction regimen could lead to better patient prognoses and a more efficient use of hospital resources.
Link to Abstract: Abstract PB2449
A Multicenter Real-World Analysis of Gemtuzumab Ozogamicin in the First-Line Treatment of CBF-AML
Authors: Philippe J. Muller, Sven Zukunft, Barbora Weinbergerová, Jiří Šrámek, et al
Background: Gemtuzumab ozogamicin (GO) added to cytarabine and daunorubicin significantly improved event-free survival (EFS) in the ALFA-0701 trial, leading to its approval for AML treatment. Although limited data exist on its use in core-binding factor AML (CBF-AML), a meta-analysis showed that GO addition significantly reduces relapse risk and improves overall survival (OS) in AML patients with favorable cytogenetics.
Overview & Results: This registry-based analysis compared outcomes of CBF-AML patients treated with intensive chemotherapy plus GO versus intensive therapy alone. The study included 265 patients, with similar baseline characteristics between the GO and non-GO cohorts. Composite complete remission rates were comparable (88.8% vs. 88.1%). After a median follow-up of 2.2 years for the GO cohort and 5.5 years for the non-GO cohort, 2-year EFS was 59% for GO and 47.6% for non-GO. OS was significantly better in the GO cohort (90.4% vs. 79.5%).
Relevance: These findings suggest that adding GO to frontline chemotherapy improves overall survival in CBF-AML patients, despite a longer platelet recovery time. This real-world data supports the use of GO in first-line treatment of CBF-AML to enhance patient outcomes by reducing the risk of relapse.
Link to Abstract: Abstract P580
Hypomethylating Agents + Venetoclax Therapy in Late Elderly AML: "To Be or Not to Be" Well Effective?
Authors: Lorenzo Rizzo, Marta Riva, Silvia Ferrari, Cosimo De Giorgio, et al
Background: AML significantly affects the elderly, with about one-third of patients being over 75 years old. Since 2020, the combination of hypomethylating agents (HMA) with venetoclax has enhanced the efficacy of less-intensive therapeutic options. Real-world data on this combination's effectiveness in the late elderly population remains limited.
Overview & Results: This retrospective study evaluated the feasibility, tolerance, safety, and efficacy of HMA + venetoclax in AML patients aged over 75 years, treated at a single center from 2020 onward. The study included 26 patients with a median age of 80.3 years. Patients received either azacitidine + venetoclax (58%) or decitabine + venetoclax (42%), with a total of 2 to 31 treatment cycles per patient. The best response (BR) included complete response (CR) in 25% of patients, and 37.5% achieved BR after two cycles. The only significant factor influencing response was previous HMA treatment. Median event-free survival (EFS) and overall survival (OS) were 5.8 and 6.3 months, respectively. Risk class and BR type were significant predictors of OS.
Relevance: This study highlights the feasibility and effectiveness of HMA + venetoclax in elderly AML patients, even in those over 75 years old. Despite the limitations of a retrospective analysis, the approach appears viable, with meaningful response rates and improved long-term survival. The study also emphasizes the importance of first-line treatment, as the loss of response or progression often leads to rapid patient death. Further prospective studies are needed to confirm the superiority of HMA + venetoclax regimens over best supportive care in this population.
Link to Abstract: Abstract PB2505
A Post Hoc Analysis of Outcomes of Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes Who Received Oral Azacitidine Maintenance Therapy in the QUAZAR AML-001 Study
Authors: Maria Teresa Voso, Stéphane De Botton, Michael Pfeilstöcker, et al
Background: AML with myelodysplasia-related changes (AML-MRC) accounts for 25%-34% of all AML cases and is associated with poor outcomes. The QUAZAR AML-001 study evaluated the efficacy of oral azacitidine (Oral-AZA) as maintenance therapy in AML patients post-remission who were ineligible for hematopoietic stem cell transplantation (HSCT).
Overview & Results: This post hoc analysis of the phase 3 QUAZAR AML-001 study aimed to report the outcomes of AML-MRC patients who received Oral-AZA versus placebo (PBO). Patients aged 55 years and older with AML in first remission and intermediate- or poor-risk cytogenetics were randomized to receive either Oral-AZA 300 mg or PBO daily for 14 days of a 28-day cycle. AML-MRC was identified using the 2008 World Health Organization criteria. In this analysis, 101 out of 472 patients had AML-MRC. The Oral-AZA arm included 56 AML-MRC patients, and the PBO arm included 45. Poor-risk cytogenetics were more common in AML-MRC patients compared to non-AML-MRC patients.
Median OS did not significantly differ between AML-MRC and non-AML-MRC patients in either treatment arm. However, median relapse-free survival (RFS) was significantly inferior for AML-MRC patients compared to non-AML-MRC patients in both treatment arms. Importantly, Oral-AZA significantly improved median OS (19.9 months vs 14.8 months) and RFS (7.5 months vs 3.7 months) compared to PBO for AML-MRC patients. The duration of measurable residual disease (MRD) negativity was also longer in the Oral-AZA group.
Relevance: This analysis indicates that Oral-AZA maintenance therapy significantly improves survival outcomes in AML-MRC patients, a group with a particularly poor prognosis. These findings suggest that Oral-AZA is an effective maintenance treatment option for this high-risk patient population.
Link to Abstract: Abstract S141
Improving Bone Marrow Microenvironment in Acute Myelogenous Leukemia Elderly Patients (AML) Through 2 Months of Pre-Induction with Azacitidine and Venetoclax
Author: Maher Salamoon
Background: AML is a heterogeneous disease traditionally treated with standard chemotherapy (3+7), which carries a high risk of mortality during the induction phase, especially in elderly patients. Recent treatments targeting FLT-3 and Bcl-2 have been combined with chemotherapy, but the induction mortality rate remains high. This study explores a new treatment method aimed at improving the bone marrow microenvironment to reduce induction mortality in elderly AML patients.
Overview & Results: This study included 20 elderly AML patients (aged 60-72, median age 66), excluding those with M3 AML. They underwent a pre-induction phase involving Azacitidine (75mg/m² for five consecutive days each month) and Venetoclax (200 mg daily) for two months. Bone marrow aspirations were performed monthly and compared with a control group of 30 similar-aged patients. Results showed a median blast clearance of 36% after the first month and 50% after the second month. Additionally, 75% of patients achieved normalization of white blood cell counts, and 90% achieved normalization of platelet counts. The mortality rate in the study group was 10%, compared to 60% in the control group. Patients achieving complete response (15 out of 20) proceeded with a (5+2) induction protocol followed by four consolidation cycles. The one-year progression-free survival (PFS) was 60%, and the overall survival (OS) at two years was also 60%.
Relevance: This study highlights the potential benefits of a pre-induction regimen with azacitidine and venetoclax in elderly AML patients, demonstrating significant improvements in bone marrow blast clearance, normalization of blood counts, and reduced induction mortality. These findings suggest a promising approach to improve outcomes in this high-risk patient group. Implementing this regimen could lead to better management of elderly AML patients, reducing induction-phase mortality and enhancing overall survival.
Link to Abstract: Abstract PB2448
Study of the Molecular Genetic Profile of High-Risk AML Patients Using Next Generation Sequencing
Authors: Ekaterina Motyko, Anna Kirienko, Daria Kustova, Tatiyana Gert, et al
Background: AML is characterized by significant genetic heterogeneity. The identification of recurrent mutations has enhanced our understanding of the disease, allowing for more precise risk stratification and targeted therapies. Despite these advancements, only a few mutations have been integrated into clinical risk models. The ELN 2022 recommendations have expanded the unfavorable prognosis group to include new molecular and cytogenetic markers. However, outcomes within this group vary significantly, necessitating further molecular-genetic profiling to develop personalized treatment approaches.
Overview & Results: This study aimed to analyze the molecular-genetic profile of high-risk AML patients using NGS and evaluate the prognostic impact of common genetic aberrations. The study included 30 high-risk AML patients according to ELN 2022 criteria, with a median age of 60 years. Patients underwent NGS to identify mutations in a targeted panel of 118 genes. A total of 137 mutations were identified across 58 genes, with frequent mutations in genes such as ASXL1, DNMT3A, PTPN11, SRSF2, and TP53. The presence of more than six mutations and mutations in ASXL1 and SRSF2 were associated with poorer overall survival. Specifically, patients with more than six mutations had a median survival of 10 months compared to 29 months for those with fewer mutations.
Relevance: The findings highlight the complexity of the molecular landscape in high-risk AML and underscore the importance of comprehensive genetic profiling for prognostication and treatment planning. The identification of specific mutations associated with poor outcomes, such as ASXL1 and SRSF2, can guide therapeutic decisions and inform the development of targeted therapies. Incorporating NGS into routine clinical practice may enhance risk stratification and enable more personalized treatment approaches, ultimately improving patient outcomes.
Link to Abstract: Abstract PB2394
Click here for more detailed summaries and insights into advances in AML as presented at EHA 2024.
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Supported by an educational grant from Pfizer, Inc.