Welcome to our comprehensive review of the latest AML research from the 2024 ASCO Annual Meeting. Below, you will find summaries of key abstracts highlighting advancements in treatment strategies, clinical outcomes, and innovative therapies in acute myeloid leukemia. Click on any title in the bulleted list to read the full abstract summary.
- Multi-Drug Algorithm to Accurately Predict Best First-Line Treatments in ND AML
- Frailty Risk Assessment and Impact on AML Outcomes (FRAIL-AML)
- Real-World Retrospective Study of Oral vs IV HMA-Induced Toxicity in MDS and AML Treatment
- Real-World Antiemetic Use and Its Association with Duration of Oral-AZA Maintenance in AML Patients
- Clinical Outcomes of AML Patients Receiving VEN-HMA in Academic and Academic-Community Partnerships
- Safety Outcomes in AML Patients Receiving Gemtuzumab Ozogamicin and Proceeding to Allogeneic HSCT
- Safety Outcomes in Adult AML Patients Who Achieved Their First Complete Remission with Gemtuzumab Ozogamicin Prior to HSCT
- Patients with RR mIDH1 AML Who Proceeded to Transplant After Olutasidenib Treatment
- Safety and Efficacy of Olutasidenib Treatment in Elderly Patients with RR mIDH1 AML
- Olutasidenib for mIDH1 AML: Final Five-Year Results from the Phase 2 Pivotal Cohort
- A Post-Hoc Analysis of Outcomes of Patients with AML with Myelodysplasia-Related Changes (AML-MRC) Who Received Oral-AZA Maintenance Therapy in the QUAZAR AML-001 Study
- Evaluation of the Toxicity and Outcomes of the Combination of Midostaurin and CLAG-M in Patients with FLT3-Mutated AML
- FLAG-IDA + VEN in ND or RR AML
- VEN-HMA for Favorable Risk AML: A Single Center Experience
- A Prospective Study of All-Trans Retinoic Acid Plus VEN-AZA in ND AML
- A First-in-Human Phase 1, Multicenter, Open-Label Study of CB-012, a Next-Generation CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy for Adults with RR AML (AMpLify)
- Phase I Study of Functionally Enhanced CD33 CAR-T Cells in RR AML Patients
- Preliminary Safety, Efficacy, and Molecular Characterization of Emavusertib (CA-4948) in Patients with R/R AML with FLT3 Mutation
- A Phase 1b/2 Study of Pivekimab Sunirine (PVEK, IMGN632) in Combination with VEN-AZA for Patients with ND CD123-Positive AML
- Identifying Eligibility Criteria That Perpetuate Race/Ethnic Disparities in AML Clinical Trial Participation
- Inequities in Timely Treatment Initiation for Patients with AML Treated in a Predominantly Community Setting in the US
Abstract # 6525
Multi-Drug Algorithm to Accurately Predict Best First-Line Treatments in Newly Diagnosed Acute Myeloid Leukemia
Authors: Pedro Rodriguez Cutillas, Weronika E. Borek, Josie A. Christopher, et al.
This study developed a multi-drug algorithm using phosphoproteomics to predict the most effective first-line treatments for newly diagnosed AML patients. The algorithm was tested on 138 patients treated with MIC (midostaurin plus intensive chemotherapy), VA (venetoclax plus azacitidine), or IC (intensive chemotherapy). The algorithm accurately stratified patients into good responders (GR) and poor responders (PR), outperforming current stratification methods with over 90% accuracy.
The findings demonstrate that phosphoproteomics can accurately predict treatment responses, potentially improving patient outcomes. This study supports the development of a predictive tool for AML treatment planning.
Relevance: For oncologists, this predictive algorithm offers a new tool to tailor first-line AML treatments, enhancing personalized therapy and improving patient outcomes.
Reference: Pedro Rodriguez Cutillas et al., Multi-drug algorithm to accurately predict best first-line treatments in newly-diagnosed acute myeloid leukemia (AML). JCO 42, 6525-6525(2024).
DOI:10.1200/JCO.2024.42.16_suppl.6525
Abstract # 6506
Frailty Risk Assessment and Impact on Acute Myeloid Leukemia Outcomes (FRAIL-AML): A Population-Based Study from Ontario, Canada
Authors: Gopila Gupta, Sho Podolsky, Ning Liu, et al.
This population-based study from Ontario, Canada, examined the impact of frailty on AML outcomes using the McIsaac's frailty index (MFI). Among 5,450 patients, 65% received intensive treatment (IT) and 35% received non-intensive treatment (NIT). Frailty was associated with worse overall survival (OS) in both IT and NIT groups. The study identified a mismatch in treatment intensity based on frailty status, with 30% of frail patients receiving IT and over 25% of fit patients receiving NIT.
The findings highlight the importance of frailty assessment in optimizing AML treatment decisions. This study supports the integration of standardized frailty evaluations in clinical practice.
Relevance: For oncologists, these results underscore the need for frailty assessments to guide treatment intensity, improving AML patient outcomes through personalized therapy.
Reference: Gopila Gupta et al., Frailty risk assessment and impact on acute myeloid leukemia outcomes (FRAIL-AML): A population-based study from Ontario, Canada. JCO 42, 6506-6506(2024). DOI:10.1200/JCO.2024.42.16_suppl.6506
Abstract # e18534
Real-World Retrospective Study of Oral Versus Intravenous HMA-Induced Toxicity in MDS and AML Treatment
Authors: Julia Palecki, Andrew Bernstein, Leland F. Damron, et al.
This retrospective study compares the toxicity profiles of oral versus intravenous (IV) hypomethylating agents (HMAs) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The study included 33 patients treated with either oral or IV HMAs. Results showed no significant differences in the severity of cytopenias or rates of severe adverse effects between the two administration routes. Both oral and IV HMA therapies had comparable rates of neutropenic fever, severe anemia, nausea, and fatigue.
The findings suggest that oral HMAs induce similar levels of myelosuppression as IV HMAs and have comparable safety profiles. This study supports the use of oral HMAs as a safe and effective alternative to IV HMAs.
Relevance: These results are valuable for oncologists considering HMA therapy options, indicating that oral HMAs can be a safe and convenient alternative to IV administration, potentially improving patient compliance and convenience.
Reference: Julia Palecki et al., Real-world retrospective study of oral versus intravenous HMA-induced toxicity in MDS and AML treatment. JCO 42, e18534-e18534(2024). DOI:10.1200/JCO.2024.42.16_suppl.e18534
Abstract # e23259
Real-World (RW) Antiemetic Use and Its Association with Duration of Oral Azacitidine (Oral-AZA) Maintenance in Patients with Acute Myeloid Leukemia (AML) in the United States (US)
Authors: Ying Qiu, Jiafan Chen, Derek Tang, et al.
This retrospective study examines the use of antiemetics and their association with the duration of oral azacitidine (Oral-AZA) maintenance therapy in AML patients. Among 189 patients, less than half received antiemetics at the start of Oral-AZA therapy. Patients with antiemetic coverage for the first two cycles had a median of 8.5 Oral-AZA cycles, compared to 6 cycles for those without. The median duration of therapy (DoT) was longer for patients with antiemetic coverage (258 days vs. 154 days).
The findings suggest that antiemetics are underutilized in real-world practice, potentially reducing the duration of Oral-AZA maintenance therapy. This study supports the guideline-recommended use of antiemetics to improve therapy adherence and outcomes.
Relevance: These results emphasize the importance of following antiemetic guidelines for AML patients on Oral-AZA, helping oncologists improve treatment adherence and achieve better clinical outcomes.
Reference: Ying Qiu et al., Real-world (RW) antiemetic use and its association with duration of oral azacitidine (Oral-AZA) maintenance in patients (pts) with acute myeloid leukemia (AML) in the United States (US). JCO 42, e23259-e23259(2024). DOI:10.1200/JCO.2024.42.16_suppl.e23259
Abstract # e23235
Clinical Outcomes of Patients Receiving Venetoclax and Hypomethylating Agents for AML in Academic and Academic-Community Partnerships
Authors: Natalie Pham, Jeffrey Lantz, Caroline Jones, et al.
This study compared treatment outcomes for AML patients receiving venetoclax and hypomethylating agents (HMAs) in academic centers versus community practices partnered with academic centers. Among 92 patients, the overall survival (OS) and overall response rate (ORR) were similar between the academic (57 patients) and community (35 patients) settings. The complete remission (CR) rates were also comparable, though the academic setting showed slightly higher CR rates after the second and third cycles of therapy. Adverse events were similar, except for increased fatigue and diarrhea in the academic setting.
The findings suggest that AML treatment outcomes in community settings, when supported by academic centers, are comparable to those in academic settings. This partnership model supports the viability and safety of community-based AML treatment.
Relevance: These results demonstrate the feasibility and safety of community-based AML treatment with academic support, helping oncologists expand treatment access while maintaining high standards of care.
Reference: Natalie Pham et al., Clinical outcomes of patients receiving venetoclax and hypomethylating agents for AML in academic and academic-community partnerships. JCO 42, e23235-e23235(2024). DOI:10.1200/JCO.2024.42.16_suppl.e23235
Abstract # 6516
Safety Outcomes in Patients with Acute Myeloid Leukemia Receiving Gemtuzumab Ozogamicin and Proceeding to Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Partow Kebriaei, Vincent Ho, Miguel-Angel Perales, et al.
This study assessed the safety of gemtuzumab ozogamicin (GO) in adult AML patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). The study included 157 patients, with 84 in first complete remission (CR1), 48 in second remission (CR2), and 25 in third or greater remission, relapse, or primary induction failure. Non-fatal hepatic veno-occlusive disease (VOD) was reported in 4% of patients, with no VOD-related deaths. The six-month transplant-related mortality (TRM) was 8%, and the 100-day VOD incidence was 5%. Median follow-up was 12.9 months.
The findings suggest that GO is safe prior to HSCT, with VOD and TRM rates comparable to historical data. No new safety concerns were identified, indicating that GO does not significantly increase the risk of serious adverse events post-HSCT.
Relevance: These results support the continued use of GO in AML patients preparing for HSCT, offering reassurance to oncologists about its safety and reinforcing its inclusion in pre-HSCT regimens.
Reference: Partow Kebriaei et al., Safety outcomes in patients with acute myeloid leukemia receiving gemtuzumab ozogamicin and proceeding to allogeneic hematopoietic stem cell transplantation. JCO 42, 6516-6516(2024). DOI:10.1200/JCO.2024.42.16_suppl.6516
Abstract # e18504
Safety Outcomes in Adult Patients with AML Who Achieved Their First Complete Remission with GO Prior to HSCT
Authors: Nelli Bejanyan, Vincent Ho, Miguel-Angel Perales, et al.
This study explored the safety of GO in AML patients in first complete remission (CR1) undergoing HSCT. Among 84 patients, non-fatal hepatic veno-occlusive disease (VOD) occurred in 7%, with most cases being mild, and no VOD-related deaths. The cumulative incidences of transplant-related mortality (TRM) were 7% at 6 months and 15% at 2 years. The 2-year relapse rate was 26%, and leukemia-free survival (LFS) outcomes at 1 and 2 years were 68% and 59%, respectively. Median follow-up was 23.9 months.
The findings suggest that GO prior to HSCT is safe, with low post-transplant VOD rates and comparable TRM and survival outcomes to historical rates. This study supports the use of GO in AML patients in CR1 before undergoing HSCT.
Relevance: For practicing oncologists, these results provide evidence supporting the safety profile of GO in AML patients achieving CR1 before HSCT, underscoring its potential benefits in clinical practice.
Reference: Nelli Bejanyan et al., Safety outcomes in adult patients with AML who achieved their first complete remission with GO prior to HSCT. JCO 42, e18504-e18504(2024). DOI:10.1200/JCO.2024.42.16_suppl.e18504
Abstract # e18516
Patients with Relapsed/Refractory mIDH1 AML Who Proceeded to Transplant After Olutasidenib Treatment
Authors: Stéphane De Botton, Justin M. Watts, Brian Andrew Jonas, et al.
This study evaluates the outcomes of relapsed/refractory (R/R) mIDH1 AML patients who proceeded to hematopoietic stem cell transplantation (HSCT) after achieving remission with olutasidenib (OLU). Among 153 patients treated with OLU, 16 proceeded to HSCT. The response rate to OLU was 75%, with 69% achieving complete remission (CR) and 6% CR with partial hematologic recovery (CRh). At 100 days post-HSCT, all patients were alive, and the overall survival probability was 94% at 12 months and 61% at 24 months.
The findings suggest that OLU is effective in achieving remission in R/R mIDH1 AML patients, enabling them to proceed to potentially curative HSCT. This study supports the use of OLU as a bridging therapy to HSCT in this patient population.
Relevance: For practicing oncologists, these results highlight the potential of OLU to enable HSCT in R/R mIDH1 AML patients, offering a pathway to improved survival outcomes in a difficult-to-treat population.
Reference: Stéphane De Botton et al., Patients with relapsed/refractory mIDH1 AML who proceeded to transplant after olutasidenib treatment. JCO 42, e18516-e18516(2024). DOI:10.1200/JCO.2024.42.16_suppl.e18516
Abstract # 6527
Safety and Efficacy of Olutasidenib Treatment in Elderly Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia
Authors: Stéphane De Botton, Brian Andrew Jonas, P. Brent Ferrell, et al.
This study evaluated the safety and efficacy of olutasidenib (OLU) in elderly patients (≥75 years) with relapsed/refractory (R/R) mIDH1 AML. Among 153 patients, 45 were elderly, with a median age of 79 years. The overall response rate (ORR) was 47%, with 31% achieving complete remission (CR) or CR with partial hematologic recovery (CRh). Grade 3 or 4 adverse events were reported in 45.8% of elderly patients, with the most common being decreases in red blood cells, platelets, and neutrophils, as well as febrile neutropenia. Median duration of CR/CRh was 25.9 months.
The findings suggest that olutasidenib is generally well tolerated in elderly patients and can induce durable remissions. Despite the challenges of treating elderly patients who have failed prior AML treatments, this study supports the potential benefits of olutasidenib in this population.
Relevance: These results are important for oncologists treating elderly AML patients, highlighting olutasidenib as a viable treatment option with manageable safety profiles and significant clinical benefits.
Reference: Stéphane De Botton et al., Safety and efficacy of olutasidenib treatment in elderly patients with relapsed/refractory mIDH1 acute myeloid leukemia. JCO 42, 6527-6527(2024). DOI:10.1200/JCO.2024.42.16_suppl.6527
Abstract # 6528
Olutasidenib for Mutated IDH1 Acute Myeloid Leukemia: Final Five-Year Results from the Phase 2 Pivotal Cohort
Authors: Jorge E. Cortes, Brian Andrew Jonas, Justin M. Watts, et al.
This study presents the final five-year results of olutasidenib, an mIDH1 inhibitor, in relapsed/refractory (R/R) AML patients. Among 153 patients, the complete remission (CR) rate was 32%, with a median duration of 25.3 months. The overall response rate was 48%, with a median overall survival of 11.6 months. In patients refractory to venetoclax, 33% achieved CR, with ongoing remissions at 54.3 months. The long-term safety profile remained consistent with no new adverse events.
The findings confirm the durability and safety of olutasidenib in heavily pretreated mIDH1 AML patients. This study supports the long-term use of olutasidenib in this population.
Relevance: These results highlight olutasidenib as a durable and safe treatment option for R/R mIDH1 AML, providing oncologists with long-term efficacy data.
Reference: Jorge E. Cortes et al., Olutasidenib for mutated IDH1 acute myeloid leukemia: Final five-year results from the phase 2 pivotal cohort. JCO 42, 6528-6528(2024). DOI:10.1200/JCO.2024.42.16_suppl.6528
Abstract # 6522
A Post-Hoc Analysis of Outcomes of Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Who Received Oral Azacitidine (Oral-AZA) Maintenance Therapy in the QUAZAR AML-001 Study
Authors: Maria Teresa Voso, Stéphane De Botton, Michael Pfeilstöcker, et al.
This post-hoc analysis of the QUAZAR AML-001 study evaluates the efficacy of oral azacitidine (Oral-AZA) maintenance therapy in patients with AML-MRC. AML-MRC patients generally have poor outcomes. The analysis showed that Oral-AZA significantly prolonged median overall survival (OS) and relapse-free survival (RFS) compared to placebo (PBO), with median OS of 19.9 months versus 14.8 months, and median RFS of 7.5 months versus 3.7 months. The duration of measurable residual disease (MRD) negativity was also significantly longer with Oral-AZA.
The findings suggest that Oral-AZA is an effective maintenance therapy for AML-MRC patients, significantly improving survival outcomes. This study supports the use of Oral-AZA in patients with AML-MRC, providing a new treatment option for this high-risk group.
Relevance: For oncologists, these results highlight Oral-AZA as a beneficial maintenance therapy for AML-MRC patients, offering improved survival and MRD negativity duration in a population with typically poor prognosis.
Reference: Maria Teresa Voso et al., A post-hoc analysis of outcomes of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) who received oral azacitidine (Oral-AZA) maintenance therapy in the QUAZAR AML-001 study. JCO 42, 6522-6522(2024).
DOI:10.1200/JCO.2024.42.16_suppl.6522
Abstract # 6523
Evaluation of the Toxicity and Outcomes of the Combination of Midostaurin and CLAG-M in Patients with FLT3-Mutated Acute Myeloid Leukemia (AML): A Multi-center Retrospective Analysis
Authors: Ashley Wen Chen, Grace Tonghwa Baek, Shannon Palmer, et al.
This retrospective study assessed the safety and efficacy of combining midostaurin with CLAG-M (cladribine, high-dose cytarabine, G-CSF, and mitoxantrone) in FLT3-mutated AML patients. Eighty patients were included, with 35 receiving CLAG-M and 44 receiving 7+3 chemotherapy. The combination showed comparable toxicity profiles, except for higher rates of diarrhea and bleeding events in the 7+3 cohort. The complete remission (CR) rate did not significantly differ between the cohorts, with 86% for CLAG-M and 70% for 7+3.
The findings suggest that CLAG-M combined with midostaurin is as safe and effective as the standard 7+3 regimen for FLT3-mutated AML patients. This study supports the use of CLAG-M as an alternative treatment option.
Relevance: These results provide oncologists with evidence supporting the use of CLAG-M plus midostaurin, offering a viable treatment option for FLT3-mutated AML patients.
Reference: Ashley Wen Chen et al., Evaluation of the toxicity and outcomes of the combination of midostaurin and CLAG-M in patients with FLT3-mutated acute myeloid leukemia (AML): A multi-center retrospective analysis. JCO 42, 6523-6523(2024). DOI:10.1200/JCO.2024.42.16_suppl.6523
Abstract # 6519
FLAG-IDA + Venetoclax in Newly Diagnosed (ND) or Relapsed/Refractory (RR) AML
Authors: Wei Ying Jen, Koichi Takahashi, Sanam Loghavi, et al.
This phase 2 study evaluated the FLAG-IDA+VEN regimen in 134 AML patients, including newly diagnosed (ND) and relapsed/refractory (RR) cases. In ND patients, the overall response rate (ORR) was 99%, with 96% achieving complete remission with incomplete hematologic recovery (CRc) and 89% achieving MRD negativity. Similar responses were observed across different European LeukemiaNet (ELN) risk groups. In RR patients, the ORR was 70%, with a 66% CRc rate. Median follow-up was 30 months, with high overall survival (OS), event-free survival (EFS), and duration of response (DOR) rates.
The findings highlight the high efficacy of FLAG-IDA+VEN in both ND and RR AML patients, with impressive survival outcomes and manageable adverse events. This regimen shows particular promise in TP53 wild-type patients.
Relevance: These results highlight the potential of FLAG-IDA+VEN as a robust treatment option for both newly diagnosed and relapsed/refractory AML patients, offering high response rates and improved survival outcomes, which are crucial for clinical decision-making.
Reference: Wei Ying Jen et al., FLAG-IDA + venetoclax in newly diagnosed (ND) or relapsed/refractory (RR) AML. JCO 42, 6519-6519(2024). DOI:10.1200/JCO.2024.42.16_suppl.6519
Abstract # e18514
Venetoclax Combined with Hypomethylating Agents for Favorable Risk Acute Myeloid Leukemia: A Single Center Experience
Authors: Shammas Bajwa, Brian Parkin, Arlene A. Gayle, et al.
This retrospective study evaluated the efficacy of venetoclax combined with hypomethylating agents (HMA-Ven) in favorable risk AML (FR-AML) patients. Twelve patients were treated with HMA-Ven, achieving a 100% complete remission (CR) rate after one cycle. The 1-year overall survival (OS) was 80%, with most patients surviving beyond one year. The regimen was well-tolerated, with only two patients experiencing relapse.
The findings suggest that HMA-Ven is an effective treatment for FR-AML, providing high remission rates and good survival outcomes. This study supports the use of HMA-Ven in FR-AML patients who are not candidates for high-intensity induction therapy.
Relevance: These results offer oncologists an effective alternative for treating FR-AML patients, demonstrating the potential of HMA-Ven to achieve high remission rates and favorable survival outcomes.
Reference: Shammas Bajwa et al., Venetoclax combined with hypomethylating agents for favorable risk acute myeloid leukemia: A single center experience. JCO 42, e18514-e18514(2024). DOI:10.1200/JCO.2024.42.16_suppl.e18514
Abstract # 6545
A Prospective Study of All-Trans Retinoic Acid Plus Venetoclax and Azacitidine in Newly Diagnosed Acute Myeloid Leukemia
Authors: Chengyuan Gu, Ruju Wang, Huizhu Kang, et al.
This prospective study evaluated the efficacy and safety of combining all-trans retinoic acid (ATRA) with venetoclax and azacitidine (AZA) in newly diagnosed AML patients. Among 35 patients, the composite complete remission (CR) rate was 74% after the first cycle and 91% after the second cycle. The median event-free survival was 390 days, and overall survival was 573 days. The combination regimen showed reduced hematologic toxicities, with significant improvements in transfusion independence.
The findings suggest that the ATRA plus venetoclax and AZA regimen is effective and well-tolerated in newly diagnosed AML patients. This study supports the use of this combination as a promising treatment option.
Relevance: These results provide oncologists with a new combination therapy that offers high remission rates and improved survival in newly diagnosed AML patients.
Reference: Chengyuan Gu et al., A prospective study of all-trans retinoic acid plus venetoclax and azacitidine in newly diagnosed acute myeloid leukemia. JCO 42, 6545-6545(2024). DOI:10.1200/JCO.2024.42.16_suppl.6545
Abstract # TPS6586
A First-in-Human Phase 1, Multicenter, Open-Label Study of CB-012, a Next-Generation CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy for Adults with Relapsed/Refractory Acute Myeloid Leukemia (AMpLify)
Authors: Naval Guastad Daver, Abhishek Maiti, David Andrew Sallman, et al.
This phase 1 study evaluates CB-012, a next-generation CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy, in adults with relapsed/refractory (R/R) AML. CB-012 is designed to target CLL-1 on AML blasts and leukemic stem cells while avoiding hematopoietic stem cells. The trial uses a 3+3 dose escalation design to determine the safety, tolerability, and recommended phase 2 dose (RP2D) of CB-012. Preliminary results from murine models show significant tumor burden reduction and increased survival.
The findings suggest that CB-012 may offer a novel and effective CAR-T cell therapy for AML patients. The study is ongoing, with dose escalation actively enrolling patients.
Relevance: These preliminary results are significant for oncologists, indicating a promising new therapeutic approach for R/R AML patients using advanced CRISPR-edited CAR-T cell technology.
Reference: Naval Guastad Daver et al., A first-in-human phase 1, multicenter, open-label study of CB-012, a next-generation CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy for adults with relapsed/refractory acute myeloid leukemia (AMpLify). JCO 42, TPS6586-TPS6586(2024). DOI:10.1200/JCO.2024.42.16_suppl.TPS6586
Abstract # 6518
Phase I Study of Functionally Enhanced CD33 CAR-T Cells in Patients with Relapsed or Refractory Acute Myeloid Leukemia
Authors: Jing Pan, Shiyu Zuo, Chuo Li, et al.
This Phase I study evaluated the safety and efficacy of functionally enhanced CD33 CAR-T cells in relapsed/refractory (R/R) AML patients. Four patients, including three post-stem cell transplantation, were treated with an initial dose of CAR-T cells. Cytokine release syndrome (CRS) occurred in 75% of patients, with one experiencing grade 4 CRS. Two patients achieved complete remission with incomplete hematologic recovery (CRi) and were MRD-negative at day 30, while two had no response. The functionally enhanced CD33 CAR-T cells showed potential, with two patients remaining disease-free for over two years.
The findings suggest that functionally enhanced CD33 CAR-T cells can induce remissions in R/R AML patients. However, the depletion of normal CD33-positive cells remains a challenge. This study supports further research to optimize CAR-T cell therapy for AML.
Relevance: These results highlight the potential of enhanced CD33 CAR-T cells in treating R/R AML, providing oncologists with insights into new therapeutic strategies.
Reference: Jing Pan et al., Phase I study of functionally enhanced CD33 CAR T cells in patients with relapsed or refractory acute myeloid leukemia. JCO 42, 6518-6518(2024). DOI:10.1200/JCO.2024.42.16_suppl.6518
Abstract # 6539
Preliminary Safety, Efficacy, and Molecular Characterization of Emavusertib (CA-4948) in Patients with Relapsed/Refractory (R/R) AML (AML) with FLT3 Mutation (FLT3)
Authors: Eric S. Winer, Amit Verma, Stefanie Groepper, et al.
This study explores the safety, efficacy, and molecular characterization of emavusertib (CA-4948) in patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3m). Among 11 patients treated with emavusertib, the response rate was promising, with significant reductions in bone marrow blast counts and FLT3-ITD levels. Common co-mutations included RUNX1, NRAS, and TET2. Treatment-related adverse events (TRAEs) were reported in 18% of patients.
The findings indicate that emavusertib has a favorable safety profile and significant monotherapy anti-cancer activity in FLT3m AML patients, even in those previously treated with other FLT3 inhibitors. This study supports further investigation of emavusertib in larger trials.
Relevance: For practicing oncologists, these results highlight emavusertib as a potential new treatment option for FLT3m AML patients, offering hope for improved outcomes in this challenging subgroup.
Reference: Eric S. Winer et al., Preliminary safety, efficacy and molecular characterization of emavusertib (CA-4948) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) with FLT3 mutation (FLT3m). JCO 42, 6539-6539(2024). DOI:10.1200/JCO.2024.42.16_suppl.6539
Abstract # TPS6585
A Phase 1b/2 Study of Pivekimab Sunirine (PVEK, IMGN632) in Combination with Venetoclax/Azacitidine for Patients with Newly Diagnosed CD123-Positive Acute Myeloid Leukemia
Authors: Naval Guastad Daver, Pau Montesinos, Jessica K. Altman, et al.
This phase 1b/2 study investigates the combination of pivekimab sunirine (PVEK, IMGN632), venetoclax (VEN), and azacitidine (AZA) in newly diagnosed (ND) CD123-positive AML patients. PVEK is an antibody-drug conjugate targeting CD123, which is highly expressed on AML cells. Patients receive PVEK with AZA and VEN in a 28-day cycle. Preliminary data showed a 76% measurable residual disease (MRD)-negative rate among 50 patients, supporting further evaluation of this regimen's antileukemia activity and safety.
The findings suggest that the PVEK+AZA+VEN triplet has promising antileukemia activity, particularly in achieving high MRD negativity rates. This study supports the potential of this combination therapy in treating ND CD123-positive AML patients, indicating a possible registration-enabling trial in the future.
Relevance: These results are crucial for oncologists as they highlight a new potential treatment combination for CD123-positive AML, offering hope for improved patient outcomes in a challenging subset of AML.
Reference: Naval Guastad Daver et al., A phase 1b/2 study of pivekimab sunirine (PVEK, IMGN632) in combination with venetoclax/azacitidine for patients with newly diagnosed CD123-positive acute myeloid leukemia. JCO 42, TPS6585-TPS6585(2024). DOI:10.1200/JCO.2024.42.16_suppl.TPS6585
Abstract # 1589
Identifying Eligibility Criteria That Perpetuate Race/Ethnic Disparities in Acute Myeloid Leukemia Clinical Trial Participation
Authors: Andrew Hantel, Yating Wang, Ivy Abraham, et al.
This study examined racial/ethnic disparities in AML clinical trial eligibility. The analysis included 1,283 patients, with 405 minoritized individuals (MI) and 878 Non-Hispanic Whites (NHW). The study found that fewer MI were eligible for non-intensive trials (42.2%) compared to NHW (54.4%). Key criteria contributing to disparities included prior malignancy, prolonged QTc, and hepatitis B infection. The study suggests that modifying these criteria could improve inclusivity in clinical trials.
The findings indicate that certain eligibility criteria disproportionately exclude minoritized individuals from AML clinical trials. Modifying these criteria, as recommended by ASCO, could enhance the inclusivity and equity of clinical trial participation.
Relevance: This study underscores the importance of equitable trial designs for oncologists, ensuring broader participation across racial/ethnic groups and addressing disparities in clinical trial access.
Reference: Andrew Hantel et al., Identifying eligibility criteria that perpetuate race/ethnic disparities in acute myeloid leukemia (AML) clinical trial participation. JCO 42, 1589-1589(2024).
DOI:10.1200/JCO.2024.42.16_suppl.1589
Abstract # 1574
Inequities in Timely Treatment (Tx) Initiation for Patients with Acute Myeloid Leukemia (AML) Treated in a Predominantly Community Setting in the United States (US)
Authors: Esprit Ma, Ann-Kathrin Eisfeld, Olatoyosi Odenike, et al.
This retrospective cohort study examines race/ethnicity and socioeconomic status (SES) disparities in timely treatment initiation for newly diagnosed AML patients. The study included 5,981 patients from the Flatiron Health database. Results showed numerical but non-significant disparities in timely treatment initiation between People of Color (POC) and White patients. Notably, fewer POC underwent stem cell transplant (SCT) post-remission compared to White patients (30.8% vs. 47.7%).
The findings indicate that, although numerical disparities exist, they are not statistically significant. However, the lower SCT rates in POC highlight a significant gap in post-remission care. This study suggests the need for further investigation into the factors contributing to these disparities.
Relevance: These results are important for oncologists, emphasizing the need to address disparities in AML treatment and post-remission care to ensure equitable treatment outcomes for all racial/ethnic groups.
Reference: Esprit Ma et al., Inequities in timely treatment (Tx) initiation for patients (pts) with acute myeloid leukemia (AML) treated in a predominantly community setting in the United States (US). JCO 42, 1574-1574(2024). DOI:10.1200/JCO.2024.42.16_suppl.1574