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This is Part 3 of Navigating the Complexities of Relapsed/Refractory AML: Identifying Mutations and Optimizing Targeted Therapy, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Uma Borate, Naval Daver, and Joshua Zeidner discuss the treatment of refractory acute myeloid leukemia (AML) with complex karyotype and TP53 mutation. The patient is a 72-year-old woman who was initially diagnosed with AML with 25% blasts, a complex karyotype, and a TP53 mutation (30% variant allele frequency [VAF]). Her disease was refractory after four cycles of decitabine and venetoclax. Although she maintains a good performance status, she is pancytopenic with residual AML at 8% blasts. Her complex karyotype and TP53 mutation (15% VAF) are still detectable. She has an HLA-identical unrelated donor identified. In the conversation that follows, the faculty discuss what treatment options are available for this patient, whether she would be a candidate for intensive chemotherapy, when to pursue transplant, and the importance of clinical trials for refractory TP53-mutated AML.
This is Part 2 of Navigating the Complexities of Relapsed/Refractory AML: Identifying Mutations and Optimizing Targeted Therapy, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Uma Borate, Naval Daver, and Joshua Zeidner discuss the treatment of relapsed/refractory FLT3-mutant acute myeloid leukemia (AML). The patient is a 71-year-old woman who was diagnosed 1 year ago with FLT3-TKD–mutated AML. She achieved complete response after one cycle of hypomethylating agents (HMA) plus venetoclax, and then became MRD negative after cycle 3, with no FLT3 detected on PCR. She was not a candidate for allogeneic stem cell transplant due to her poor ECOG performance status. She continued receiving HMA plus venetoclax every 6 weeks and now presents with a recent pneumonia that has not improved after antibiotics, as well as new-onset leukocytosis. Lab work shows an elevated white blood cell count, lowered platelets, anemia, 35% circulating blasts, and an elevated LDH. Her bone marrow biopsy confirms a relapse of AML with 73% blasts and 54% cellularity. Her karyotype shows trisomy 8, and her molecular profile shows FLT3-TKD, WT1, and no NPM1 mutation. Her ECOG performance status is 2. In the conversation that follows, the faculty discuss the next steps for this patient with relapsed AML, FLT3 as a targetable mutation, managing side effects of FLT3 inhibitors, and more.
This is Part 1 of Navigating the Complexities of Relapsed/Refractory AML: Identifying Mutations and Optimizing Targeted Therapy, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Uma Borate, Naval Daver, and Joshua Zeidner discuss the treatment of relapsed KMT2A-rearranged acute myeloid leukemia (AML). The patient is a 35-year-old woman who was diagnosed 3 years ago with breast cancer and treated with systemic chemotherapy and radiation therapy. She has now developed new-onset pancytopenia, and a bone marrow biopsy reveals hypercellular marrow with 68% blasts, with a phenotype consistent with AML. Her cytogenetics show t(9;11), and fluorescence in situ hybridization confirms a KMT2A rearrangement. Comprehensive next-generation sequencing reports no actionable mutations. She has adequate cardiac function, and her performance status is zero. In the conversation that follows, the faculty discuss front-line treatment options for this patient, whether their recommendations would change if she were older or unfit, the role of menin inhibitors in patients with KMT2A rearrangements, and side effects to look out for when treating with menin inhibitors.
The recent approval of the oral menin inhibitor revumenib brought much-needed treatment to patients with a challenging subset of disease: adults and children with relapsed or refractory acute leukemia harboring a lysine methyltransferase 2A gene (KMT2A) translocation or rearrangement. Approval was...
In a Children’s Oncology Group (COG) study (AAML1831) reported in Journal of Clinical Oncology, Huang et al found that hematopoietic stem cell transplantation (HSCT) was associated with improved outcomes in pediatric patients with high-risk acute myeloid leukemia (AML). Study Details The study...
Sequential molecular measurable residual disease (MRD) testing and monitoring led to a survival benefit among younger patients with acute myeloid leukemia (AML) and NPM1 and FLT3-ITD mutations, according to the results of a study published in The Lancet Haematology. Patients with both mutations...
“Knowledge is like a lion; it cannot be gently embraced.” –South African Proverb Long-term efficacy and safety confirm that a hypomethylating agent and venetoclax is an improvement in the standard of care for patients with AML who are not eligible for intensive chemotherapy because of advanced age...
A new gene-expression atlas developed using single-cell RNA sequencing data sheds light on how normal hematopoietic cells differentiate and was used to catalog the multiple ways aberrant differentiation can lead to acute myeloid leukemia (AML). Andy G.X. Zeng, PhD, an MD/PhD candidate at the...
The U.S. Food and Drug Administration (FDA) approved the first chimeric antigen receptor (CAR) T-cell therapy in 2017 to treat children with acute lymphoblastic leukemia. Over the past decade, other CAR T-cell therapies have been FDA-approved to treat adults with blood cancers, including...
Statin use during targeted therapy treatment led to a 61% improvement in the risk of dying of cancer for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to the results of a study published in Blood Advances. The investigators sought to determine the...
There has been remarkable progress in treating EGFR-variant lung adenocarcinoma with tyrosine kinase inhibitors such as gefitinib, erlotinib, osimertinib, and afatinib. However, several important issues remain unresolved, including whether there remains a role for chemotherapy, who should receive a ...
In a UK phase III trial (UKALL 2011) reported in the Journal of Clinical Oncology, Kirkwood et al found that a shorter duration of induction dexamethasone did not reduce steroid-related toxicity and that high-dose methotrexate (HDM) did not reduce central nervous system (CNS) relapse among patients ...
Researchers have found that patients with chronic lymphocytic leukemia (CLL) should continue to receive Bruton tyrosine kinase (BTK) inhibitors while being vaccinated against COVID-19 infections, according to a recent study published by Cook et al in The Lancet Haematology. Background CLL is the...
The clinical application of BCR::ABL1 digital polymerase chain reaction (PCR) testing may reliably quantify stable deep molecular remission in patients with chronic myeloid leukemia (CML), which could help determine when maintenance therapy may be discontinued successfully, according to a recent...
“Care more particularly for the individual patient than for the special features of the disease.” —Sir William Osler Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common leukemia in the Western hemisphere. The majority of patients who require treatment are older than ...
An innovative combination of treatment strategies involving myeloid cell leukemia (MCL)-1 inhibitors and a kinase inhibitor targeting the SRC oncogene could be effective at triggering cell death in acute myeloid leukemia (AML) cells, according to a recent study published by Hu et al in Signal...
“Care more particularly for the individual patient than for the special features of the disease.”—Sir William Osler Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common leukemia in the Western hemisphere. The majority of patients who require treatment are older than ...
As reported in The New England Journal of Medicine by Jennifer Brown, MD, and colleagues, the phase III AMPLIFY trial found that fixed-duration acalabrutinib combined with venetoclax or venetoclax/obinutuzumab improved progression-free survival vs chemoimmunotherapy in fit, previously untreated...
A record-breaking number of abstracts were submitted for the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, and nearly 8,000 were accepted. The ASCO Post strives to provide in-depth coverage of those with the greatest impact. Here, we offer snapshots of others of...
The recently approved menin inhibitor revumenib is poised to improve the treatment of acute myeloid leukemia (AML), specifically for disease with a KMT2A rearrangement. Promising results for other novel menin inhibitors now in development—with their unique safety and activity profiles—suggest the...
On January 21, the U.S. Food and Drug Administration (FDA) approved treosulfan (Grafapex), an alkylating agent, with fludarabine as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in adult and pediatric patients 1 year of age and older with acute myeloid leukemia ...
A novel bicistronic CD19/CD22-directed CAR T-cell therapy (B019) has demonstrated high remission rates, durable responses, and a favorable safety profile among children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), including those with isolated or combined extramedullary...
Two pivotal phase III trials presented at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition mark a significant shift toward chemotherapy-free approaches in chronic lymphocytic leukemia (CLL), offering potentially more effective and tolerable treatment options for both...
Researchers have identified factors that could determine whether donor lymphocyte infusion—a type of adoptive cell therapy—will result in remission among patients with acute myeloid leukemia (AML) who have relapsed following allogeneic hematopoietic stem cell transplant (HSCT), according to a...
Results of a phase III study suggest that the addition of the immunotherapy agent blinatumomab—a bispecific T-cell engager targeting CD19—to standard chemotherapy may help to prevent relapse in more children with B-cell acute lymphoblastic leukemia (B-ALL), the most common pediatric cancer,...
Pediatric patients with cancer who have obesity at the time of diagnosis may face an elevated risk of mortality, according to a recent study published by Sassine et al in Cancer. Study Methods and Results In the retrospective study, investigators examined data from the Cancer in Young People in...
In an AIEOP-BFM and COG-SWOG intergroup collaborative study reported in the Journal of Clinical Oncology, Tregnago et al found that patients with acute myeloid leukemia (AML) with NPM1 type D variants had significantly poorer event-free and overall survival vs those with non-D variants. Study...
First responders who worked at Ground Zero in the aftermath of the 2001 attacks on the World Trade Center in New York City were three times more likely to have genetic changes associated with an increased risk of leukemia compared with other first responders or members of the public who were not...
At the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 883), Alexey Danilov, MD, PhD, of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope National Medical Center, Duarte, California, reported that single-agent epcoritamab led...
In a German phase III trial (CLL12), reported in the Journal of Clinical Oncology, Langerbeins et al found that ibrutinib prolonged the time to symptomatic disease in patients with early-stage chronic lymphocytic leukemia (CLL) vs placebo. However, no differences in overall survival were observed....
Researchers may have discovered a factor contributing to cancer cell evasion of chimeric antigen receptor (CAR) T-cell therapy, according to a recent study published by Chen et al in Cell. The findings could lead to more personalized therapies that improve survival among patients with cancer....
The addition of blinatumomab to chemotherapy may improve disease-free survival in pediatric patients newly diagnosed with National Cancer Institute (NCI) standard-risk B-cell acute lymphoblastic leukemia (ALL) at average or high risk of relapse, according to new findings presented by Rau et al at...
A follow-up study investigating the coadministration of CD19- and CD22-targeted chimeric antigen receptor (CAR) T-cell therapy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) found the therapy is safe and effective and achieved durable remissions in these patients, ...
Researchers have found that the noncovalent Bruton's tyrosine kinase inhibitor (BTK) pirtobrutinib may offer superior progression-free survival in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to recent findings presented by Sharman et al at the 2024...
A combination of the oral drugs acalabrutinib and venetoclax may be more effective at improving progression-free survival and minimizing serious adverse events in patients with previously untreated chronic lymphocytic leukemia (CLL) compared with one of two standard multidrug treatment regimens,...
Matthew S. Davids, MD, MMSc, of Dana-Farber Cancer Institute, Boston, discusses the primary endpoint evaluation of a phase II trial of the triplet regimen of acalabrutinib, venetoclax, and obinutuzumab in a population of patients with TP53-aberrrant chronic lymphocytic leukemia (CLL). The triplet was active and well tolerated as a front-line therapy, Dr. Davids noted, and these findings support its use for such patients with high-risk CLL (Abstract 1865).
Rachel E. Rau, MD, of Seattle Children’s Hospital, and Sumit Gupta, MD, PhD, of the Hospital for Sick Children in Toronto, review results from Children’s Oncology Group Study AALL1731, which assessed the addition of blinatumomab to chemotherapy in newly diagnosed childhood standard-risk B-cell acute lymphoblastic leukemia (ALL). She explains how the combination may be considered a major breakthrough and new treatment standard in this patient population (Abstract 1).
Nitin Jain, MD, of The University of Texas MD Anderson Cancer Center, Houston, discusses the results of a recent trial (Abstract 1011) evaluating the time-limited, combination therapy of the noncovalent Bruton’s tyrosine kinase inhibitor pirtobrutinib with the BCL2 inhibitor venetoclax and the CD20 monoclonal antibody obinutuzumab in previously untreated chronic lymphocytic leukemia (CLL). Dr. Jain reviews the findings at both 6 and 12 months of combined therapy.
Danielle Wolfe Cohen, MD, of the William L. Carroll Laboratory at New York University Grossman School of Medicine, describes data illuminating the role of an inflammatory phenotype in driving clonal evolution in B-cell acute lymphoblastic leukemia. The new findings may indicate promising avenues for further research on treatment resistance and disease relapse (Abstract 633).
Anne Sophie Michallet, MD, PhD, of Centre Léon Bérard Hospital, Lyon, France, discusses the final results of the phase II ERADIC trial (Abstract 584), which compared measurable residual disease (MRD)-guided therapy with ibrutinib and venetoclax with a standard combination regimen in patients with intermediate-risk chronic lymphocytic leukemia (CLL). Dr. Michallet also emphasizes the importance of defining the best patient profile for this MRD-guided combination given its potential for cardiologic toxicity.
A large prospective observational study of patients with acute myeloid leukemia (AML) has found that lower socioeconomic status is a barrier to accessing hematopoietic cell transplantation (HCT) but does not affect posttransplant outcomes. Interventions that address financial issues, improve...
Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, Boston, discusses the findings from the prespecified interim analysis of the phase III AMPLIFY trial (Abstract 1009), which compared fixed-duration acalabrutinib/venetoclax—with or without obinutuzumab—with investigator’s choice of chemoimmunotherapy in fit patients with treatment-naïve chronic lymphocytic leukemia (CLL). According to Dr. Brown, this trial met its primary endpoint, with improved progression-free survival reported with this first all-oral fixed-duration regimen.
Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, Boston, discusses the findings from the prespecified interim analysis of the phase III AMPLIFY trial (Abstract 1009), which compared fixed-duration acalabrutinib/venetoclax—with or without obinutuzumab—with investigator’s choice of chemoimmunotherapy in fit patients with treatment-naïve chronic lymphocytic leukemia (CLL). According to Dr. Brown, this trial met its primary endpoint, with improved progression-free survival reported with this first all-oral fixed-duration regimen.
The U.S. Food and Drug Administration (FDA) recently has approved an oral solution of the tyrosine kinase inhibitor, imatinib mesylate, called Imkeldi, to treat certain types of leukemia and other cancers. The new solution is an advanced liquid formulation of imatinib designed to provide dosing...
A second-generation chimeric antigen receptor (CAR) T-cell therapy may offer a new option for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), an aggressive blood cancer with few treatment options. Results from the phase Ib/II FELIX trial, published by Roddie et al in ...
As reported in the Journal of Clinical Oncology by Russell et al, the NCRI AML18 trial has shown survival benefit with treatment intensification in fit older patients with measurable residual disease (MRD)-positive response after first induction for acute myeloid leukemia (AML). Study Details In...
The U.S. Food and Drug Administration (FDA) announced the approval of imatinib (Imkeldi) oral solution, the first oral liquid formulation of the drug to treat certain types of leukemias and other cancers. Background In 2024, an estimated 9,280 patients will be diagnosed with chronic myeloid...
The studies summarized below were reported online over the past month in The ASCO Post, generating a high number of visitors. For comprehensive reviews of these studies and more, visit ASCOPost.com. Trastuzumab Duocarmazine in Previously Treated HER2-Positive Metastatic Breast Cancer In the phase...
The U.S. Food and Drug Administration (FDA) approved the CD19-directed genetically modified autologous T-cell immunotherapy obecabtagene autoleucel (Aucatzyl) for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). Efficacy and Safety Efficacy was evaluated in...
Researchers have provided new insights into acute myeloid leukemia (AML) and its resistance to venetoclax, according to a recent study published by Sango et al in Nature. Although AML is a rare disease, approximately 20,800 U.S. patients will be diagnosed in 2024, according to the American Cancer...