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An international study conducted by the Alliance for Clinical Trials in Oncology and the Acute Myeloid Leukemia Cooperative Group has revealed that age-based classifications in the treatment of acute myeloid leukemia (AML) may be outdated and overly simplistic. Their findings were published by...
As reported in the Journal of Clinical Oncology by Wang et al, a phase I/II trial (KOMET-001) has shown activity of the oral menin inhibitor ziftomenib in patients with relapsed or refractory NPM1-mutant acute myeloid leukemia (AML). Study Details In the phase II portion of the trial, 92 patients...
As reported in the Journal of Clinical Oncology by Wieduwilt et al, findings in a cohort of the phase II Alliance study A041703 indicate that the chemotherapy-free regimen of inotuzumab ozogamicin followed by blinatumomab was highly active in patients aged ≥ 60 years with newly diagnosed B-cell...
A recent study has found that mutations in blood-forming cells may explain the increased risk for leukemia and other blood disorders among first responders exposed to the 9/11 World Trade Center (WTC) disaster site and its toxic dust. The study also points to a novel strategy for use against...
Treatment with obecabtagene autoleucel was the focus of the phase Ib/II multicenter FELIX study of more than 100 adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).1 The initial report in 2024 revealed a rate of complete remission or complete remission with incomplete...
Patients with acute myeloid leukemia (AML) who achieve cytogenetic remission may have better survival outcomes than patients with new or sustained cytogenetic abnormalities, according to findings from a study published in the American Journal of Hematology. The study elucidated how cytogenetic...
Bijal Shah, MD, of Moffitt Cancer Center, summarizes his presentation on the role of chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia (ALL), touching on its use in the front-line setting for newly diagnosed patients with high risk-features as well as in patients with relapsed or refractory disease. Dr. Shah also discusses the role of measurable residual disease, improving the duration of response after CAR T-cell therapy, how stem cell transplantation fits into this treatment paradigm, and ongoing/upcoming clinical trials in the space.
New study findings show that children with acute lymphoblastic leukemia (ALL) who were exposed to pesticides during their mother's pregnancy may have a higher risk of death, according to findings published in Cancers. “This study highlights that exposures in the home environment, even before a...
In a phase I, first-in-human trial of nearly 50 patients with relapsed or refractory B-cell malignancies, the orally administered, small molecule degrader bexobrutideg (NX-5948) was reported to be well tolerated, including in those with a longer duration of treatment and higher doses. Clinical...
Chronic myeloid leukemia (CML) is one of the success stories among the hematologic malignancies. Now, with decades of data informing its management, it is time to change some of the practices to which clinicians have become accustomed, said leukemia expert Hagop M. Kantarjian, MD, FASCO, Professor...
Nicholas J. Short, MD, of The University of Texas MD Anderson Cancer Center, discusses TP53 abnormalities in acute lymphoblastic leukemia (ALL), which are uncommon in pediatric patients but may occur in 10% to 15% of adult patients with ALL. Dr. Short reviews recent research into their impact on outcomes, relapse, and the development of secondary cancers, and discusses novel therapeutic algorithms being employed.
Naval G. Daver, MD, of The University of Texas MD Anderson Cancer Center, and Uma Borate, MBBS, of The Ohio State University Comprehensive Cancer Center, give highlights of a lively debate they engaged in at the SOHO meeting. They discuss concomitant vs sequential use of lower-intensity regimens in acute myeloid leukemia (AML), as well as ongoing trials in this space and the role of measurable residual disease.
Michael J. Mauro, MD, of Memorial Sloan Kettering Cancer Center, reviews findings from the phase Ia/Ib ENABLE study, which evaluated ELVN-001, a highly selective, active-site inhibitor designed to target BCR-ABL1, in heavily pretreated patients with chronic myeloid leukemia (CML).
Nirav N. Shah, MD, MSHP, of the Medical College of Wisconsin, presents results from a phase Ia study of bexobrutideg, a Bruton’s tyrosine kinase (BTK) degrader. The agent was tested in a heavily pretreated population of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and resulted in a response rate of over 80%.
As reported in the Journal of Clinical Oncology by Platzbecker et al, the European intergroup phase III APOLLO trial showed that an all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO; ATRA-ATO)–based regimen was associated with improved event-free survival vs a standard ATRA plus...
Farhad Ravandi, MD, provides an overview of acute myeloid leukemia (AML) research highlighted in a session at SOHO, including data on menin inhibitors in NPM1-mutated disease; FLT3 inhibitors in FLT3-mutated disease; IDH inhibitors in IDH1-mutated disease; the role of measurable residual disease; what’s on the horizon for immunotherapy; risk stratification; and a discussion of the use of lower-intensity regimens.
Elias Jabbour, MD, discusses long-term findings and predictors of sustained remission among adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) who did not undergo a stem cell transplant, but received the chimeric antigen receptor (CAR) T-cell therapy obecabtagene autoleucel.
Based on the results of a single-center phase II trial published by Bhatt et al in the American Journal of Hematology, pretreatment geriatric assessment in older adults with acute myeloid leukemia (AML) appeared to be feasible, to identify several functional impairments, to help guide the selection ...
Researchers have discovered that an isoform of the transcription factor RUNX1 orchestrates chemoresistance in patients with acute myeloid leukemia (AML), according to findings published in Blood Cancer Discovery. They identified that the long-isoform RUNX1C's connection to BTG2 may enable cellular...
Immunoglobulin replacement therapy did not lead to a reduction in the risk for serious infections leading to hospitalizations for patients with chronic lymphocytic leukemia (CLL), according to the results of a real-world Australian cohort study published in Blood Advances. This finding is at odds...
The ASCO Post is pleased to present Hematology Expert Review, an ongoing feature that quizzes readers on issues in hematology. In this installment, Syed Ali Abutalib, MD, and L. Jeffrey Medeiros, MD, explore the impact of the prognostic marker RUNX1::RUX1T1 fusion on the diagnosis and treatment of...
Children born by planned cesarean section (C-section) may have an increased risk of developing acute lymphoblastic leukemia (ALL) later in life, according to a recent study published by Kampitsi et al in the International Journal of Cancer. Alhough the researchers did find an association, they...
Investigators have bioengineered an organotypic immunocompetent chip—a laboratory device that combines the physical structure of human leukemia bone marrow and a functioning immune system—to empower real-time spatiotemporal monitoring of CAR-T cell functionality for leukemias. The preclinical...
In a single-center study reported in the Journal of Clinical Oncology, DiNardo et al investigated whether frontline triplet regimens consisting of a hypomethylating agent, venetoclax, and an isocitrate dehydrogenase inhibitor were active in intensive chemotherapy-ineligible patients with IDH-mutant ...
A combination of menin inhibition and KAT6A/7 inhibition significantly improved survival for NUP98-rearranged pediatric acute myeloid leukemia (AML) in AML model systems, even in menin inhibitor–resistant cells, according to findings published in Cancer Discovery. The MYST gene family histone...
In an update from the UK phase III FLAIR trial reported in The New England Journal of Medicine, Munir et al compared the survival benefit of measurable residual disease (MRD)–guided therapy with ibrutinib/venetoclax vs ibrutinib alone in chronic lymphocytic leukemia. An interim analysis showed...
Ropeginterferon alfa-2b demonstrated superior efficacy and safety compared with anagrelide as second-line therapy for patients with essential thrombocythemia (ET) who were intolerant or resistant to hydroxyurea, according to data from the phase III SURPASS-ET trial presented at the European...
In a phase III trial (BRUIN CLL-321) reported in the Journal of Clinical Oncology, Sharman et al compared treatment outcomes with the noncovalent Bruton's tyrosine kinase (BTK) inhibitor pirtobrutinib vs investigator choice of idelalisib/rituximab (IdelaR) or bendamustine/rituximab (BR) in patients ...
A new combination of azacitidine, venetoclax, and revumenib demonstrated high rates of complete response and clinical activity in older adults with newly diagnosed acute myeloid leukemia (AML) and an NPM1 mutation or KMT2A rearrangement. The regimen was also shown to be safe in updated results from ...
Nitin Jain, MD, Professor in the Department of Leukemia and Director of the Leukemia CAR-T Program at The University of Texas MD Anderson Cancer Center, shares his expert point of view on data presented on front-line therapies for chronic lymphocytic leukemia (CLL) presented at the 2025 ASCO Annual Meeting.
The investigational agent ziftomenib, a menin-MLL inhibitor, demonstrated activity in patients with relapsed or refractory NPM1-mutant acute myeloid leukemia (AML), regardless of prior venetoclax treatment, according to findings from the phase II KOMET-001 trial. Findings from the study were...
Mazyar Shadman, MD, PhD, of Fred Hutchinson Cancer Center and the University of Washington, presents results from arm D of the SEQUOIA trial, which evaluated the combination of zanubrutinib and venetoclax in treatment-naive patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (Abstract 7009).
Constantine Si Lun Tam, MD, FRACP, FRCPA, MBBS, of Alfred Hospital and Monash University, reviews results from the 5-year follow-up of arm C of the SEQUOIA trial of treatment-naive patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (Abstract 7011).
William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses two abstracts on lisocabtagene maraleucel (liso-cel) in relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In Abstract 7037, liso-cel with ibrutinib demonstrated better efficacy and safety compared with liso-cel monotherapy, with statistically significant differences for complete response rate and overall response rate. In Abstract 7039, patients with R/R CLL/SLL who had received two or more prior lines of therapy had improved response, delayed progression, and prolonged survival with liso-cel compared with a real-world cohort treated with standard-of-care therapy.
William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, reviews the final analysis of phase II CAPTIVATE study demonstrating the long-term efficacy and safety of ibrutinib plus venetoclax for previously untreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), including in patients with high-risk genomic features. The 5.5-year progression-free survival and overall survival rates were 66% and 97%, respectively (Abstract 7036).
With the currently available BCR::ABL1 tyrosine kinase inhibitors, chronic myeloid leukemia (CML) has transformed from an invariably fatal disorder (10-year overall survival < 10%) to an indolent one, associated with a near-normal life expectancy on optimal tyrosine kinase inhibitor...
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...
This is Part 3 of Treatment Approaches to Relapsed/Refractory CLL: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Nicole Lamanna, John Allan, and Inhye Ahn discuss the third-line treatment of chronic lymphocytic leukemia (CLL). The patient in question originally presented with CLL with a white blood cell (WBC) count of 13 x 109/L and normal hemoglobin and platelets. She was observed for 4 years and then developed progressive disease with weight loss, splenomegaly, and lymphadenopathy. At this point, her WBC was 220 x 109/L, her hemoglobin was 9.4, and her platelet count was 102,000. Sequencing revealed unmutated IGHV, TP53 wildtype, deletion 13q, and trisomy 12. She was initially treated with acalabrutinib for 4 years but developed progressive disease, and then received venetoclax and rituximab for 2 years. She was monitored but developed progressive disease approximately 30 months off therapy, at age 74 years. In the conversation that follows, the faculty discuss potential third-line treatment options for this patient, whether she would be a candidate for CAR T-cell therapy if she were younger, whether venetoclax re-treatment would be an option, and more.
This is Part 2 of Treatment Approaches to Relapsed/Refractory CLL: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Nicole Lamanna, John Allan, and Inhye Ahn discuss second-line treatment strategies for chronic lymphocytic leukemia (CLL). The patient is a 71-year-old man who presented in 2014 with symptomatic CLL after being monitored for 4 years. He then developed progressive fatigue, organomegaly, and bulky lymph nodes. Sequencing revealed unmutated IGHV and deletion 11q. He was initially treated with ibrutinib at 420 mg daily and then developed progressive disease after 5 years. In the conversation that follows, the faculty discuss how they would approach treatment sequencing in later lines of therapy, whether it is necessary to test for BTK inhibitor resistance, how their treatment recommendations might change if the patient’s cytogenetic profile evolved, and more.
This is Part 1 of Treatment Approaches to Relapsed/Refractory CLL: What Comes Next, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. To set the stage, Drs. Nicole Lamanna, John Allan, and Inhye Ahn discuss front-line treatment strategies for chronic lymphocytic leukemia (CLL). The patient is a 71-year-old man who presented in 2020 with symptomatic CLL after he was monitored for a period of 4 years. He developed progressive fatigue, weight loss, splenomegaly, and bulky lymphadenopathy. He has a good performance status and adequate renal function. He has a white blood cell count of 113 x 109/L, hemoglobin of 10.3 g/dL, and a platelet count of 105,000/µL. Sequencing reveals deletion 13q, trisomy 12, unmutated IGHV, and TP53 wild-type. In the conversation that follows, the faculty discuss the patient’s prognosis, how comorbidities impact treatment options, time-limited vs continuous therapy, and more.
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 ...