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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 ...
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...