© 2025 HSP News Service, L.L.C.
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%.
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.
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.
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).
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.
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.
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.
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.
William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses up to 5.5 years of follow-up data from the phase II CAPTIVATE study, showing that in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), fixed duration ibrutinib plus venetoclax continues to provide clinically meaningful progression-free disease in those with high-risk genomic features as well as in the overall population (Abstract 7009).
Allison M. Winter, MD, of the Cleveland Clinic Taussig Cancer Institute, discusses real-world outcomes with lisocabtagene maraleucel in patients with Richter transformation, a difficult-to-treat population with a poor prognosis. Data from the Center for International Blood and Marrow Transplant Research showed this therapy provided clinical benefit with a high complete response rate (Abstract 7010).
Yucai Wang, MD, PhD, of the Mayo Clinic, discusses the increased efficacy of combination therapy with pembrolizumab plus a BCR kinase inhibitor compared with pembrolizumab alone in patients with Richter transformation of chronic lymphocytic leukemia (CLL; Abstract 7050).
Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Center, discusses an ongoing phase III study of the BCL2 inhibitor sonrotoclax plus zanubrutinib vs venetoclax and obinutuzumab for patients with treatment-naive chronic lymphocytic leukemia. The investigators are recruiting internationally (see NCT06073821; Abstract TPS7087).
Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Center, discusses a network meta-analysis showing that zanubrutinib appears to be the most efficacious Bruton’s tyrosine kinase (BTK) inhibitor for patients with high-risk relapsed or refractory chronic lymphocytic leukemia. It offers delayed disease progression and favorable survival and response, compared with alternative BTK inhibitors (Abstract 7048).
Muhit Özcan, MD, of Turkey’s Ankara University School of Medicine, discusses the ongoing phase III BELLWAVE-010 study of nemtabrutinib plus venetoclax vs venetoclax plus rituximab in previously treated patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (Abstract TPS7089).
Ibrahim Aldoss, MD, of City of Hope National Medical Center, discusses phase II safety and efficacy results from the Augment-101 study. This trial showed that patients with heavily pretreated, relapsed or refractory KMT2-rearranged acute leukemia benefited from monotherapy with the menin-KMT2A inhibitor revumenib, with high overall response rates and undetectable measurable residual disease (Abstract LBA-5).
Harinder Gill, MD, MBBS, of The University of Hong Kong, discusses findings showing the use of an “AAA” regimen (pure oral arsenic trioxide combined with all-trans retinoic acid) in a risk-adapted strategy that minimized chemotherapy was highly effective and safe in patients with newly diagnosed acute promyelocytic leukemia of all risk categories and age groups. However, he cautions, early deaths remain an obstacle to realizing a cure for all with this disease (Abstract 157).
Jeffrey E. Rubnitz, MD, PhD, of St. Jude Children’s Research Hospital, discusses study findings suggesting that pharmacogenomic differences between Black and White patients should be considered when tailoring induction regimens to improve outcomes of all patients and bridge the racial disparity gap in acute myeloid leukemia treatment (Abstract 386).
Adam S. Kittai, MD, of The Ohio State University, discusses his data supporting the use of CAR T-cell therapy for patients with Richter’s transformation. Given the high response rate to CD19 CAR T-cell treatment, along with early relapse in most patients, allogeneic stem cell transplantation at response should also be considered, he says (Abstract 108).
Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center, discusses phase I/II findings of the BRUIN study on the use of pirtobrutinib after covalent Bruton’s tyrosine kinase (BTK) inhibitors in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). The results suggest that continuing BTK pathway inhibition following a covalent BTK inhibitor may be an important sequencing approach to consider in the treatment of CLL/SLL (Abstract 325).
William G. Wierda, MD, PhD, of The University of Texas MD Anderson Cancer Center, discusses results from the phase I/II BRUIN study, which shows encouraging response and overall survival in patients with Richter transformation. Although this condition remains a challenging diagnosis, pirtobrutinib represents a potential treatment option that warrants further investigation, according to Dr. Wierda (Abstract 1737).
Mikkael A. Sekeres, MD, of the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, reviews key abstracts from ASH 2023 on treatment of myelofibrosis, chronic lymphocytic leukemia, large B-cell lymphoma, and acute myeloid leukemia (Abstracts 620, 631, 781, 425).
Nicholas J. Short, MD, of The University of Texas MD Anderson Cancer Center, discusses findings from a phase II study subgroup analysis that explored the question of whether ponatinib and blinatumomab, both active in Philadelphia chromosome–positive acute lymphoblastic leukemia, could offer an effective chemotherapy-free treatment for patients with newly diagnosed disease as well as reduce the need for allogeneic stem cell transplantation (Abstract S118).
Nigel Russell, MD, of Guy’s and St. Thomas’ NHS Foundation Trust, discusses the latest results from the AML19 trial, which showed the chemotherapy regimen FLAG-Ida (fludarabine, high-dose cytarabine, idarubicin, and granulocyte-colony stimulating factor), when combined with gemtuzumab ozogamicin, reduced levels of measurable residual disease and improved overall survival in patients with NPM1-mutated acute myeloid leukemia after induction therapy.
Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, discusses phase I/II findings from the Bruin study of resistance to pirtobrutinib in patients with covalent BTK inhibitor–pretreated chronic lymphocytic leukemia (CLL). The aim of the study was to explore the genomic evolution of resistance to this agent.
Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center, discusses results of a phase III study showing that progression-free survival with ibrutinib plus obinutuzumab plus venetoclax is not superior to ibrutinib plus obinutuzumab for treatment-naive older patients with chronic lymphocytic leukemia (CLL) in the setting of the COVID-19 pandemic. Long-term follow-up will determine whether there are advantages to obinutuzumab plus venetoclax, with special attention to measurable residual disease and therapy discontinuation (Abstract 7500).
Sarah K. Tasian, MD, of Children’s Hospital of Philadelphia, summarizes three studies presented at ASCO: genomic determinants of outcome in acute lymphoblastic leukemia (ALL), a phase III trial of inotuzumab ozogamicin for high-risk B-cell ALL, and preliminary results from the first-in-child phase II trial of bosutinib in pediatric patients with newly diagnosed chronic myeloid leukemia (Abstracts 10015, 10016, and 10017).
Paula Aristizabal, MD, MAS, of the University of California, San Diego, and Rady Children’s Hospital, talks about using a health systems strengthening approach to improve leukemia care and survival in a public Mexican hospital in the region of the border between the United States and Mexico. The demonstrated increase in overall survival across a decade after implementation of the program seems to validate the use of such models, not only to improve clinical outcomes, but also to build sustainable hospital capacity, financially and organizationally (Abstract 1502).
Claire Roddie, PhD, MBChB, of University College London, discusses results of the FELIX study, which showed that the second-generation chimeric antigen receptor (CAR) T-cell therapy obecabtagene autoleucel is safe for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, even those with a high burden of disease. This agent yielded high rates of complete response and ongoing CAR T-cell persistence in most patients whose disease responded (Abstract 7000).
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, and Gregory Roloff, MD, of the University of Chicago, discuss data that are the first to demonstrate post–FDA approval efficacy and toxicity rates of brexucabtagene autoleucel in adults with relapsed or refractory B-cell acute lymphoblastic leukemia. Although the data may confirm high response rates associated with this agent, they also highlight the need for interventions to reduce associated toxicities (Abstract 7001).
LaQuisa C. Hill, MD, of Baylor College of Medicine, Houston Methodist Hospital, discusses study findings showing that CD5 chimeric antigen receptor (CAR) T cells may induce clinical responses in heavily treated patients with relapsed or refractory T-cell acute lymphoblastic leukemia. Manufacturing CD5 CAR T cells with tyrosine kinase inhibitors seemed to improve their potency and antitumor activity (Abstract 7002).
Deborah M. Stephens, DO, of the Huntsman Cancer Institute at the University of Utah, discusses NCCN’s updates to treatment recommendations for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Dr. Stephens details the key factors in selecting front-line and subsequent therapies, including IGHV status, del(17p)/TP53 mutation status, age, comorbidities, and resistance mutations.
Jennifer R. Brown, MD, PhD, of Dana-Farber Cancer Institute, discusses phase III findings of the ALPINE study, which showed that zanubrutinib is more efficacious and better tolerated than ibrutinib as a treatment for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In this first head-to-head comparison of the two BTK inhibitors, the superior progression-free survival of zanubrutinib was observed across all major subgroups, including high-risk patients (Abstract LBA-6).
Mark R. Litzow, MD, of the Mayo Clinic, discusses phase III results from the ECOG-ACRIN E1910 Trial, which show that adding blinatumomab to consolidation chemotherapy resulted in a significantly better overall survival in adult patients aged 30 to 70 years with newly diagnosed B-lineage acute lymphocytic leukemia (ALL) who were measurable residual disease–negative after receiving intensification chemotherapy. The authors believe this may represent a new standard of care for this population (Abstract LBA-1).
Irene Roberts, MD, of Oxford’s Weatherall Institute of Molecular Medicine, discusses children with Down syndrome, who have a more than 100-fold increased risk of developing acute myeloid leukemia before their fourth birthday compared to children without Down syndrome. Their risk of acute lymphoblastic leukemia is also increased by around 30-fold. Dr. Roberts details current knowledge about the biologic and molecular basis of this relationship between leukemia and Down syndrome, the role of trisomy 21 in leukemogenesis, and the clinical implications of these findings.