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Leukemia
Immunotherapy

Higher Doses of CAR T-Cell Therapy May Improve Survival for Young Patients With B-Cell ALL

Young people with B-cell acute lymphoblastic leukemia (ALL) who received doses of tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy, at the higher end of the approved dosing range had significantly better survival rates at 1 year compared with those who received lower doses within...

Leukemia

Study Finds AYA Leukemia Survivors Have Higher 10-Year Mortality Rates Than the General Population

Although considered a rare occurrence in adolescents and young adults (AYAs), aged 15 to 39 years, the incidence of cancer in this age group has been increasing by approximately 30% since the 1970s. This year, it is estimated that nearly 90,000 new cases of cancer will be diagnosed in this...

Issues in Oncology
Leukemia

Study Evaluates Availability of Imatinib in Online Pharmacies

Patients seeking to purchase chemotherapy drugs online face a confusing array of websites, over half of which potentially operate unsafely or illegally, according to a study published by Sun et al in JNCCN–Journal of the National Comprehensive Cancer Network. A survey of online pharmacies claiming...

Leukemia
Lymphoma

Zandelisib in Continuous or Intermittent Dosing Schedules With or Without Rituximab for Relapsed or Refractory B-Cell Malignancies

In a first-in-patients phase Ib study reported in The Lancet Oncology, John M. Pagel, MD, PhD, and colleagues identified the safety profiles of the PI3Kδ inhibitor zandelisib given in intermittent vs continuous dosing schedules with or without rituximab in patients with relapsed of refractory...

leukemia

Nicholas J. Short, MD, on ALL: Updated Phase II Study Results on Ponatinib and Blinatumomab

Nicholas J. Short, MD, of The University of Texas MD Anderson Cancer Center, discusses updated results from a phase II study that suggests the chemotherapy-free regimen of simultaneous ponatinib and blinatumomab is safe and effective in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. For patients with newly diagnosed disease, stem cell transplantation does not appear to be needed in first remission (Abstract S114).

Leukemia

Venetoclax Plus Gilteritinib in FLT3-Mutated Relapsed or Refractory Acute Myeloid Leukemia

In a phase Ib study reported in the Journal of Clinical Oncology, Naval Daver, MD, and colleagues found that the doublet of venetoclax plus gilteritinib produced a high modified composite complete response rate in patients with FLT3-mutated relapsed or refractory acute myeloid leukemia. Dose...

Leukemia

Study Reports Time-Limited Venetoclax-Based Regimens of Benefit in Front-Line Treatment of CLL

Time-limited venetoclax-based regimens provide deeper and more durable remissions than chemoimmunotherapy combinations in patients with previously untreated chronic lymphocytic leukemia (CLL), regardless of patients’ fitness, according to late-breaking data presented during the European Hematology...

Leukemia

WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues

The ASCO Post is pleased to present Hematology Expert Review, an ongoing feature that quizzes readers on issues in hematology. In this installment, Drs. Syed Ali Abutalib and L. Jeffrey Medeiros explore the World Health Organization (WHO) classification of hematopoietic and lymphoid tissue...

Leukemia
Myelodysplastic Syndromes

Eprenetapopt/Azacitidine Maintenance After Allogeneic HSCT for TP53-Mutant AML and MDS

In a phase II trial reported in the Journal of Clinical Oncology, Mishra et al found that maintenance treatment with the first-in-class small-molecule p53 reactivator eprenetapopt plus azacitidine following allogeneic hematopoietic stem cell transplantation (HSCT) was associated with “encouraging”...

Leukemia
Lymphoma

Zanubrutinib vs Bendamustine/Rituximab in Previously Untreated Patients With CLL or SLL

As reported in The Lancet Oncology by Constantine S. Tam, MBBS, PhD, and colleagues, an interim analysis in the phase III SEQUOIA trial has shown significantly improved progression-free survival with first-line zanubrutinib vs bendamustine/rituximab in patients with chronic lymphocytic leukemia...

Leukemia

Initial Risk Factors and ‘Time to Cure’ in Childhood and Young Adult Acute Lymphoblastic Leukemia

In an analysis of long-term follow-up of the UKALL2003 trial reported in the Journal of Clinical Oncology, Anthony V. Moorman, PhD, and colleagues found that whereas initial risk of relapse in children and young adults with acute lymphoblastic leukemia differed according to risk factors, risk...

Leukemia

Phase III Trial Reports Quizartinib Doubles Overall Survival in FLT3-ITD–Positive AML

A new treatment option has doubled overall survival for a difficult-to-treat subset of patients with acute myeloid leukemia (AML), according to data presented during the Presidential Symposium at the European Hematology Association (EHA) 2022 Congress in Vienna.1 Findings from the phase III...

Leukemia

Study Examines High Early Death Rates, Treatment Resistance, and Short Survival Among Black AYA Patients With AML

New research published by Larkin et al in the journal Blood Advances has found that Black adolescent and young adult (AYA) patients with acute myeloid leukemia (AML) were five times more likely than comparable White patients to die within 30 days of beginning treatment—and were twice as likely to...

Leukemia
Lymphoma

FDA Warns About Possible Increased Risk of Death and Serious Side Effects With Duvelisib

The U.S. Food and Drug Administration (FDA) is warning that results from the phase III DUO clinical trial show a possible increased risk of death with duvelisib compared to ofatumumab among patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The trial also found...

Leukemia
Survivorship

Long-Term Morbidity in AML Survivors Treated With Blood or Bone Marrow Transplantation

As reported in the Journal of Clinical Oncology by Saro H. Armenian, DO, MPH, and colleagues, findings from the BMT Survivor Study (BMTSS) indicated that survivors of acute myeloid leukemia (AML) treated with blood or marrow transplantation (BMT) are at a markedly increased risk of...

Leukemia

Venetoclax Plus Cladribine and Low-Dose Cytarabine Alternating With Azacitidine and Venetoclax in Newly Diagnosed Older or Unfit Patients With AML

In a single-institution phase II study reported in the Journal of Clinical Oncology, Tapan M. Kadia, MD, and colleagues found that venetoclax and a lower-intensity backbone of cladribine and low-dose cytarabine alternating with azacitidine and venetoclax resulted in a high response rate in older...

Leukemia

MRD-Guided Cessation of Treatment in Patients Receiving Venetoclax/Ibrutinib for Relapsed or Refractory CLL

In a phase II trial (HOVON141/VISION) reported in The Lancet Oncology, Arnon P. Kater, MD, PhD, and colleagues found a high rate of 12-month progression-free survival among patients with relapsed or refractory chronic lymphocytic leukemia (CLL) who stopped venetoclax/ibrutinib after achieving...

leukemia

Eunice S. Wang, MD, on AML: Long-Term Results With Crenolanib Plus Chemotherapy

Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, discusses long-term phase II findings of a trial evaluating crenolanib plus chemotherapy in newly diagnosed adults with FLT3-mutant acute myeloid leukemia. The study showed a composite complete remission rate of 86%. With a median follow-up of 45 months, median overall survival has not been reached. A phase III trial is ongoing (Abstract 7007).

Genomics/Genetics
Myelodysplastic Syndromes
Leukemia

Demethylation and Upregulation of the Oncogene SALL4 After Hypomethylating Therapy

In a study reported in The New England Journal of Medicine, Liu et al found that hypomethylating therapy was associated with upregulation of the oncogene SALL4 in a high proportion of patients with myelodysplastic syndrome. They also identified the gene region that is demethylated and responsible...

Leukemia

Adding Targeted Therapy to Chemoimmunotherapy May Offer Long-Term Benefits for Patients With IGHV-Mutated CLL

In a phase II study, researchers evaluated the efficacy of ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab—a chemoimmunotherapy and targeted therapy combination—in 45 previously untreated patients with IGHV-mutated chronic lymphocytic leukemia (CLL). Nitin Jain, MD, of the Department of...

Leukemia

Magrolimab Plus Azacitidine in TP53-Mutant AML

High-risk patients with TP53-mutated acute myeloid leukemia (AML) have limited treatment options and very poor prognoses. Magrolimab is a monoclonal antibody designed to block CD47, an immune macrophage checkpoint molecule that signals “don’t eat me,” thereby allowing leukemia cell destruction....

Leukemia
Genomics/Genetics

Triplet Combination Therapy Yields High Response Rates in Patients With FLT3-Mutated AML

FLT3-ITD–mutated acute myeloid leukemia (AML) is an aggressive disease usually resistant to available treatment options, resulting in high front-line response rates but short response durations and low survival rates. Quizartinib—a potent selective FLT3 inhibitor—can work synergistically with...

Leukemia
Myelodysplastic Syndromes
Genomics/Genetics

Targeted Therapy Emavusertib Shows Activity in Patients With MDS or AML With Specific Mutations

Mutations in SF3B1 and U2AF1 can drive overexpression of activated IRAK4—which regulates inflammation and promotes cancer cell growth and survival—and are associated with a poor prognosis for patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Emavusertib is a...

Leukemia
Immunotherapy

Ponatinib Plus Blinatumomab for Patients With Philadelphia Chromosome–Positive ALL

The tyrosine kinase inhibitor ponatinib and monoclonal antibody blinatumomab—which targets CD19 on leukemia cells—are highly effective as monotherapies for patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). The combination of the two therapies may provide an...

Leukemia

FLT3 Inhibitor Crenolanib in Combination With Chemotherapy for Newly Diagnosed Patients With FLT3-Mutant AML

Eunice Wang, MD, Chief of Leukemia at Roswell Park Comprehensive Cancer Center, and colleagues presented the long-term results of a phase II clinical trial combining crenolanib, a second-generation FLT3 inhibitor, with standard intensive chemotherapy for the treatment of adults with newly diagnosed ...

leukemia

Courtney D. DiNardo, MD, MSCE, and Stéphane de Botton, MD, PhD, on AML: New Data on IDH2-Mutant Alleles, Enasidenib, and Conventional Care

Courtney D. DiNardo, MD, MSCE, of The University of Texas MD Anderson Cancer Center, and Stéphane de Botton, MD, PhD, of Institut Gustave Roussy, discuss phase III findings from the IDHENTIFY trial, which showed that mutational burden and co-mutational profiles differed between patients with relapsed or refractory acute myeloid leukemia that exhibited IDH2-R140 and IDH2-R172 mutations. Enasidenib improved survival outcomes for patients with IDH2-R172 mutations: median overall survival and 1-year survival rates were approximately double those in the conventional care arm (Abstract 7005).

leukemia

Courtney D. DiNardo, MD, MSCE, and Jorge E. Cortes, MD, on CML: New Efficacy and Safety Results for Asciminib

Courtney D. DiNardo, MD, MSCE, of The University of Texas MD Anderson Cancer Center, and Jorge E. Cortes, MD, of Georgia Cancer Center at Augusta University, discuss phase III results from the ASCEMBL trial, which showed that after more than 2 years of follow-up, asciminib continued to yield superior efficacy and better safety and tolerability vs bosutinib in patients with chronic myeloid leukemia (CML) in chronic phase. These results continue to support the use of this kinase inhibitor as a new CML therapy, says Dr. Cortes, with the potential to transform the standard of care (Abstract 7004).

Leukemia

FDA Approves Ivosidenib/Azacitidine for Certain Patients With Newly Diagnosed AML

On May 25, the U.S. Food and Drug Administration (FDA) approved ivosidenib (Tibsovo) in combination with azacitidine for patients with newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test in adults aged 75 or older, or who have...

Leukemia

FDA Approves Azacitidine for Newly Diagnosed Juvenile Myelomonocytic Leukemia

On May 20, the U.S. Food and Drug Administration approved azacitidine (Vidaza) for pediatric patients with newly diagnosed juvenile myelomonocytic leukemia (JMML). AZA-JMML-001 Efficacy was evaluated in AZA-JMML-001 (ClinicalTrials.gov identifier NCT02447666), an international, multicenter,...

Leukemia
Multiple Myeloma

Using a Transcriptomic Profile to Identify Plasma Cell Leukemia–Like Disease in Patients With Newly Diagnosed Multiple Myeloma

In a study reported in the Journal of Clinical Oncology, Bruinink et al constructed a transcriptomic classifier for primary plasma cell leukemia (PCL) that identified high-risk PCL-like disease in patients with newly diagnosed multiple myeloma. As stated by the investigators, “Primary PCL is an...

Leukemia
Survivorship

AYA Leukemia Survivors Have Higher Mortality Rates Than the General Population

Although considered a rare occurrence in adolescents and young adults (AYAs), aged 15 to 39 years, the incidence of cancer in this age group has been increasing by approximately 30% since the 1970s. This year, it is estimated that nearly 90,000 new cases of cancer will be diagnosed in this...

Hematologic Malignancies
Multiple Myeloma
Lymphoma
Leukemia

Prevalence of Plasma Cell and Lymphoproliferative Disorders in Relatives of Probands With Light Chain Amyloidosis

In a study reported in the British Journal of Haematology, Staron et al found that the prevalence of plasma cell and lymphoproliferative disorders among blood relatives of probands with light chain (AL) amyloidosis was low overall and varied according to proband AL amyloidosis subtype. Despite...

Immunotherapy
Hematologic Malignancies
Leukemia
Lymphoma

Rehospitalization and Emergency Department Visits After CAR T-Cell Therapy in Commercially Insured Patients With Cancer

In a single-institution study reported in a research letter in JAMA Oncology, Kenzik et al found substantial rates of rehospitalization and emergency department visits after chimeric antigen receptor (CAR) T-cell therapy among commercially insured patients with cancer. Study Details The study...

Hematologic Malignancies
Leukemia
Lymphoma
Multiple Myeloma
Immunotherapy

Hematologic Oncology 2021–2022 Almanac

Ongoing evaluation of novel, targeted, and immunotherapies has led to exciting advances across the array of hematologic malignancies over the past year. The availability of new treatment options, along with emerging data on novel combinations and sequencing approaches, is rapidly changing...

Leukemia

Improved Outcomes With Time-Limited Venetoclax Combinations vs Chemoimmunotherapy in Fit Patients With CLL

Administering time-limitedcombination regimens of venetoclax plus obinutuzumab or venetoclax plus obinutuzumab and ibrutinib was superior to chemoimmunotherapy in achieving undetectable measurable residual disease (MRD) in the peripheral blood at month 15 in fit patients with chronic lymphocytic...

Leukemia

Expert Point of View: Joshua Brody, MD

Joshua Brody, MD, Director of the CLL/Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai, New York, who was not involved in these trials, commented: “CLL is an extremely prevalent disease affecting nearly 200,000 patients in the United States. Most patient do not require...

Leukemia

Fixed-Duration Venetoclax Plus Ibrutinib Achieves Deep and Durable MRD Remissions in CLL

Two different trials presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition found that fixed-duration treatment with ibrutinib and venetoclax achieved deep and sustained undetectable measurable residual disease (MRD) status when used as first-line therapy for...

Lymphoma
Leukemia

Zanubrutinib Superior to Ibrutinib for CLL/SLL in Phase III ALPINE Trial

Zanubrutinib, a second-generation Bruton’s tyrosine kinase (BTK) inhibitor, significantly improved response rates and delayed disease progression as compared with the standard of care, ibrutinib, in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma...

Leukemia

ELEVATE-RR Trial: Acalabrutinib as Effective as Ibrutinib, With Fewer Cardiac Effects, in Resistant CLL

Acalabrutinib was equally efficacious with less toxicity when compared directly with ibrutinib in patients with previously treated relapsed or refractory chronic lymphocytic leukemia (CLL), according to the results of an open-label, randomized, noninferiority phase III trial presented at the 2021...

Leukemia

Addition of Ivosidenib to Azacitidine in Newly Diagnosed IDH1-Mutated Acute Myeloid Leukemia

In the phase III AGILE trial reported in The New England Journal of Medicine, Montesinos et al found that the addition of ivosidenib to azacitidine in induction therapy significantly prolonged event-free survival in patients with newly diagnosed IDH1-mutated acute myeloid leukemia. An overall...

Leukemia

AML Study Shows Benefit of CPX-351 vs Hypomethylating Agent Plus Venetoclax in Subgroup of Older Adults

For older patients with acute myeloid leukemia (AML), front-line treatment with liposomal daunorubicin/cytarabine (CPX-351) appears to be equivalent to treatment with a hypomethylating agent plus venetoclax, according to data presented at the 2021 American Society of Hematology (ASH) Annual Meeting ...

Leukemia

Patients With ALL and Certain Gene Regulation Patterns May Be Less Likely to Respond to CAR T-Cell Therapy

Acute lymphoblastic leukemia (ALL) cells from patients whose cancers did not respond to CD19-targeted chimeric antigen receptor (CAR) T-cell therapy had gene regulation signatures that could potentially facilitate treatment resistance, according to results presented at the American Association for...

Leukemia

Study Examines Disparities in Relapse Among Pediatric Patients With ALL

According to a large multiethnic study presented by Sok et al at the American Association for Cancer Research (AACR) Annual Meeting 2022, Latinx children with acute lymphoblastic leukemia (ALL) and measurable residual disease (MRD)-negative status were more likely to relapse compared with...

leukemia
immunotherapy

Yaqi Zhao, MSc, on ALL: Molecular Profile and Efficacy of Inotuzumab Ozogamicin

Yaqi Zhao, MSc, of St. Jude Children’s Research Hospital, discusses findings from the phase III INO-VATE trial, which showed that inotuzumab ozogamicin reduced the signs and symptoms of acute lymphoblastic leukemia associated with a variety of gene and chromosome changes. Future studies may confirm which patients are more likely to benefit from this agent (Abstract CT027).

Leukemia

Addition of Sorafenib to Standard Chemotherapy in Pediatric Patients With High Allelic Ratio FLT3-ITD–Positive AML

In an analysis from the Children’s Oncology Group protocol AAML1013 reported in the Journal of Clinical Oncology, Pollard et al found that the addition of sorafenib to standard chemotherapy may benefit pediatric patients with high allelic ratio FLT3-ITD–positive acute myeloid leukemia (AML). Study...

leukemia

Therapy Options for MRD-Positive AML

In this video, Drs. Richard Stone, Courtney DiNardo, and Eunice Wang discuss therapy options for minimal residual disease (MRD)-positive acute myeloid leukemia (AML). The case is a 44-year-old man with no past medical history who presents with fevers and fatigue. He is diagnosed with AML and achieves morphologic remission after treatment with 7+3 (cytarabine/daunorubicin) plus gemtuzumab; however MRD flow cytometry reveals 0.1% blasts, which persists after consolidation with high-dose cytarabine. The faculty discuss how they would approach the next steps for this patient and the importance of reducing the disease burden prior to the initiation of allogeneic stem cell transplant.

leukemia
genomics/genetics

Therapy Options for Primary Refractory FLT3-ITD–Positive AML

In this video, Drs. Richard Stone, Courtney DiNardo, and Eunice Wang treatment options for primary refractory FLT3-ITD–positive acute myeloid leukemia (AML). The case is a 60-year-old man with a history of hypertension and hyperlipidemia who presents with fatigue. He is diagnosed with FLT3-ITD–positive AML and is enrolled in a clinical trial where he receives 7+3 (cytarabine/daunorubicin) and midostaurin; after achieving complete remission, his disease eventually recurs. The faculty discuss potential treatment options for this patient, such as FLAG-IDA-VEN and gilteritinib both alone and in combination.

leukemia
genomics/genetics

Induction Therapy for an Older Patient With IDH1-Mutant AML

In this video, Drs. Richard Stone, Courtney DiNardo, and Eunice Wang discuss the management of newly diagnosed older patients with acute myeloid leukemia (AML). The case is a 75-year-old woman with no past medical history who presents with fever and bone pain. She is diagnosed with AML, and next-generation sequencing reveals a mutation in IDH1, among others. The faculty discuss the potential choices for induction therapy in older patients such as this, debating the merits of intensive chemotherapy vs lower-intensity options such as azacitidine/venetoclax and azacitidine/ivosidenib.

leukemia

Induction Therapy for a Young Patient With AML

This is Part 1 of Updates in Acute Myeloid Leukemia, a four-part video roundtable series. Scroll down to watch the other videos from this Roundtable. In this video, Drs. Richard Stone, Courtney DiNardo, and Eunice Wang discuss the management of newly diagnosed younger patients with acute myeloid leukemia (AML). The case is a 23-year-old woman with no past medical history who presents with very heavy menstrual periods and fatigue, and is diagnosed with AML with key mutations found in DNMT3A, NPM1, and IDH2. The faculty discuss the evolution of induction therapy options for younger patients with AML, as oncologists move from standard 7+3 (cytarabine/daunorubicin) chemotherapy to more personalized approaches.

Hematologic Malignancies
Leukemia
Lymphoma
Myelodysplastic Syndromes

Allogeneic Transplantation for Hematologic Neoplasms in Adults

“The value of experience is not in seeing much, but in seeing wisely.” —Sir William Osler To complement The ASCO Post’s continued comprehensive coverage of the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition, here are several abstracts selected from the meeting...

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