Data from the following clinical trials are discussed:

223: Molecular Characterization of Clinical Response and Relapse in Patients with 

m ND-AML Treated with Ivo+AZA in the AGILE Study

61: Phase I/II Study of Azacitidine (AZA) with Venetoclax (VEN) and Magrolimab (Magro) in Patients (pts) with Newly Diagnosed (ND) Older/Unfit or High-Risk Acute Myeloid Leukemia (AML) and Relapsed/Refractory (R/R) AML

2746: Phase Ib/2 Study of Oral Decitabine/Cedazuridine (ASTX727) and Venetoclax in Combination with the Targeted Mutant IDH1 Inhibitor Ivosidenib or the Targeted Mutant IDH2 Inhibitor Enasidenib in IDH Mutated Acute Myeloid Leukemia

2758: A Phase 1/2 Dose Escalation Study of the Myeloid Kinase Inhibitor HM43239 in Patients with Relapsed or Refractory Acute Myeloid Leukemia

Supported in part by Amgen Oncology, Servier, and Takeda Oncology. Content developed independently by OncLive®.

Videos

Shared insight on recently updated data in acute myeloid leukemia following the ASH 2022 annual meeting.

Acute Myeloid Leukemia: Updates From The ASH 2022 Annual Meeting

620: Three-Year Update from the OPTIC Trial: A Dose-Optimization Study of 3 Starting Doses of Ponatinib

333: Outcome of Third-Line Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia in Chronic Phase: A Propensity Score Analysis

 Is Predictive of Positive Outcomes in Treatment-Resistant Patients with Chronic Phase Chronic Myeloid Leukemia (CP-CML) Treated with Ponatinib from the Phase 2 Optic Trial

4339: Outcomes in Patients with Chronic Myeloid Leukemia in the Chronic Phase Randomized to Dasatinib or Imatinib after Suboptimal Responses to 3 Months of Imatinib Therapy: Final 5-Year Results from DASCERN

Experts in hematologic oncology review and analyze updated data in chronic myeloid leukemia from ASH 2022.

ASH 2022: Recent Advances in Chronic Myeloid Leukemia

LBA1: Consolidation Therapy with Blinatumomab Improves Overall Survival in Newly Diagnosed Adult Patients with B-Lineage Acute Lymphoblastic Leukemia in Measurable Residual Disease Negative Remission: Results from the ECOG-ACRIN E1910 Randomized Phase III National Cooperative Clinical Trials Network Trial

2727: Safety and Pharmacokinetics of Subcutaneous Blinatumomab (SC blinatumomab) for the Treatment of Adults with Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL); Results from a Phase 1b Study

2732: Blinatumomab Alternating With Low-Intensity Chemotherapy (CT) Treatment for Older Adults With Newly Diagnosed Philadelphia (Ph)-Negative B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is Well Tolerated and Efficacious: Safety Run-In Results for the Phase 3 Randomized Controlled Golden Gate Study

213: Ponatinib and Blinatumomab for Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Subgroup Analysis from a Phase II Study

4046: Ponatinib and Blinatumomab for Patients with Relapsed/Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia in Lymphoid Blast Phase: A Subgroup Analysis from a Phase II Study

906: Comparison of Overall Survival Among Adolescents and Young Adults (AYA) with Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) Treated with Pediatric-Inspired or Non-Pediatric Inspired Regimens: A Real-World Analysis Using Claims Data

Following the ASH 2022 Annual Meeting, hematologic oncology experts discuss updated data in acute lymphocytic leukemia.

ASH 2022: Updates in the Acute Lymphocytic Leukemia Treatment Landscape

Sameem Abedin, MD, an assistant professor at the Department of Medicine, Division of Hematology and Oncology at the Medical College of Wisconsin, discusses the safety and efficacy of ibrutinib (Imbruvica) in the treatment of patients with chronic lymphocytic leukemia (CLL).

Ibrutinib is one of the most utilized options for this patient population in the clinic, according to Abedin. The frequent use of the agent has allowed for a better understanding regardingdose modification and other strategies that can increase tolerability, Abedin says. As such, when selecting among the BTK inhibitors that are available to patients with CLL, ibrutinib continues to be a beneficial option, Abedin notes.

Adverse effects (AEs), such as heartrate abnormalities and high blood pressure, have been reported with ibrutinib, and as such, it is important to consider how to navigate away from these toxicities—especially in the frontline setting, where the agent is most likely to be used, Abedin explains. If toxicity challenges prevent the use of ibrutinib, recent studies suggest that acalabrutinib (Calquence) is a well-tolerated treatment option for these patients, Abedin concludes.

Sameem Abedin, MD, discusses the safety and efficacy of ibrutinib in the treatment of patients with chronic lymphocytic leukemia.

Dr. Abedin on the Safety and Efficacy of Ibrutinib in CLL

Sameem Abedin, MD, an assistant professor in the Department of Medicine, Division of Hematology and Oncology, at the Medical College of Wisconsin, discusses managing cardiac toxicities with acalabrutinib (Calquence) vs ibrutinib (Imbruvica) in patients with chronic lymphocytic leukemia (CLL).

Cardiac toxicities, such as ventricular tachycardia and atrial fibrillation, appear to occur less frequently in patients who are treated with acalabrutinib vs ibrutinib, according to Abedin. Additionally, hypertension is reported in approximately 6% of patients receiving acalabrutinib, with ibrutinib eliciting rates of up to 30%, Abedin says.

These features are important to consider, as many of the patients receiving treatment with these agents are older, Abedin adds. Moreover, while not every patient in this population needs to be started on acalabrutinib, it is important to have this option for those who are at risk for cardiac adverse effects, Abedin concludes.


Sameem Abedin, MD, discusses managing cardiac toxicities with acalabrutinib vs ibrutinib in patients with chronic lymphocytic leukemia.


Dr. Abedin on Managing Cardiac Toxicities With Acalabrutinib vs Ibrutinib in CLL

Sameem Abedin, MD, an assistant professor in the Department of Medicine, Division of Hematology and Oncology, at the Medical College of Wisconsin, discusses frontline treatment considerations for patients with chronic lymphocytic leukemia (CLL).

Many factors are considered in terms of patient preference and toxicities when managing CLL, although one of the most important considerations from a patient standpoint is duration of therapy, according to Abedin. For example, if a patient could potentially do equally well receiving venetoclax (Venclexta) and an anti-CD20 therapy, which is a fixed duration therapy, or a BTK inhibitor, it is important to present that 1 treatment is a fixed duration approach while the other is continuous, Abedin explains.

Additionally, toxicities must be discussed in that context, Abedin adds. With venetoclax-based treatment, more monitoring is required, as patients are at increased risk for tumor lysis syndrome, as well as subsequent cytopenia and neutropenia. As such, throughout the year they are on treatment, patients may be subject to more blood monitoring, as well as adjustments to their therapy, Abedin concludes.

Sameem Abedin, MD, discusses frontline treatment considerations for patients with chronic lymphocytic leukemia.

Dr. Abedin on Frontline Treatment Considerations in CLL 

Sameem Abedin, MD, assistant professor, Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, discusses the clinical significance of undetectable minimal residual disease (uMRD) status in chronic lymphocytic leukemia (CLL).

uMRD is a concept reserved for venetoclax (Venclexta)–based treatment where significant rates of uMRD have been observed, says Abedin. Conversely, assessing for MRD status may not be needed in patients receiving BTK inhibitors, Abedin explains.

Currently, the significance of achieving uMRD is not fully realized but appears to be dependent on patients’ biologic factors, Abedin says. For example, patients with uMRD and mutated 

 often have prolonged remissions, whereas a significant proportion of patients with uMRD and a 

 mutation or loss progress within 4 or 5 years, Abedin explains. As such, achieving uMRD could predict for a significant period of disease control in some patients but be less clinically meaningful in others, concludes Abedin.

Sameem Abedin, MD, discusses the clinical significance of undetectable minimal residual disease status in chronic lymphocytic leukemia.



Dr. Abedin on the Clinical Significance of Undetectable MRD in CLL 

Sameem Abedin, MD, assistant professor, Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, discusses the need for risk stratification prior to giving chemoimmunotherapy to patients with chronic lymphocytic leukemia (CLL).

Risk stratification can inform which patients are most likely to respond to chemoimmunotherapy, says Abedin. As such, it is important to obtain molecular results regarding 11q deletions, 17p loss or mutations, and 

 mutational status, which can all be prognostic indicators of response to chemoimmunotherapy, Abedin says. 

Chemoimmunotherapy remains the standard frontline treatment regimen for up to half of patients with CLL, so ensuring patients are risk stratified before treatment initiation is important, concludes Abedin. 

Sameem Abedin, MD, discusses the need for risk stratification prior to giving chemoimmunotherapy to patients with chronic lymphocytic leukemia. 



Dr. Abedin on the Need for Risk Stratification Before Chemoimmunotherapy in CLL 

Sameem Abedin, MD, assistant professor, Medical College of Wisconsin, discusses the use of PI3K inhibitors in the treatment of patients with chronic lymphocytic leukemia (CLL).

There are two approved PI3K inhibitors in CLL: duvelisib (Copiktra) and idelalisib (Zydelig). In 2018, the FDA approved duvelisib for the treatment of patients with relapsed/refractory CLL based on results from the phase III DUO study. In the trial, patients with relapsed/refractory CLL who had received ≥2 prior lines of therapy experienced a 60% reduction in the risk of disease progression or death versus ofatumumab (Arzerra).

In 2014, idelalisib was approved for use in combination with rituximab (Rituxan) in the relapsed/refractory setting based on data from the phase III Study 116 trial (NCT01539512). The trial was stopped early due to the dramatic improvement in progression-free survival (PFS) with the combination. At 24 weeks, the PFS rate of PFS was 93% in the combination arm and 46% in the rituximab-alone arm. The agents have slightly different mechanisms of action, and duvelisib has more immune properties, says Abedin.

In terms of administration, duvelisib is given as monotherapy, whereas idelalisib is given in combination with rituximab. For patients, the ease of taking a pill may be preferable to the combination, according to Abedin.

Dr. Abedin on PI3K Inhibitors in CLL

Sameem Abedin, MD, assistant professor, Medical College of Wisconsin, discusses the role of venetoclax (Venclexta) plus obinutuzumab (Gazyva) in chronic lymphocytic leukemia (CLL).

In May 2019, the FDA approved the combination of venetoclax and obinutuzumab for the frontline treatment of patients with CLL or small lymphocytic lymphoma. This is great for patients, Abedin says, mainly because frontline ibrutinib (Imbruvica)-based regimens can be toxic. The BTK inhibitor can cause bleeding, nausea, and atrial fibrillation, so having an alternative in the frontline setting is important.

However, there are more data supporting the use of ibrutinib in this setting, Abedin notes. Two randomized trials have compared ibrutinib with the previous standard of care, and there are more follow-up data with the drug as opposed to the newly approved venetoclax/obinutuzumab combination. The current data with the novel combination show promising response rates and depth of response, Abedin concludes.

Sameem Abedin, MD, assistant professor, Medical College of Wisconsin, discusses the role of venetoclax plus obinutuzumab in chronic lymphocytic leukemia.

Dr. Abedin on the Role of Venetoclax Plus Obinutuzumab in CLL

Sameem Abedin, MD, assistant professor, Medical College of Wisconsin, discusses key updates in the treatment of patients with chronic lymphocytic leukemia (CLL).

Arguably the biggest advancement in this space is the FDA approval of ibrutinib (Imbruvica) in the frontline setting, though physicians have been using the BTK inhibitor informally in that setting for some time. This approval signifies significant progress, he adds.

In the relapsed/refractory setting, the efficacy of venetoclax (Venclexta) as a single agent and in combination has generated excitement. The PI3K delta and gamma inhibitor duvelisib (Copiktra) is also FDA approved in the relapsed/refractory setting. Both of these agents are favorable options because they are associated with decent response rates and progression-free survival after disease progression.

However, venetoclax has a slight edge over duvelisib due to the fact that clinical trial data include patients who failed on a BTK inhibitor, Abedin says.

Sameem Abedin, MD, assistant professor, Medical College of Wisconsin, discusses key updates in the treatment of patients with chronic lymphocytic leukemia.

Sameem Abedin, MD

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