Acute Myeloid Leukemia (AML): Highlights from ASH 2020

December 13, 2020

From 05th to 08th December 2020, the Acute Leukemia Advocates Network (ALAN) attended the virtual 62nd ASH Annual Meeting and Exposition.

Samantha Nier, Network Manager reports on the AML sessions she attended and this comes in addition to has been posted on social media (https://twitter.com/AcuteLeuk)

The recent wave of new drug approvals for AML by the FDA has resulted in overlapping treatment options, especially in older patients or those considered unfit for intensive chemotherapy and in patients with relapsed or refractory disease. These therapies are a welcome advance for patients with AML but present physicians with new treatment challenges, such as the timely identification of actionable mutations at diagnosis and again at relapse; choosing which drugs to use; and the need for increased awareness of how to anticipate, mitigate, and manage common complications associated with these new agents.

FDA approved agents for AML

Until recently, treatment options for patients with newly diagnosed and relapsed/refractory AML were limited to cytotoxic chemotherapeutic agents that possessed little specificity for the cytogenetic and molecular mutations known to risk stratify patients with this disease. Furthermore, treatment was often started very soon after the diagnosis was made with limited consideration of these disease specific characteristics.

While the advent of targeted therapies for AML has led to new hope for patients, it has also introduced new challenges in management.

AML treatment options – how do you decide.

Recommendations for the ongoing management of patients who are receiving these new treatments

But also

And

Genetic and functional determinants of response have therefore become increasingly important in treatment decision making irrespective of chronological age.

Frontline AML induction therapy for older patients has evolved
AML treatment – the past …
AML treatment: now

Take home messages

-Clinical fitness (geriatric assessment informs on risks and outcomes in AML patients), mutations and patient preference (see below) should guide treatment selection now that more options are available.

-Recent approved frontline therapies offer hope but there are still many areas for improvement

-Stay tuned for intensive and non-intensive combination strategies and functional biomarkers that can further tailor therapy for individual patients.

-Treatment should not follow one-size fits-all approach. 

Patient Preference: importance of shared decision making

Principles

-for situations where clinicians would agree that there exists one more than one correct choice

-information about existing options, including risks and benefits are shared with patients

-patients are encouraged to consider their personal preferences and to make decision based on what matters most to them

In general, new diagnosis discussions

-tend to be one-sided, technical

-focus on information delivery

-lay out treatment options

And less likely to ask patients

-what are their values

-what information do they already have / know /want to know

-how do they want to receive the information

-how do they want to participate in the decision process

Shared decision making is based on the belief that the patient’s needs and desired outcomes should form the basis for all decisions and is not about providing the patients with a list of all possible treatment and ask them to decide. Available data do not suggest a difference in the length of a clinic consultation but that the structure of the consultation changes.

Many studies are ongoing and are showing some results that we’ll keep monitoring and share when preliminary data will be confirmed:

Novel therapies and treatment approaches

-Phase Ib First-in-Class Anti-CD47 Antibody Magrolimab Combined with Azacitidine Is Well-Tolerated and Effective in AML Patients

-lotetuzumab As Salvage Therapy for Primary Induction Failure and Early Relapse AML

-Phase 1b/2 Study of the BCL-2 Inhibitor Venetoclax in Combination with Standard Intensive AML Induction/Consolidation Therapy with FLAG-IDA in Patients with Newly Diagnosed or Relapsed/Refractory AML

-Phase 1b Study Efficacy and Safety of Venetoclax in Combination with Gilteritinib for Relapsed/Refractory FLT3-Mutated AML

Novel combination therapies in treatment of newly diagnosed AML

-A Phase 1 Study of Gilteritinib in Combination with Induction and Consolidation Chemotherapy in Patients with Newly Diagnosed AML

-Phase II Study of Venetoclax Added to Cladribine + Low Dose AraC (LDAC) Alternating with 5-Azacytidine Demonstrates High Rates of Minimal Residual Disease Negative Complete Remissions and Excellent Tolerability in Older Patients with Newly Diagnosed AML

-Phase IB/II Study Quizartinib with Decitabine +/- Venetoclax Is Highly Active in Patients with FLT3-ITD Mutated AML

-Phase 3, Multicenter, Open-Label Study of Gilteritinib, Gilteritinib Plus Azacitidine, or Azacitidine Alone in Newly Diagnosed FLT3 Mutated AML Patients Ineligible for Intensive Induction Chemotherapy

-Phase II Study of CPX-351 Plus Venetoclax in Patients with AML

Novel promising therapies for relapsed/refractory AML

-Phase III QUAZAR AML-001 Maintenance Trial Escalated Dosing Schedules of CC-486 Are Effective and Well Tolerated for Patients Experiencing First AML Relapse

-SY-1425, a Potent and Selective RARα Agonist, in Combination with Azacitidine Demonstrates a High Complete Response Rate and a Rapid Onset of Response in RARA-Positive Newly Diagnosed Unfit AML

-Phase 1/2A First in Human Study of the Menin-KMT2A Inhibitor KO-539 in Patients with Relapsed or Refractory AML

Advances in immunotherapeutics for management of AML

-A Phase I Study of Lintuzumab Ac225 in Combination with CLAG-M Chemotherapy in Relapsed/Refractory AML

-A WT-1 and PRAME “Fast-DC” Immunotherapy As a Potential Post-Remission Strategy for AML

-Safety and Efficacy of Decitabine Plus Ipilimumab in Relapsed or Refractory MDS/AML in the Post-BMT or Transplant Naïve Settings

-Overexpression of CD200 Is a Stem Cell-Specific Mechanism of Immune Escape in AML

Commercially Available Therapy

-Intensive Fludarabine, High Dose Cytarabine and Idarubicin-Based Induction for Younger NPM1-Mutated AML Patient: Overcoming the Negative Prognosis of FLT3-ITD Mutation

-Delays in Time to Deterioration of Health-Related Quality of Life Were Observed in Patients with AML Receiving Venetoclax in Combination with Azacitidine or in Combination with Low-Dose Cytarabine

-Phase 2 Study of Sorafenib Versus Placebo in Combination with Intensive Chemotherapy in Previously Untreated Patients with FLT3-ITD AML

-Newly Diagnosed Childhood AML Patients Treated with Bortezomib Show Superior Survival If CD74 Is Expressed

-Phase 3b Study Assessing the Safety and Efficacy of Midostaurin in Younger and Older Patients with Newly Diagnosed, FLT3-Mutated AML Who Are Eligible for 7+3 or 5+2 Chemotherapy

-Frontline Selinexor and Chemotherapy Is Highly Active in Older Adults with AML

-Azacitidine Vs. Decitabine in Unfit Newly Diagnosed AML

-Phase 3 Study of CPX-351 Versus 7+3 in Older Adults with Newly Diagnosed High-Risk/Secondary AML: Outcomes By Age Subgroup and Among Responders

-Enasidenib Monotherapy with Addition of Azacitidine in Non-Responders Is Effective in Older Patients with Newly Diagnosed IDH2 Mutated AML

-A Propensity Score Matched Analysis: Ten-Day Decitabine with Venetoclax Versus Intensive Chemotherapy in Relapsed or Refractory AML

Potpourri of Potential Practice Changing Studies

-Daunodouble Trial; remission and Survival after Single Versus Double Induction with 7+3 for Newly Diagnosed AML

-Comparison of Subcutaneous Injection Versus Intravenous Infusion of Cytarabine for Induction Therapy in Young Adult AML

-Phase I study: Complete Responses in Relapsed/Refractory AML Patients on a Weekly Dosing Schedule of Vibecotamab (XmAb14045), a CD123 x CD3 T Cell-Engaging Bispecific Antibody

-Venetoclax and Azacitidine Combination in Chemotherapy Ineligible Untreated Patients with AML with IDH 1/2 Mutations

For sure, there will be more to come at the European Hematology Association (EHA) meeting in June 2021 and again at ASH in December 2021. Stay tuned for more updates on what’s happening in the world of acute leukemia!