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Adult ALL Advancements: Optimizing Cure in 2024

Program: Education Program
Hematology Disease Topics & Pathways:
Diseases, Treatment Considerations, Biological therapies, Immunotherapy, Lymphoid Malignancies, Transplantation (Allogeneic and Autologous)
Monday, December 9, 2024: 2:45 PM-4:00 PM
Ballroom 20AB (San Diego Convention Center)

Description:
Acute lymphoblastic leukemia (ALL) in adults is an aggressive condition with historically few long-term survivors. Fortunately, the outlook for ALL in adults is improving rapidly as years of scientific research and clinical investigation begins to pay dividends. Improved understanding of the heterogeneity and varied biological behavior of ALL subtypes has led to routine immunophenotypic and genetic characterization of individual ALL cases in the clinic. Profiling of ALL at diagnosis as well as better ability to track measurable residual disease (MRD) after therapy now permits personalized, risk-adapted treatment recommendations in ALL including the rational application of allogeneic stem cell transplantation. In addition, multiple new targeted and immune therapies have been approved by regulatory authorities for Philadelphia chromosome-positive (Ph+) and negative B-ALL. The rapid pace of scientific and therapeutic advancement in ALL is challenging established standards of care for upfront treatment of adults with newly diagnosed ALL. In this session, the impact of scientific and therapeutic advancements in the initial treatment approach for ALL will be reviewed, with a focus on recent evidence generation.

Dr. Marlise Luskin will review data supporting the selection of various approaches to initial treatment of Ph+ ALL in adults. She will discuss data justifying the use of specific BCR-ABL1 kinase inhibitors including dasatinib, nilotinib, and ponatinib. In this session, she will also review evidence defining the role of conventional chemotherapy, allogeneic transplantation, and the bi-specific T-cell engager (BiTE) blinatumomab in first-line post-remissiont treatment of Ph+ ALL in adults of different ages.

Prof. Matthias Stelljes will discuss the role of novel antibody-based and cell-based immunotherapies in the treatment of ALL in adults. Blinatumomab, the antibody-drug conjugate inotuzumab ozogamicin, and CD19-directed CAR-T cells are current standard-of-care options for patients with relapsed or refractory B-cell ALL. The CD20-targeting monoclonal antibody rituximab and blinatumomab are established components of frontline therapy for patients with CD20-positive ALL and patients with persistent MRD, respectively. More recently, blinatumomab and inotuzumab have shown promising results in the upfront treatment of patients with B-cell ALL. These data form the basis for evaluating and defining new treatment standards, which will be discussed in this educational session.

Dr. Partow Kebriaei will review risk profiling in adult patients with ALL, and specifically how disease risk informs the decision to recommend transplant in first complete remission. Additionally, she will highlight advancements in GVHD prophylaxis that facilitate greater donor availability and decreased toxicity of transplant. Finally, Dr. Kebriaei will review the optimal sequence for transplant within the context of CAR T therapy.

Chair:
Marlise R Luskin, MD, MSCE, Dana-Farber Cancer Institute
Disclosures:
Luskin: AbbVie: Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria; KITE: Honoraria; Jazz: Honoraria.

Acute lymphoblastic leukemia (ALL) in adults is an aggressive condition with historically few long-term survivors. Fortunately, the outlook for ALL in adults is improving rapidly as years of scientific research and clinical investigation begins to pay dividends. Improved understanding of the heterogeneity and varied biological behavior of ALL subtypes has led to routine immunophenotypic and genetic characterization of individual ALL cases in the clinic. Profiling of ALL at diagnosis as well as better ability to track measurable residual disease (MRD) after therapy now permits personalized, risk-adapted treatment recommendations in ALL including the rational application of allogeneic stem cell transplantation. In addition, multiple new targeted and immune therapies have been approved by regulatory authorities for Philadelphia chromosome-positive (Ph+) and negative B-ALL. The rapid pace of scientific and therapeutic advancement in ALL is challenging established standards of care for upfront treatment of adults with newly diagnosed ALL. In this session, the impact of scientific and therapeutic advancements in the initial treatment approach for ALL will be reviewed, with a focus on recent evidence generation.

Dr. Marlise Luskin will review data supporting the selection of various approaches to initial treatment of Ph+ ALL in adults. She will discuss data justifying the use of specific BCR-ABL1 kinase inhibitors including dasatinib, nilotinib, and ponatinib. In this session, she will also review evidence defining the role of conventional chemotherapy, allogeneic transplantation, and the bi-specific T-cell engager (BiTE) blinatumomab in first-line post-remissiont treatment of Ph+ ALL in adults of different ages.

Prof. Matthias Stelljes will discuss the role of novel antibody-based and cell-based immunotherapies in the treatment of ALL in adults. Blinatumomab, the antibody-drug conjugate inotuzumab ozogamicin, and CD19-directed CAR-T cells are current standard-of-care options for patients with relapsed or refractory B-cell ALL. The CD20-targeting monoclonal antibody rituximab and blinatumomab are established components of frontline therapy for patients with CD20-positive ALL and patients with persistent MRD, respectively. More recently, blinatumomab and inotuzumab have shown promising results in the upfront treatment of patients with B-cell ALL. These data form the basis for evaluating and defining new treatment standards, which will be discussed in this educational session.

Dr. Partow Kebriaei will review risk profiling in adult patients with ALL, and specifically how disease risk informs the decision to recommend transplant in first complete remission. Additionally, she will highlight advancements in GVHD prophylaxis that facilitate greater donor availability and decreased toxicity of transplant. Finally, Dr. Kebriaei will review the optimal sequence for transplant within the context of CAR T therapy.

Marlise R Luskin, MD, MSCE

Division of Leukemia, Dana-Farber Cancer Institute, Boston, MA

Matthias Stelljes, MD

Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany

Partow Kebriaei, MD

MD Anderson Cancer Center, Houston, TX

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