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Key Studies: ASH 2019

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Preview of ASH 2019: Key Expert-Selected Studies

Physicians : maximum of 1.00 AMA PRA Category 1 {Credit}

Released: December 05, 2019

Expiration: December 04, 2020

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At the 2019 ASH annual meeting, important results from many clinical trials in malignant and nonmalignant hematology will be reported. Below, hematology experts have highlighted their most anticipated abstracts, which will be covered online as a part of CCO’s Independent Conference Coverage of ASH 2019. As the ASH annual meeting unfolds, remember to check the CCO Web site often for downloadable slidesets summarizing the data from these studies and more and then again after the meeting for CME-certified online activities featuring expert commentaries on the clinical implications of the data.

Top Picks: Chronic Lymphocytic Leukemia/Lymphomas
John M. Burke, MD, and Jeff P. Sharman, MD, have identified key studies in chronic lymphocytic leukemia (CLL) and lymphomas that they are eager to see at ASH 2019. The phase III ELEVATE-TN trial stands out as one of the pivotal studies leading to the recent approval of acalabrutinib in CLL. Key findings from this trial showing that acalabrutinib with or without obinutuzumab significantly improved PFS compared with chlorambucil plus obinutuzumab in previously untreated CLL will be presented. Combination therapies using targeted agents are likely to become a standard of care in CLL in the near future. Tam and colleagues will report results from the measurable residual disease (MRD) cohort of the phase II CAPTIVATE trial investigating ibrutinib plus venetoclax as frontline treatment for CLL. In addition, updated results from the phase I/II TRANSCEND CLL 004 trial evaluating lisocabtagene maraleucel (liso-cel), a CD19-directed CAR T-cell therapy, in patients with relapsed/refractory CLL will be presented.

In pretreated B-cell malignancies, Mato and colleagues will present results from a first-in-human phase I trial of LOXO-305, a next-generation, highly selective, noncovalent BTK inhibitor, in patients with CLL and mantle cell lymphoma (MCL). CAR T-cell therapies have demonstrated robust activity in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Long-term follow-up data from the phase I TRANSCEND NHL 001 trial of liso-cel in relapsed/refractory large B-cell lymphomas will be reported. Wang and colleagues will present results from the phase II ZUMA-2 trial, assessing KTE-X19, another CD19-directed CAR T-cell therapy, in patients with relapsed/refractory MCL. Mosunetuzumab is a novel bispecific antibody targeting CD3 to CD20. At ASH 2019, results from the phase I/II GO29781 trial evaluating mosunetuzumab in patients with heavily pretreated B-cell NHL including those who progressed after CAR T-cell therapies will be reported.

Top Picks: Leukemias
Elias J. Jabbour, MD, and Eunice Wang, MD, have identified a number of potentially clinically impactful studies at ASH 2019 for patients with leukemias. In acute myeloid leukemia (AML), results will be presented from the phase III QUAZAR AML-001 maintenance trial of CC-486 (oral formulation of azacitidine) in patients with AML in first remission, as well as important conclusions from a study of the impact on outcomes of time from diagnosis to treatment in intensively treated patients with newly diagnosed AML. In acute lymphoblastic leukemia (ALL), key studies will highlight results from the phase III Children’s Oncology Group Study AALL1331 of blinatumomab vs chemotherapy as post-reinduction therapy in high-risk and intermediate-risk first relapse of B-ALL in children and adolescents/young adults. Another study will report long-term safety and efficacy of frontline therapy with hyper-CVAD plus ponatinib for adults with Philadelphia chromosome–positive ALL. Finally, a report on the safety and efficacy of venetoclax in combination with navitoclax in adult and pediatric relapsed/refractory ALL and lymphoblastic lymphoma will be reported.

Top Picks: Multiple Myeloma
Shaji Kumar, MD, and Sagar Lonial, MD, have identified key studies in multiple myeloma (MM) that are highly anticipated at ASH 2019. The late-breaking abstract for the phase III CANDOR trial will present primary results on the efficacy and safety of daratumumab plus Kd vs Kd alone in patients with relapsed/refractory MM. The online abstract suggests a significant PFS advantage and deeper responses with the addition of daratumumab to Kd in this setting. An extended follow-up (> 3 years) including a prespecified interim OS analysis from the phase III ALCYONE clinical trial comparing Dara-VMP with VMP in patients with transplant-ineligible newly diagnosed MM will also be presented. The CASSIOPET companion study of the CASSIOPEIA clinical trial will report on the prognostic value of PET/CT at diagnosis, postconsolidation PET-complete response (PET-CR) rates, and concordance of PET CR and MRD negativity in patients with transplant-eligible newly diagnosed MM. Finally, preliminary safety and efficacy data will be presented from a dose-finding phase I study of a novel T-cell engager targeting B-cell maturation antigen and CD3ε, CC-93269, in patients with heavily pretreated MM.

Top Picks: Myeloproliferative Neoplasms/Myelodysplastic Syndromes
Rami S. Komrokji, MD, and Raajit K. Rampal, MD, PhD, have identified several highly anticipated studies that will be presented at ASH 2019. We will see data from 2 notable phase II studies that assessed APR-246 plus azacitidine for patients with TP53-mutated myelodysplastic syndromes (MDS) and AML. APR-246 is a small molecule that binds to mutant p53, inducing proapoptotic conformational changes.

In addition, 2 presentations will provide data on luspatercept, an erythroid maturation agent that was recently approved for treating anemia in adult patients with β-thalassemia who require regular red blood cell (RBC) transfusions. The first of these is a longer-term analysis of MEDALIST, a phase III trial in which patients with non-del(5q), lower-risk MDS and ring sideroblasts who were RBC transfusion dependent were randomized to receive either luspatercept or placebo. In the initial report of data from this trial, luspatercept significantly reduced transfusion burden and improved hemoglobin levels compared with placebo, and it will be very interesting to see longer-term data from this study. Luspatercept is also being assessed for the management of anemia in patients with myelofibrosis (MF). At ASH 2019, we will see preliminary results from an ongoing, open-label phase II study of luspatercept for the management in patients with MF-associated anemia (either those not receiving ruxolitinib or RBC transfusions, those not receiving ruxolitinib but with RBC transfusion–dependent anemia, or those with anemia and on a stable dose of ruxolitinib). For a closer look at MF abstracts of interest at ASH 2019, please see the expert commentary here.

Finally, we will see data from a phase Ib study of venetoclax with or without azacitidine for patients with relapsed/refractory MDS. Key findings on safety, recommended phase II dosing, and efficacy will be presented.

Top Picks: Nonmalignant Hematologic Disorders
Hanny Al-Samkari, MD, and Sujit Sheth, MD, have identified key studies in autoimmune hematologic disorders and hemoglobinopathies, respectively, that they are eager to see at ASH 2019. In the setting of hemoglobinopathies, progress in gene therapy is the feature this year. For transfusion-dependent β-thalassemia, potentially practice-changing interim results will be presented from the phase III NORTHSTAR-3 study assessing lentiglobin gene therapy in patients with β0-thalassemia and thereby broadening the thalassemia population in whom gene therapy may offer the potential for “cure.” For sickle cell disease, a late-breaking abstract will share proof-of-principle results on a novel approach of gene editing using posttranscriptional gene silencing of BCL11A to increase fetal hemoglobin levels in sickle cell disease.

In the setting of pretreated immune thrombocytopenia (ITP), an area of unmet need, promising early phase results are being presented for 2 novel agents. For ITP (primary or secondary) that previously responded to ≥ 1 prior therapies, phase I/II results are being presented on a novel BTK inhibitor, PRN1008, that avoids the off-target platelet dysfunction associated with other BTK inhibitors used in various hematologic malignancies. For severe ITP with inadequate response to ≥ 2 prior therapies, phase I results are being reported for sutimlimab, an anticomplement C1s monoclonal antibody, that inhibits complement activation by platelet surface autoantibodies, an important mechanism by which platelets are cleared in ITP. Sutimlimab is also highlighted in a late-breaking abstract on the phase III CARDINAL study assessing this agent for the treatment of patients with cold agglutinin disease, an autoimmune hemolytic anemia, and a recent history of transfusions.

Remember to Check the CCO Web Site Often!
These are just a few of the interesting and important abstracts selected by our expert faculty from ASH 2019. Downloadable slideset summaries of these studies and more will be available on our Web site as the data are presented at ASH. After the meeting, analyses by these experts will explore the clinical implications of the data in CME-certified clinical commentaries.

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