By Binod Dhakal, MD, MS

Each year on the final day of the ASH annual meeting, the Late-Breaking Abstracts (LBAs) Session presents novel, substantive, and groundbreaking research that was not available in time for the standard ASH abstract submission deadline. And if you are still looking for that moment — that one breakthrough study or some other fitting end to this remarkable meeting — then I am sure this year’s sensational LBAs will not disappoint you. Co-chaired by Elisabeth Battinelli, MD, and Jason Gotlib, MD, this breathtaking 90-minute clinical and scientific session takes place Tuesday at 7:30 a.m. in Hall D of the Orange County Convention Center (map it).

Acute lymphoblastic leukemia (ALL), one of the most common forms of childhood leukemias, has seen several landmark advances, with a cure rate of approximately 90 percent. Despite this, some relapse with dismal outcomes. The first abstract, presented by Patrick A. Brown, MD, reports on the results of the randomized, phase III trial of blinatumomab (CD3-CD19 BiTE®) versus chemotherapy as post-reinduction therapy in high- and intermediate-risk B-cell ALL in children and adolescent young adults. Blinatumomab was superior because it resulted in higher minimal residual disease response, improved disease-free and overall survival, and allowed more patients to proceed to allogeneic transplantation. “We are excited that these patients, whose survival has not substantially improved for decades, now have a new and better standard of care,” said Dr. Brown.

The second abstract, presented by Alexander Roeth, MD, of University Hospital Essen in Ger- many, shows the results of the Cardinal study, an open-label, single-arm, multicenter study of sutimlimab in patients with cold agglutinin disease (CAD).

Sutimlimab is a first-in-class humanized monoclonal anti-C1s antibody that selectively inhibits the C1 complex of complement pathway. The study met its primary end point as it prevented hemolysis and improved baseline hemoglobin and the quality of life of patients. This novel agent could prove practice-changing in CAD, a rare disease with high mortality and morbidity burden.

The third abstract, being presented by Andrew H. Wei, MBBS, sets the stage to influence the role of maintenance in patients with acute myeloid leukemia (AML) in first remission. The phase III QUAZAR AML-001 maintenance trial evaluated the safety and efficacy of CC-486 (an oral formulation of azacitidine) in patients aged 55 years or older after intensive induction chemotherapy for AML. These transplant-ineligible patients, when randomized to CC-486, achieved significant improvement in OS (HR, 0.69; 95% CI, 0.55-0.86) and relapse-free survival (HR, 0.65; 95% CI, 0.52-0.81) compared to placebo. As Dr. Gotlib remarked, “These data establish that post-remission maintenance therapy is now a clinical paradigm in AML to favorably alter the natural course of the disease.”

In the past decade, genetic studies have enabled the identification of a set of recurrently mutated genes central to the pathogenesis of MDS and AML. However, the discovery of novel mutational pat- terns and gene expression clusters is limited with this methodology. To overcome these limitations, Ilaria Iacobucci, PhD, will present the sequencing (while genomic and transcriptomic) results of a large cohort of patients with AML (n=598) and MDS (n=706) in the fourth LBA. “This study identified several genetic alterations that were not previously appreciated and were missed by gene panel sequencing,” said Dr. Iacobucci. These constellations of mutations have both prognostic and therapeutic relevance.

In the fifth LBA, Erica B. Esrick, MD, of Children’s Hospital Boston will present the results of a pilot study looking at the feasibility of gene therapy in adult patients with sickle cell disease (SCD). Using a lentiviral vector (BCH-BB694), the study targeted BCL11A, a potential regulator of hemoglobin F (HbF) expression, to induce erythroid-specific γ globulin expression and β-sickle globulin repression to increase HbF levels. The results (in 3 patients) showed the acceptable safety profile of infusion of BCH-BB694 transduced autologous CD34+ cells in severe SCD. It validated BCL11A as an effective therapeutic target for HbF induction, and though early, the results show promise in mitigating the SCD pathology. “This study demonstrated the efficacy of this approach, and results are very promising,” said session co-chair Dr. Battinelli. Adoption of lenalidomide (LEN) maintenance in both transplant-eligible and ineligible patients has resulted in an increasing need for effective treatments for patients with LEN-refractory multiple myeloma (MM). In the sixth LBA, Saad Usmani, MD, will present the results of the CANDOR study, a randomized, open-label phase III study that compared the benefit of adding daratumumab (D) to an approved backbone regimen containing carfilzomib and dexamethasone (Kd). The study showed that KdD resulted in significant improvement of progression-free survival (HR, 0.63; 95% CI, 0.46-0.85), deeper responses, and an acceptable safety profile. Dr. Usmani said, “As many of our patients receive LEN as maintenance/first- line or receive a LEN-based triplet as second-line therapy, the combination of KdD is an effective regimen for relapsed patients with MM, including the LEN-exposed or LEN-refractory patients.”

Dr. Dhakal indicated no relevant conflicts of interest.




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