Alliance E-News | December 2025
Scientific Annual Meetings
Alliance investigators are presenting six abstracts at the 67th Annual Meeting of the American Society Hematology (ASH), to be held December 6-9, 2025, in Orlando, FL.
At this year’s meeting, Alliance researchers will showcase findings with the latest insights into cancers such as acute myeloid leukemia (AML), acute lymphocytic/lymphoblastic leukemia (ALL) and multiple myeloma. These studies represent the collective efforts of our community to improve outcomes and expand treatment options for patients.
ASH is the world's largest professional society concerned with the causes and treatments of blood disorders. Its members work to further the understanding, diagnosis, treatment and prevention of disorders affecting the blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training and advocacy in hematology. The society's scientific meetings facilitate the exchange of scientific information and clinical results related to the field of hematology.
The six Alliance for Clinical Trials in Oncology and Alliance Foundation Trials presented at ASH include:
Oral Presentation
Abstract: 444, Alliance: A041703
Oral presentation: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Emerging Treatment Paradigms in ALL
December 7, 2025, 9:30 AM - 11 AM | OCCC - W224ABEF
First author: Matthew J. Wieduwilt, Wake Forest University School of Medicine
Summary: Older adults with a type of blood cancer called B-cell acute lymphoblastic leukemia (ALL) often struggle with traditional chemotherapy because of toxicity of the treatments and disease relapses. Alliance A041703 tested a new approach that avoids chemotherapy by using two targeted treatments instead—inotuzumab ozogamicin and blinatumomab. These medicines work by helping the immune system attack cancer cells. In the study, treatment with inotuzumab followed by blinatumomab led to high remission rates. After long-term follow-up, about half of patients remain cancer-free and most are still alive, with no relapses or deaths reported in the later years of observation. These findings support this chemotherapy-free approach as a promising option for older adults with aggressive leukemia.
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Poster Presentations
Abstract: 2289, Alliance: A062102
654. Multiple Myeloma: Pharmacologic Therapies: Poster I
December 6, 2025, 5:30 PM – 7:30 PM | OCCC - West Halls B3-B4
First author: Sascha A. Tuchman, University of North Carolina
Summary: Multiple myeloma is a blood cancer that remains incurable, even with major advances like CAR-T cell therapy. CAR-T works by taking a patient’s own immune cells (T-cells), engineering them to recognize cancer, and reinfusing them to attack the disease. Idecabtagene vicleucel (ide-cel) is type of a CAR-T therapy that targets a protein called BCMA on myeloma cells. Researchers are testing whether adding a new drug called iberdomide after CAR-T can help patients stay cancer-free longer. Iberdomide kills myeloma cells and boosts immune function, which may strengthen CAR-T’s effects. The phase II CADMIUM study will compare iberdomide maintenance therapy to standard observation in patients who recently received ide-cel.
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A randomized phase II study of daratumumab, lenalidomide, ixazomib and dexamethasone in transplant-ineligible or deferred patients with newly diagnosed multiple myeloma-Alliance Foundation Trial 41 (AFT-41)
Abstract: 4053, AFT: 41
654. Multiple Myeloma: Pharmacologic Therapies: Poster II
December 7, 2025, 6 PM - 8 PM | OCCC - West Halls B3-B4
First author: Andrew Yee, Massachusetts General Hospital Cancer Center
Summary: Multiple myeloma is a blood cancer that often affects older adults. The AFT-41 study tested a four-drug combination of daratumumab, lenalidomide, ixazomib and dexamethasone for older, transplant-ineligible patients with newly diagnosed multiple myeloma. The goal was to see if this regimen would be effective and easier to tolerate for patients who could not have a stem cell transplant. In this trial, most participants showed strong to therapy, with many reaching very low levels of detectable disease and maintaining control of their cancer over time. Side effects were general manageable, with no cases of severe nerve damage and no treatment-related deaths reported. Most patients were able to continue on maintenance therapy, supporting the regimen’s overall tolerability and effectiveness.
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Abstract: 3415, Alliance: A041701
616. Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Poster II
December 7, 2025, 6 PM - 8 PM | OCCC - West Halls B3-B4
First author: Geoffrey L. Uy, Washington University School of Medicine
Summary: Researchers studied whether adding a drug called uproleselan to standard chemotherapy could help older adults with acute myeloid leukemia. Uproleselan works by blocking E-selectin, a molecule in the bone marrow that leukemia cells use to stick to blood vessels and hide from chemotherapy. By preventing this interaction, uproleselan was expected to make chemotherapy more effective. In this trial, patients received standard chemotherapy with or without uproleselan to see if adding uproleselan improved event-free survival or overall survival. Results showed that while patients who received uproleselan had slightly higher rates of deep remission and fewer early deaths, the drug did not significantly improve survival compared to chemotherapy alone. Interestingly, patients with a specific gene mutation (ASXL1) seemed to benefit more from uproleselan, suggesting it may help certain subgroups.
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Other Abstracts
Abstract: 1590, Alliance: A041501
First Author: Andrew Hughes, Washington University School of Medicine
Summary: Researchers evaluated ChromoSeqV2, a rapid whole-genome sequencing (WGS) test, to detect genetic changes in Ph-like B-cell acute lymphoblastic leukemia (B-ALL), a high-risk leukemia subtype often identified by gene rearrangements. Traditional tests like cytogenetics and RNA sequencing can be slow or may miss certain cases, so investigators applied ChromoSeqV2 to patient samples from the Alliance A041501 trial. The test successfully identified clinically important genetic changes, including Ph-like rearrangements, and demonstrated complete accuracy compared to other molecular methods. It also outperformed standard cytogenetics testing while providing results consistent with RNA sequencing.
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Abstract: 1723, CALGB (Alliance): 20202
First author: Maria Velegraki, The Ohio State University Comprehensive Cancer Center
Summary: In some men with the blood cancer acute myeloid leukemia (AML), the male-specific Y chromosome is missing in leukemia cells—a condition called Loss of Y (LOY). This was long thought to be harmless and just related to aging, but new research shows LOY may define a unique AML subtype and indicative of better outcomes for younger men. Researchers analyzed patients under 60 years old treated with intensive chemotherapy on CALGB (Alliance) trials and in the Flatiron Health database. Men with AML and LOY had 3-year survival rates like the most favorable risk group in current guidelines—much better than other risk groups. They also found that lower activity of Y-linked genes was linked to better survival. Additional research showed that LOY AML cells behave differently. These cells seem to activate genes for tissue structure and blood vessel growth but suppress immune-related genes, creating an environment that weakens immune defenses. Interestingly, LOY was found only in leukemia cells, not in immune cells, suggesting the cancer drives these changes.
