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Limited-duration bispecific antibody therapy for multiple myeloma
Bispecific antibodies are a new, highly effective immunotherapy for multiple myeloma. Most bispecific antibody therapies have been tested as continuous therapies in which patients continue receiving the treatment until the myeloma starts growing again. Preliminary results suggest that patients with good responses may be able to stop therapy and enjoy a period of time off-therapy with close observation, which may limit long term toxicities caused by continuous therapy.
What’s Next in Blood Cancer: Looking Ahead to 2023
The most important blood cancer scientific meeting, the American Society of Hematology (ASH), is held every December.
Development of LILRB1-based immunotherapy for multiple myeloma treatment
LILRB1 is a human immune inhibitory receptor expressed on a variety of immune cells. Based on preliminary data, we hypothesize that blocking LILRB1 signaling in immune effector cells of myeloma patients will lead to increased anti-cancer activities of immune cells. We will identify subsets of myeloma patients with higher LILRB1 expression on immune cells, and determine whether anti-LILRB1 antagonizing antibodies can improve the function of immune cells for multiple myeloma treatment.Daratumumab and hyaluronidase-fihj
Darzalex Faspro® is a combination of daratumumab, a CD38-directed cytolytic antibody, and hyaluronidase, an endoglycosidase, and is indicated for the treatment of adult patients with:
Targeting the Osteogenic Lineage as a Therapeutic Strategy in Multiple Myeloma
Multiple myeloma causes devastating bone disease characterised by focal bone lesions and generalise bone loss, which leads to an increase in bone fractures. Current therapies only stop bones from getting worse so patients continue to suffer fractures. We discovered that inhibiting a molecule called sclerostin in mice increases bone and is much better than current treatments. In this program we will investigate whether inhibiting sclerostin is able to restore lost bone and reduce fractures in patients with myeloma.Anti-Sox2 immunotherapy to prevent multiple myeloma relapse
Advances in multiple myeloma (MM) therapy have improved survival, but serial cycles of response and relapse still lead to treatment-refractory and fatal disease in nearly all patients. To specifically target mechanisms of MM relapse, we propose to develop an immunotherapy targeting Sox2, a stem-cell transcription factor implicated in clonogenic MM growth that enables relapse.Carfilzomib
Carfilzomib is indicated in combination with
Immunotherapies on a Roll at #ASH20
More than three years after the first chimeric antigen receptor (CAR) T-cell therapy achieved U.S. Food and Drug Administration (FDA) approval, the revolutionary approach that has upended blood cancer treatment continues to generate excitement.
Elotuzumab
Elotuzumab is FDA approved for the treatment of multiple myeloma
- In combination with lenalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received one to three prior therapies.
- In combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
Novel targeted therapies for acute myeloid leukaemia and multiple myeloma
Outcomes for acute myeloid leukemia (AML) and multiple myeloma (MM) patients remain inadequate and new treatment options to combat resistance against existing agents are urgently needed. My research aims to identify and target selective vulnerabilities of AML and MM cells. I am particularly interested in epigenetic and metabolic pathways that control self-renewal and differentiation of hematopoietic cells and that can be leveraged to modulate cell fate for therapeutic benefit.Adenylate Kinase 2-A Novel Therapeutic Target in Multiple Myeloma
We identified the adenine nucleotide regulator AK2 as a selective dependency in multiple myeloma (MM) that is more essential for survival of MM cells overexpressing the histone methyltransferase NSD2. Here, we propose a series of experiments to understand the role of AK2 in MM cell fitness and response to existing therapies and elucidate the molecular basis of the increased dependence on AK2 driven by NSD2 overexpression. This study will elucidate the effects of AK2 inhibition in MM and will credential the enzyme as a therapeutic target.Preclinical optimization of statin/BH3 mimetic combinations in multiple myeloma
This project will evaluate a novel two-drug combination to improve killing of multiple myeloma (MM) cells. First, we will test the hypothesis that statins increase killing of MM cells by BH3 mimetics including venetoclax and the MCL-1 inhibitor AMG 176. Second, we will identify biomarkers that predict response. This project will have significant positive impact on two fields: repurposing statins for blood cancer, and application of BH3 mimetics to improve health and survival of MM patients.Investigating anti-neoplastic effects of beta blockers in multiple myeloma
Multiple myeloma (MM) relies on the bone marrow (BM) niche to progress to refractory disease. We found that beta blockers alter BM niche elements fostering MM growth and also reduce MM cell survival. Our objective is to elucidate the cellular and metabolic basis of how beta adrenergic signals impact the BM niche and MM progression. Knowledge of the prophylactic and therapeutic utility of beta blockers in MM will unravel new means to target neural niche remodeling fueling this fatal malignancy.Selinexor
Selinexor is FDA approved
Designed biosensor to enhance CAR T cell therapy for multiple myeloma
We will develop a novel T cell therapy strategy for multiple myeloma (MM) that will combine existing chimeric antigen receptors (CARs) with a novel designed biosensor responding to soluble factors abundantly present in the MM bone marrow environment in patients. The biosensor will be expressed as novel type of chimeric receptor in T cells concomitantly with the CAR and signal the T cells to persist longer and keep eliminating cancer cells from the body. We will deeply characterize the effects of our novel biosensor in CAR T cells to precisely understand how the treatment works.Stem cell features and Notch signaling in p53 deleted multiple myeloma
We have investigated the consequences of p53 loss on stem cell properties, namely clonogenic growth, self-renewal, and drug resistance in multiple myeloma. We have found that both the level of Notch signaling and BCMA impact these properties, and we will explore novel strategies to improve outcomes in p53 mutant multiple myeloma.Denosumab
Denosumab is FDA approved for the prevention of skeletal-related events in patients with multiple myeloma.
Highlights from ASH 2021
The American Society of Hematology (ASH) annual meeting is the premier scientific forum on blood cancers. More than 5,000 potentially game-changing research abstracts were presented at this year’s meeting. Every year, I come away with a strengthened sense of hope about new treatments on the horizon and renewed pride in The Leukemia & Lymphoma Society’s (LLS) role in supporting so many of them.