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The impact of non-coding somatic mutations on the prognosis and progression of multiple myeloma

Past studies of protein-coding regions have extensively characterized the genome of multiple myeloma (MM), but there has been little information on the prognostic impact of non-coding variants that may affect gene expression and regulation. Using a well-defined set of patient samples at different stages of disease progression we will define non-coding mutational hotspots in MM that contribute to progression and poor prognosis, identifying novel targets for alternative treatment strategies.

Inflammation-responsive mechanisms of malignant stem cell generation and eradication in multiple myeloma

The focus of my research is to elucidate the core molecular regulators of malignant stem cell generation in multiple myeloma. My approach addresses the tumor cell-intrinsic versus niche-dependent mechanisms of myeloma regeneration by exploring transcription factor expression and stemness profiles within single cells from primary samples and patient-derived models. The central goal of my research is to uncover novel therapeutic strategies and translate these into new myeloma treatments.

Isatuximab-irfc

Isatuximab-irfc is FDA approved

  • 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.
  • In combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.

Validation of Critical 1q21 Vulnerabilities in multiple myeloma

In previous studies of recurrently amplified 1q21 genes in myeloma, we identified ILF2 as a modulator of the DNA repair pathway, which promotes adaptive responses to genotoxic stress. Thus, ILF2 may have clinical utility as a biomarker of aggressive myeloma and blocking the ILF2-mediated repair signaling may enhance the effectiveness of current DNA-damaging agent-based therapies.

Enhancing the “fitness” of anti-BCMA CAR T cells for improved efficacy in multiple myeloma

Chimeric antigen receptor (CAR) T cell therapy is a form of immune-based therapy where a patient’s own immune cells are genetically engineered to recognize and kill the tumor cells. This therapy has revolutionized the treatment of certain blood cancers and excitingly, two CAR T cell products were recently approved for the treatment of multiple myeloma.

Targeting the MMP-13/PD-1H signaling axis for multiple myeloma bone disease and immunosuppression

Multiple myeloma is an incurable blood cancer complicated by bone diseases and compromised immune system. Our work indicated that checkpoint inhibitor PD-1H(VISTA) functions as the MMP-13 receptor, and the MMP-13/PD-1H signaling axis plays a critical role in multiple myeloma induced bone disease and immunosuppression. Therefore, immunotherapy targeting the novel MMP-13/PD-1H interaction module represents a novel approach to cure this devastating cancer.
A scientist stands above a petri dish with a dropper and places a liquid solution on the dish.

The Immune System and Blood Cancer: 4 Things You Need to Know

Immunotherapy uses the power of the immune system to treat blood cancer. Today it is a standard treatment that has a profound effect in some blood cancer patients, but it still falls short in others. 

The Leukemia & Lymphoma Society (LLS) has been a champion of this type of cancer treatment for decades, supporting some of the earliest and most game-changing immune-based treatments for blood cancer. The advances have been astonishing, but there is so much further to go. 

Defining the Biologic and Therapeutic Significance of the Novel Long Noncoding RNA MYND in Multiple Myeloma

Long non-protein coding RNAs (lncRNAs) are fundamental for proper cell function, but their purpose is poorly understood in multiple myeloma. To systematically identify myeloma-promoting lncRNAs, we integrated gene expression profiling of myeloma patients with high-throughput loss-of-function studies in cell lines. Moreover, we optimized strategies to antagonize myeloma-promoting lncRNAs, thus paving the way to developing lncRNA inhibitors as the next generation of therapy.

New Study Shows 9/11 Responders Have Higher Rates of Leukemia

 

All 9/11 responders put their own lives at risk to save others from the events that occurred at the World Trade Center (WTC) on September 11, 2001, in New York City. Since then, several studies have shown elevated rates of cancers such as multiple myeloma, prostate cancer and thyroid cancer among first responders and those who worked nearby.

Peripheral blood-based disease monitoring by mass spectrometry in patients with multiple myeloma

The present project will investigate the ability of quantitative immune precipitation mass spectrometry (QIP-MS) to anticipate relapsed or progressive disease in peripheral blood samples from patients with multiple myeloma. In the context of the GEM2014MAIN trial (lenalidomide and dexamethasone plus or minus ixazomib as maintenance), we will assess the presence of disease by QIP-MS in parallel with conventional methods in serum and next generation flow in bone marrow samples.

Improving CAR-T cell therapy outcomes for patients with for aggressive lymphoma and multiple myeloma

Despite the promise of CAR-T cell immunotherapy for patients with lymphoma and multiple myeloma, a significant proportion of patients fail to respond or relapse following treatment. This project will focus on the clinical translation of a new treatment designed to improve durable response rates by combining CAR-T cell therapy with a new class of anticancer drugs called SMAC-mimetics. The results will provide the evidence base to drive a first-in-human clinical trial of this combination strategy.
Breaking News

Another First: FDA Approves Car T-Immunotherapy for Treatment of Aggressive Form of Indolent Non-Hodgkin Lymphoma

The U.S. Food and Drug Administration (FDA) today approved the CAR T-cell treatment axicabtagene ciloleucel (Yescarta®) for patients with follicular lymphoma (FL) that has returned or worsened despite earlier treatment. FL is the most common slow-growing non-Hodgkin’s lymphoma and while the disease can generally be managed, reoccurrence is common.

Gut microbiota modulation to prevent progression of smoldering multiple myeloma to active disease

Blocking the progression of smoldering multiple myeloma (SMM) to active MM is an unmet clinical need. In primary mouse models of MM, we aim at demonstrating that modulation of the gut microbiota by vaccination against the commensal Prevotella heparinolytica and/or colonization by P. melaninogenica, also in combination with anti-PD-L1 antibodies, inhibit the progression of asymptomatic MM to full-blown disease. Our findings are expected to provide the ground for clinical trials in SMM patients.

#ASH18: The Beat Goes On

On Sunday, I reported on a press briefing  at the 60th ASH Annual Meeting where the preliminary findings of our Beat AML Master Clinical Trial were unveiled. This innovative collaborative study is designed to bring the hope of precision medicine to patients with acute myeloid leukemia (AML). (Read about our Friday ASH satellite symposium on immunotherapy here).

Daratumumab

Daratumumab is FDA approved for the treatment of adult patients with multiple myeloma:

A researcher analyzes a specimen in a test tube.

Blood Cancer Research Poised for Another ‘Banner Year’ in 2024

More than 25,000 medical professionals from across the world came together in December to discuss the latest blood cancer developments during the annual meeting of the American Society of Hematology (ASH). This annual event gives us the opportunity to think about what advances are on the horizon as LLS works to strengthen cures, care and quality of life for people with blood cancer and their families.   

Lenalidomide

Lenalidomide is FDA approved to treat patients with:

Role of Health Insurance and Medicaid Expansion in Racial Inequity in Patterns of Care and Outcomes in Multiple Myeloma

Multiple myeloma is the most common blood cancer in African Americans. Thanks to advances in treatment, over 50% of patients now survive 5 years compared to 35% in 2000. However, African American patients may not be enjoying the same health gain as White patients, possibly due to poorer access to healthcare. This study will examine the role of health insurance and living in states with expanded eligibility for Medicaid on treatment patterns and survival in African Americans compared to White patients with multiple myeloma.

Multiple Myeloma Support from the Microenvironment: Bone Marrow Adipocytes and the Fatty Acid Binding Proteins

Our project’s goal is to change how multiple myeloma is understood and treated by interrogating a novel part of the cellular “soil” (the bone marrow adipocyte), in which myeloma cells, or “seeds”, land and grow. We will discover new forms of cancer drug resistance that are driven by adipocyte-derived factors and the fatty acid binding proteins. This work will expose new ways to overcome drug resistance to improve survival and quality of life for myeloma and other hematological cancer patients.