Jennifer Mcquade

University of Texas MD Anderson Cancer Center | MD Anderson · Department of Melanoma Medical Oncology

Importance: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota prof...

Background: Immune checkpoint inhibitors (ICIs) have revolutionized management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increa...

Obesity, defined by body mass index (BMI), is an established risk factor for specific renal cell carcinoma (RCC) subtypes such as clear cell RCC, the most common RCC histology. Many studies have identified an association between obesity and improved survival after diagnosis of RCC, a potential "obesity paradox." Clinically, there is uncertainty whe...

The androgen receptor (AR) is one of the oldest therapeutic targets in oncology and continues to dominate the treatment landscape for advanced prostate cancer, where nearly all treatment regimens include some form of AR modulation. In this regard, AR remains the central driver of prostate cancer cell biology. Emerging preclinical and clinical data...

There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommen...

Historically, cancer research and therapy have focused on malignant cells and their tumor microenvironment. However, the vascular, lymphatic and nervous systems establish long-range communication between the tumor and the host. This communication is mediated by metabolites generated by the host or the gut microbiota, as well by systemic neuroendocr...

Importance Increased survival with immune checkpoint inhibitors has been reported for patients with obesity vs a normal body mass index (BMI). However, the association of obesity with the safety of immune checkpoint inhibitors warrants study. Objective To investigate associations between BMI and immune-related adverse events (irAEs) among patients...

Background: Immune checkpoint inhibitor (ICI) therapy can be complicated by gastrointestinal adverse events (AEs). Similarly, gastrointestinal AEs have been reported with the use of serine/threonine-protein kinase B-Raf (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitor therapy. We investigated the characteristics and management of...

Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma ¹ . We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480 mg...

Background: Gynecologic tract melanoma (GTM) is a rare malignancy with historically poor outcomes. The current study examines patterns of care and oncologic outcomes in a large single-institution cohort from the contemporary therapeutic era. Methods: Patterns of care and predictors of outcomes were evaluated for all GTM patients without metastat...

Purpose: Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICIs) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome feat...

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed1,2. Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy (NCT02231775, n = 51) and observed...

Encorafenib, a BRAF kinase inhibitor, in combination with binimetinib, a selective MEK inhibitor have known gastrointestinal adverse events; however, adverse colitis events have not been well studied. We report a case series of 4 patients with melanoma who developed inflammatory colitis after BRAF and MEK inhibition with encorafenib and binimetinib...

Immune-related adverse events (irAEs) are common in patients receiving immune checkpoint inhibitors for metastatic melanoma and other advanced malignancies. Cutaneous, gastrointestinal, and endocrine (thyroid) irAEs are most prevalent, whereas neurologic irAEs are rare. We present a 73-year-old man with dementia and metastatic melanoma who develope...

PURPOSE Currently, there are no robust biomarkers that predict immunotherapy outcomes in metastatic melanoma. We sought to build multivariable predictive models for response and survival to anti-programmed cell death protein 1 (anti–PD-1) monotherapy or in combination with anticytotoxic T-cell lymphocyte-4 (ipilimumab [IPI]; anti–PD-1 ± IPI) by inc...

The commensal microbiome is a unique set of bacteria, viruses, and fungi that exist on and in a person’s body. As these organisms are increasingly understood as a necessary and symbiotic part of human health, they have also been associated with the development and progression of a variety of cancers. Additionally, these organisms have been noted to...

Another benefit of dietary fiber The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al . add to our understanding of how dietary habits affect microbiota and clinical outcomes to immunotherapy. In an ob...

p>Immune checkpoint inhibitors (ICI) and BRAF targeted therapies improve overall survival (OS) for patients (pts) with MM, but treatment responses are heterogeneous. Recent data strongly implicates host factors in response and resistance to these agents. We and others have shown that overweight/obese BMI [OW/OB: body mass index (BMI≥25)] is associa...

Background and objective: Immune-mediated diarrhea and colitis (IMDC) is a common adverse event in cancer patients receiving immune checkpoint inhibitors (ICIs). Gastrointestinal (GI) infections can co-occur with IMDC, and its impact on the course and outcome of IMDC remains unclear. Patients and methods: We retrospectively reviewed cancer patie...

Background: The adoptive transfer of tumor-infiltrating lymphocytes (TIL) has demonstrated robust efficacy in metastatic melanoma patients. Tumor antigen-loaded dendritic cells (DCs) are believed to optimally activate antigen-specific T lymphocytes. We hypothesized that the combined transfer of TIL, containing a melanoma antigen recognized by T ce...

Background Anti‐programmed cell death protein 1 (PD‐1) antibodies are a standard treatment for metastatic melanoma patients. However, the understanding of the efficacy of anti‐PD‐1 for acral melanoma (AM) and mucosal melanoma (MM) is limited as these subtypes are relatively rare compared to cutaneous melanoma (CM). Methods This single institution,...

Background Immune-mediated diarrhea and colitis (IMDC) is currently diagnosed and monitored by evaluating clinical symptoms. Deep remission is determined by endoscopic and histologic evaluation of the disease process. However, repeating these invasive procedures frequently can become cumbersome. We sought to assess the role of fecal calprotectin (F...

Background Recently, we showed that melanoma brain metastases (MBMs) are characterized by increased utilization of the oxidative phosphorylation (OXPHOS) metabolic pathway compared to melanoma extracranial metastases (ECMs). MBM growth was inhibited by a potent direct OXPHOS inhibitor, but observed toxicities support the need to identify alternativ...

Immune checkpoint inhibitors and adoptive tumor-infiltrating lymphocyte (TIL) therapies have profoundly improved the survival of melanoma patients. However, a majority of patients do not respond to these agents, and many responders experience disease relapse. While numerous innovative treatments are being explored to offset the limitations of these...

Elevated serum lactate dehydrogenase (sLDH) is associated with poor clinical outcomes in patients with stage IV metastatic melanoma (MM). It is currently unknown if sLDH elevation correlates with distinct molecular, metabolic, or immune features of melanoma metastases. The identification of such features may identify rational therapeutic strategies...

Purpose of review: We review emerging evidence regarding the impact of gut microbes on antitumor immunity, and ongoing efforts to translate this in clinical trials. Recent findings: Pre-clinical models and human cohort studies support a role for gut microbes in modulating overall immunity and immunotherapy response, and numerous trials are now u...

With the advent of next-generation sequencing approaches, there has been a renaissance in the microbiome field. Microbial taxonomy and function can now be characterized relatively easily and rapidly—no longer mandating complex culturing approaches. With this renaissance, there is now a strong and growing appreciation for the role of the microbiome...

PURPOSE Improved understanding of the incidence, risk factors, and timing of CNS metastasis is needed to inform surveillance strategies for patients with melanoma. PATIENTS AND METHODS Clinical data were extracted from the databases of 2 major melanoma centers in the United States and Australia for 1,918 patients with American Joint Committee on C...

Anti-programmed cell death protein-1 (anti-PD-1) therapy has greatly improved outcomes of patients with melanoma; however, many fail to respond. Although preclinical studies suggest a potentially synergistic relationship with anti-PD-1 therapy and certain concurrent medications, their clinical role remains unclear. Here, we retrospectively evaluate...

Background Although targeted therapies (TT) and immunotherapies (IMT) have improved survival for pts with BRAF V600 mutated stage IV MM, many pts progress and will ultimately die from this disease. Preclinical data has shown that BRAF inhibition (BRAFi) in BRAF-mutated tumors is associated with increased T cell infiltration, supporting the rational...

Purpose: The purpose of this study is to determine if inhibition of mitochondrial oxidative phosphorylation (OxPhos) is an effective strategy against MAPK pathway inhibitor (MAPKi)-resistant BRAF-mutant melanomas. Experimental design: The antimelanoma activity of IACS-010759 (OPi), a novel OxPhos complex I inhibitor, was evaluated in vitro and i...

Popular views of what constitutes a healthy diet may shift, but the professional consensus is comparatively static and largely supported by our growing understanding of diet–microbiota interactions. The gut microbiome's responsiveness to diet and ability to calibrate immune and metabolic function shape new research opportunities across the cancer c...

Purpose of Review We discuss how potentially modifiable factors including obesity, the microbiome, diet, and exercise may impact melanoma development, progression, and therapeutic response. Recent Findings Obesity is unexpectedly associated with improved outcomes with immune and targeted therapy in melanoma, with early mechanistic data suggesting...

Advances in the treatment of metastatic melanoma have improved responses and survival. However, many patients continue to experience resistance or toxicity to treatment, highlighting a crucial need to identify biomarkers and understand mechanisms of response and toxicity. Neoadjuvant therapy for regional metastases might improve operability and cli...

There is a critical need to improve our understanding of the pathogenesis of melanoma brain metastases (MBM). Thus, we performed RNA sequencing on 88 resected MBMs and 42 patient-matched extracranial metastases; tumors with sufficient tissue also underwent whole-exome sequencing, T-cell receptor sequencing, and IHC. MBMs demonstrated heterogeneity...

Although novel therapies, including immunotherapy, have dramatically improved outcomes for many patients with cancer, overall outcomes are heterogeneous and existing biomarkers do not reliably predict response. To date, predictors of response to cancer therapy have largely focused on tumour-intrinsic features; however, there is growing evidence tha...

p> Purpose: BRAF V600E and V600K melanomas have distinct clinicopathologic features, and V600K appear to be less responsive to BRAFi ± MEKi . We investigated mechanisms for this and explored whether genotype affects response to immunotherapy. Experimental Design: Pretreatment formalin-fixed paraffin-embedded tumors from patients treated with BRAFi...

Background HDIL-2 is approved for advanced melanoma based on its durable antitumor activity. MAGE-A3 cancer immunotherapeutic (MAGE-A3 CI) is a recombinant MAGE-A3 protein combined with an immunostimulant adjuvant system and has shown antitumor activity in melanoma. We assessed the safety and anti-tumor activity of HDIL-2 combined with MAGE-A3 CI i...

Background: Anti-programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) immunotherapy is now routinely used to treat several cancers. Clinical trials have excluded several populations, including patients with solid organ transplant, HIV infection and hepatitis B/C infection. We examined the safety outcomes of these populations trea...

Oncology training focuses primarily on biomedical content rather than psychosocial content, which is not surprising in light of the enormous volume of technical information that oncology fellows assimilate in a short time. Nonetheless, the human connection, and specifically communication skills, remains as important as ever in caring for highly vul...

Combined MEK and CDK4/6 inhibition (MEKi+CDK4i) has shown promising clinical outcomes in NRAS mutant melanoma patients. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi+CDK4i therapy but subsequently developed resistance. Whole exome sequencing and functional validation identified an acquired PIK3CAE545K mu...

BACKGROUND: MBMs are a common and lethal complication of advanced melanoma. An improved understanding of the molecular features of MBMs could facilitate the development of more effective treatments for patients (pts). Further, identification of differences between MBMs and ECMs would indicate the need for organ-specific treatment strategies. METHOD...

Purpose: We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, and here we queried response to anti-PD1. Experimental Design: We analyzed the relationship between age, response to anti-PD1, and prior therapy in 538 patients. We used mouse models of melanoma, to analyze the intratumor...

It has long been recognized that female sex is associated with a lower risk of and improved survival in melanoma (Joosse et al., 2012). However, the mechanism underlying this disparity in outcomes is not understood. One potential explanation is behavioral‐ i.e. differences by sex in UV exposure, screening and detection, and healthcare utilization....

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS-mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3C...

Background: Obesity has been linked to increased mortality in several cancer types; however, the relation between obesity and survival outcomes in metastatic melanoma is unknown. The aim of this study was to examine the association between body-mass index (BMI) and progression-free survival or overall survival in patients with metastatic melanoma...

Background: Dual BRAF and MEK inhibition produces a response in a large number of patients with stage IV BRAF-mutant melanoma. The existing standard of care for patients with clinical stage III melanoma is upfront surgery and consideration for adjuvant therapy, which is insufficient to cure most patients. Neoadjuvant targeted therapy with BRAF and...

Background Immune checkpoint inhibitors, including antibodies against programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are being used with increasing frequency for the treatment of cancer. Immune-related adverse events (irAEs) including colitis, dermatitis, and pneumonitis are well described, but less frequent events are now...

Melanomas are metabolically heterogeneous, and they are able to adapt in order to utilize a variety of fuels that facilitate tumor progression and metastasis. The significance of metabolism in melanoma is supported by growing evidence of impact on the efficacy of contemporary therapies for this disease. There is also data to support that the metabo...

Autoimmune myocarditis is a rare but often fatal toxicity of checkpoint inhibitor immunotherapy. To improve the understanding of this complication, we performed immune profiling on post-mortem tissue from a patient with metastatic melanoma who had steroid-responsive hepatitis, steroid-refractory myocarditis, and shrinking lung metastases after ipil...

While the FDA approval of targeted and immune therapies in metastatic melanoma (MM) have dramatically improved outcomes in this disease, de novo and/or acquired resistance can limit the clinical benefit of these agents. The IGF-1/PI3K/AKT pathway has been implicated in resistance to both targeted and immune therapy. The IGF-1/PI3K/AKT pathway has a...

Purpose: Research in the area of cultural response pattern on questionnaires in the oncological setting and direct cross-cultural comparisons are lacking. This study examined response pattern in the reporting of depressive symptoms in Chinese and US women with breast cancer. We hypothesized that Chinese women are less likely to endorse positive af...

Background: Integrative oncology (IO) seeks to bring non-conventional approaches into conventional oncology care in an evidence-based, coordinated manner. Little is known about the effects of such consultations on patient-reported symptoms. Methods: We reviewed data from patients referred for an IO outpatient consultation between 2009 and 2013, com...

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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant problem for cancer patients, and there are limited treatment options for this often debilitating condition. Neuromodulatory interventions could be a novel modality for patients trying to manage CIPN symptoms; however, they are not yet the standard of care. This study ex...

Background: Integrative oncology (IO) is a relatively new field that seeks to bring evidence-based, non-conventional approaches into conventional oncology care in a coordinated and safe manner. Though complementary and alternative medicine (CAM) are highly utilized by cancer patients, little is known about the characteristics of patients seeking IO...

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Background: BRAF(V600) , NRAS, TP53, and BRAF(Non-V600) are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF(V600) and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BR...

Poster presentation from the 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer.

84 Background: Patients (pts) receiving cancer care are increasingly interested in complementary health approaches to improve symptoms and quality of life. We report on demographics and patient reported outcomes in an integrative oncology (IO) clinic. Methods: Pts presenting for IO consultation or follow-up completed: Measure Yourself Concerns and...

27 Background: Oncologists engage in emotionally charged conversations with patients and families about prognosis, goals of care, and end of life transitions. Many oncologists lack key skills for guiding patients through such conversations. Key skills include posing open ended questions to elicit the patient’s perspective, using silence effectively...

Background : Anti-PD-1 antibodies (anti-PD-1) have clinical activity in a number of malignancies. All clinical trials have excluded patients with significant preexisting autoimmune disorders (ADs), and only one has included patients with immune-related adverse events (irAEs) with ipilimumab. We sought to explore the safety and efficacy of anti-PD-1...

Objective: It has been speculated that cancer survivors in Asia may have lower quality of life (QOL) compared with their Western counterparts. However, no studies have made international comparisons in QOL using a comprehensive measure. This study aimed to compare Chinese breast cancer survivors' QOL with US counterparts and examine if demographic...