Alzheimer's - Dementia, Author Interviews, Immunotherapy, Nature / 01.09.2016
Experimental Antibody Reduced Amyloid Plaques in Alzheimer’s
MedicalResearch.com Interview with:
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Prof. Roger Nitsch[/caption]
Roger M. Nitsch, MD
Professor and Director
Institute for Regenerative Medicine · IREM
University of Zurich Campus Schlieren
Switzerland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The main finding is that treatment with aducanumab resulted in an unprecedented reduction of brain amyloid plaques in patients with Alzheimer's disease. The removal of amyloid from patients brains were both dose- and time-dependent. We also observed initial hints for stabilized brain functions in patients receiving aducanumab. In contrast, patients in the placebo group continued to declined as usual in this stage of Alzheimer's disease.
The main safety finding in 22% of all treated patients was ARIA - an Amyloid-Related Imaging Abnormality - suggestive of fluid shifts in the brains. In most cases, ARIA occurred in the absence of clinical signs and resolved spontaneously. In one third of the ARIA cases, patients experienced transient headaches. None of the patients had to hospitalized because of ARIA.
Prof. Roger Nitsch[/caption]
Roger M. Nitsch, MD
Professor and Director
Institute for Regenerative Medicine · IREM
University of Zurich Campus Schlieren
Switzerland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The main finding is that treatment with aducanumab resulted in an unprecedented reduction of brain amyloid plaques in patients with Alzheimer's disease. The removal of amyloid from patients brains were both dose- and time-dependent. We also observed initial hints for stabilized brain functions in patients receiving aducanumab. In contrast, patients in the placebo group continued to declined as usual in this stage of Alzheimer's disease.
The main safety finding in 22% of all treated patients was ARIA - an Amyloid-Related Imaging Abnormality - suggestive of fluid shifts in the brains. In most cases, ARIA occurred in the absence of clinical signs and resolved spontaneously. In one third of the ARIA cases, patients experienced transient headaches. None of the patients had to hospitalized because of ARIA.
Prof. Frances Balkwill[/caption]
Professor Frances Balkwill OBE, FMedSci
Lead, Centre for Cancer and Inflammation
Barts Cancer Institute
Queen Mary University of London
London
MedicalResearch.com: What is the background for this study?
Prof. Balkwill: We wanted to find out if chemotherapy altered patients immune system especially the immune cells that co-exist with cancer cells in tumors.
We studied women with ovarian cancer who often receive chemotherapy after diagnosis but before surgery. This meant, at least in some of them, we could study a biopsy taken before treatment began and also a biopsy taken during the operation.
Dr. Arjun Balar[/caption]
Dr. Arjun Balar MD
Assistant Professor, Department of Medicine
Co-Leader Genitourinary Cancers Program
NYU Langone Medical Center
Laura and Isaac Perlmutter Cancer Center
MedicalResearch.com: What is the background for this study?
Dr. Balar: Standard treatment for advanced urothelial cancer includes cisplatin chemotherapy. But more than half of patients are not expected to tolerate
it well and alternative treatment is inferior to cisplatin. The average survival for these patients is in the range of 9-10 months with carboplatin-based treatment, which is the most commonly used alternative
to cisplatin. Atezolizumab is a PD-L1 blocking antibody that reactivates
the body¹s immune system to fight bladder cancer and has been recently
FDA approved in the management of advanced urothelial cancer in the
second-line setting after failure of platinum-based chemotherapy.
Dr. Robert Ferris[/caption]
Robert L. Ferris, M.D., Ph.D.
Robert L. Ferris, M.D., Ph.D.
UPMC Endowed Professor and Vice-Chair
Associate Director for Translational Research
Co-Leader, Cancer Immunology Program
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Ferris: Investigators at the University of Pittsburgh Cancer Institute<http://upci.upmc.edu/> (UPCI) co-led CheckMate-141<https://clinicaltrials.gov/ct2/show/NCT02105636> a large, randomized international phase III clinical trial that enrolled 361 patients with recurrent or metastatic head and neck squamous cell carcinoma who had not responded to platinum-based chemotherapy, a rapidly progressing form of the disease with an especially poor prognosis. Patients were randomized to receive either nivolumab or a single type of standard chemotherapy until tumor progression was observed.
Nivolumab, which belongs to a class of drugs known as immunotherapeutics, enables the body’s immune system to destroy cancer cells. It currently is approved to treat certain types of cancers, including melanoma and lung cancer. The nivolumab group achieved better outcomes than the standard chemotherapy group by all accounts. After 12 months, 36 percent of the nivolumab group was alive, compared to just 17 percent of the standard chemotherapy group.
Nivolumab treatment also doubled the number of patients whose tumors shrunk, and the number whose disease had not progressed after six months of treatment. Importantly, these benefits were achieved with just one-third the rate of serious adverse events reported in the standard chemotherapy group. In addition, on average, patients receiving nivolumab reported that their quality of life remained stable or improved throughout the study, while those in the chemotherapy group reported a decline. The new trial was considered so successful that it was stopped early to allow patients in the comparison group to receive the new drug.
Dr. William Sandborn[/caption]
William J. Sandborn, MD
Professor of Medicine and Adjunct Professor of Surgery
Chief, Division of Gastroenterology
Director, UCSD IBD Center
University of California San Diego and UC San Diego Health System
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sandborn: The Phase 3 IM-UNITI study investigated the efficacy and safety of Stelara (ustekinumab) in the treatment of moderate to severe Crohn’s disease as an every 8 or 12 week maintenance therapy.
The study showed a significant proportion of adults with moderate to severe Crohn’s disease who received Stelara maintenance treatment achieved clinical remission.
Dr. Wayne Furman[/caption]
Wayne L. Furman, MD
Department of Oncology
Jude Children's Research Hospital
Memphis, TN 38105-3678
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Furman: Despite improvement in 2-yr EFS from 46% to 66% with the inclusion of dinutuximab, a monoclonal antibody that recognizes a glycoprotein on neuroblasts called ‘GD2’ (disialoganglioside), more than one-third of children with high-risk neuroblastoma still are not cured. Therefore novel therapeutic approaches are needed for this subset of patients. The clinical evaluation of various anti-GD 2 monoclonal antibodies in children with neuroblastoma has been exclusively focused on treatment of patients after recovery from consolidation, in a state of ‘minimal residual disease’. This is because traditionally chemotherapy has been thought to be too immunosuppressive to combine with monoclonal antibodies. However recent studies suggest, even in the setting of “bulky” solid tumors, the combination of chemotherapy with monoclonal antibodies can enhance the effectiveness of the antibodies. First, chemotherapy can increase the efficacy of antibodies by depleting cells of the immune system that suppress immune function. Also chemotherapy-induced tumor cell death can trigger tumor antigen release, uptake by antigen processing cells and an enhanced antitumor immune response. There is also data that anti-GD2 monoclonal antibodies can suppress tumor cell growth independent of immune system involvement. Furthermore anti-GD2 monoclonal antibodies and chemotherapy have non-overlapping toxicities. All of these reasons were good reasons to evaluate the addition of a novel anti-GD2 monoclonal antibody, called hu14.18K322A, to chemotherapy, outside the setting of minimal residual disease, in children with newly diagnosed children with high-risk neuroblastoma.
Dr. Benjamin Perry[/caption]
Benjamin M. Perry, DO
Silver Falls Dermatology
Salem, OR 97302
MedicalResearch.com: What is the background for this study?
Dr. Perry: Our interest in this subject developed when a patient came into our clinic with concern of multiple new nevi developing on palmoplantar surfaces following initiation of treatment with Rituximab. We conducted a review of the existing literature and found that this wasn’t a known adverse effect. From that point, we wanted to know the pathogenesis, prognosis, and management for eruptive nevi that developed in the setting of medication use. A collective review had not been previously performed on this subject. In essence, we had questions that were unanswered and set out to find the answers.
Dr. Melissa Wilson[/caption]
Melissa A. Wilson, MD, PhD
Assistant professor of Medical Oncology
NYU Langone Perlmutter Cancer Center
MedicalResearch.com: What are the most common types of skin cancer?
Dr. Wilson: Basal cell carcinoma, squamous cell carcinoma and melanoma. With rare exception, all are related to sun exposure.
MedicalResearch.com: Are some types of skin cancer more serious than others?
Dr. Wilson: Melanoma is the most serious form of skin cancer, with the highest risk of developing into metastatic disease. Most basal cell and squamous cell carcinomas are superficial and not as invasive, so removal is the treatment. Rarely, these can cause invasive and metastatic disease, but this occurs infrequently. Melanoma is much more serious. Of course, the earlier melanoma is detected and the earlier stage that it is, is more predictive of a favorable outcome.
MedicalResearch.com: Who is most prone to skin cancer?
Dr. Wilson: Persons with excessive sun exposure, fair skin, light hair and blue eyes - although it can certainly occur in anyone.
Dr. Mathias Buttmann[/caption]
PD Dr. Mathias Buttmann
Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic
University of Wuerzburg
Wuerzburg, Germany
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer.
Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer.
Dr. Jennifer Graves[/caption]
Jennifer Graves, MD, PhD, MAS
Adult and Pediatric Multiple Sclerosis Centers
UCSF
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Graves: Cessation of medications with effects on immune trafficking may be more likely to cause rebound inflammatory activity in autoimmune diseases such as multiple sclerosis. We observed 5 strikingly severe relapses consistent with rebound events following cessation of fingolimod treatment and identified several similar cases in the literature. At our center the rebound events occurred with an approximate 10% frequency.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Graves: Fingolimod cessation may be complicated by rebound phenomena in some patients, similar to what has been observed with natalizumab. Both of these medications have effects on immune cell trafficking, likely explaining the association with rebound events. Careful consideration must be taken in stopping these medications.
Dr. Paul Nghiem[/caption]
Paul Nghiem, MD, PhD
Professor & Head, University of Washington Dermatology
George F. Odland Endowed Chair
Affiliate Investigator, Fred Hutchinson Cancer Research Center
Professor, Adjunct, of Pathology and Oral Health Sciences
Clinical Director, Skin Oncology, Seattle Cancer Care Alliance
UW Medical Center at Lake Union
Seattle WA 98109
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Nghiem: Merkel cell carcinoma (MCC) is about 30 times less common than malignant melanoma, but about 3 times more likely to kill a patient than a melanoma. There is no FDA-approved therapy for this cancer & chemotherapy typically only provides about 90 days prior to the cancer progressing. Because of the strong links between MCC and the immune system, including the fact that most MCCs are caused by a virus, there was interest in trying to use immune checkpoint therapy to treat advanced Merkel cell carcinoma. The response to immune stimulation with anti-PD1 therapy was about as frequent as to chemotherapy (56% of patients responded) but importantly, among the responders, 86% remained in ongoing responses at a median of 7.6 months. While still early, this appears to be strikingly more durable than responses to chemotherapy.
Dr. David Gallego Ortega PhD[/caption]
MedicalResearch.com Interview with:
David Gallego Ortega, PhD
Group Leader, Tumour Development Group Cancer Division
Garvan Institute of Medical Research
Conjoint Lecturer, St Vincent’s Clinical School, Faculty of Medicine, UNSW, Australia
National Breast Cancer Foundation and Cure Cancer Foundation Australia Fellow
Medical Research: What is the background for this study? What are the main findings?
Dr. Ortega: We have identified a protein that 'goes rogue’ in breast cancer. The protein, called Elf5, ‘tricks' the immune system producing inflammation so that the immune cells now help the breast cancer cells to spread throughout the body.
Cancer spread, or metastasis, is the ultimate cause of death of 
Dr. Diefenbach[/caption]
MedicalResearch.com Interview with:
Dr. Catherine S. M. Diefenbach MD
Assistant Professor of Medicine
NYU Langone
Laura and Isaac Perlmutter Cancer Center
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Diefenbach: The background of the study is that through an understanding of the unique immunobiology of Hodgkin lymphoma we can derive rational treatment strategies which may heighten the efficacy of existing therapies, and improve the outcomes for patients with relapsed disease. In E4412 which is a national study sponsored by the Eastern Cooperative Oncology Group (ECOG-ACRIN) we explore the safety and efficacy of combination of the antibody drug conjugate brentuximab vedotin which targets CD30 on the surface of the Hodgkin lymphoma tumor cells, and immune stimulation of the T cells in the tumor microenvironment using checkpoint inhibitors. We reported the data from the first arm of the study Brentuximab Vedotin and Ipilimumab. To date 23 patients with relapsed Hodgkin lymphoma have been treated; the combination of brentuximab and