Georgetown University School of Medicine

MONDAY, Sept. 9, 2024 -- The time is now to prepare for a potential pandemic involving the H5N1 bird flu, says a group of international vaccine and public health experts. Avian influenza vaccines need to developed, stockpiled and even delivered to people at highest risk of contracting the bird flu, the experts argue in an editorial published Sept. 4 in the Journal of the American Medical Association . “At this critical juncture, decisions about vaccine development, stockpiling and deployment will shape our ability to respond to immediate and future pandemic risks,” the researchers wrote. There have been 14 human cases of bird flu in the United States since 2022, four following exposure to dairy cows and 10 following exposure to poultry, according to the U.S. Centers for Disease Control and Prevention. On Friday, the Centers for Disease Control and Prevention announced that a new case had emerged in a patient hospitalized in Missouri who had no known contact with animals. That case is being throughly investigated, the agency said. Bird flu has also sickened more than 100 million poultry and infected 196 U.S. diary herds, the CDC says. Outbreaks in poultry have occurred in 48 states, and dairy cows have become infected in 14 states. “It is highly concerning that this H5N1 strain, compared with prior ones, has had unprecedented spread among mammals,” said editorial co-author Dr. Jesse Goodman , a professor and infectious disease specialist at Georgetown University School of Medicine, in Washington, D.C. “Although human cases have so far been relatively mild, the threat of a pandemic is real, given the virus’ widespread and continued presence close to humans and its potential to re-assort with human influenza viruses or mutate to acquire the ability to transmit among humans,” Goodman said in a Georgetown news release. The U.S. government is readying 4.8 million stockpiled doses of H5N8 flu vaccine, which is expected to offer cross-protection against the H5N1 strains now spreading, the experts said. These stockpiled H5N8 vaccines should be offered voluntarily to farm workers in close contact with poultry and cattle, to help protect them against infection, the editorial says. The government also needs to refresh its vaccine stockpiles with doses that are better matched to H5N1, the experts added. The goal is to ensure that at least 20 million people -- particularly critical workforce members -- can be rapidly immunized in the event of a pandemic, they said. In the long term, public health officials should explore immunization strategies that could head off potential pandemics, they noted. People at high risk of severe infection could be vaccinated in between pandemics, to build population immunity that could blunt the ability of any new and dangerous viral strains to spread quickly between humans, the editorial says. The public and private sectors should also work together to create a comprehensive strategy to protect both human and animal health by developing vaccines, tests and therapies for emerging threats, the experts stressed. “The time for decisive action is not when a pandemic strikes, but today, while we have the opportunity,” the experts concluded. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

A new detailed analysis of a patient's second cancer after receiving CAR-T therapy for the initial cancer provides rare but important insights intended to offer helpful guidance for oncologists and pathologists about the clinical presentation and pathologic features involved in a CAR-T related second cancer. A new detailed analysis of a patient's second cancer after receiving CAR-T therapy for the initial cancer provides rare but important insights intended to offer helpful guidance for oncologists and pathologists about the clinical presentation and pathologic features involved in a CAR-T related second cancer. The finding is reported June 13, 2024, in the New England Journal of Medicine. CAR-T therapy is described by many as a new and promising treatment for blood cancers. CAR-T therapy is made from a patient's own cells whereby immune system T cells are collected and re-engineered in the laboratory to produce proteins on their surface, called chimeric antigen receptors, or CARs. The CARs can recognize and then bind to specific proteins on the surface of cancer cells. The therapy is used to treat blood cancers such as multiple myeloma, the type of cancer the patient in the case study had when treated with CAR-T. "The established value of CAR-T treatment and its benefits to cancer patients is significant," says the study's first author, Metin Ozdemirli, MD, PhD, professor of pathology at Georgetown University School of Medicine and attending physician and director of Hematopathology and Hematology Laboratories at MedStar Georgetown University Hospital. "Our case study describes a rare event in a patient who received CAR-T therapy and provides very useful information for physicians treating patients with this approach. Armed with our insights, physicians can be on the lookout for similar conditions and potentially detect secondary tumors earlier and manage them better." Of the estimated 30,000 patients treated with CAR-T therapy, reported second cancers are rare; the U.S. FDA has tracked approximately 25 cases of CAR-T cell second cancers, usually lymphomas, as occurred in the patient in this case study following CAR-T cell therapy. How the CAR-T cell became a lymphoma is not known. It is possible that the cells had lymphoma-causing mutations when they were originally collected from the patient and CAR-T treatment caused activation and expansion of those cells; or the mutations might have occurred when the CAR-T cells were prepared outside the patient; or the CAR-T cells may have acquired the mutations after they were given back to the patient; or any combination of these circumstances. Four months after receiving CAR-T therapy, the patient in the case study developed progressively worsening non-bloody diarrhea and lost 12 pounds. Results of bloods tests led to an endoscopic exam revealing ulcerations in the duodenum, the first part of the small intestine. The patient received treatment, but symptoms persisted, resembling an autoimmune disease. After numerous additional tests, biopsies taken revealed the culprit -- indolent T-cell lymphoma of the gastrointestinal tract, similar to other cases, but further molecular analysis showed this to be a CAR-T positive case. Ozdemirli says this case study suggests that physicians treating patients with CAR-T should always consider CAR-T a potential source for new cancers and autoimmune problems. "When we know what to look for ahead of time, it becomes easier to catch problems earlier," he says. Ozdemirli also points out, "An interesting finding here is the type of cells that survived the initial treatment and became cancerous. Immune cells that are collected from patients to prepare the CAR-T cocktail are not a homogenous single-cell type. They contain a mixture of multiple cells, and in the case of this patient, what is called a helper T cell, an essential infection-fighting cell, unexpectedly was the culprit." Though uncommon, second cancers following chemotherapy or radiation therapy can develop. Just like any tissue in the body has the risk of developing cancer during a lifespan, CAR-T cells carry the same risk. Ozdemirli says so far there is no evidence to suggest that the process of preparing the CAR-T population outside the body increases that risk. Importantly for diagnostic and treatment purposes in the future, the researchers note that switchable cell therapies might allow patients to take a medication to tune the amount of CAR-T cell activity from day to day, hopefully reducing toxic side effects. Advancing this research and knowledge is an important next step for the investigators.

Patients Bear the Brunt of CMS Restrictions Introduced Over a Year Ago that Limit Access to Rejection Monitoring Blood Tests Unless Tied to an Invasive Biopsy 26 Doctors Pen Letter to CMS Administrator Brooks-LaSure Urging Immediate Restoration of Coverage for Blood Test that Catches Early Signs of Rejection WASHINGTON, April 16, 2024 /PRNewswire/ -- The Honor the Gift Coalition, representing organ transplant patients across the nation, raises the alarm after over two dozen leading transplant clinicians sent a letter to the Centers for Medicare & Medicaid Services (CMS) Administrator, Chiquita Brooks-LaSure, detailing the negative impacts of Medicare policy changes made by a private contractor, MolDX, in March 2023. Most detrimentally, the changes hinder expert transplant doctors from using non-invasive post-transplant blood tests for surveillance unless an invasive biopsy would otherwise have been performed, eliminating a key benefit of the tool, and removing surveillance testing altogether for community nephrologists who don't perform biopsies. Clinicians are now reporting a distressing rise in rejection events among organ transplant recipients, an uptick believed to be associated with these restrictions. The tests, including donor-derived cell-free DNA (dd-cfDNA) and gene expression profiling (GEP), have been pivotal in early detection of organ rejection, enabling swift interventions to help extend the life of transplanted organs. The billing restriction is directly counter to long-standing coverage, mounting clinical evidence, and clear guidance from the transplant community about the importance of these tests for monitoring organ health. "While CMS and MolDX repeatedly asserted that there had been no change in coverage policy, CMS recently admitted there was a staggering 50% reduction in the ordering of these vital tests that catch early signs of transplant rejection following the imposition of the new restrictions. A year after the restrictions, we fear that many patients are now actively facing organ rejection, or are at increased risk, due to these policy constraints," said Steven Potter, MD, Professor of Surgery at Georgetown University School of Medicine. "This not only affects patient well-being but also runs counter to the shared national goal of enhancing the success rate of organ transplantation. Now more than ever, transplant providers should be empowered to order these essential tests for patients without being hamstrung by a policy that ties their hands." Layal Abdel Rahman, MD, Medical Director of the kidney transplant program at the Transplant Institute of Florida, shared the devastating impact on her patients: "Prior to the billing change, my center was giving donor-derived cell-free DNA tests every three months to all kidney transplant patients as a part of their ongoing care. Once the restrictive guidance came out, we stopped using the tests for surveillance, and could only use them if patients were experiencing symptoms. That has backfired—we currently have three patients in severe rejection, which is very unusual for our center. If we had continued giving the tests regularly, we would have detected the rejections earlier, while there was still time to intervene." Further, as the nation works to expand access to transplants, there is a pressing need to engage community nephrologists in long-term, post-transplant care, a practice impeded by the current changes. Community nephrologists, who are now restricted from ordering non-invasive testing methods for surveillance since they do not perform biopsies, are significantly disadvantaged by these changes. Independence from biopsy for transplant surveillance is vital because it offers early detection of potential rejection episodes and more personalized and targeted management strategies, in addition to being a safer, less invasive, and cost-effective method. These limits on non-invasive testing jeopardize the survival of transplant recipients and their transplanted organs. Additionally, The American Association of Kidney Patients (AAKP), the nation's largest kidney patient organization, recently released a special report exposing an alarming new disparity for kidney transplant patients caused by MolDx and Medicare. BlueCross BlueShield of South Carolina, the parent entity of MolDX, extended comprehensive access to these same critical blood tests for its private insurance beneficiaries with organ transplants, while its MolDx subsidiary, responsible for issuing Medicare coverage decisions, did the exact opposite. This new disparity between private and public transplant healthcare coverage is unjust and leaves many vulnerable patients trapped in a dangerous coverage gap. Transplant clinicians, with the strong support of a growing coalition of allies including the Honor the Gift coalition, the Health Equity in Transplantation Coalition (HEiTC) and AAKP, implore CMS to immediately engage transplant care providers and patient advocates to devise policies that better protect the long-term health of transplant recipients and their life-saving organ transplants. Their united concerns are escalating in advance of a pending CMS decision on a draft Local Coverage Determination (LCD), which could formalize the restrictions imposed in March of 2023 —restrictions that transplant clinicians across the nation believe will be detrimental to patient care. Lawmakers from both sides of the aisle have weighed in. In August, a bipartisan letter signed by 14 members of the House of Representatives led by Reps. Anna Eschoo (D-CA) and Dr. Michael Burgess (R-TX), expressing concerns about the March rollbacks was sent to CMS and earlier this year, Congressional Black Caucus Chair Steven Horsford also raised this issue in a letter to CMS and the Department of Health and Human Services. The coalition remains hopeful that CMS will align its policies with the on-the-ground realities of patient needs and the expertise of transplant professionals. Stephanie Wight (301) 512-5583 SOURCE Honor the Gift