Cyclophosphamide

The purple ribbon denotes World Lupus Day, May 10. As study of patients with lupus uncovers a root cause of the condition we take a deeper look at the autoimmune disease and how it is currently treated A study of patients with lupus has uncovered a root cause of the disease that may eventually lead to new treatments, researchers reported in a study published in Nature. The immune disorder affects more than 1.5 million people in the US alone, and damages skin, joints, the kidneys, the brain and other organs. Comparing blood samples from 19 patients suffering from lupus with healthy people, researchers found that the patients had an imbalance in immune-system cells called ‘T cells’. There was reduced production of T cells that aid in healing, and increased production of T cells that produce autoantibodies to attack healthy cells. In the wake of the study, we take a look at lupus – at its effects and the available treatments. What is lupus? Lupus is an autoimmune disease that causes the body's immune system to attack its own tissues and organs. This condition can affect various parts of the body, including skin, joints, kidneys, brain, heart and lungs. Diagnosis can be complex, as symptoms often mimic those of other ailments. Treatment options for lupus depend on the severity of symptoms and which organs are affected. The cause of lupus remains unknown, but researchers believe it involves a combination of genetic and environmental factors. Women are more likely to develop lupus than men, and it is more prevalent in certain ethnic groups. Patients with lupus are advised to protect themselves from sun exposure, as ultraviolet light can trigger flares in some individuals. How is lupus treated? Medications include anti-inflammatory drugs, antimalarial drugs and immunosuppressants. Research has shown antimalarial drugs such as hydroxychloroquine and chloroquine can decrease the frequency and severity of lupus flare-ups. They work by modulating the immune system, which is overactive in lupus patients. This helps reduce inflammation and pain, particularly in the skin and joints. These medications also help protect the heart, and are thought to lower the risk of blood clots in lupus patients. This is significant as individuals with lupus have an increased risk of cardiovascular complications. Antimalarials are used in combination with immunosuppressants for more severe cases. Immunosuppressants are used to treat lupus because the condition results in the body's immune system mistakenly attacking healthy tissue, causing inflammation and damage to organs including the kidneys, heart and lungs. Common immunosuppressants used in lupus treatment include methotrexate, azathioprine, mycophenolate mofetil, and cyclophosphamide. These can be administered orally or intravenously, depending on the specific drug and the patient's condition. The use of immunosuppressants carries risks, as a suppressed immune system makes the patient more susceptible to infections. Companies that specialise in lupus medicines Medications used to treat lupus include anti-inflammatory drugs, antimalarial drugs and immunosuppressants. The following are among the companies that produce treatments in these three categories. Immunosuppressants GlaxoSmithKline : Benlysta (based on belimumab) AstraZeneca : Saphnelo (anifrolumab-fnia) Aurinia Pharmaceuticals: Lupkynis (voclosporin) Roche : Rituxan (rituximab) Bristol Myers Squibb : Orencia (abatacept) Eli Lilly : Olumiant (baricitinib) Pfizer : Xeljanz (tofacitinib) Antimalarials Sanofi : Plaquenil (hydroxychloroquine) Anti-inflammatories Novartis : Ilaris (canakinumab) Janssen Pharmaceuticals: Remicade (infliximab) UCB: Cimzia (certolizumab pegol)

MINNEAPOLIS--( BUSINESS WIRE )--Research results from NMDP℠ and CIBMTR® (Center for International Blood and Marrow Transplant Research®)—published today in the peer-reviewed Journal of Clinical Oncology —found no discernable difference in overall survival (OS) among patients with blood cancer receiving blood stem cell transplant when investigators used an unrelated donor matched at 7/8 human leukocyte antigen (HLA) markers, compared to a fully matched 8/8 unrelated donor when using a post-transplant cyclophosphamide-based (PTCy) graft-versus-host disease (GVHD) prevention strategy. Conducted by CIBMTR—a research collaboration between the Medical College of Wisconsin® and NMDP—the observational study also showed no discernable differences in GVHD-free, relapse-free survival (GRFS) for adults with blood cancers who had a 7/8 or an 8/8 unrelated donor transplant when using PTCy. The study, “ Post-Transplant Cyclophosphamide–Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors,” evaluated 10,025 adult patients at 153 U.S. transplant centers who underwent initial unrelated donor blood stem cell transplant for acute leukemia or myelodysplastic syndromes from 2017–2021 and reported outcomes to CIBMTR. The most clinically significant outcome observed showed that when compared to 8/8 unrelated donor transplant using PTCy, 7/8 unrelated donor transplant with PTCy had similar OS (hazard ratio [HR], 0.96 [95% Confidence Interval, 0.823-1.11]; P = .60) and similar GRFS (HR, 0.90 [0.79-1.02]; P = .1). Previously established methods to prevent GVHD involved use of immunosuppressants called calcineurin inhibitors, yet outcomes were traditionally worse with mismatched donors. In this study, when compared to 8/8 unrelated donor transplant using traditional calcineurin-inhibitor GVHD prevention methods, OS was improved after 8/8 PTCy transplant (HR, 0.88 [0.80-0.96]; P = .004) and similar with 7/8 PTCy transplant (HR, 0.92 [95% CI, 0.80 to 1.05]; P = .2062). GRFS was improved after 8/8 (HR, 0.61 [0.57-0.66]; P < .0001) or 7/8 PTCy transplant (HR, 0.68 [0.60-0.76]; P < .0001). Investigators showed adoption of novel treatment modality PTCy can eliminate disparities in survival, greatly reduce GVHD risk, and expand safe and effective transplant access to people for whom a matched unrelated donor is unavailable, which disproportionally impacts patients who are racially and ethnically diverse. “ These data confirm we are at the forefront of transplant practice change. As our global population becomes more diverse and geographically disparate, patients facing blood cancer are increasingly looking for a safe and effective method to increase their survival and longevity,” Brian Shaffer, MD, co-first author; bone marrow transplant specialist & cellular therapist, Memorial Sloan Kettering Cancer Center, said. “ Achieving recognition from one the most prestigious, peer-reviewed medical publications demonstrates the credibility of these data and builds the evidential case for using mismatched unrelated donors to expand access to blood stem cell therapy for all patients.” In the U.S., patients with blood cancers from Asian/Pacific Islander backgrounds currently have a 47% chance of finding a fully matched, 8/8 unrelated donor on the NMDP Registry℠ of potential volunteer donors. However, those odds increase to 92% when searching for a 7/8 match or greater. African American and Black patients’ chances jump from 29% with an 8/8 match, to as high as 84% with a 7/8 match—while patients with Latino / Hispanic or non-Hispanic White ancestry improve their odds from 48% (8/8) to 90% (7/8) and 79% (8/8) to 99% (7/8), respectively. 1 “ This novel approach transforms the landscape for physicians, researchers, patients and families, expanding the definition of a ‘suitable donor,’” said Steven Devine, MD, chief medical officer, NMDP and senior scientific director, CIBMTR . “ Not only does achieving significantly greater outcomes give patients another chance at life, it breaks down the barriers to transplant for all patients, regardless of their ancestry.” These results are part of NMDP’s ongoing research commitment to expand access to cell therapy to all patients and close the donor availability gap. NMDP’s network of transplant centers, many of which participate in CIBMTR trials, are collaborating to bring new research to light that is challenging previously established blood stem cell transplantation science. NMDP’s Donor for All initiative includes several research efforts, including this published study, that aim to establish a new, safe and effective approach for using mismatched unrelated donor transplants in the U.S. and abroad. Operational data from NMDP-facilitated transplants show 60% year-over-year growth in mismatched unrelated donor transplant—the majority of which are from unrelated donors matched at 7/8 HLA markers, indicating how the U.S. medical community is seeking other safe and effective, evidence-based methods to prolong patients’ ability to survive and thrive. 2 “ This is scientific evidence showing we are addressing an unmet need,” Dr. Devine added. CIBMTR presented findings from this study at the American Society for Transplantation and Cellular Therapy’s scientific congress, Tandem 2024 , in February 2024. About CIBMTR® CIBMTR® (Center for International Blood and Marrow Transplant Research®) is a nonprofit research collaboration between NMDP℠, in Minneapolis, and the Medical College of Wisconsin, in Milwaukee. CIBMTR collaborates with the global scientific community to increase survival and enrich quality of life for patients. CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, a large network of centers, and a unique database of long-term clinical data for more than 675,000 people who have received hematopoietic cell transplantation and other cellular therapies. Learn more at cibmtr.org . About NMDP ℠ At NMDP℠, we believe each of us holds the key to curing blood cancers and disorders. As a global nonprofit leader in cell therapy, NMDP creates essential connections between researchers and supporters to inspire action and accelerate innovation to find life-saving cures. With the help of blood stem cell donors from the world’s most diverse registry and our extensive network of transplant partners, physicians and caregivers, we’re expanding access to treatment so that every patient can receive their life-saving cell therapy. NMDP. Find cures. Save lives. Learn more at nmdp.org . 1 Chowdhury AS, Maiers M, Spellman SR, Deshpande T, Bolon YT, Devine SM. Existence of HLA-mismatched unrelated donors closes the gap in donor availability regardless of recipient ancestry. Transplant Cell Ther . 2023:29(11):686.e1-686.e8. doi: 10.1016/j.jtct.2023.08.014 . 2 Internal data on file, 2021-2023.