Abatacept for Prophylaxis of Acute Graft Versus Host Disease
The FDA approved abatacept for the prophylaxis of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX), in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor.
This is the first drug approved to prevent aGVHD. The application included use of real-world data (RWD) in the determination of clinical effectiveness. RWD is clinical data routinely collected from a variety of sources, including registry data, to generate real-world evidence. Efficacy was evaluated in two studies in patients 6 years and older undergoing HSCT from a matched or 1 allele-mismatched unrelated donor.
GVHD-1 (NCT01743131) was a randomized (1:1), double-blind, placebo-controlled clinical trial of patients who underwent an 8 of 8 Human Leukocyte Antigen (HLA)-matched HSCT and received abatacept or placebo in combination with a CNI and MTX. While severe (Grade 3-4) aGVHD-free-survival assessed at Day 180 after transplantation was not significantly improved in patients who received abatacept compared to patients who received a placebo (HR 0.55; 95% CI 0.26, 1.18), the OS rate at Day 180 after HSCT was 97 percent (95% CI: 89%, 99%) for patients who received abatacept compared to 84 percent (95% CI: 73%, 91%) for patients who received a placebo (HR 0.33; 95% CI: 0.12, 0.93). The moderate-severe (Grade 2-4) aGVHD-free survival rate at Day 180 after HSCT was 50 percent (95% CI: 38%, 61%) for patients who received abatacept compared to 32 percent (95% CI: 21%, 43%) for patients who received a placebo (HR 0.54; 95% CI: 0.35, 0.83).
Additional evidence of effectiveness was provided by GVHD-2, a clinical study using data from the Center for International Blood and Marrow Transplant Research (CIBMTR) in patients who underwent a 7 of 8 HLA-matched HSCT between 2011 and 2018. This registry-based study analyzed outcomes of 54 patients treated with abatacept for the prophylaxis of aGVHD, in combination with a CNI and MTX, versus 162 patients randomly selected from the CIBMTR registry treated with a CNI and MTX alone. The OS rate at Day 180 after HSCT was 98 percent (95% CI: 78%, 100%) for patients who received abatacept in combination with CNI and MTX compared to 75 percent (95% CI: 67%, 82%) for patients who received CNI and MTX alone.
The most common adverse reactions (>=10%) of abatacept for the prophylaxis of aGVHD are anemia, hypertension, CMV reactivation/CMV infection, pyrexia, pneumonia, epistaxis, CD4 lymphocytes decreased, hypermagnesemia, and acute kidney injury. Patients who receive abatacept should receive antiviral prophylaxis for Epstein-Barr virus infection before starting treatment and for 6 months post-transplantation and be monitored for cytomegalovirus infection/reactivation for 6 months post-transplant.
P-MUC1C-ALLO1, a Fully Allogeneic CAR-T Targeting Multiple Solid Tumors
The FDA has cleared an Investigational New Drug (IND) application for P-MUC1C-ALLO1, an allogeneic CAR-T product candidate targeting multiple solid tumor indications.
P-MUC1C-ALLO1 is the second fully allogeneic CAR-T product candidate to receive IND clearance in 2021 following P-BCMA-ALLO1 for the treatment of relapsed/refractory multiple myeloma. The product will be evaluated in a Phase I multi-center, open-label, dose-escalation study in adults with locally advanced or metastatic epithelial-derived solid tumors refractory to standard-of-care therapy, or those deemed ineligible or refused another existing treatment option.
The study will evaluate the safety, tolerability, and preliminary efficacy of P-MUC1C-ALLO1 and will follow a 3+3 design of dose-escalating cohorts. After a subject enrolls, P-MUC1C-ALLO1 allogeneic CAR-T cells will be administered, following a standard chemotherapy-based conditioning regimen. The study protocol allows for exploration of additional dosing regimens, including re-dosing once initial safety has been established.
P-MUC1C-ALLO1 is an allogeneic CAR-T product candidate in preclinical development for multiple solid tumor indications. P-MUC1C-ALLO1 has the potential to treat a wide range of solid tumors derived from epithelial cells, such as breast, colorectal, lung, ovarian, pancreatic and renal cancers, as well as other cancers expressing a cancer-specific form of the Mucin 1 protein, or MUC1C. P-MUC1C-ALLO1 is designed to be fully allogeneic, with genetic edits to eliminate or reduce both host-vs-graft and graft-vs-host alloreactivity.
AI Software Medical Smart Ultrasound for Thyroid & Breast Cancer Diagnosis
The FDA granted clearance for an artificial intelligence (AI)-based software platform used to diagnose thyroid and breast cancer. The new system, built using ultrasound data from a network of 48 sites around the world, aids physicians in accurately diagnosing disease and improves speed to treatment while reducing avoidable surgical procedures.
"Thyroid DS is a game-changer for thyroid ultrasound imaging. Not only will it aid diagnosis of thyroid cancer, it will allow for more standardized and reproductive reporting of thyroid nodules preventing potentially unwarranted biopsies on benign lesions" said Shah Islam, PhD, at the National Hospital for Neurology & Neurosurgery, London.
Researchers performed studies that proved physicians using the software dramatically improved accuracy, consistency, and efficiency. Physicians' thyroid cancer detection rates jumped by up to 14 percent while simultaneously reducing false-positive biopsy orders by over 35 percent. Interpretation variability was lowered by over 50 percent and time spent per case dropped by 24 percent.
The patented AI software aligns AI-generated findings directly to the American College of Radiology's BI-RADS and TI-RADS rating systems, as well as the American Thyroid Association's system for tissue classification, scoring, and patient management.
The AMA recently announced new CPT Category 3 codes for whenever the software is utilized interpreting, classifying, and reporting traditional ultrasound exams.