Tag Archives: Drug treatments/trials/dosing (see also Pharmaceuticals)

January 2024—Sometimes even superb ideas can also turn out to be quite, well, bothersome. Zoom meetings. Bridal showers. Bike lanes. Parking apps. QR menu codes. And—if laboratories aren’t careful—the same can be true of pharmacogenomic testing. Just ask Ann Moyer, MD, PhD, associate professor, laboratory medicine and pathology, Mayo Clinic. When it comes to pharmacogenomic testing, laboratory medicine brings significant expertise to the table. But in clinical settings, physicians who prescribe the medications need to be familiar with how to use the test results. They also need to work with the lab to decide which tests, for which genes or gene-drug pairs, will be most helpful for their patients, she says. “Especially if you’re going to start incorporating clinical support alerts into the EHR,” adds Dr. Moyer, who was chair of (until Dec. 31; she is now advisor to) the CAP/ACMG Biochemical and Molecular Genetics Committee. “If the practice doesn’t actually want them, then you’re just going to end up annoying them.”

May 2023—For fluid biomarkers in the diagnosis of Alzheimer’s disease, the pace of research and related industry and regulatory developments in the past year has been brisk.

September 2022—It may not be the oldest story in the world, but in clinical laboratories it’s an oft-told tale: Tumor meets biomarker; drug meets companion diagnostic; both meet FDA approval; clinicians meet with patients offering new hope—and those in the lab are left trying to figure out how to make it all work. That story is playing out again in the realm of measuring tumor mutational burden. In mid-2020 the FDA approved pembrolizumab as a new treatment option in adult and pediatric patients with TMB-high (≥10 mutations/megabase) solid tumors, as determined by the FDA-approved FoundationOne CDx assay. “That doesn’t sound too controversial, right?” says Alain Borczuk, MD, vice chair of anatomic pathology and director of oncologic pathology, Northwell Health Cancer Institute. “It’s not the only way in, but it’s one of the ways in. If you’re arguing for your patient that this is the biomarker that makes them eligible for the drug, then the next questions will be, What was the number? And what was the test?” And it’s off to the races.

June 2022—The latest advance in breast cancer treatment is a big one—the promising antibody drug conjugate fam-trastuzumab deruxtecan-nxki, or T-DXd (Enhertu). The drug was granted break­through therapy designation this spring for patients with HER2-low metastatic breast cancer, and the drug and trial on which the decision was based were the focus of the plenary session at the ASCO annual meeting in early June. “This drug in particular is a variant of a drug we are all very familiar with—Herceptin, or trastuzumab,” says David Rimm, MD, PhD, the Anthony N. Brady professor of pathology, professor of medicine (oncology), director of the translational pathology and Yale pathology tissue services, and director of the physician scientist training program in pathology, Department of Pathology, Yale University School of Medicine. Also familiar: the IHC test to determine eligibility for the drug, a companion diagnostic developed decades ago. But that’s where easy familiarity ends.

August 2021—The FDA’s approval in June of a new drug to treat Alzheimer’s disease has incited motley responses, a sort of Grand Tour of emotions and reactions. As with any stormy action, the aftermath becomes clear only over time, during the hard work of cleaning up. What comes next?

August 2021—Pharmacogenetic testing is not standard of care at most transplant centers, nor do the FDA or others mandate it. But “transplant medicine is ripe for observing the benefits of pharmacogenetics,” said Gwendolyn A. McMillin, PhD, D(ABCC), in an AACC virtual session last year.

June 2021—Mastocytosis is not for quitters. Not at any point, from considering the possible diagnosis, to doing a complement of stains, to looking for mutations beyond KIT D816V, to being curious about the presence of mast cells even after making a diagnosis of another myeloid disease. Patients have already learned this grueling lesson. They can easily spend years seeking answers before their disease is properly identified. Pathologists can speed up that process—and the time to do so is now, says Tracy George, MD, chief medical officer and incoming president of ARUP Laboratories, and medical director of hematopathology. Notes Dr. George: “There’s some exciting stuff going on with systemic mastocytosis.” New targeted KIT inhibitors appear to be quite effective, including at least one agent for advanced systemic mastocytosis that has been submitted to the Food and Drug Administration. “We anticipate there’s going to be approval by the FDA this summer,” says Dr. George, who’s been involved in the clinical trials for avapritinib (Blueprint Medicines).

February 2021—Absorbing new biomarkers into lung cancer workups makes for a complicated diplomacy. How best to balance so many rivals? Does it make the most sense for laboratories to try to do everything at once, a full-court press involving next-generation sequencing panels? Or is it more practical to add a new marker only as a new targeted therapy receives approval? Where do RNA-based assays fit in? What about IHC? When do you make the switch? Or do you? And how best to handle cell-free DNA tests (which seem to be the rogue states in all this)? How do you weight external factors, such as reimbursement, existing equipment and capital expenditures, and physician expertise? Driving this all are medical breakthroughs. As with all forms of statecraft, the latest incident can change everything. For lung cancer, the most recent advance comes from the ADAURA trial, which showed a significant benefit of using osimertinib to treat stage IB to IIIA EGFR-mutation positive non-small-cell lung cancer.

February 2021—Eighteen months after introducing a next-generation sequencing assay to detect CMV antiviral resistance in the transplant population, Matthew Binnicker, PhD, D(ABMM), in an AMP presentation, shared a patient’s case and his laboratory’s broader experience.

July 2019—In the early, heady days of biologic therapies, use of these drugs resembled a common military tactic of the Civil War: charge and retreat, charge and retreat, charge and retreat. The approach, though modern at the time, often proved disastrous. Jeffry Katz, MD, recalls the excitement that greeted the arrival of anti-tumor necrosis factor-α agents, starting with infliximab (Remicade) in 1998. “What we used to do is we would give patients a drug, and we would wait for them to get sicker,” says Dr. Katz, medical director, inflammatory bowel diseases, University Hospitals Cleveland Medical Center, and professor of medicine, Case Western Reserve University School of Medicine.

September 2018—When a miracle drug comes along that is predicted to cause havoc in the laboratory, the drug could well seem like a double-edged sword. In the case of emicizumab (Genentech’s Hemlibra), for patients with hemophilia A, the mix of both benefits and drawbacks is likely to settle in for the long term.

October 2017—The expert and advisory panels for the CAP/IASLC/AMP guideline on molecular testing for lung cancer biomarkers started updating the guideline in 2014, and an important but fairly routine revision process may have seemed to lie ahead. Something like sedately stepping onto a moving sidewalk. The key question at that point was quotidian: Have new data emerged to warrant changing the original recommendations?

October 2016—As fans of spycraft know, offensive counterintelligence can include an arsenal of strategies: initiating a diversion, sowing confusion, creating false identities—anything that makes another party believe something that isn’t true. If the cancer treatment drug daratumumab were capable of deceptive intent, it might be accused of all those ploys when it comes to interfering with blood transfusion crossmatching. The reason: For patients receiving daratumumab, marketed as Darzalex by Janssen Pharmaceuticals, antibody testing for transfusion is subject to erratic false-positives, often leaving transfusion services confused, uncertain, and on hold.

September 2016—In December 2007, American hematopathologist Tracy I. George, MD, spent a weekend in the small town of Ansbach in central Bavaria in the laboratory of Hans-Peter Horny, MD, whom she calls “the father of mast cell pathology.” Dr. Horny was at that time a privately practicing hematopathologist after having spent most of his career in academia. Plans for an international clinical trial were underway to evaluate the investigational drug midostaurin in advanced systemic mastocytosis, a rare group of diseases for which there was no effective therapy, and Dr. Horny would be the study pathologist. Dr. George, who had been diagnosing mast cell diseases for several years, wanted to take part as well.

April 2015—St. Jude Children’s Research Hospital, Memphis, brings a razor-sharp focus to its mission: the 78-bed institution cares for children with catastrophic illnesses, including leukemias and lymphomas, solid tumors, hematology disorders (including sickle cell disease), and infectious diseases. It doesn’t have an emergency department. Consistent with its goal of advancing cures, all its patients are enrolled in research protocols.

September 2013—For good or bad, Matthew Hiznay seems to be an odds beater. First, a minority of lung cancer patients have never smoked. He’s one of them, having been diagnosed with late-stage non-small-cell lung cancer in August 2011. Obviously, that’s the bad.