Blood & Cancer

Existing biosimilars are safe, effective alternatives to their reference biologics, and are increasingly being incorporated into oncology treatment guidelines. Technological advances that have emerged in the years since biologic agents entered the market allow for the careful assessment of “critical clinical attributes” of biosimilar agents. This helps ensure the safety and efficacy of biosimilars, as well as their structural, functional, and behavioral similarities to the original reference biologics, according to Gary Lyman MD, MPH, professor and senior lead, health care quality and policy at the Hutchinson Institute for Cancer Outcomes Research at Fred Hutchinson Cancer Research Center, Seattle. Biosimilars are increasingly being included as acceptable alternatives in treatment guidelines, and in this episode Dr. Lyman discussed the reasons why they are considered safe and effective, how they can add value for oncology patients, and the need for ongoing diligence in monitoring their effects. Biosimilars i

Systemic treatment for advanced urothelial cancer is quickly evolving. On this week’s podcast, Arjun Balar, MD, director of the genitourinary medical oncology program at New York University discusses his approach amid changing times with guest host Alan Lyss, MD, a community-based medical oncologist and clinical researcher in the St. Louis area before his recent retirement.  Chemotherapy or immunotherapy first line? With the negative phase 3 results for chemotherapy in combination with either pembrolizumab or atezolizumab, “if I use immunotherapy, I use it alone,” Dr. Balar said. Patients who need “a response right away” for aggressive disease get chemotherapy. In general, first-line chemotherapy “probably is the better route for a lot of people,” he said. There is a role for immunotherapy in the first line when chemotherapy can’t be tolerated because of age or other reasons, and in the second line, immunotherapy is standard of care. PD-1/PD-LI expression is too inconsistent to help guide the decision. It’s

A “very basic” type of gene therapy could potentially cure hemophilia, but a major hurdle has been the lack of an effective mode of delivery. Recent strides in using adeno-associated virus (AAV) vectors are changing that, and Glenn Pierce, MD, World Federation of Hemophilia Vice President, Medical, predicts approvals in the next 12-18 months. Dr. Pierce shared his personal experience with hemophilia and discussed his and others’ ongoing research on the use of AAV-mediated gene therapy with host David Henry, MD, in this episode. Hemophilia and AAV gene therapy key points: Hemophilia is caused by a monogenic defect and could, theoretically, be cured by gene replacement or augmentation, says Dr. Pierce, who notes that “it sounds disarmingly simple, but behind that simplicity is a very complex procedure.” The approach uses “gene addition,” which is a basic gene therapy involving the addition of a normal gene to the variant in an individual. This ultimately corrects the clotting factor deficiency. The complexity

At least 17 cases of thrombosis and thrombocytopenia have been reported in patients who received the Johnson & Johnson COVID-19 vaccine in the United States. Such events have been reported in patients who received the AstraZeneca vaccine as well. In this episode, Adam C. Cuker, MD, of the University of Pennsylvania, Philadelphia, tells host David H. Henry, MD, how to identify and manage patients with these vaccine-induced events. What’s in a name? The phenomenon of vaccine-induced thrombosis and thrombocytopenia has been given different names, including: Vaccine-induced immune thrombotic thrombocytopenia (VITT) Vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) Thrombosis and thrombocytopenia syndrome (TTS). Dr. Cuker’s preferred acronym is VITT. VITT is an immune-mediated reaction to the Johnson & Johnson and AstraZeneca vaccines that “results in thrombocytopenia and a strong propensity for thrombosis,” Dr. Cuker explained. Dr. Henry noted that VITT is reminiscent of heparin-induced

The combined clinical cell-cycle risk (CCR) score uses clinical and genetic factors to assess the risk of metastasis after radiation therapy in patients with prostate cancer. The CCR score has proven accurate in studies and can guide post-radiation treatment decisions in practice, according to Jonathan D. Tward, MD, PhD, of the University of Utah, Salt Lake City. Dr. Tward discusses the CCR score with host David Henry, MD, in this episode. About the score The CCR score combines the cell-cycle progression (CCP) score (available commercially as the Prolaris test) and the Cancer of the Prostate Risk Assessment (CAPRA) score to more precisely determine the postradiation risk for metastatic disease. Investigators identified a threshold for determining precise risk levels (2.112), which allows for personalized treatment decision-making based on more individual characteristics than standard risk-group categorizations, according to Dr. Tward. He noted that standard risk groups can include a broad range of actual ri

Pediatric oncologists are used to dealing with emotional, heart-wrenching situations, but oncology took on a new dimension for Michael Weiner, MD, when both he and his daughter were diagnosed with cancer. Dr. Weiner, a pediatric oncologist at Columbia University, New York, describes his roles as oncologist, patient, and caregiver to host David H. Henry, MD, in this episode.  Oncologist as patient: Lessons learned Dr. Weiner’s journey as a cancer patient began when he felt a lymph node on his neck that he knew wasn’t “normal.” A colleague examined Dr. Weiner and suggested the “watch-and-wait” approach, but Dr. Weiner insisted on immediate biopsy. The diagnosis was follicular lymphoma, and Dr. Weiner had a hard time accepting that his malignancy was treatable but not curable. One of the things Dr. Weiner learned as a cancer patient is that “you really need to connect with your doctor,” so he chose a doctor who felt like a good fit for him. Another lesson Dr. Weiner learned was that cancer can be very isolating

Studies have shown that chimeric antigen receptor (CAR) T-cell therapies produce responses in patients with relapsed/refractory B-cell lymphomas, but researchers continue to look for ways to improve efficacy, decrease toxicity, and overcome treatment resistance. Leslie Kean, MD, PhD, of Boston Children’s Hospital, discusses some of this research with host David H. Henry, MD, in this episode. Dr. Kean outlines four recent studies of CAR T-cell therapies in lymphoma. The studies were selected as part of the “Best of ASH” session at the 2020 annual meeting of the American Society of Hematology. Primary Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma This study was designed to assess the efficacy and safety of axicabtagene ciloleucel (axi-cel) in patients with indolent lymphomas. In follicular lymphoma, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 80%. In marginal zone lymphoma, the OR

Researchers have tracked the evolution of genetic germline testing in women with breast or ovarian cancer in recent years and reported the results in the Journal of Clinical Oncology. Study author Allison W. Kurian, MD, of Stanford (Calif.) University, describes the group’s findings (https://bit.ly/31RaSGR) to guest host Alan Lyss, MD, subprincipal investigator emeritus for Heartland Cancer Research NCORP, in this episode. Study rationale and methods Dr. Kurian said that an inflection point for breast cancer genetics was in 2013 when the U.S. Supreme Court ruled that gene patenting was not allowed for the purposes of genetic testing. As a result, the cost of testing BRCA1/2 genes fell, and testing became much more accessible. With their study, Dr. Kurian and colleagues aimed to look at trends following the increase in accessibility. The researchers used Surveillance, Epidemiology, and End Results Program (SEER) records of women aged 20 years and older who were diagnosed with breast or ovarian cancer from 20

A program called Drive By Flu-FIT has allowed for socially distanced colorectal cancer (CRC) screening during the COVID-19 pandemic. Armenta Washington, senior research coordinator at the University of Pennsylvania, describes the program to guest host Alan Lyss, MD, subprincipal investigator emeritus for Heartland Cancer Research NCORP, in this episode. What is Drive By Flu-FIT? Drive By Flu-FIT is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program. Flu-FIT was designed to increase access to CRC screening by offering take-home FIT tests to patients at the time of their annual flu shots. The goal of Drive By Flu-FIT is to provide a COVID-safe approach to CRC screening and counteract the decrease in CRC screening seen during the pandemic. Drive By Flu-FIT is a joint effort of the University of Pennsylvania, the Einstein Healthcare Network, Chi Eta Phi Sorority, and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region. How does Drive By Flu-FIT

Earlier this year, clinical practice guidelines for the diagnosis and management of von Willebrand disease (VWD) were published in Blood Advances. The guidelines (https://bit.ly/2OIfKLE) are a collaborative effort from the American Society of Hematology, the International Society on Thrombosis and Haemostasis, the National Hemophilia Foundation, and the World Federation of Hemophilia. Guideline author Paula James, MD, of Queens University, Kingston, Ont., reviews some of the recommendations in these guidelines with host David H. Henry, MD, in this episode. Case discussion A patient presents with the complaint of heavy menstrual bleeding, which could indicate a bleeding disorder such as VWD. How does one diagnose or rule out VWD? Tests to order include CBC, prothrombin time (PT), and partial thromboplastin time (PTT). Results of CBC, PT, and PTT could be normal, which would necessitate special testing to specifically look at factor VIII and von Willebrand factor (VWF). A patient’s family history may be helpfu

We continue our review of drugs recently approved by the Food and Drug Administration (FDA) in the hematology/oncology space. In part 1 of our review, David M. Mintzer, MD, of Pennsylvania Hospital, highlighted 11 therapies, including newly-approved treatments and new indications for older drugs. Part 1 was published Feb. 18 (https://bit.ly/38JR782). Now, in part 2, Dr. Mintzer tells host David H. Henry, MD, about another 11 therapies recently approved by the FDA, including monoclonal antibodies, kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and more. Margetuximab-cmkb (Margenza) In Dec. 2020, margetuximab-cmkb was approved for use in combination with chemotherapy to treat adults with metastatic, HER2-positive breast cancer who had received at least two prior anti-HER2 regimens, including at least one for metastatic disease. https://bit.ly/38JAiKg Tafasitamab-cxix (Monjuvi) In July 2020, tafasitamab-cxix received accelerated approval for use in combination with lenalidomide to treat

Treatments for chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) have advanced in recent years, with more new developments on the horizon. James Gerson, MD, of the University of Pennsylvania, Philadelphia, reviewed some of these advances and future directions while describing how he would treat three patients. Host David H. Henry, MD, posed the following cases for consideration. Case 1 In a 75-year-old male with no comorbid illness, routine blood work revealed a WBC count of 15,000/mcL. The manual differential showed mature lymphocytes and smudge cells. The patient has no constitutional symptoms, but there is suspicion of CLL. What to do? An incidental finding of elevated WBC is the most common presentation for CLL, Dr. Gerson noted. Flow cytometry is how most diagnoses are made. If the patient’s blood sample is CD5+ and CD20+, in the vast majority of cases, the patient has CLL. The main alternative diagnosis is MCL, so Dr. Gerson recommends checking for cyclin-D1 overexpression and transloca

When should cancer patients receive a COVID-19 vaccine? The National Comprehensive Cancer Network (NCCN) has issued recommendations to provide guidance on the topic. Guideline author Steven Pergam, MD, of Fred Hutchinson Cancer Research Center, Seattle, explains NCCN’s recommendations to host David H. Henry, MD, in this episode. Prioritization Prioritization for COVID-19 vaccination should be given to cancer patients currently receiving chemotherapy, those who just finished active treatment, or those about to receive treatment. Additional factors that should be taken into consideration include age, comorbidities, and sociodemographic characteristics. Transplant and cellular therapy Patients who undergo allogeneic or autologous transplant or those who receive cellular therapy should be vaccinated at least 3 months after this treatment. This recommendation is based on best practices used for other vaccines, as there are insufficient data on COVID-19 vaccination in these patients, Dr. Pergam noted. Hemato

Ifeyinwa (Ify) Osunkwo, MD, MPH, joins us to talk about her approach to pain management in patients suffering from sickle cell crisis as well as the cognitive and behavioral effects of long-term opioid use in these patients. She and our host David H. Henry, MD, cover these topics and more in this episode. Dr. Osunkwo is a professor of medicine at Atrium Health and the director of the Sickle Cell Enterprise at the Levine Cancer Institute, part of Atrium Health, in Charlotte, N.C. Over the course of a decade, the life expectancy of patients with sickle cell disease has increased. Today 99% of children with sickle cell disease will live to become adults. When treating patients with sickle cell pain it is important to consider their disease trajectory, and to weigh the pros and cons for initiation of opioid therapy. Management of sickle cell disease in the acute setting: In children, therapy usually includes use of intravenous fluid and intravenous opioids, then an eventual transition to oral opioids and NSAID

In this episode, we review drugs recently approved by the Food and Drug Administration in the hematology/oncology space. David M. Mintzer, MD, of Pennsylvania Hospital, joins host David H. Henry, MD, to highlight some first-time approvals and new indications for older drugs. Approvals in 2020 Pembrolizumab (Keytruda) was approved for a range of new indications last year, including: First-line treatment of patients with unresectable or metastatic microsatellite instability–high or mismatch repair deficient colorectal cancer. https://bit.ly/2OKw8uF. Treatment of adult and pediatric patients who have tumor mutational burden–high (≥10 mutations/megabase) solid tumors that progressed after prior treatment and who have no satisfactory alternative treatment options. https://bit.ly/2NCddkX. For use in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1 (combined positive score ≥10) as determined by an

The NCI-MATCH trial was designed to reveal mutations in underexplored cancer types, allowing researchers to match patients to appropriate targeted therapies. Study investigator Alice P. Chen, MD, from the National Cancer Institute, reviews the goals and results of NCI-MATCH with host David H. Henry, MD, in this episode. Trial details NCI-MATCH has more than 1,000 participating sites. The trial is open to patients with advanced cancers that have progressed on standard treatment or rare cancers for which there is no standard treatment. Investigators use next-generation sequencing to identify mutations in tumor biopsies taken before the start of therapy. Sequencing is performed at MD Anderson Cancer Center, Houston; Massachusetts General Hospital, Boston; MoCha at NCI’s Frederick (Md.) National Lab; Yale University, New Haven, Conn.; and commercial labs. Matching patients to treatment When a patient is found to have an actionable mutation, that patient is assigned to an investigational treatment, typically mo

How do the various COVID-19 vaccines work, and when should patients be vaccinated? We tackle these topics and more in this episode. Our host David H. Henry, MD, is joined by Drew Weissman, MD, PhD, a professor at the University of Pennsylvania, Philadelphia. Dr. Weissman codeveloped the messenger RNA (mRNA) technology being used in the COVID-19 vaccines produced by Pfizer/BioNTech and Moderna. History of mRNA vaccines Testing of mRNA vaccines began in the 1990s. An initial problem with these vaccines was that the RNA was highly inflammatory. Dr. Weissman and his colleague, Katalin Karikó, PhD, discovered how to fix that problem in 2005. The pair found that placing modified nucleosides into mRNA made it noninflammatory and allowed for increased production of protein from the RNA – up to a 1,000-fold increase in mice. This technology is the basis of the Moderna and Pfizer/BioNTech COVID-19 vaccines. Immunology and vaccines To produce a good immune response, antigen must be present for a long time, though t

The greatest barrier to clinical trial enrollment is patients not knowing an appropriate trial exists, according to a survey of gynecologic cancer survivors. The most common reason survey respondents gave for not enrolling in clinical trials was that their medical team didn't tell them about any trials. Annie Ellis and Mary (Dicey) Jackson Scroggins – who are both patient advocates and ovarian cancer survivors – conducted this survey and presented the results at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer last year (https://bit.ly/3plI1Vg). Ms. Ellis discussed the survey results and other related research with host David H. Henry, MD, in this episode. Ms. Ellis and Ms. Scroggins distributed their 26-question survey online. The survey was completed by 189 survivors of gynecologic cancers. Most respondents (65.6%) had never participated in a clinical trial. Reasons for nonparticipation included: The medical team never discussed trial participation (50.4%) The patient didn’t qual

New studies have shed additional light on how convalescent plasma may affect patients with COVID-19, how blood type impacts bleeding risk, the effects of race on cancer-associated thrombosis, and iron deficiency in pregnancy. These studies were presented as part of the “Best of ASH” session at the 2020 annual meeting of the American Society of Hematology. Alisa S. Wolberg, PhD, of the University of North Carolina at Chapel Hill, who cochaired the session, reviews these studies with host David H. Henry, MD, in this episode.   Abstract #572: Association of ABO Blood Group with Bleeding Severity in Patients with Bleeding of Unknown Cause. https://bit.ly/2Mc0R2A. This study, which included 422 patients, indicated that blood group O is overrepresented in patients with bleeding of unknown cause. Blood group O was associated with a more severe bleeding phenotype, especially oral mucosal bleeding, independent of the levels of von Willebrand factor and factor VIII. Patients with blood group O had increased clot densi

Three studies revealed new findings on thrombosis in patients with cancer and/or COVID-19. These studies were presented at the 2020 annual meeting of the American Society of Hematology. One study suggested the Khorana score may be ineffective for predicting venous thromboembolism (VTE) in cancer patients. Another study revealed factors that can predict VTE in patients with cancer and COVID-19. And a third study indicated that antithrombotic agents don’t improve outcomes in patients with severe COVID-19.  Kristen M. Sanfilippo, MD, of Washington University, St. Louis, reviews these studies with host David H. Henry, MD, in this episode. Abstract 202: Performance of Khorana Score to Predict One-Year Risk of Venous Thromboembolism in Over Two Million Patients With Cancer. https://bit.ly/3oCHOfQ. The study included 2,112,260 patients with cancer. At 1 year after diagnosis, 227,170 (10.8%) patients had developed VTE. The Khorana score was a weak to modest predictor of the 1-year risk of VTE (area under the curve,