ASH_hematology Tag

17 Dec

Posted at 11:11h in Author Interviews, Lymphoma
[caption id="attachment_71819" align="alignleft" width="150"]Marco Davila Dr. Davila[/caption] MedicalResearch.com Interview with: Marco Davila, MD, PhD Hematologist/Oncologist, Senior Vice President and Associate Director for Translational Research at Roswell Park Comprehensive Cancer Center (Buffalo, NY) - study senior author [caption id="attachment_71820" align="alignleft" width="150"]Co-author Meredith Stone, PhDAssistant Director for Cell Therapy Translation in Dr. Davila’s lab at Roswell Park - presenting author Dr. Stone[/caption] Co-author Meredith Stone, PhD Assistant Director for Cell Therapy Translation in Dr. Davila’s lab at Roswell Park - presenting author       MedicalResearch.com: What is the background for this study? Response: While CD19-targeted CAR T cell therapy has garnered clinical success and FDA approval for the treatment of large B cell lymphoma, approximately half of patients suffer from primary resistance or relapse. Increasing evidence suggests that resistance mechanisms are supported by the tumor microenvironment (TME). Cytokines secreted by CAR T cells can remodel the TME, determining the phenotype and function of other immune cells.

27 Jan

Posted at 10:59h in Author Interviews, Immunotherapy, Lymphoma
MedicalResearch.com Interview with: [caption id="attachment_66115" align="alignleft" width="130"]Joshua Brody MDDirector, Lymphoma Immunotherapy Program Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine New York, New York 10029 Dr. Brody[/caption] Joshua Brody MD Director, Lymphoma Immunotherapy Program Icahn School of Medicine at Mount Sinai Hess Center for Science and Medicine New York, New York 10029   MedicalResearch.com: What is the background for this study?
  • Patients with relapsed diffuse large B-cell lymphoma (DLBCL) have poor outcomes.
  • Standard chemotherapy e.g. Gemcitabine + Oxaliplatin (GemOx) yields complete response in ~30% of these patients.
  • Epcoritamab, a CD3xCD20 bispecific antibody immunotherapy was recently approved for relapsed DLBCL as monotherapy but is not yet approved as part of combination therapy.
  • Other immunotherapies e.g. CAR-T have been difficult to combine with standard therapies.

17 Dec

Posted at 16:25h in Author Interviews, Clots - Coagulation, Environmental Risks
MedicalResearch.com Interview with: [caption id="attachment_65560" align="alignleft" width="200"]Pamela L Lutsey PhD, MPHProfessor, Division of Epidemiology & Community Health University of Minnesota Minneapolis, Minnesota Dr. Lutsey[/caption] Pamela L Lutsey PhD, MPH Professor, Division of Epidemiology & Community Health University of Minnesota Minneapolis, Minnesota MedicalResearch.com: What is the background for this study? Response: Air pollution is ubiquitous. In order to understand the impact of exposure on health, it is necessary to look across diverse health conditions. Associations with lung disease and atherosclerotic cardiovascular disease are more established. Less is known about the role of air pollution exposure on coagulation and venous thromboembolism (VTE). MedicalResearch.com: Are individuals less ambulatory in heavily polluted areas? The study did not address this question directly. The association did persist across a wide range of subgroups of the sample, including those who were not smokers and who had no evidence of lung disease.

10 Dec

Posted at 11:44h in Author Interviews, Hematology, Pain Research, Pediatrics
MedicalResearch.com Interview with: [caption id="attachment_61133" align="alignleft" width="124"]David Brousseau, MD, MSChair of Pediatrics Nemours Children’s Health, Delaware and the Sidney Kimmel Medical College at Thomas Jefferson University Dr. Brousseau[/caption] David Brousseau, MD, MS Chair of Pediatrics Nemours Children’s Health, Delaware and the Sidney Kimmel Medical College at Thomas Jefferson University  MedicalResearch.com: What is the background for this study? Response: Sickle cell disease (SCD) is an inherited red blood cell disorder – the most common genetic disorder in the United States, affecting about 100,000 Americans (1 of every 365 Black births and 1 of every 16,3000 Hispanic-American births) (source: CDC). Pain is its most common symptom. Patients may experience acute or chronic pain or both. Acute episodes of pain, or pain crises, can vary in duration and severity. Many are treated at home; however when the pain is excruciating and cannot be treated at home, they lead to Emergency Department (ED) visits and even hospitalization. Reducing pain through prompt administration of pain medication in the ED is a core principle of national guidelines for SCD care. However, little data exists on how pain scores and changes in pain scores in the ED are associated with the patient’s disposition and the odds of a return visit.

18 Apr

Posted at 09:46h in Author Interviews, Cancer Research, Clots - Coagulation
MedicalResearch.com Interview with: [caption id="attachment_59045" align="alignleft" width="150"]Dr. med. univ. Cornelia Englisch Medical University of Vienna Dr. Englisch[/caption] Dr. med. univ. Cornelia Englisch Medical University of Vienna MedicalResearch.com:  What is the background for this study?  Response: Patients with cancer are at high risk for developing venous thromboembolism (VTE). Venous thromboembolism includes deep vein thrombosis (DVT), when blood clots form in the deep veins of the legs and pulmonary embolism (PE), a potential life-threatening condition when a clot breaks free and lodges in the arteries of the lung. Having a non-O blood type, meaning blood types A, AB or B, is a known risk factor for VTE in the general – non-cancer – population. Interestingly, it is the most common genetic risk factor for thrombosis. If this is also the case in patients with cancer has not been clarified yet. We therefore wanted to assess the role of ABO blood type in cancer-associated thrombosis. To achieve our goal, we utilized the dataset of the Vienna Cancer and Thrombosis Study (CATS); an observational cohort study including adult patients with active cancer.

08 Dec

Posted at 11:33h in Author Interviews, Genetic Research, Hematology
MedicalResearch.com Interview with: [caption id="attachment_56175" align="alignleft" width="148"]Steven Pipe, MD Professor of Pediatrics and Pathology Laurence A. Boxer Research Professor of Pediatrics and Communicable Diseases Pediatric Medical Director, Hemophilia and Coagulation Disorders Program Director, Special Coagulation Laboratory University of Michigan Dr. Pipe[/caption] Steven Pipe, MD Professor of Pediatrics and Pathology Laurence A. Boxer Research Professor of Pediatrics and Communicable Diseases Pediatric Medical Director, Hemophilia and Coagulation Disorders Program Director, Special Coagulation Laboratory University of Michigan MedicalResearch.com: What is the background for this study? Response: Hemophilia B is an inherited bleeding disorder where patients are missing clotting factor IX (9), a critical blood clotting protein.  Patients with a severe deficiency are at risk for traumatic and spontaneous bleeds – primarily into joints.  Repeated bleeding into joints causes more than acute pain and swelling but also leads to inflammatory and degenerative changes in joints that eventually leads to severe debilitating arthritis that can be crippling.  To try to prevent this, patients as young as infants are placed on regular infusions of clotting factor IX concentrates.  The relatively short half-life of factor IX means patients must infuse on average once to twice a week.  These can only be delivered intravenously – parents and then patients themselves have to learn this.  Prophylaxis must be continued lifelong to try to prevent bleeding events and protect joint health over the lifespan.  This is a tremendous burden on the patient and their caregivers. Even with regular prophylaxis, joint bleeds may still occur and arthropathy may still ensue.  This is because the blood levels often reach critically low levels prior to the next infusion.  Gene therapy aims to deliver a functional copy of the factor IX gene such that the patient’s own liver will make a continuous supply of factor IX that is delivered to the bloodstream.  At steady state with levels close to or within the normal range, patients would no longer be subject to bleeding events and would not require prophylaxis any longer.  We hope that such a one-time treatment would produced durable, “functionally curative” levels of factor IX.

19 Dec

Posted at 17:38h in Author Interviews, Hematology
MedicalResearch.com Interview with: [caption id="attachment_52512" align="alignleft" width="80"]Tadeusz Robak MD, Ph.D. Professor of Hematology Medical University of Lodz, Poland Dr. Robak[/caption] Tadeusz Robak MD, Ph.D. Professor of Hematology Medical University of Lodz, Poland MedicalResearch.com: What is the background for this study? What are the main findings?
  • Rozanolixizumab is an advanced SC anti-neonatal FcRn therapy currently in clinical development which has the potential to provide a targeted, convenient option to optimize individualized patient care.
  • The rozanolixizumab Phase II (TP0001) study was specifically designed to explore multiple dose regimens in order to inform the dosing strategy for further development in primary immune thrombocytopenia (ITP). Patients received either a single dose (1 x 15 mg/kg or 1 x 20 mg/kg) or multiple doses (5 x 4 mg/kg, 3 x 7 mg/kg, 2 x 10 mg/kg) of subcutaneous (SC) rozanolixizumab. The total dose was similar in all treatment groups, ranging from 15 to 21 mg/kg.
  • Rozanolixizumab was well tolerated by patients with primary ITP across all dose groups, consistent with previous rozanolixizumab studies. Additionally, improved platelet counts and reduced immunoglobin G (IgG) levels were seen at all doses and regimens of rozanolixizumab treatment, with higher response rate, higher percentage of responders and shorter time to response achieved by the 1 x 15 mg/kg, 1 x 20 mg/kg and the 3 x 7 mg/kg rozanolixizumab dose groups. These safety, tolerability and efficacy data support the Phase III development in patients with primary ITP.

12 Dec

Posted at 00:04h in Author Interviews, Hematology, Lymphoma
MedicalResearch.com Interview with: Genentech Priscilla White, spokesperson Senior Manager, Corporate Relations Genentech MedicalResearch.com: What is the background for this study? What are the main findings?
  • Response: Mosunetuzumab is a T-cell engaging bispecific antibody designed to target CD20-positive B-cell blood cancers, by binding to both CD20 (on the surface of B-cells) and CD3 (on the surface of T-cells).
  • Analyses from the ongoing Phase I/Ib GO29781 study indicate that mosunetuzumab can produce durable responses in patients who have relapsed or who are refractory to prior treatment(s), including those who have relapsed or who are resistant to CAR T-cell therapy.
  • Results from this dose-escalation study showed encouraging efficacy with an objective response rate (ORR) of 62.7 percent (n=42/67) in slow-growing Non-Hodgkin Lymphoma and 37.1 percent (n=46/124) in aggressive NHL across all dose levels assessed.
  • Additionally, data demonstrated a complete response (CR) rate of 43.3 percent (n=29/67) in slow-growing NHL and 19.4 percent (n=24/124) in aggressive NHL. CRs showed durability, with 82.8 percent (n=24/29) of patients with slow-growing NHL remaining in remission up to 26 months off initial treatment and 70.8 percent (n=17/24) of patients with aggressive NHL, remaining in remission up to 16 months off initial treatment.
  • Of the participants who received prior CAR T-cell therapy, the ORR was 38.9 percent (n=7/18), and 22.2 percent (n=4/18) achieved a CR.
  • Adverse reactions included cytokine release syndrome (CRS) in 28.9 percent of patients with 20.0 percent at Grade 1 and 1.1 percent at Grade 3. Grade 3 neurological adverse events occurred in 3.7 percent of patients.

11 Dec

Posted at 00:15h in Author Interviews, Cancer Research, Leukemia
MedicalResearch.com Interview with: [caption id="attachment_52430" align="alignleft" width="167"]Bridget Marcellino, MD Icahn School of Medicine at Mount Sinai Mount Sinai Hospital Dr. Marcellino[/caption] Bridget Marcellino, MD Icahn School of Medicine at Mount Sinai Mount Sinai Hospital MedicalResearch.com: What is the background for this study? Response: Our work focuses on elucidating the mechanisms that drive the pathogenesis and progression of myeloproliferative neoplasms (MPN). Dysregulation of the TP53 pathway is associated with MPN progression evidenced by the association of TP53 loss of heterozygosity with transformation to acute myeloid leukemia (AML) and the presence of inactivating mutations of TP53 found in a proportion of MPN-related AML patients.   Studies have shown that TP53 mutations, TP53 deletions and overexpression of the negative regulator of TP53, Murine Double Minute 2 (MDM2) all contribute to TP53 downregulation in MPNs and we therefore are interested in exploring other potential means by which TP53 is downregulated. Protein Phosphatase, Mg2+/Mn2+ Dependent 1D (PPM1D) is another negative regulator of the TP53 pathway and activating mutations in this gene are present in myeloid malignancies including MPNS. We therefore hypothesized that genomic alterations in PPM1D and/or overexpression of PPM1D would be found in the hematopoietic cells of MPN patients.

10 Dec

Posted at 12:29h in Author Interviews, Hematology, Lymphoma
MedicalResearch.com Interview with: [caption id="attachment_52400" align="alignleft" width="200"]Steven M. Horwitz, MD Memorial Sloan Kettering Cancer Center New York, NY Dr. Horwitz[/caption] Steven M. Horwitz, MD Memorial Sloan Kettering Cancer Center New York, NY MedicalResearch.com: What is the background for this study? Response: Relapsed or refractory Peripheral T-Cell Lymphoma (R/R PTCL) remains a disease of significant unmet medical need. Duvelisib is an oral dual inhibitor of PI3K-δ and PI3K-γ approved for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies, relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies, and is being developed for the treatment of additional hematologic malignancies including R/R PTCL. In early studies, we saw a suggestion of quite good activity of duvelisib as a single agent in a range of subtypes of T-cell lymphoma. The PRIMO study is an ongoing, multi-center, open-label, registration-directed Phase 2 study evaluating duvelisib in patients with R/R PTCL that is expected to enroll approximately 120 patients. The study includes both a dose optimization phase and an expansion phase. The Primo study will be sufficiently powered to give a much more precise estimate of the activity in peripheral t cell lymphomas. However, prior to initiating the main cohort we needed to first try to identify an optimal dose. That “dose optimization cohort” is the subject of our presentation here.

10 Dec

Posted at 12:17h in Author Interviews, Hematology, Lymphoma
MedicalResearch.com Interview with: Prof. John Seymour, MBBS, Ph.D Lead investigator of the MURANO Trial Director. Department of Hematology at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia MedicalResearch.com: What is the background for this study? What are the main findings?
  • MURANO is an international, multicenter, open-label, randomized Phase 3 study designed to evaluate the efficacy and safety of venetoclax in combination with rituximab compared with bendamustine in combination with rituximab in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).
  • At this year’s American Society of Hematology (ASH) annual meeting, we presented results from the four-year updated analysis from the study, which showed an 81 percent reduction in the relative risk of disease progression or death in patients randomized to the chemotherapy-free, two year fixed-duration treatment course of venetoclax plus rituximab and higher rates of minimal residual disease (MRD)-negativity compared to the standard of care regimen, bendamustine plus rituximab.
  • The long-term data further support the sustained clinical benefit of fixed-duration treatment with venetoclax in combination with rituximab for this patient population.
  • The safety profile of the combination is consistent with the known safety profile of each individual therapy alone. There were no new serious safety issues observed in the MURANO study since the last update. 

07 Dec

Posted at 21:02h in Author Interviews, Hematology, Lymphoma
MedicalResearch.com Interview with: [caption id="attachment_52376" align="alignleft" width="145"]Constantine Tam, M.D. Hematologist and Disease Group Lead Low Grade Lymphoma and CLL at Peter MacCallum Cancer Centre Victoria, Australia, and Lead study investigator of CAPTIVATE Prof. Tam[/caption] Constantine Tam, M.D. Hematologist and Disease Group Lead Low Grade Lymphoma and CLL at Peter MacCallum Cancer Centre Victoria, Australia, and Lead study investigator of CAPTIVATE MedicalResearch.com: What is the background for this study? Response: The Phase 2 CAPTIVATE (PCYC-1142) clinical trial evaluated 164 patients younger than 70 years (median age of 58 years) with previously untreated CLL/SLL. Patients were planned to receive ibrutinib for 3 cycles, followed by 12 cycles of ibrutinib and venetoclax in combination. Ninety percent of patients was able to complete the planned therapy. MRD status was evaluated in PB after 6, 9, and 12 cycles and in BM after 12 cycles of the combination.

06 Dec

Posted at 15:27h in Author Interviews, Cancer Research, Lymphoma
MedicalResearch.com Interview with: [caption id="attachment_52370" align="alignleft" width="200"]Dr. Matthew S. Davids MD MSC Associate Director of the Dana-Farber CLL Center Attending physician Lymphoma Program, Division of Hematologic Malignancies Dana-Farber Dr. Davids[/caption] Dr. Matthew S. Davids MD MSC Associate Director of the Dana-Farber CLL Center Attending physician Lymphoma Program, Division of Hematologic Malignancies Dana-Farber [caption id="attachment_52369" align="alignleft" width="150"]Dr. Jennifer Crombie MD Instructor in Medicine Harvard Medical School  Dr. Crombie[/caption]   Dr. Jennifer Crombie MD Instructor in Medicine Harvard Medical School    MedicalResearch.com: What is the background for this study? Response: New data from our investigator-sponsored Phase 1 study exploring duvelisib in combination with venetoclax will be presented at ASH on December 7. In relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), duvelisib plus venetoclax demonstrated promising clinical activity, a manageable tolerability profile, and identified a recommended Phase 2 dosing (RP2D) regimen.