Hematology, Leukemia / 02.07.2024

bone-marrow-aspirateBone marrow aspiration is a medical procedure where a small amount of the liquid part of your bone marrow is removed for examination. A bone marrow aspirate can be essential in diagnosing and monitoring various conditions affecting your blood cells, such as anemia, leukemia, and infections. Understanding this procedure can provide insight into why your doctor may recommend it and what to expect. During a bone marrow aspiration, your healthcare provider will take a sample using a needle inserted into a larger bone, typically the hip. The process is usually performed alongside a bone marrow biopsy, which involves taking a small amount of solid bone marrow tissue. These procedures can yield valuable information about the health and functionality of your bone marrow. Preparation for bone marrow aspiration involves a few straightforward steps to ensure your comfort and safety. Knowing the potential risks and benefits can help you feel more at ease and prepared for this critical diagnostic tool. (more…)
Author Interviews, Genetic Research, Hematology / 08.12.2020

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Hematology / 25.06.2020

MedicalResearch.com Interview with: TakedaDr. med. Wolfhard Erdlenbruch, M.D. Vice President Head of Global Medical Affairs Hematology MedicalResearch.com: What is the background for this study? Response: At the World Federation of Hemophilia Virtual Summit 2020 (WFH 2020), results were presented from a real-world, post-marketing surveillance study aimed to evaluate the safety and effectiveness of RIXUBIS® in adult and pediatric patients with hemophilia B in South Korea, entitled “Safety and Effectiveness of Rixubis in Patients with Hemophilia B in South Korea: A Real-World, Prospective, Post-marketing Surveillance Study”. Data from the study demonstrate the safety and efficacy profile of RIXUBIS® for treatment of bleeds, perioperative/surgery, and prophylaxis in adult and pediatric patients with hemophilia B in the real-world setting in South Korea. The study showed that 86.6% (123/142) of hemostatic effectiveness assessments for RIXUBIS® were reported as good or excellent, and of the 11 adverse events reported, all were mild in severity, with 10 resolved/recovered events not related to RIXUBIS®, and one event (inhibitory antibody development) unconfirmed.1 RIXUBIS® [Nonacog gamma, recombinant FIX concentrate] is a recombinant coagulation factor IX product, indicated for the control and prevention of bleeding episodes in patients with hemophilia B. (more…)
Author Interviews, Cancer Research, Leukemia / 11.12.2019

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Hematology, Lymphoma / 10.12.2019

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Hematology, Lymphoma / 10.12.2019

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. 
(more…)
Author Interviews, Biomarkers, Hematology, Transplantation / 09.12.2019

MedicalResearch.com Interview with: Hrishikesh Srinagesh MD The Tisch Cancer Institute at Mount Sinai MedicalResearch.com: What is the background for this study? Response: Graft-versus-host disease (GVHD) is the leading cause of non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT). Acute GVHD occurs in approximately 50% of HCT patients and targets the skin, liver, and gastrointestinal tract primarily. The change in clinical symptoms (e.g. reduction in volume of diarrhea) is used as the primary endpoint in most trials of acute GVHD treatment, but more accurate metrics are needed to predict long-term survival. Over the past decade, the Mount Sinai Acute GVHD International Consortium (MAGIC) has studied two biomarkers important in GVHD pathogenesis: suppressor of tumorigenesis 2 (ST2) and regenerating islet-derived 3 alpha (REG3). These proteins are shed into the bloodstream when the gastrointestinal tract is damaged during GVHD, the most lethal form of acute GVHD. The concentrations of ST2 and REG3 can be used generate an individual’s estimated probability of 6 month NRM known as the MAGIC Algorithm Probability (MAP). Our study evaluated whether the MAP measured at the start of GVHD treatment and four weeks later could predict long-term survival and we compared the MAP to clinical response after four weeks, the gold standard of response.  (more…)
Author Interviews, Hematology, Lymphoma / 07.12.2019

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Hematology, NEJM / 07.09.2018

MedicalResearch.com Interview with: Dr. Johnny Mahlangu  MBBCh Faculty of Health Sciences University of the Witwatersrand and National Health Laboratory Service Johannesburg, South Africa MedicalResearch.com: What is the background for this study? What are the main findings? Response: Current unmet needs in patients with haemophilia without inhibitors are the high disease burden imposed by the frequent injections which have to be given intravensously . Emicizumab which is given subcutaneously weekly or fortnightly aims to address these unmet needs. (more…)
Abuse and Neglect, Hematology, Lancet, Medical Imaging, Transplantation / 07.03.2018

MedicalResearch.com Interview with: Kirsten Williams, M.D. Blood and marrow transplant specialist Children’s National Health System  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: This study addressed a life-threatening complication of bone marrow transplantation called bone marrow failure. Bone marrow transplantation has provided a cure for patients with aggressive leukemias or acquired or genetic marrow dysfunction. The process of bone marrow transplantation involves giving chemotherapy and/or radiation, which removes the diseased blood cells from the bone marrow. After this, new bone marrow stem cells are infused from a healthy individual. They travel to the bone marrow and start the slow process of remaking the blood system. Because these new cells start from infancy, it takes upwards of four to five weeks for new mature healthy cells to emerge into the blood, where they can be identified. Historically, there has been no timely way to determine if the new cells have successfully repopulated unless they can be seen in the blood compartment. This condition of bone marrow failure is life-threatening, because patients don't have white blood cells to protect them from infection. Once bone marrow failure is diagnosed, a second new set of stem cells are infused, often after more chemotherapy is given. However, for many individuals this re-transplantation is too late, because severe infections can be fatal while waiting cells to recover. We were the first group to use a new imaging test to understand how the newly infused bone marrow cells develop inside the patient. We have recently published a way to detect the new bone marrow cell growth as early as five days after the cells are given. We used an investigational nuclear medicine test to reveal this early cell growth, which could be detected weeks before the cells appear in the blood. This radiology test is safe, does not cause any problems and is not invasive. It is called FLT (18F-fluorothymidine) and the contrast is taken up by dividing hematopoietic stem cells. The patients could even see the growth of their new cells inside the bone marrow (which they very much enjoyed while waiting to see recovery of the cells in their blood). We could use the brightness of the image (called SUV) to determine approximately how many weeks remained before the cells were visible in the blood. Finally, we actually could see where the new cells went after they were infused, tracking their settling in various organs and bones. Through this, we could see that cells did not travel directly to all of the bones right away as was previously thought, but rather first went to the liver and spleen, then to the mid-spine (thorax), then to the remainder of the spine and breastplate, and finally to the arms and legs. This pattern of bone marrow development is seen in healthy developing fetuses. In this case, it occurs in a similar pattern in adults undergoing bone marrow transplant. (more…)
Author Interviews, Cancer Research, Hematology / 21.12.2017

MedicalResearch.com Interview with: janseen-oncologyMaria-Victoria Mateos, MD, PhD University Hospital of Salamanca/IBSAL Salamanca, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Phase 3 ALCYONE study data showed DARZALEX (daratumumab) in combination with bortezomib, melphalan, and prednisone (VMP) significantly improved clinical outcomes, including reducing the risk of disease progression or death by 50 percent, in newly diagnosed patients with multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT) at a median follow-up of 16.5 months (Hazard Ratio [HR] = 0.50; 95 percent CI [0.38-0.65], p<0.0001). The median progression-free survival (PFS) for DARZALEX-VMP had not yet been reached, compared to an estimated median PFS of 18.1 months for patients who received VMP alone. In addition to reducing the risk of disease progression or death, DARZALEX significantly improved the overall response rate (ORR) as compared to VMP alone, including more than doubling rates of stringent complete response, significantly improved rates of very good partial response or better and complete response or better (CR). The most common (≥10 percent) Grade 3/4 treatment-emergent adverse events (TEAEs) for DARZALEX-VMP vs. VMP were neutropenia (40 percent vs. 39 percent), thrombocytopenia (34 percent vs. 38 percent), anemia (16 percent vs. 20 percent) and pneumonia (11 percent vs. 4 percent). One patient in each arm discontinued treatment due to pneumonia, and 0.9 percent of patients discontinued DARZALEX due to an infection. Twenty-eight percent of patients experienced infusion reactions (IRs) due to DARZALEX.. In the DARZALEX-VMP arm, 42 percent of patients experienced a serious adverse event (SAE), compared to 33 percent in the VMP arm. The study findings were as a late-breaking abstract (Abstract #LBA-4) at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta, and simultaneously published in the New England Journal of Medicine (NEJM). (more…)
Author Interviews, Hematology / 16.12.2017

MedicalResearch.com Interview with: Dr. Charles T. Nakar, MD Indiana Hemophilia and Thrombosis Center Pediatrics Indianapolis, IN   MedicalResearch.com: What is the background for this study? Response: Congenital plasminogen deficiency is a rare genetic disorder that is caused by mutations in the PLG gene. Mutations in this gene lead to clinical manifestations such as fibrinous deposits on mucous membranes leading to disruption of tissue or organ function. These symptoms, when untreated, lead to significant morbidity and decreased quality of life. Life-threatening episodes may occur especially when the respiratory system is affected. There is currently no established approach to treatment of type 1 plasminogen deficiency and the available topical and systemic therapies (e.g. FFP, corticosteroids, immunomodulatory drugs, anticoagulants, amongst others) lack consistent efficacy. Patients may undergo multiple surgeries to remove lesions, but this approach typically leads to regrowth of lesions. Prometic’s intravenous plasminogen replacement therapy represents the first direct treatment for this serious disorder. (more…)
Author Interviews, Cancer Research, Hematology, NEJM / 15.12.2017

MedicalResearch.com Interview with: Dr. Meletios A. Dimopoulos MD Professor and Chairman Department of Clinical Therapeutics University Athens School of Medicine Athens, Greece MedicalResearch.com: What is the background for this study? What are the main findings? Response: Updated data from the Phase 3 POLLUX trials showed DARZALEX, in combination with lenalidomide and dexamethasone, reduced the risk of disease progression or death by 56 percent, compared to lenalidomide and dexamethasone alone (Hazard Ratio [HR]=0.44; 95 percent CI [0.34-0.55], p<0.0001). After a median follow-up of 32.9 months, the median progression-free survival (PFS) in the DARZALEX arm has not been reached, compared with a median PFS of 17.5 months for patients who received lenalidomide and dexamethasone alone. DARZALEX in combination with lenalidomide and dexamethasone also significantly increased the overall response rate (ORR) compared to lenalidomide and dexamethasone alone (93 percent vs. 76 percent, p<0.0001), including rates of complete response (CR) or better (55 percent vs. 23 percent, p<0.0001). DARZALEX also showed significantly higher (>3-fold) MRD-negative rates compared to lenalidomide and dexamethasone alone. These data were featured as an oral presentation (Abstract #739) at the 59th American Society of Hematology (ASH) Annual Meeting in early December. (more…)
Author Interviews, Hematology / 13.12.2017

MedicalResearch.com Interview with: Craig C. Hofmeister, MD, MPH The Ohio State University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Preliminary data presented from the randomized, open-label, Phase 2 CENTAURUS (SMM2001) study evaluated three dosing schedules for DARZALEX monotherapy in patients with intermediate or high-risk smoldering multiple myeloma. A total of 123 patients were enrolled, with a median time since initial smoldering multiple myeloma diagnosis of 6.83 months (0.4-56). Patients were randomized to one of three treatment arms receiving DARZALEX 16 mg/kg intravenously in 8-week cycles: 1.) a long-intense dosing schedule (LONG) where DARZALEX was administered weekly in Cycle 1, every other week in Cycle 2-3, every 4 weeks in Cycle 4-7, and every 8 weeks up to Cycle 20; 2.) an intermediate dosing schedule (INT), where DARZALEX was given weekly for 1 cycle, and every 8 weeks up to Cycle 20 and; 3.) a short intense dosing schedule (SHORT), where DARZALEX was given weekly for 1 cycle. Results from the study showed DARZALEX monotherapy had a tolerable safety profile in patients with intermediate or high-risk smoldering multiple myeloma, with the most common treatment-emergent adverse events (TEAEs) being fatigue, cough, headache and insomnia. The efficacy endpoints included overall response rate, progression free survival, time to next treatment, and overall survival rate at 4 years. These study results serve as the basis for a Phase 3 study for DARZALEX in smoldering multiple myeloma, which is actively enrolling. These findings demonstrated DARZALEX had a manageable safety profile in patients with intermediate or high-risk smoldering multiple myeloma. (more…)
Author Interviews, Cost of Health Care, Hematology / 28.11.2017

MedicalResearch.com Interview with: Carol Mansfield, PhD, Senior Research Economist Health Preference Assessment RTI Health Solutions www.rtihs.org  MedicalResearch.com: What is the background for this study? Response: As the most prevalent form of leukemia, chronic lymphocytic leukemia (CLL) affects approximately 130,000 people in the United States. More than 20,000 new cases are diagnosed each year. In recent years, more treatment options–each with its own associated benefits, side effects, and price tag–have been approved. This leaves patients and physicians with a variety of factors they must consider when choosing a treatment plan. While every patient wants the most effective drug with the fewest side effects, most people don’t have that option available. By asking patients to make tradeoffs and rank their preferences, we can form an understanding of how patients approach their treatment. This study showed that patients with CLL value medicines that provide the longest progression-free survival, but are willing to trade some benefits for a lower risk of serious adverse events. Additionally, we found that cost clearly has an impact on which treatment a patient would choose. When patients get prescribed something they can’t afford, they are forced to make very difficult choices. (more…)
Author Interviews, Gender Differences, Hematology, JAMA / 17.10.2017

MedicalResearch.com Interview with: Rutger Middelburg, PhD Assistant Professor in clinical epidemiology Sanquin Research and LUMC  MedicalResearch.com: What is the background for this study? Response: Six years ago we found transfusions from female donor to be associated with increased mortality among male recipients, especially under 50 years of age. This was an unexpected observation and we considered the probability of a false positive finding (i.e. a chance association) to be relatively high. We therefore immediately started a follow-up study with two main objectives. First, we wanted to confirm our findings in an independent and much larger cohort. Second, since some complications of blood transfusion are known to be related to pregnancy history of the donor, we wanted to study a possible relationship with previous pregnancy of the blood donors. (more…)
Author Interviews, Hematology, Lancet / 09.04.2017

MedicalResearch.com Interview with: Dr. med. Kathleen Selleng, OÄ, QB Hämotherapie Universitätsmedizin Greifswald Institut für Immunologie und Transfusionsmedizin, Abt. Transfusionsmedizin Sauerbruchstraße Greifswald Deutschland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Red blood cell concentrates (RBCs) of blood group O RhD negative are frequently used as universal blood for emergency transfusions in patients with unknown blood type. This leads to an over-proportional use of these red blood cell concentrates and regular shortages of O RhD negative RBCs. Due to these shortages, patients with known RhD negative blood type sometimes have to be transfused with RhD positive RBCs. The present study shows that the overall risk to induce an anti-D by transfusing all emergency patients with unknown blood type with O RhD positive RBCs is in the range of 3 to 6%, while this risk is much higher (20-30%) in RhD negative patients which have to be transfused with RhD positive RBCs due to RhD negative RBC shortages. (more…)
Anemia, Author Interviews, Genetic Research, Hematology / 27.10.2016

MedicalResearch.com Interview with: Peter M. Glazer, MD, PhD Robert E. Hunter Professor of Therapeutic Radiology and Professor of Genetics; Chair, Department of Therapeutic Radiology Yale University MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is generally recognized that gene editing in blood stem cells could provide a strategy for treatment of inherited disorders such as sickle cell disease and thalassaemia. Recent excitement has focused on CRISPR/Cas9 technology because of it is so easy to use. However, the CRISPR approach introduces an active DNA cutting enzyme into cells, which can lead to off-target cuts in the genome. As an alternative, we have pursued triplex-forming peptide nucleic acids (PNAs) designed to bind site-specifically to genomic DNA via strand invasion and formation of PNA/DNA/PNA triplexes. PNAs consist of a charge-neutral peptide-like backbone and nucleobases enabling hybridization with DNA with high affinity. PNA/DNA/PNA triplexes recruit the cell’s own DNA repair machinery to initiate site-specific editing of the genome when single-stranded ‘donor DNAs’ are co-delivered as templates containing the desired sequence modification. We found that triplex-forming PNAs substituted at the gamma position yielded high levels of gene editing in blood stem cells in a mouse model of human β-thalassaemia. Injection of thalassemic mice with nanoparticles containing gamma PNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood hemoglobin levels into the normal range and up to 7% β-globin gene correction in stem cells, with extremely low off-target effects. We conclude that the combination of nanoparticle delivery and next generation PNAs may offer a minimally invasive treatment for genetic disorders of the blood that can be achieved safely and simply by intravenous administration. (more…)
Author Interviews, Hematology, NEJM / 11.02.2016

MedicalResearch.com Interview with: Dr. Filip Callewaert PhD Senior Clinical Scientist Clinical Development, Ablynx Zwijnaarde, Belgium Medical Research: What is the background for this study? What are the main findings? Dr. Callewaert: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening coagulation disorder, in which accumulation of ultra-large von Willebrand factor (ULvWF) multimers is implicated, leading to an increased risk of thrombus formation in small blood vessels due to excessive platelet aggregation. There are no approved pharmacological therapies for acquired TTP. Despite treatment with the current standard of care (plasma exchange and immunosuppressive therapy), mortality remains at 10-20% and there is significant neurological, cardiac, and renal morbidity. Caplacizumab is a bivalent Nanobody that binds to the A1 domain of vWF thereby preventing vWF-mediated platelet aggregation. The clinical effects of caplacizumab were demonstrated in the phase II randomised, placebo-controlled TITAN study in 75 patients with acquired TTP. Compared to placebo, there was a nearly 40% reduction in median time to platelet count normalisation in the caplacizumab group (p = 0.005). Treatment with caplacizumab reduced the use of daily plasma exchange and prevented further consumption of platelets in microthrombi and small blood vessel occlusion. In addition, there were fewer recurrences of TTP requiring re-initiation of daily plasma exchange during treatment with caplacizumab (N=3) vs. placebo (N=11). The safety profile of caplacizumab was favorable, with a slightly higher tendency of mostly mild bleeding events.  (more…)
Author Interviews, Cancer Research, JAMA / 09.03.2015

Prof. Sigurdur Y Kristinsson Professor of Hematology University of IcelandMedicalResearch.com Interview with: Prof. Sigurdur Y Kristinsson Professor of Hematology University of Iceland MedicalResearch: What is the background for this study? What are the main findings? Prof. Kristinsson: Multiple myeloma is always preceded by a precursor condition called monoclonal gammopathy of undetermined significance (MGUS). MGUS is characterized by a detectable monoclonal protein in persons without evidence for end-organ damage or other related plasma cell or lymphoproliferative disorders. MGUS is very common and is detected in approximately 5 percent of persons 70 years or older. However, only a small proportion of MGUS progresses to a malignant disorder, in fact the annual risk of progression to multiple myeloma or other related disorders is on average 1 percent, with varying risks according to risk groups. Current guidelines suggest, depending on the individual patient’s clinical risk score, life-long monitoring of MGUS individuals to detect progression to multiple myeloma or related disorders. At this time, the impact of annual monitoring on the outcome of patients who eventually develop multiple myeloma is unclear. Using high-quality population-based data from Sweden, we estimated the impact of prior knowledge of MGUS diagnosis and comorbidities on multiple myeloma survival, by performing a large population-based study using data on more than 14,000 multiple myeloma patients diagnosed in Sweden 1976-2005, with follow-up through 2007. The hypothesis that detection and follow-up of MGUS may influence survival in multiple myeloma is unlikely to ever be tested in a prospective clinical study due to the large sample size required with long follow-up time, and consequent extreme costs. We found that multiple myeloma patients with prior knowledge of MGUS had significantly 15% better survival, despite having significantly more comorbidities. Interestingly, low-risk MGUS (with very low M-protein) had highest risk of death. The observation that low M-protein concentration at MGUS diagnosis was associated with poorer multiple myeloma survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in MGUS, regardless of risk stratification. (more…)