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Видео добавленное пользователем “VJHemOnc – Video Journal of Hematological Oncology”
How to manage monoclonal gammopathy of undetermined significance (MGUS)
 
02:02
Niels van de Donk, MD, PhD of VU University Medical Center, Amsterdam, Netherlands discusses monoclonal gammopathy of undetermined significance (MGUS) at the 2016 European Multiple Myeloma Academy (EMMA) in Madrid, Spain. MGUS is a very common disorder, the incidence increases with age and patients are generally asymptomatic. It is important for clinicians to check whether there has been transformation towards malignancy, such as myeloma or lymphoma. In addition, Dr van de Donk explains that it is necessary to check if the patient has developed systemic manifestations that are attributable to the monoclonal protein (M protein), which is generated by the plasma cell disorder. The M protein can either deposit in tissues and cause tissue damage or function as an autoantibody, binding to cells and causing tissue damage through this mechanism. In this case, it is important to treat the plasma cell disorder to stop the M protein-related tissue damage and allow the patient to recover. This programme has been supported by Celgene and Amgen through an unrestricted educational grant to the Video Journal of Hematological Oncology.
Is CLL curable today?
 
03:22
Michael Hallek, MD from the University of Cologne, Cologne, Germany discusses the debate around whether chronic lymphocytic leukemia (CLL) is curable. Prof Hallek argues that it is possible to cure CLL patients and points out that allogeneic stem cell transplants cure approximately 30-40% of patients. In terms of non-transplant therapies, there is evidence that long-term remission is achievable. Some patients who have received FCR (fludarabine, cyclophosphamide, rituximab) remain in remission after many years and can be categorized according to their IGHV mutation status, whereby IGHV-mutated patients have a good prognosis. Within the group of IGHV-mutated patients, patients with trisomy 12, 13q deletion and 11q deletion, benefit particularly highly from FCR chemoimmunotherapy and some might call this group of patients cured according to Prof Hallek. He further discusses the combination of venetoclax with antibodies as well as triplet combinations and minimal residual disease (MRD) negative remission, which has been observed in some patients treated with these newer therapies. Recorded at the European Hematology Association (EHA) 2016 Annual Congress in Copenhagen, Denmark.
How far are we from a cure for CLL?
 
03:48
Thomas Kipps, MD from the University of California, San Diego, CA, discussed the current treatment landscape in chronic lymphocytic leukemia (CLL), considering the novel therapies being presented at the American Society of Hematology (ASH) 2015 Annual Meeting.
Advances in low grade lymphoma over the past 40 years
 
02:06
Nathan Fowler, MD from the University of Texas MD Anderson Cancer Center, Houston, TX talks about the history of chemotherapy and advances in low grade lymphoma. Dr Fowler explains that in the last 30-40 years, we have seen an improvement in survival of patients with low grade lymphoma every decade and today, most patients will never die of follicular lymphoma. He points out that we now have to pay attention to long-term toxicity and the financial burden associated with the new drug regimens. Dr Fowler also mentions how new regimens such as lenalidomide, rituximab, and ibrutinib may ultimately lead to a cure or prolonged remissions. Recorded at the 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA.
Promising approaches and clinical trials in MDS
 
01:56
A number of promising therapeutic approaches are under investigation for the treatment of myelodysplastic syndromes (MDS). We got on update on these exciting developments from David Steensma, MD, of the Dana-Farber Cancer Institute, Boston, MA, at the 2018 Society of Hematologic Oncology (SOHO) Annual Meeting, held in Houston, TX. Dr Steensma highlights the potential combination of hypomethylating agents with immunotherapies such as checkpoint inhibitors, or the BCL2 inhibitor venetoclax. He also expresses his excitement for the telomerase inhibitor imetelstat and APR-246, which targets p53, before briefly mentioning the potential for CAR T-cells in MDS.
The power of venetoclax
 
05:52
Claire Dearden, MBBS, MD, FRCP, FRCPath from the Royal Marsden Hospital, London, UK discusses the latest drug in CLL treatment, venetoclax at the 2017 British Society for Hematology (BSH) Annual Scientific Meeting in Brighton, UK. There are various regulations in place for venetoclax before it can be administered to a patient such as, the patient must have failed or is intolerant to alternative therapy involving B-cell receptor inhibitors. Response rates for venetoclax are very high and can even result in MRD negative responses. The administration of venetoclax results in the unblocking of BCL-2, causing rapid cell apoptosis. This in turn releases a high volume of chemicals into the body, left untreated this can result in tumor lysis syndrome (TLS). Therefore, it is crucial that administration of treatment is gradual as to mitigate the TLS risk. This video has been supported by Napp Pharmaceuticals Ltd through an unrestricted educational grant to Magdalen Medical Publishing.
CAR T-cells and CRISPR: The future of AML treatment
 
03:39
New and invigorating methods of tackling acute myeloid leukemia (AML) are being researched at present. In this interview, Saar Gill, MD, PhD from the University of Pennsylvania, Philadelphia, PA talks about his research into AML, which focuses on CD33 and CD123 using CAR T-cell therapy. Dr Gill discusses the current issues with this therapy and provides an overview of how his group is planning to overcome these problem by utilising CRISPR-Cas9. This interview was recorded at the International Conference of Acute Myeloid Leukaemia 2017, Estoril, Portugal by the European School of Hematology (ESH).
What can be learnt about using interferon in patients with myelofibrosis?
 
02:28
Treating patients who suffer from myelofibrosis with interferon used to be considered inappropriate due to the drug being poorly tolerated. Now, speaking from the American Society of Hematology (ASH) 2017 Annual Meeting and Exposition, held in Atlanta, GA, Jean-Jacques Kiladjian, MD, PhD, of Saint-Louis Hospital & Paris Diderot University, Paris, France, explains the promising long-term outcomes of this treatment. Prof. Kiladjian highlights the results observed in patients with myelofibrosis being treated with pegylated interferon alpha-2a, which were acquired from the French Intergroup of myeloproliferative neoplasms (FIM) study.
Mechanism of action of daratumumab
 
02:03
Niels van de Donk, MD, PhD, from the University Medical Center, Amsterdam, Netherlands discusses the use and mechanism of action of daratumumab. Daratumumab is an anti-CD38 targeting antibody and has shown high activity in end stage patients with multiple myeloma (MM). Dr van de Donk further explains that it has been shown to eliminate CD38 positive immune suppressor cells. This means that a sub-population of regulatory T-cells, which are CD38 positive, are killed during daratumumab therapy. According to Dr van de Donk, CD38 high regulatory T-cells are very immunosuppressive and the elimination of these kinds of cells by daratumumab, is thought to be important as it allows the immune system to recover. Recorded at the Myeloma 2016 meeting held in Boston, MA.
AL amyloidosis and a critical, early diagnosis
 
06:47
Giampaolo Merlini, MD of Fondazione IRCCS Policlinico, San Matteo Pavia, Italy gives an overview of his talk on light-chain amyloidosis or AL amyloidosis at the 2016 European Multiple Myeloma Academy (EMMA) in Madrid, Spain. Although it is a rare disease, it represents 12–15% of patients with multiple myeloma (MM). Further, there is a condition called primary AL amyloidosis, where there is a small clone in the bone marrow that produces a protein (a light chain) with an abnormal confirmation and, due to this, the protein tends to aggregate; it can move to the kidney, heart and other organs where it causes progressive dysfunction and damage. It is possible to recover completely if intervention occurs in time; early diagnosis can change the outlook for the patient. Therefore, time is of the essence, as Dr Merlini explains, and it is vital for doctors to consider that their patient may be affected. Dr Merlini further highlights how this concerns the management of monoclonal gammopathy of undetermined significance (MGUS) patients. Dr Merlini further outlines how the diagnosis is made and that there are several proteins that can cause systemic amyloidosis. The second-most common one is produced by the liver; it is called transthyretin and can also affect the heart, in particular, in older men (known as wild-type ATTR amyloidosis). The available treatments now are extremely powerful, according to Dr Merlini. The treatment of AL amyloidosis is the most successful treatment of all types of amyloidosis because it is possible to suppress the production of the proteins that is causing the disease with drugs. Therefore, the production of light chains is stopped and this usually translates into very rapid improvement in the clinical condition of the patient. If the treatment is started early, organ dysfunction can be recovered and survival is extended; more than 30% of patients survive more than 10 years, which was unthinkable a few years ago. Further, the same drug that is used for treatment is also being developed in myeloma as the clone is very similar. This programme has been supported by Celgene and Amgen through an unrestricted educational grant to the Video Journal of Hematological Oncology.
Major breakthroughs in AL amyloidosis treatment from ASH 2017
 
04:12
Several major breakthroughs in the treatment of amyloid light-chain (AL) amyloidosis were presented at the American Society of Hematology (ASH) 2017 Annual Meeting and Exposition in Atlanta, GA. In this interview, Laurent Garderet, MD, PhD, of Saint Antoine Hospital, Paris, France, provides an overview of the exciting updates from the meeting, including new understanding of the disease, promising new treatment results with daratumumab and what these advances mean for amyloidosis treatment.
CLL therapy - current status and issues
 
02:55
John Pagel, MD, PhD of the Swedish Cancer Institute, Seattle, WA provides an overview of an educational session on the current issues in therapeutic endeavors for chronic lymphocytic leukemia (CLL) at the American Society of Oncology (ASCO) 2016 Annual Meeting held in Chicago, IL. The current status of CLL therapy was discussed with a focus on using different agents for different patients. For example, chemoimmunotherapy may not be appropriate for elderly or unfit patients but provides a major benefit for younger, fit patients in terms of long-term survival without additional therapy. For patients who cannot receive immunotherapy, the option of using drugs such as ibrutinib (a BTK inhibitor), idelalisib, acalabrutinib and TGR-1202 was discussed. According to Dr Pagel, there are open questions with regard to the use of these agents, such as length of therapy, whether therapy can be stopped and started again at a later stage and how and if to sequence these agents as well as how to overcome to resistance and Richter syndrome.
Monoclonal gammopathy of unknown significance (MGUS) & importance of regularly monitoring patients
 
01:18
Irene Ghobrial, MD, of Dana-Farber Cancer Institute, Boston, MA, discusses monoclonal gammopathy of unknown significance (MGUS). It is known that 3% of the population over the age of 50 have MGUS and for many patients it is completely asymptomatic. However, there are patients who actually experience problems, these include: neuropathy, fatigue, nephropathy, and monoclonal gammopathy of renal significance (MGRS). There are still questions around how to follow up patients with MGUS and whether these patients should be followed up regularly or not. There is evidence that suggests that following these patients regularly can potentially prevent multiple myeloma (MM) from suddenly occurring and prevent end organ damage. Recorded at the 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA.
Panel discussion on immune therapies for lymphoma - CAR T-cell therapy and the question of cure
 
15:44
Anas Younes, MD of Memorial Sloan Kettering Cancer Center, New York, NY discusses immune therapies for lymphoma with David Maloney, MD, PhD of Seattle Cancer Care Alliance, Seattle, WA, James Kochenderfer, MD of the National Cancer Institute, Bethesda, MD and Nathan Fowler, MD of the University of Texas MD Anderson Cancer Center, Houston, TX. Prof. Maloney talks about the role of CAR T-cells for B-cell and Hodgkin lymphoma. He explains that they are seeing encouraging response rates with anti-CD19 CAR T-cell therapy for lymphoma, with an approximately 50% complete remission rate in aggressive lymphomas, and overall response rates as high as 80%. Dr Kochenderfer talks about the data he presented; they treated patients with a low-dose chemotherapy conditioning regimen followed by anti-CD19 CAR T-cell therapy. The overall response rate in advanced lymphoma was 73%, with 55% complete remission (CR) and some responses have been durable. Dr Kochenderfer points out that these patients would not have alternative treatment options. They also discuss minimal residual disease (MRD) in this context. Dr Fowler talks about the developments in the field in terms of therapy. He points out that since the introduction of rituximab, they have been looking for new potential targets. He explains that we are seeing nice responses with therapies targeting CD19 with conjugated antibodies, monoclonal antibodies, BiTEs and DARTs. He also discusses other potential targets. Next, discuss lymphodepletion and Dr Kochenderfer talks about a trial with a fully human anti-CD19 CAR T-cell therapy. Further, the discuss targets for CAR T-cell therapy, such as ROR1, BCMA, and CD30. They then talk about PD-1/PD-L1 targeted agents for lymphoma and treatment duration. Finally, they talk about CR and whether some patients are cured with therapy. Recorded at the 2016 International Workshop on Non-Hodgkin Lymphoma (iwNHL) meeting held in San Diego, CA.
The significance of FLT3 mutations in AML
 
01:39
Ali Bazarbachi, MD, from the American University of Beirut, Beirut, Lebanon provides an overview of FLT3 mutations in acute myeloid leukemia (AML) at the 2016 Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) in Valencia, Spain. FLT3 is a tyrosine kinase and FLT3 mutations are seen in over 30% of AML patients according to Prof Bazarbachi. FLT3 mutations are associated with a poor prognosis and currently, researchers are investigating the use of tyrosine kinase inhibitors to target FLT3 mutations.
A new era of treatment for elderly acute myeloid leukemia (AML) patients?
 
01:21
Hagop M. Kantarjian, MD of MD Anderson Cancer Center, Houston, TX discusses the new era of treatment for elderly acute myeloid leukemia (AML) patients at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. Up until the 80s, some leukemia experts argued that it is not worth treating elderly AML patients due to modest survival prolongation and low cure rates. Today, even among patients who cannot receive intensive chemotherapy, there are options including epigenetic therapy with azacitidine or decitabine, combinations with monoclonal antibodies such as venetoclax, and checkpoint inhibitors. According to Prof. Kantarjian these new strategies mean that we are entering a new era of low intensity therapy and targeted and immunomodulatory therapies that mean we can cure more elderly AML patients with less side effects.
Mechanism of action of proteasome inhibitors
 
04:05
Michel Delforge, MD, PhD from the University Hospital Leuven, Leuven, Belgium gives an overview of the mechanism of action of proteasome inhibitors. Prof Delforge gives a detailed outline of how the proteasome is targeted. He further discusses the different classes of proteasome inhibitors, i.e. the boronic acid derivatives (bortezomib, ixazomib), epoxyketone derivatives (carfilzomib, oprozomib) and salinosporamide derivatives (marizomib). Recorded at the 2016 World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France.
Erythromer, a nanoscale bio-synthetic artificial red cell
 
04:28
Press brief by Allan Doctor, MD of Washington University School of Medicine, St. Louis, MO, on erythromer (EM), a nanoscale bio-synthetic artificial red cell: proof of concept and In vivo efficacy results. Recorded at the 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA.
The use of CAR T-cells in multiple myeloma
 
09:48
The utilization of CAR T-cells for the treatment of multiple myeloma (MM) has great potential, with numerous different targets and production approaches. In this video, this exciting upcoming area is discussed by Adam Cohen, MD from the Abramson Cancer Center, Philadelphia, PA, Yi Lin, MD, PhD from the Mayo Clinic, Rochester, MD and Sabrina Prommersberger, PhD from the University Hospital Würzburg, Würzburg, Germany at the engaging Myeloma 2017 meeting in Edinburgh, UK. The experts summarize the promising findings of CAR T-cell clinical trials in MM patients thus far, including NCT02546167 and NCT02658929. Looking towards the future, the speakers discuss the next steps for the use of CAR T-cells in MM and what updates we can expect at the American Society of Hematology (ASH) 2017 annual meeting.
Mechanism of action of venetoclax (ABT-199) and its side effects
 
03:06
William Wierda, MD, PhD from the University of Texas MD Anderson Cancer Center, Houston, TX talks about venetoclax (ABT-199), which is a Bcl-2 inhibitor. Bcl-2 is an apoptosis regulator expressed in high levels in chronic lymphocytic leukemia (CLL) cells, and it is responsible for the prolonged survival of these cells. Venetoclax will block and modulate the activity of Bcl-2. Prof. Wierda also discusses the clinical trials and side-effects associated with this drug. Recorded at the American Society of Hematology (ASH) 2015 Annual Meeting, held in Orlando, FL.
Common side-effects of BTK inhibitors (ibrutinib and acalabrutinib) in the treatment of CLL
 
01:26
Peter Hillmen, MBChB, PhD from St. James' University Hospital, Leeds, UK, explains how Bruton's tyrosine kinase inhibitors, like ibrutinib and acalabrutinib (ACP-196), target chronic lymphocytic leukemia (CLL) cells and the common side-effects experienced by these drugs. Recorded at the American Society of Hematology (ASH) 2015 Annual Meeting, held in Orlando, FL.
Developments in therapies for AML - chemotherapy, targeted therapy and immunotherapy
 
04:20
Hagop M. Kantarjian, MD of MD Anderson Cancer Center, Houston, TX gives an overview of developments in therapies for acute myeloid leukemia (AML) at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. Prof. Kantarjian explains that we are in a revolutionary period for both acute lymphoblastic leukemia (ALL) and AML and we will see changes in how we treat and cure these diseases. In AML, we have reached a limit in terms of curing the disease with chemotherapy combinations such as 7+3 or the more intensive FLAG-Ida using high-dose cytarabine (Ara-C). Many targeted therapies as well as immunomodulatory strategies are available now. AML cells express CD33 and CD123 and monoclonal antibodies conjugated to toxins and antibody constructs can target these surface proteins. Further, patients may have FLT3, IDH1 or IHD2 abnormalities and inhibitors are available for these mutations. He further discusses the development of BCL-2 inhibitors, such as venetoclax (ABT-199), which in combination with epigenetic therapy or intensive chemotherapy shows promising results. In terms of the microenvironment, checkpoint inhibitors have also been shown to be active in hematologic malignancies. Further, there are new modified chemotherapy agents such as CPX-351 and vosaroxin, which may improve our ability to give chemotherapy more effectively. In conclusion, there are now several agents available and Prof. Kantarjian believes that their development will lead to an improvement in the cure rate of AML.
bb2121: bringing CAR T-cells into the multiple myeloma world
 
03:14
bb2121 is a chimeric antigen receptor (CAR) T-cell product targeting the B-cell maturation antigen (BCMA), which is universally expressed on plasma cells (myemola cells). At the European Hematology Association (EHA) 2017 meeting, Yi Lin, MD, PhD from the Mayo Clinic, Rochester, MN, presented the latest data from a multicenter study in patients with relapsed/refractory multiple myeloma.
Treatment-associated atrial fibrillation: ibrutinib-specific or class-specific?
 
05:20
Anthony Mato, MD, MSCE from the University of Pennsylvania, Philadelphia, PA presents the latest data from a cross-center study, investigating the incidence of ibrutinib-associated atrial fibrillation in chronic lymphocytic leukemia (CLL) patients. Up to 11% of patients receiving ibrutinib treatment will develop atrial fibrillation in the long term. By identifying those patients who are at a higher risk of developing this secondary condition, physicians can monitor patients and provide intervention when necessary. Dr Mato details the methods and results from this investigation. In addition, he goes on to discuss the incidence of atrial fibrillation following treatment with other classes of drugs in CLL. This interview was recorded at the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2017 held in New York, NY.
CAR T-cells vs. CAR NK-cells
 
02:31
Chimeric antigen receptor (CAR) T-cells have been a key focus in cancer research over recent years; however, T-cells are not the only cells into which it is possible to integrate a CAR. In this video, recorded at the 23rd Congress of the European Hematology Association (EHA) in Stockholm, Sweden, William Wierda, MD, PhD, of the MD Anderson Cancer Center, Houston, TX, discusses the recent creation of CAR NK-cells. He outlines the potential benefits of CAR NK-cells over CAR T-cells, explaining that toxicity from cytokine release is lower with CAR NK cells, and that CAR NK treatments do not have to be tailored to each specific patient, but can be cultivated in an ‘off-the-shelf’ manner.
Can we cure 50% of all multiple myeloma patients in the next five years?
 
01:32
Hervé Avet-Loiseau, MD, PhD from the Cancer Research Center of Toulouse, Toulouse, France talks about the progress that has been made in treatment of multiple myeloma (MM). According to Prof Avet-Loiseau, in five years from now, it may be possible to cure around 50% of patients with MM with intensive therapy. Recorded at the 2016 World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France.
Ropeginterferon alpha-2b as an effective treatment against PV
 
03:00
Polycythemia vera (PV), a disorder which results in the over-production of red blood cells, is commonly treated with the drug hydroxyurea. Jean-Jacques Kiladjian, MD, PhD from Saint-Louis Hospital and Paris Diderot University, Paris, France, talks about the results of PROUD-PV (NCT01949805), the first randomized trial to compare the efficacy of ropeginterferon alpha-2b against hydroxyurea, as a first-line treatment against PV. He also talks us through a second study, which focused on examining the effect of ropeginterferon and hydroxyurea treatment on mutated bone marrow cells, and their ability to restore normal hematopoiesis. This interview was filmed at the European Hematology Association (EHA) 2017 Annual Congress in Madrid, Spain.
Are CAR NK-cells the future of CLL therapy?
 
01:49
CAR T-cells have the potential to revolutionize tthe reatment of multiple hematological malignancies; however, they do not come without setbacks, as William Wierda, MD, PhD, of the MD Anderson Cancer Center, Houston, TX, explains. Therapies must be individually cultivated, which is time consuming and therefore dangerous in an aggressive disease, and the toxicities associated with CAR T-cells are considerable. Prof. Wierda discusses an alternative: CAR NK-cells. CAR NK-cell therapy appears, from early clinical trial data, to be highly effective and importantly, more tolerable than CAR T-cell therapy. This video was recorded at the 2018 Society of Hematologic Oncology (SOHO) Annual Meeting in Houston, TX.
Overview of CLL therapies and sequencing of therapies
 
09:00
Jacqueline Barrientos, MD of Northwell Health Cancer Institute, Lake Success, NY gives an overview of chronic lymphocytic leukemia (CLL) therapies and sequencing of therapies at the 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA. Dr Barrientos explains the importance of taking into account patient characteristics at the time of therapy; before therapy is started, it is important to check for TP53 mutation and 17p deletion as it affects the choice of therapy. For patients who do not tolerate ibrutinib, venetoclax is now available for patients with a 17p deletion or TP53 mutation; she also mention the use of idelalisib for this indication. For patients without these mutations, therapy choice depends on their characteristics and particularly their fitness. If they are fit, regimens such has fludarabine, cyclophosphamide, rituximab (FCR) should be considered. She further explains the complications associated with FCR therapy and explains the alternative, i.e. bendamustine-rituximab (BR). A trial that has finished accrual will compare FCR against ibrutinib in combination with rituximab and another trial will look at BR against ibrutinib in combination with rituximab or as monotherapy. She further explains the issues with targeted therapy, i.e. the question of discontinuation, and discusses the combinations of obinutuzumab with chlorambucil and ofatumumab with chlorambucil. She then outlines considerations behind sequencing therapies, including options for patients who relapse within the first three years and patients treated with tyrosine kinase inhibitors (TKIs). Further, she discusses data presented at ASH 2016 by Anthony Mato on venetoclax, ibrutinib and idelalisib and data on acalabrutinib and other new agents that are in the pipeline.
2 years on: Deborah discusses her venetoclax trial and becoming MRD negative
 
08:26
Deborah Henderson, chronic lymphocytic leukemia (CLL) patient advocate and journalist, and her doctor John Gribben, MD, DSc, FRCP, FRCPath, FMed Sci meet up during the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2017 held in New York, NY to discuss Deborah’s current CLL status. Two years after they first met, Deborah is now minimal residual disease (MRD) negative after taking part in a clinical trial (NCT01685892) of venetoclax in combination with obinutuzumab that was recommended to her by Prof. Gribben. The pair talk about Deborah’s treatment journey and experience so far, the importance of patient-doctor communication and touch on the idea of a future cure for CLL.
Long and deep responses to CAR T-cell therapies in multiple myeloma
 
02:43
CAR T-cells seem to be taking the hematology world by storm. Here. Rakesh Popat, MD, PhD from the University College London, London, UK talks to us about the different approaches being taken in multiple myeloma, such as the novel CAR T-cell construct bb2121, and a novel unnamed construct from Legend Biotech, both targeting the B-cell maturing antigen (BCMA). In the UK, Dr Rakesh's group is working on an different approach to targeting BCMA, by using APRIL, a natural bi-specific binding molecule of BCMA and TACI. Despite the deep and durable responses to this type of immunotherapy, side effects are still present and should be monitored closely.
Enhancing immunotherapy for CLL patients with ibrutinib
 
02:02
Meixiao Long, MD from the Ohio State University, Columbus, OH discusses his work on immune modulating therapies for chronic lymphocytic leukemia (CLL) at the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2017 held in New York, NY. His work is based on modulating T-cell immunity to essentially improve T-cell immunotherapy. Dr Long highlights some of his findings from his study on ibrutinib. His main finding is how ibrutinib can promote persistence of T-cells. This finding is not of any significance on its own. However if ibrutinib is combined with for e.g. tumour targeting T-cells such as CAR T-cells, it could definitely enhance the effect of this mode of immunotherapy and many others.
A decade of advances in multiple myeloma and unanswered questions
 
05:42
Vincent Rajkumar, MD, from the Mayo Clinic, Rochester, MN discusses the questions that remain at the heart of multiple myeloma (MM) research, and the absence of a cure based on his talk at the International Myeloma Workshop (IMW) 2017. Dr Rajkumar identifies the need to focus research and studies on these unanswered questions in the next decade. The field requires a movement that shifts the concept of multiple myeloma as one disease, when in fact it is an assortment of diseases, where each disease needs its own treatment plan. Also, it is important to set goals for future research in terms of finding a cure for multiple myeloma or simply controlling it. There is no benefit of research, however, if drugs that are approved and brought into the market are not affordable for a significant number of patients, mainly in developing countries. Moreover, further evaluation and identification of new endpoints is required to speed up drug development and approval. Lastly, physicians need to work together and get involved in developing clinical trials that answer these big strategic questions, that will eventually aid in conquering the disease. This interview was recorded at the 2017 World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France.
Overcoming the shortfalls of ibrutinib with fludarabine in CLL patientss
 
05:45
Inhye Ahn, MD from the National Institutes of Health, Bethesda, MD discusses the leading kinase inhibitor, ibrutinib, at the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2017 in New York, NY. Despite being a leading drug, Dr Ahn mentions some of the shortfalls of using ibrutinib as a single agent including the lack of deep response and the acquisition of drug resistance. Knowing this, a new Phase II study (NCT02514083) was designed using ibrutinib combined with a short course of fludarabine. Dr Ahn reports very encouraging results with an even reduction of the disease in systemic organs.
Current landscape and future directions for lower-risk MDS treatment
 
01:39
Speaking from the 2018 Society of Hematologic Oncology (SOHO) Annual Meeting, held in Houston, TX, David Steensma, MD, of the Dana-Farber Cancer Institute, Boston, MA, discusses the current treatment landscape for lower-risk myelodysplastic syndromes (MDS), as well as future directions for therapy. Dr Steensma highlights how the majority of low-risk MDS patients are treated with hematopoietic growth factors or lenalidomide, although certain patients will respond to immunosupressants and hypomethylating agents. He expresses his hopes for the potential of luspatercept, a recombinant fusion protein, as well as oral hypomethylating agents, the telomerase inhibitor imetelstat and splicing inhibitors.
Richter’s syndrome and its impact on CLL patients
 
02:08
Matthew Davids, MD, MMSc, from the Dana-Farber Cancer Institute, Boston, MA, discusses the poor outcomes of chronic lymphocytic leukemia (CLL) patients who develop Richter’s syndrome upon receiving treatment and describes a multi-institutional study evaluating a cohort of these patients and their remission rates, which were generally low, thereby highlighting a clear unmet medical need for these patients. There does appear to be some promise though, as highlighted by Prof. Davids, since a few patients did achieve complete remission. This interview was filmed at the American Society of Oncology (ASCO) 2017 Annual Meeting in Chicago, IL.
Asciminib: overcoming TKI resistance and reducing toxicity in CML
 
03:26
Asciminib, a new TKI, is being investigated in combination with imatinib in chronic phase chronic myeloid leukemia (CML) currently (NCT03578367). Timothy Hughes, MD, FRACP, FRCPA, of the Royal Adelaide Hospital, Adelaide, Australia, gives us an update on this exciting development here. Speaking from the 2018 Society of Hematologic Oncology (SOHO) Annual Meeting in Houston, TX, Prof. Hughes discusses the drug's mechanism of action; as an allosteric inhibitor of BCR-ABL, it is less susceptible to the typical mutations driving TKI resistance and is more specific so has a lower toxicity. He also explores where in the treatment sequence asciminib would be best placed.
An overview on NK/T-cell lymphoma treatment
 
01:58
Won Seog Kim, MD, PhD from Sungkyunkwan University, Seoul, South Korea gives an overview of his talk on the treatment of extranodal NK/T-cell lymphoma, nasal type (ENKTL). NK/T-cell lymphoma is very rare in western countries and is a newly discovered lymphoma compared to all the others. Therefore, very few treatments have been available specifically for NK/T-cell lymphoma, and have mainly been taken from strategies treating other lymphomas. This has resulted in poor outcomes. The introduction of asparingase, optimal inclusion of radiotherapies and not using anthracyclines, has resulted in better outcomes. He discusses new therapies such as immuno-oncology, check-point inhibitors and monoclonal antibodies targeting CD38. This interview was recorded at the International Conference on Malignant Lymphoma (ICML) 2017 in Lugano, Switzerland and has been supported by Napp Pharmaceuticals Ltd through an unrestricted educational grant to Magdalen Medical Publishing.
PDL1 and CD38 antigen expression in NSCLC
 
03:03
Torben Plesner, MD, from the Vejle Hospital and University of Southern Denmark, Vejle, Denmark, discusses antigen expression in non-small cell lung cancer (NSCLC) at the 2017 World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France. Patients with NSCLC that expresses PDL1 tend to have a better response with a PDL1 rather than chemotherapy. Expression of CD38 has been found to be associated with refractoriness, and removal of this antigen improves response to other treatments, such as checkpoint inhibitors. However, there is concern that less expression of CD38 increases resistance to daratumumab, but Dr Plesner explains that it will allow other treatments to come into play, it’s just a matter of finding the right one.
How can doctors help empower CLL patients?
 
09:38
Deborah Henderson, chronic lymphocytic leukemia (CLL) patient advocate and journalist, comes together with her doctor Constantine Tam, MBBS, MD, FRACP, FRCPA from the University of Melbourne, Melbourne, Australia and Matthew Davids, MD from Dana-Farber Cancer Institute, Boston, MA to discuss patient-doctor relationships. Deborah begins by asking the CLL experts how they handle patients who, like her, want to empower themselves with information regarding their condition. The panel talk about different ways that patients can educate themselves and how their doctor can assist them in evaluating and processing this information. This discussion highlights the importance of patients and doctors being able to collaborate and have open conversations together. This video was recorded at the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2017 held in New York, NY.
Do Philadelphia chromosome-positive ALL patients need a stem cell transplant?
 
03:27
Susan O'Brien, MD from the University of California, Irvine, CA discusses Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) and the question of stem cell transplantation at the American Society of Oncology (ASCO) 2016 Annual Meeting held in Chicago, IL. Historically, Ph+ ALL was considered one of the most high-risk ALLs as the disease always recurred. Allogeneic stem cell transplant was seen as the only possible cure, however, this was limited by factors such as age. Dr O'Brien explains how the outcome for Ph+ ALL and chronic myeloid leukemia (CML) patients was changed with the use of tyrosine kinase inhibitors (TKI) targeting the Philadelphia chromosome. The first commercially available TKI was imatinib followed by dasatinib. Dr O'Brien explains that these drugs have revolutionized the outcomes of these diseases; patients can achieve remission and it is also possible to get them into a minimal residual disease (MRD) state. In this context, Dr O'Brien discusses whether patients need to have stem cell transplants and an upcoming trial on the question.
Current treatment options for CLL
 
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John Gribben, MD, DSc, FRCPath, FMed Sci, from Barts Cancer Institute, London, UK discusses treatment options for CLL at the 2017 British Society for Haematology (BSH) Annual Scientific Meeting in Brighton, UK. The optimal way to treat a patient is in a clinical trial. If this is not possible, current guidelines state that patients without a p53 abnormality are candidates for FCR chemotherapy. Patients who also have an immunoglobulin mutation respond particularly well to FCR. Currently, in patients who do have p53 abnormalities, chemoimmunotherapy, BCR inhibitors, and ibrutinib are used, reserving venetoclax for patients who have failed or are intolerant to BCR inhibitors. Stem cell transplantation is currently less commonly used, and it is safe to defer, as long as there is a back up drug available if it fails. However, for patients that have already had chemoimmunotherapy, ibrutinib or venetoclax, there are limited options. The biggest challenge, however, is in treating patients with Richter’s transformation, as there are no current effective treatments. This video has been supported by Napp Pharmaceuticals Ltd through an unrestricted educational grant to Magdalen Medical Publishing.
Is gilteritinib the new breakthrough in the treatment of FLT3-mutated AML?
 
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Mark Levis, MD, PhD, from John Hopkins University, Baltimore, MD, USA, presents us with an insight on how gilteritinib, a next-generation FLT3 inhibitor, is superior over previous FLT3 inhibitors in treating FLT3-mutated acute myeloid leukemia (AML). He also details the difficulty in quantifying responses from patients with relapsed FLT3-mutated AML who have been treated with a single agent, but adds that his team have developed an assay using next-generation sequencing that has allowed them to overcome these issues. He concludes with a statement on the recent retrieval of Phase I/II trial data (NCT02014558) focused on the study of gilteritinib in treating FLT-mutated AML and adds that the drug is now undergoing Phase III trials. This interview was filmed at the European Hematology Association (EHA) 2017 Annual Congress in Madrid, Spain.
What is the potential of daratumumab in combination therapy for myeloma?
 
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Torben Plesner, MD, from the Vejle Hospital and University of Southern Denmark, Vejle, Denmark, discusses the efficacy and mechanism of the monoclonal antibody daratumumab as part of a combination therapy in treating advanced and refractory multiple myeloma (MM), at the 2017 World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France. He explains the importance of the immune modulatory mechanism of daratumumab in prolonging the survival of patients by activating immune cells to control disease development, without necessarily altering M-protein levels. Prof. Plesner highlights the advantage of this mechanism for use as part of a combination therapy with other immunomodulatory agents, and gives an overview of a recent randomized POLLUX study (NCT02076009) reporting favorable outcomes of treatment with daratumumab, lenalidomide and dexamethasone compared to treatment with lenalidomide and dexamethasone alone. Finally, he mentions he is awaiting the data from a new study using this combination therapy as a first-line treatment for elderly or non-transplant eligible patients. Prof. Plesner predicts that daratumumab in combination with lenalidomide and dexamethasone will become the new standard treatment regime for relapsed/refractory myeloma, particularly for patients who are ineligible for transplant.
How can plasma cell leukemia be managed?
 
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Saad Usmani, MD, FACP, from the Levine Cancer Institute, Charlotte, NC, discusses the management of the rare myeloma plasma cell leukemia at the 2017 World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France. He outlines the definition of plasma cell leukemia, and highlights that there is a very poor prognosis. Dr Usmani speaks about results of studies using new techniques including cytogenetic profiling, fluorescence in situ hybridization (FISH) and gene mutation panel analysis, with the aim of devising new treatment regiments. He introduces ongoing plasma cell leukemia clinical trials, and discusses the design and some of the results of these.
The Progression and Evolution of CLL: Mechanisms and Therapies
 
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Nicole Lamanna, MD, from Columbia University Medical Centre, New York, NY, provides an overview from the session on ‘Progression/Evolution of CLL: Mechanisms and Therapies’, which she co-chaired with Christopher Vakoc during the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2017 held in New York, NY. The session included presentations by leading chronic lymphocytic leukemia (CLL) experts, Dan Landau, Lesley Ann Sutton, Gianluca Gaidano and John C. Byrd, and focused on the development of clonal and subclonal mutations in CLL. Dr Lamanna describes how mutational evolution remains a significant challenge in the treatment of CLL, especially in the relapsed/refractory setting. As treatments move away from traditional chemotherapy and immunotherapy, there is interest in how this will affect the evolution of mutations over time. Dr Lamanna describes the benefits to being able to sequentially monitor patients’ mutations throughout their treatment and to track mutation evolution, with the aim of devising more effective therapy plans. Dr Lamanna also details the discussions on Richter’s transformation syndrome, a challenging and life-threatening condition for patients with CLL.
How can standard risk multiple myeloma (MM) patients be cured?
 
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Philippe Moreau, MD, from the University Hospital of Nantes, Nantes, France, speaks about new possibilities to cure multiple myeloma (MM) at the 2017 World Congress on Controversies in Multiple Myeloma (COMy) in Paris, France. He highlights that in patients with standard risk, all the drugs that are available need to be used, in combination with stem cell transplantation and monoclonal antibodies. Prof. Moreau explains that rather than treating patients until remission, the aim is to achieve fast and deep response as well as minimal residual disease (MRD) negativity. He outlines the treatment strategy including duration of treatment and subsequent monitoring, and gives an estimate of the proportion of patients that can be cured using this approach.
The standard of care for DLBCL and double-hit lymphoma
 
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Laurie Sehn, MD of British Columbia Cancer Agency, Vancouver, Canada discusses the standard of care for patients with diffuse large B-cell lymphoma (DLBCL). For patients with advanced stage DLBCL, the standard is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). According to Dr Sehn, for a large proportion of patients this is adequate with cure rates of around 60-65%. The challenging group are those patients who aren't cured as their chances of being cured with salvage therapy are very low. Therefore, improving frontline therapy is very important. Dr Sehn explains that in her clinic, they don't treat patients who have so-called double-hit lymphoma (with a dual translocation of MYC and BCL2) with R-CHOP upfront because it is clear that they have a poor prognosis if they receive R-CHOP. They are treated with dose-adjusted EPOC-R (etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone) but it is not clear yet if the outcome for those patients will be better on this treatment. Recorded at the 2016 International Workshop on Non-Hodgkin Lymphoma (iwNHL) meeting held in San Diego, CA.
Relapsed follicular lymphoma: hope from a non-chemotherapy regimen of lenalidomide and obinutuzumab
 
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Nathan Fowler, MD from The University of Texas MD Anderson Cancer Center, Houston, TX provides an overview of the results of a Phase I/II study measuring the activity of lenalidomide combined with obinutuzumab (NCT01995669) presented at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting held in Chicago, IL. Prof. Fowler highlights the promising results of the trial which included patients with relapsed/refractory follicular and low grade lymphoma, for which there are very few options left. The initial phase of escalating doses of lenalidomide with obinutuzumab resulted in no significant dose-limiting toxicities (DLTs), leading to expansion of the trial. The combined regimen has shown encouraging results in a difficult cohort of patients who have already received aggressive therapy, with 30% being rituximab refractory. A 100% oveall response rate and a complete remission rate (CRR) of 70% has been achieved. Follow up of patients still continues; however, at 2 years, progression-free survival (PFS) is approximately 60%.
Graft versus host disease: how to treat it?
 
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John Murray, clinical nurse at the Christie NHS Foundation Trust, Manchester, UK, discusses the highlights from the nurses session on graft versus host disease (GVHD) at the 2017 annual meeting of the European Society for Blood and Marrow Transplantation (EBMT) in Marseille, France. One of the highlights of this session was the presentation by Dr Nathanial Treister, who spoke about patients with oral GVHD. Dr Treister spoke about the difficulties that patients face, what to look for and the treatments that are available for it. Dr Dominique Vexiau-Robert then spoke about vaginal GVHD, an incredibly under-reported disease. It is very important for nurses to openly talk to patients about this and address this problem, as usually patients will shy away from bringing it up themselves. The final presentation of this session focused on scleroderma of the skin, by Prof. Hildegard Greinix. Scleroderma is a debilitating condition, which causes contractions of the skin, tightening around the joints, lack of mobility and increased amounts of pain. Although there are many therapies available, unfortunately the best treatment is unknown. During his talk, Prof. Greinix spoke about how to best improve patients quality of life.