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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
Carlo Croce, MD of The Ohio State University, Columbus, OH provides an overview of microRNA and ROR1 as part of an overview of his research on the epigenetics and genetic of chronic lymphocytic leukemia (CLL) while at the 2016 International Workshop of the German CLL Study Group (GCLLSG) in Cologne, Germany. Prof. Croce explains that microRNA have a number of targets and that there could be other genes besides BCL2 that are dysregulated because of the loss of the microRNA. This led to the discovery of MCL1. He explains that his talk at GCLLSG was about another target, ROR1, which was discovered by Tom Kipps. It is an antigen on the cell surface and seems to be expressed only on leukemic cells. When investigating the question if there are any CLL cells that are ROR1 negative, they found that 10% of CLL cells are indeed ROR1 negative. Prof. Croce screened samples of ROR1 positive and ROR1 negative cells for ROR1 microRNA. The difference between ROR1 positive and negative cells were miR-15 and miR-16 whereby the ROR1 positive cells are the ones which lost miR-15 and miR-16. The loss of miR-15 and miR-16 in CLL leads to the overexpression of BCL2, MCL1 and ROR1. Prof. Croce believes that cytotoxic antibodies can be made against ROR1. The problem with targeted therapy, as Prof. Croce points out, is that there is always some mutant resistant to therapy. However, you can target the same cells with two drugs and he believes that with this approach, the cells will not be able to survive and therefore it will become possible to cure patients.
Michael Wang, MD from the MD Anderson Cancer Center, Houston, TX discusses the results from the successful WINDOW study (NCT02427620), presented at the International Conference on Malignant Lymphoma (ICML) 2017 held in Lugano, Switzerland. Prof. Wang explains the study design, which saw young, newly diagnosed mantle cell lymphoma patients receive a combination of ibrutinib and rituximab followed by reduced chemo-immunotherapy. This combination of targeted therapy achieved a response in 100% of patients and complete remission in 90%. By reducing the need for chemotherapy, treatment associated toxicities can be decreased thus giving this subset of patients a better quality of life.
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.
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.
Gilles Salles, MD, PhD, from South Lyon Hospital Complex, Lyon, France provides an overview of his presentation on 'chemo-free' in follicular lymphoma held at the 2016 Annual Meeting of the British Society of Haematology (BSH) and International Society of Hematology (ISH), in Glasgow, Scotland. Prof Salles outlines the limitations of chemotherapy and the reasons why he supports a 'chemo-free' approach. He argues that chemotherapy is not curative and that agents that can modify the microenvironment, may be successful at managing the disease. For example, monoclonal antibodies such as anti-CD20, either alone or when combined with chemotherapy, can improve the survival of patients. According to Prof Salles, the aim is to develop further combinations with anti-CD20 antibodies and he discusses the evidence in favor of this approach. For example, the combinations of lenalidomide plus rituximab, lenalidomide plus inotuzumab and anti-PD-1 antibody plus rituximab have shown some encouraging results according to Prof Salles.
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.
There are two primary routes of therapy for amyloidosis: treating the underlying plasma cell dyscrasia, and clearing amyloid deposits. In this insightful interview, recorded at the Myeloma 2017 meeting in Edinburgh, UK, Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM, from University College London, London, UK, gives an overview of some of the most exciting data in the field, including bortezomib combinations, single agent daratumumab, and ixazomib, which have shown great potential. Dr Wechalekar highlights ongoing studies of monoclonal antibodies that act through clearing amyloid deposits, including a highly anticipated anti-SAP antibody being developed (NCT03044353), and NEOD001, currently being investigated in the Phase III VITAL study (NCT02312206).
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.
In a large, international, randomized Phase III trial, patients with previously treated cutaneous T-cell lymphoma (CTCL) who received the investigational targeted drug mogamulizumab had significantly better progression-free survival, response rate, and quality of life than patients who received vorinostat, a U.S. Food and Drug Administration (FDA)-approved standard-of-care treatment for patients with CTCL. The adverse events observed with mogamulizumab treatment were generally mild to moderate in severity. The primary endpoint was progression-free survival — the time elapsed until the cancer began to show signs of getting worse — or death for any reason. Among 372 patients included in the trial, the median progression-free survival was 7.7 months for patients treated with mogamulizumab, compared with 3.1 months for those treated with vorinostat, reported lead study author Youn H. Kim, MD, professor of dermatology and director of the Multidisciplinary Cutaneous Lymphoma Program at the Stanford University School of Medicine. “We found that mogamulizumab has convincing clinical activity, not just in skin, but also in clearing malignant T-cells in the blood and lymph nodes,” said Dr. Kim. “Progression-free survival and overall global response outcomes are clearly superior, the side effects are tolerable, and we see measurable improvements in quality of life with mogamulizumab compared with vorinostat. Taken together, these findings represent a durable and clinically meaningful benefit for patients with CTCL.” This session was recorded at the American Society of Hematology 2017 Annual Meeting, held in Atlanta, GA.
At the German Cancer Congress 2016, held in Berlin, Germany, from 24 to 27 February 2016, Wolfgang Hiddemann, MD, PhD, from the University of Munich, Munich, Germany, provides an overview of chemotherapy-free approaches in clinical development for the treatment of patients with indolent lymphoma. Promising approaches include the Bruton tyrosine kinase inhibitor, ibrutinib, and PI3K-delta inhibitor, idelalisib, in combinations with anti-CD20 monoclonal antibodies; Bcl-2 inhibitors; and PD-1 immune checkpoint inhibitors. Institution website: http://www.klinikum.uni-muenchen.de/Medizinische-Klinik-und-Poliklinik-III/de/team/hiddemann_w/index.html
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.
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.
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.
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.
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.
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.
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.
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.
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.
Donia Moujalled, PhD, from the Australian Center for Blood Diseases, Melbourne, Australia, guides us through her team’s investigation on using BH3 mimetics to target the Bcl2 family of pro-survival proteins with the aim of treating acute myeloid leukemia (AML). She describes the differences in efficacies of using Bcl2-targeted and MCL1-targeted BH3 mimetics as either monotherapy or in combination and mentions the promising results, namely improved survival, obtained from murine models of AML which were treated with this dual regimen. With the goal of achieving a chemotherapy-free treatment option for AML patients, she believes that this dual regimen may potentially become an alternative to chemotherapy in the treatment of AML. This interview was filmed at the European Hematology Association (EHA) 2017 Annual Congress in Madrid, Spain.
Systemic mastocytosis, though a rare disease, is more common than clinicians may think and diagnosis of the condition can often be missed. In this insightful interview, Deepti Radia, MBBS, MRCPI, FRCPath, of Guy’s and St Thomas’ Hospital NHS Foundation Trust, London UK, details the latest updates in the field, such as the new WHO classification guidelines for diagnosis and classification. Dr Radia also discusses the treatment options for this condition, which often consists of symptomatic treatment, but in cases of aggressive systemic mastocytosis there are now targeted treatments available, such as midostaurin, BLU-285 and DCC-2618. This video was recorded at the Myeloproliferative Neoplasms Advances Day 2017, London, UK.
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.
A novel BTK inhibitor, acalabrutinib, is showing promise in the early clinical trial stages for chronic lymphocytic leukemia (CLL). Speaking from the American Society of Hematology (ASH) 2017 Annual Meeting and Exposition in Atlanta, GA, Susan O’Brien, MD, of the University of California, Irvine, CA, discusses the benefits of acalabrutinib over ibrutinib and why this may be. Prof. O’Brien highlights the main studies of this agent for CLL, including as a monotherapy (ACE-CL-001; NCT02029443) and in combination with ACP-319 (ACE-CL-002; NCT02157324) in the relapsed/refractory setting, and in the frontline setting in combination with obinutuzumab (ACE-CL-003; NCT02296918).
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.
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.
Haifa Kathrin Al-Ali, MD from University of Leipzig, Leipzig, Germany discusses the unmet medical need of patients with polycythemia vera (PV) and essential thrombocythemia (ET), by outlining her arguments for new treatment options. Currently, all treatment guidelines are based on the risk of thrombosis. If the patient is low-risk based on age or history of thrombosis, they receive phlebotomy or low dose aspirin. If they are high risk they will receive high-dose aspirin and hydroxyurea, or a second line of treatment of interferon alpha. However even with these treatments thrombotic events still occur, highlighting how these drug are ineffective. Furthermore, recent studies have shown these treatments are related to disease-burden symptoms in patients with PV and ET. Dr Al-Ali also discusses hydroxyurea resistance. Recorded at the European Hematology Association (EHA) 2016 Annual Congress in Copenhagen, Denmark.
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.
Noopur Raje, MD from the Massachusetts General Hospital, Boston, MA gives an overview of the Phase III POLLUX trial on (NCT02076009) on combining daratumumab with lenalidomide and dexamethasone vs lenalidomide and dexamethasone in relapsed/refractory multiple myeloma (MM) presented at the European Hematology Association (EHA) 2016 Annual Congress in Copenhagen, Denmark. According to Dr Raje, patients who received daratumumab with lenalidomide and dexamethasone had more than a doubling in response rate; progression-free survival (PFS) and duration of response are also striking. The future is going to be drug combinations according to Dr Raje. She also highlights the CASTOR trial (NCT02136134) presented at ASCO 2016, which looks at the combination of daratumumab with bortezomib and dexamethasone vs bortezomib and dexamethasone.
While CAR T-cells are an approved therapy option in acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL), the research in chronic lymphocytic leukemia (CLL) is somewhat behind. In this video, recorded at the 2018 Society of Hematologic Oncology (SOHO) Annual Meeting in Houston, TX, William Wierda, MD, PhD, of the MD Anderson Cancer Center, Houston, TX, gives an overview of the current data, explaining how CAR T-cell therapy appears to be less effective in CLL than in other diseases. He discusses how their potency in this disease might be improved, potentially via the addition of ibrutinib, and highlights three upcoming clinical trials in the field, which might be the turning point for this therapy in CLL.
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.
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.
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.
Thomas Martin, MD, from the UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, discusses the use of monoclonal antibody therapy in multiple myeloma (MM). Daratumumab and elotuzumab are already approved and according to Prof Martin, the next monoclonal antibody to be approved will be isatuximab. Isatuximab like daratumumab, targets CD38 and responses to the drug in pre-clinical work and clinical trials have been good. In the initial Phase I trial in relapsed/refractory myeloma (NCT01749969), the response rate to isatuximab was over 30% and in combination with lenalidomide and dexamethasone, the response rate was in the 60% range. Prof Martin further discusses preliminary data on combining isatuximab with carfilzomib, which showed a response rate of 77%. According to Prof Martin, it is now time for the Phase III studies of isatuximab. Recorded at the Myeloma 2016 meeting held in Boston, MA.
Simon Rule, MD of Plymouth University, Plymouth, UK discusses highlights in mantle cell lymphoma (MCL) from the 2016 American Society of Hematology (ASH) Annual Meeting, held in San Diego, CA. The first presentation Prof. Rule mentions is the follow-up of the Lysa study of younger patients treated with four cycles of R-DHAP, transplant and randomization to rituximab maintenance (NCT00921414). There is a strong progression-free survival (PFS) advantage in favor of the rituximab arm as well as an overall survival (OS) advantage. Further, the Nordic group presented on giving four doses of rituximab after patients become minimal residual disease (MRD) positive. While MRD is only used in clinical trials for now, Prof. Rule believes MRD will affect therapy in future. Further, the first trials of combinations of ibrutinib were presented. In the relapse setting, the Nordic group presented on the PHILEMON trial of lenalidomide, rituximab and ibrutinib (NCT02460276); the combination was well-tolerated with high complete remission (CR) rates. Also, Michael Wang presented his trial on ibrutinib plus rituximab with hyper-CVAD consolidation in newly diagnosed young patients (NCT02427620). It showed that if you use ibrutinib/rituximab frontline, 100% of patient respond and the majority get a CR.
Traditional treatment of amyloidosis has been directed at the plasma cells responsible for the production of amyloid; however, that does not affect the deposit of amyloid already established. In this video, Morie Gertz, MD, MACP from the Mayo Clinic, Rochester, MN talks about the novel monoclonal antibody NEOD001, which binds directly to the amyloid fibers and can assist in the dissolution of those fibers. Data of a study using NEOD001 was presented at the European Hematology Association (EHA) 2017 meeting.