During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the Multiple Myeloma Hub spoke to Elisabet E. Manasanch, MD Anderson Cancer Center, Houston, US, and Taxiarchis Kourelis, Mayo Clinic, Rochester, US. They discuss new findings regarding the role of the immune microenvironment presented at ASH 2020In this podcast, Manasanch and Kourelis describe two studies on immune microenvironment changes in myeloma. The first study is a preliminary analysis of peripheral blood and bone marrow samples from patients with smoldering myeloma. This included identifying changes to immune cell composition and using RNA/DNA sequencing to identify biomarkers associated with immune changes in patients with disease progression. From the data, they outline possible new avenues in immune cell profiling for the prognosis of high-risk precursor patients, as well as therapeutic targeting, including the potential for curing at the precursor stage. The second study for discussion compared major components of tumor ecosystems in patients with newly diagnosed/relapsed myeloma that are triple-class refractory. Kourelis brings attention to unhealthy T-cell compartments in more heavily pretreated patients compared with patients with newly diagnosed/relapsed disease and the implications for their response to T-cell-based immunotherapies. Hosted on Acast. See acast.com/privacy for more information.

During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the Multiple Myeloma Hub spoke to Francesca Gay (University of Turin, Turin, IT) and Jonathan L. Kaufman (Emory University, Atlanta, US) about the best partner for lenalidomide maintenance after autologous stem cell transplantation.In this podcast, Kaufman and Gay discuss data from studies evaluating multiple myeloma treatment with proteasome inhibitors (bortezomib or carfilzomib) + lenalidomide. Both highlight improved progression-free survival with combination therapy vs monotherapy, particularly in high-risk patients. They also discuss difficulties related to patient compliance with combination therapy and issues related to continuous hospital visits resulting from the method of administration and therefore suggest potential oral alternatives to improve compliance. Kaufman then moves on to data from the phase II GRIFFIN trial, evaluating the addition of daratumumab (DARA) to lenalidomide, bortezomib, and dexamethasone induction and consolidation, followed by maintenance therapy with lenalidomide or DARA + lenalidomide. Gay also mentions the MAIA study evaluating DARA + lenalidomide and dexamethasone in transplant-ineligible patients. Kaufman concludes by highlighting the importance of evaluating methods to shorten post-transplant maintenance time without losing any long-term benefits. Hosted on Acast. See acast.com/privacy for more information.

During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the Multiple Myeloma Hub spoke to Nikhil C. Munshi, Dana-Farber Cancer Institute, Boston, US. We asked, Should we still use high-dose melphalan in the era of novel agents? In this podcast, Munshi discusses the role of high-dose chemotherapy combined with stem cell transplantation in the era of novel agents. Upon analyzing data from a genomic-focused study, he concludes that high-dose melphalan can still achieve good and deep responses, while maintenance therapy should also be an important treatment component for multiple myeloma. Hosted on Acast. See acast.com/privacy for more information.

During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the Multiple Myeloma Hub spoke to Efstathios Kastritis, National and Kapodistrian University of Athens, Athens, GR. We asked, What are the unmet needs in AL amyloidosis in Europe? AL amyloidosis is a rare disease caused by the accumulation of amyloid fibers in tissues and organs. In this podcast, Kastritis outlines the need for a more accurate and earlier diagnosis of AL amyloidosis. Kastritis then discusses the need for new therapeutic strategies in patients with advanced (stage IIIb) AL amyloidosis. Finally, he mentions the need for optimized treatment in patients who relapse. Hosted on Acast. See acast.com/privacy for more information.

During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the Multiple Myeloma Hub spoke to Marc Braunstein, NYU Langone Health, New York, US, and Mohamad Mohty, Hôpital Saint-Antoine and Sorbonne University, Paris, FR, about the role of upfront transplant consolidation in the era of novel agents.Long-term follow-up data about upfront autologous hematopoietic stem cell transplantation (auto-HSCT) were presented at the 62nd ASH Annual Meeting and Exposition. Mohty and Braunstein agree on the importance of auto-HSCT and on the fact that, when possible, it should not be delayed.They outline the value of upfront auto-HSCT even in the era of novel agents being developed for multiple myeloma. They also talk about consolidation and maintenance therapy after transplant. Hosted on Acast. See acast.com/privacy for more information.

During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, the Multiple Myeloma Hub spoke to Maximilian Merz, Heidelberg University Hospital, Heidelberg, DE, and Nizar Bahlis, University of Calgary, Calgary, CA. We asked, Can single cell sequencing help to better define and monitor multiple myeloma?Merz highlights the importance of defining what you want to study, the myeloma cells or the tumor microenvironment. He explains that with single cell sequencing it is possible to analyze different clones that are present in every patient with myeloma, and that in the future it will be important to look at risk-stratified therapy and identify modes of resistance. He also states that with single cell sequencing we can understand why certain therapies work in certain patients. Bahlis focuses on non-plasma cell compartment and single cell techniques. He gives an overview of the studies on single cell sequencing presented at ASH 2020. He also reports the results of a study performing a broad immunophenotypic and transcriptomic characterization, at the single cell level, of the peripheral blood and bone marrow T cells of sensitive and resistant patients with multiple myeloma treated with B-cell maturation antigen-targeted chimeric antigen receptor T-cell and bispecific T-cell engager therapies. Hosted on Acast. See acast.com/privacy for more information.

During the European School of Haematology (ESH) 5th Translational Research E-Conference on Multiple Myeloma, the Multiple Myeloma Hub was pleased to speak to Hermann Einsele, University of Würzburg, Würzburg, DE, about novel immunotherapies.Bispecific antibodies and chimeric antigen receptor (CAR) T cells represent a novel interesting therapeutic option for patients with multiple myeloma. In this podcast, after explaining their mechanism of action, Hermann Einsele gives an overview of the major findings from clinical trials evaluating efficacy and safety of bispecific antibodies and CAR T cells. The advantage of bispecific antibodies in comparison to CAR T cells is that they are probably less toxic, with less severe cytokine release syndrome and lower neurotoxicity, thus more suitable for patients who are less fit. However, CAR T cells seem to be more effective, with response rates of up to 100% and complete remission rates that can be above 80%. In summary, both bispecific antibodies and CAR T cells are new immunotherapeutic strategies that show promising results in patients with multiple myeloma. Hosted on Acast. See acast.com/privacy for more information.

During the American Association of Cancer Research (AACR) Virtual Annual Meeting I, the MM Hub was pleased to speak to Christine Spencer, Parker Institute for Cancer Immunotherapy, San-Francisco, US and Diwakar Davar, University of Pennsylvania Medical Center, Pittsburgh, US. We asked: how can we use the microbiome to improve cancer immunotherapy and alleviate side effects such as graft-versus-host-disease?In this podcast, Dr Davar starts by providing a background on the importance of the microbiome in adaptive and innate immunity, while Dr Spencer states the importance of the cross-talk between the microbiome and immune system through microbial products, peptides, and metabolites. Dr Davar then explains the concept of immunosurveillance, immunoediting, and checkpoint inhibitors. Dr Spencer describes fecal microbiome transplant studies that showed features of the microbiome can predict response to immunotherapy and effect T-cell expression. Dr Davar then describes some of the studies that are looking at fecal microbiome transplant in combination with checkpoint inhibitors. He goes on to discuss studies investigating the use of live bacterial products to elicit the same effects as fecal microbiome transplant, particularly the mediation of CD8 T cells. Dr Spencer also talks about probiotics, antibiotics, and diet and explains how this can affect the gut microbiome and describes studies looking at these features in terms of response to immunotherapies. She also describes the microbiome research related to graft-versus-host-disease and the impact of higher alpha diversity on post-transplant survival, while Dr Davar explains how the microbiome may also affect toxicity and side-effects of cancer immunotherapies.  Hosted on Acast. See acast.com/privacy for more information.

During COMy 2020, Multiple Myeloma Hub Steering Committee Member Paul Richardson, Dana-Farber Cancer Institute, Boston, US, spoke to the Multiple Myeloma Hub about advances in the novel, peptide-conjugated alkylator, melphalan flufenamide (melflufen).Melflufen has been successful in overcoming resistance to standard chemotherapeutics as well as novel agents, such as proteasome inhibitors and immunomodulatory drugs. The high lipophilicity of melflufen facilitates rapid entry into myeloma cells. Furthermore, its alkylating activity is initiated by aminopeptidases, which are often overexpressed by myeloma cells, making the agent particularly selective. As a result, melflufen is better tolerated, with fewer off-target effects than its predecessor, melphalan.Here, Paul Richardson discusses the major findings from preclinical studies and topline data from ongoing clinical trials evaluating melflufen for the treatment of multiple myeloma. Hosted on Acast. See acast.com/privacy for more information.

During the American Society of Clinical Oncology (ASCO) Annual Meeting, the Multiple Myeloma Hub was pleased to speak to Katja Weisel, University Cancer Center Hamburg, Hamburg, DE. In this podcast she discusses the quadruplet combination of isatuximab with carfilzomib, lenalidomide and dexamethasone for the treatment of high-risk newly diagnosed multiple myeloma.In this podcast, Katja Weisel describes the interim results of the phase II GMMG-CONCEPT trial including deep and durable responses, measurable residual disease negativity, remissions, and overall survival of the first 50 patients enrolled. She also discusses the trial design, including the cytogenetic features that classify patients as high risk, as well as the safety profile and dosing regimens. Hosted on Acast. See acast.com/privacy for more information.