VJHemOnc Podcast

Currently, five chimeric antigen receptor T-cell (CAR-T) therapies are approved for the treatment of hematological malignancies including acute lymphoblastic leukemia, B-cell lymphoma, non-Hodgkin lymphoma and multiple myeloma. Despite reporting high response rates, the use of CAR-T therapy is associated with a number of challenges, including treatment-related adverse events such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), as well as high costs and manufacturing difficulties. It is thus crucial to reduce the incidence and optimize the management of toxicities through careful patient selection and monitoring. CAR-T therapy is also being explored as a treatment option for chronic lymphocytic leukemia (CLL), where attempts with CAR-T have been unsuccessful due to CLL-induced T-cell dysfunction, a process that is not well understood.

In this podcast, Arnon Nagler, MD, MSc, of the Chaim Sheba Medical Center, Tel-Hashomer, Israel, Anna Sureda, MD, PhD, of the Catalan Institute of Oncology, Barcelona, Spain, Christian Chabannon, MD, PhD, of the Institut Paoli Calmettes, Marseille, France, and Arnon Kater, MD, PhD, of the University of Amsterdam, Amsterdam, Netherlands, discuss key considerations for the use of CAR-T therapy in clinical practice, as presented at the 4th Annual Meeting of the International Academy for Clinical Hematology (IACH) 2021.

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The treatment of chronic myeloid leukemia (CML) has substantially evolved since the FDA approval of the tyrosine kinase inhibitor imatinib in 2001 – the first targeted therapy for CML. Since then, several second- and third- generation TKIs have emerged in the field, as well as other novel therapies. Despite this, around 20-30% of patients with CML will require changes of treatment due to resistance, intolerance or suboptimal responses and thus alternative treatment approaches are needed.

In this podcast, Joaquin Martinez-Lopez, MD, PhD, of the Universidad Complutense de Madrid, Madrid, Spain, gives a brief overview of unmet needs and novel therapeutic approaches for patients with CML, as discussed at the 18th International Myeloma Workshop (IMW 2021).

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Continuous therapy has been a key aspect of the standard of care approaches for the treatment of multiple myeloma for many years, prolonging disease control and improving progression-free survival in comparison to fixed-duration approaches; however, it is now being discussed whether treatment-free interval strategies could be incorporated into the treatment paradigm. Evidence from the IFM/DFCI2009 (NCT01191060) study has suggested that patients with myeloma who achieve measurable residual disease (MRD) negativity have good outcomes without continuous treatment, and similar findings have been reported in part 2 of the Phase III Cassiopeia (NCT02541383) trial. Despite this, potential surrogate markers, such as MRD, still require validation in order to determine patient eligibility for management strategies involving treatment-free intervals in multiple myeloma.

In this podcast, Phil McCarthy, MD, of the Roswell Park Comprehensive Cancer Center, Buffalo, NY, and Luciano Costa, MD, PhD, of the UAB School of Medicine, Birmingham, AL, discuss the evidence for and against treatment-free intervals in the treatment of multiple myeloma, as debated at the 18th International Myeloma Workshop (IMW 2021).

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The management of chronic lymphocytic leukemia (CLL) has evolved drastically over the last few years, with the introduction of novel therapies and the identification of new genetic markers. The current most effective therapies for CLL include venetoclax, obinutuzumab and BTK inhibitors, whilst ongoing clinical trials are investigating the use of BTK inhibitors in combination with BCL-2 inhibitors. Furthermore, novel genomic markers are increasingly being used to guide treatment decisions, as well as for prediction and prognostication purposes, and research into the optimal sequencing of targeted therapies is also showing promise in improving outcomes for patients who develop resistance to BCL-2 and BTK inhibitors.

In this podcast, Paolo Ghia, MD, PhD, of Università Vita-Salute San Raffaele and the IRCCS Ospedale San Raffaele, Milan, Italy, Barbara Eichhorst, MD, of University Hospital Cologne, Cologne, Germany, Lydia Scarfò, MD, of Vita-Salute San Raffaele University & the IRCCS San Raffaele Scientific Institute, Milan, Italy, Adrian Wiestner, MD, PhD, of the National Institutes of Health, Bethesda, MD, and Richard Rosenquist, MD, of the Karolinska Institute, Stockholm, Sweden, share some of the latest updates in CLL treatment, as presented at the 19th International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Biennial Meeting in 2021.

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Measurable residual disease (MRD) is emerging as an important prognostic marker in the management of multiple myeloma. Promising clinical evidence from trials, such as the MYELOMA XI trial, has linked MRD-negativity to improved outcomes in myeloma. Whilst research into MRD as a prognostic marker continues, MRD is further being explored as a tool to guide the adaptive treatment of patients with myeloma, such as by intensifying treatment for MRD-positive patients, or by de-escalating treatment for MRD-negative patients. Future trials investigating the relative safety and efficacy of MRD-guided adaptive treatment will help to determine the optimal role of MRD in multiple myeloma.

In this podcast, Natalie Callander, MD, of the University of Wisconsin School of Medicine and Public Health, Madison, WI, Luciano Costa, MD, PhD, of the UAB School of Medicine, Birmingham, AL, Fredrik Schjesvold, MD, PhD, of the Oslo Myeloma Center Oslo University, Oslo, Norway, Lanny Kirsch, MD, Senior Vice President in Translational Medicine at Adaptive Biotechnologies, Seattle, WA, and Philippe Moreau, MD, of the Nantes University Hospital, Nantes, France, discuss the latest data on the use of MRD in the management and treatment of multiple myeloma, as presented at the 18th International Myeloma Workshop (IMW 2021).

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