VJHemOnc Podcast

The Lymphoma Sessions: post-ASH 2021

The 63rd American Society of Hematology (ASH) annual meeting saw a plethora of updates in lymphoma. While most of them generated a lot of fruitful conversations, some of the breakthroughs have the potential to change practice.

In this roundtable discussion, Graham Collins, MA, MBBS, MRCP, FRCPath, DPhil, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, and Wendy Osborne, MBBS (Hons), MRCP, FRCPath, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK, review the most exciting updates in lymphoma from the 2021 ASH annual meeting and reflect on how the data may impact clinical practice in the UK.

COSTEM: maintenance therapies for FLT3+ AML

The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in approximately 30% of patients with acute myeloid leukemia (AML) and is indicative of a poor prognosis. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is commonly recommended to this patient population as a consolidation therapy after first complete remission. Nevertheless, the rate of relapse post-alloHSCT remains high and effective post-transplant maintenance therapies represent an unmet clinical need. The FLT3 tyrosine kinase inhibitors (TKIs), including sorafenib, midostaurin and gilteritinib, have demonstrated improved outcomes for patients undergoing alloHSCT. Multiple ongoing trials are currently investigating these agents as maintenance therapies.

In this deep dive, Andreas Burchert, MD, University of Marburg, Marburg, Germany, discusses updates on post-transplant maintenance therapies for patients with FLT3+ AML, focusing on data from clinical trials evaluating four tyrosine kinase inhibitors: sorafenib, midostaurin, gilteritinib and quizartinib, as presented at the 6th Congress on Controversies in Stem Cell Transplantation and Cellular Therapies (COSTEM).

COSTEM: the role of alloHSCT in ALL

Over the past few years, the therapeutic landscape for acute lymphoblastic leukemia (ALL) has dramatically evolved, with the development of highly effective tyrosine kinase inhibitors (TKIs) and bispecific antibodies. These therapies have considerably improved outcomes for patients and many achieve durable remissions, raising the debate of whether allogeneic hematopoietic stem cell transplantation (alloHSCT) should still be offered to all patients with ALL.

In this podcast featuring Mohamad Mohty, MD, PhD, Saint-Antoine Hospital and Sorbonne University, Paris, France, and Robin Foà, MD, Sapienza University of Rome, Rome, Italy, discuss the relevance of alloHSCT in the current therapeutic landscape for ALL.

SOHO 2021: amyloidosis treatment updates

Over the last two decades the outcomes of patients with amyloidosis have substantially improved with timely diagnosis, the use of chemotherapeutic agents and improved patient selection for autologous stem cell transplantation (ASCT); however, for patients who are diagnosed at later stages or who are ineligible for ASCT the prognosis is poorer. Recently, the introduction of daratumumab has shown promising results for patients with both newly diagnosed and relapsed/refractory amyloidosis and there have been a number of Phase II/III trials aiming to help guide treatment decision-making and improve patient outcomes.

In today’s podcast, Angela Dispenzieri, MD, of the Mayo Clinic, Rochester, MN, gives an overview of key updates in the treatment landscape of amyloidosis, as presented at the ninth annual meeting of the Society of Hematologic Oncology (SOHO 2021) congress.

IACH 2021: CAR-T in clinical practice

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 practical 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 currently 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.

Unmet needs and recent updates in CML

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).

IMW 2021: treatment-free intervals in multiple myeloma

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).

Highlights from iwCLL 2021

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 IRCCS Ospedale San Raffaele, Milan, Italy, Barbara Eichhorst, MD, of University Hospital Cologne, Cologne, Germany, Lydia Scarfò, MD, of Vita-Salute San Raffaele University & 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.

IMW 2021: MRD in myeloma

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, 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).

CAR-T vs bispecifics: replacing ASCT in myeloma

Autologous stem cell transplantation (ASCT) has been the standard of care patients with multiple myeloma for the past three decades; however, high-risk patients still have poor outcomes. Many bispecific antibody therapies are currently under investigation for the treatment of myeloma, such as blinatumomab, teclistamab, talquetamab and cevostamab, and the chimeric antigen receptor (CAR) T-cell therapy, idecabtagene vicleucel, became the first CAR-T therapy to receive FDA approval for the treatment of multiple myeloma in March 2021. With CAR-T and bispecific antibodies demonstrating deep and sustained remissions, the role of ASCT in the future treatment of myeloma has become a subject of debate.

In this podcast, Hermann Einsele, MD, FRCP, of the University of Würzburg, Würzburg, Germany, and Parameswaran Hari, MD, MRCP, MS, of the Froedtert Hospital Cancer Center, Milwaukee, WI, discuss the benefits and drawbacks of the two immunotherapeutic modalities, CAR-T and bispecific antibodies as a replacement for ASCT in multiple myeloma.