VJHemOnc Podcast

ASH 2021: evaluating the impact of screening for multiple myeloma precursor diseases

Multiple myeloma is always preceded by two precursor conditions known as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. Smoldering myeloma is associated with a higher disease burden and higher risk of progression to active disease than MGUS. The management of these precursor conditions remains unclear and the optimal timing of therapy in multiple myeloma has been a subject of debate. Whilst it would be useful to identify high-risk and asymptomatic individuals that could benefit from therapy to prevent progression to multiple myeloma, there is currently no evidence supporting the use of asymptomatic screening in clinical practice.

 

In this exclusive podcast recorded at the 63rd ASH Annual Meeting and Exposition Congress, Atlanta, GA, 2021, Irene Ghobrial, MD, Dana-Farber Cancer Institute, Boston, MA, and Sigurdur Kristinsson, MD, PhD, University of Iceland, Reykjavik, Iceland, explore the benefits and risks of screening for multiple myeloma precursor conditions, presenting the design and findings of the iStopMM (NCT03327597) and PROMISE (NCT03689595) studies. Dr Ghobrial and Prof. Kristinsson talk on emerging technologies to identify patients with myeloma precursor conditions and question the clinical significance of MGUS and smoldering myeloma, commenting on the mental impact of screening.

ASH 2021: the future of cell therapies in lymphoma

Cell therapies including chimeric antigen receptor (CAR) T-cell therapy represent novel treatments for patients with lymphoma, especially for those who have progressed on existing chemotherapy or autologous hematopoietic stem-cell transplantation (ASCT). CAR T-cell therapy involves modified immune cells from the patient to attack the cancer and there are currently five approved by the FDA: idecabtagene vicleucel, lisocabtagene maraleucel, tisagenlecleucel, brexucabtagene autoleucel, and axicabtagene ciloleucel.

In this exclusive podcast, Yi Lin, MD, PhD, Mayo Clinic, Rochester, MN, Krish Patel, MD, Swedish Cancer Institute, Seattle, WA, Nathan Fowler, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, Michael Bishop, MD, University of Chicago, Chicago, IL, and Stephen Ansell, MD, PhD, Mayo Clinic, Rochester, MN, discuss important data from the ELARA (NCT03568461) and BELINDA (NCT03570892) trials, NK cell therapies, and the role of cell therapies in treating lymphoma. This interview took place at the 63rd ASH Annual Meeting and Exposition Congress, Atlanta, GA, 2021.

ASH 2021: highlights in CLL clinical trials

Treatments such as ibrutinib and venetoclax, which target the Bruton tyrosine kinase (BTK) pathway and the B-cell lymphoma 2 (BCL-2) protein respectively, have proven to be efficacious as targeted therapies for previously untreated patients with chronic lymphocytic leukemia (CLL). For patients who have progressed on existing therapies, novel BTK inhibitors such as pirtobrutinib and MK1026 represent promising alternative treatment options.

In today’s podcast, Jennifer Woyach, MD and Adam Kittai, MD, Ohio State University College of Medicine in Columbus, OH, provide their perspectives on key themes and topics in the treatment and management of CLL. They evaluate findings from the CAPTIVATE, GLOW and CLL13 clinical trials, long-term follow up data of the ALLIANCE A041202 and SEQUOIA trials, novel agents and the role of MRD in CLL.

This interview took place at the 63rd ASH Annual Meeting and Exposition Congress, Atlanta, GA, 2021.

ASH 2021: updates in FLT3-mutated AML

FMS-like tyrosine kinase 3 (FLT3) mutations are common in patients with acute myeloid leukemia (AML), and is often associated with a poor prognosis. Despite the development of FLT3 inhibitors such as midostaurin, sorafenib, and qauizartinib, patients often progress on these therapies due to secondary mutations. Various strategies to improve patient outcomes such novel combinations with other agents including hypomethylating agents or venetoclax are currently under investigation.

In this podcast, Naval Daver, MD, University of Texas MD Anderson Cancer Center, Houston, TX, and Eunice Wang, MD, Roswell Park Comprehensive Cancer Center, Buffalo, have an insightful discussion on FLT3-mutated acute myeloid leukemia (AML) updates presented at the ASH 2021 annual meeting. They give an overview of the use of FLT3 inhibitors in combination with other agents, as well as trial data from the LACEWING trial (NCT02752035) of gilteritinib in combination with azacitidine in the frontline setting.

This interview took place at the 63rd ASH Annual Meeting and Exposition Congress, Atlanta, GA, 2021.

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).