VJHemOnc Podcast

Genomics in the age of immuno-oncology

Immunotherapies are at the forefront of myeloma treatment and there are many questions remaining. Defining high-risk is important when making treatment decisions in myeloma and including genomic data may allow for a more personalized risk strategy to be formed for each patient. Highly proliferative cells remain an important indicator of disease, and another factor to consider is the susceptibility of dormant cells to apoptosis, which can influence patient relapse. With the emergence of novel immunotherapies, it is still important to consider genomic data when identifying high-risk patients and use this information to better understand prognosis and potential mechanisms of resistance to novel agents.

In this exclusive podcast, Gareth Morgan, MD, PhD, FRCP, FRCPath of NYU Langone, New York City, NY, Francesco Maura, MD, of the Sylvester Comprehensive Cancer Center, Miami, FL, and Leo Rasche, MD, of the University of Würzburg, Würzburg, Germany, have a fascinating discussion in which they explore genomics in 2022, highlighting key topics including the impact of genomics on the success of immunotherapies, changing risk stratification, and the role of dormant cells in disease progression. This discussion took place at The International Workshop on Myeloma 2022, held in Scottsdale, AZ.

Understanding multiple myeloma at the single-cell level

Relapsed/refractory (R/R) multiple myeloma remains an incurable hematological malignancy with an unmet clinical need.  It is necessary to gain a deeper understanding of the mechanisms driving disease progression and drug resistance in order to find new therapeutic targets for this patient population. In recent years, single-cell approaches including genomic, transcriptomic, and proteomic technologies have emerged as promising tools to decipher this complex disease.

In this episode chaired by Irene Ghobrial, MD, of Dana-Farber Cancer Institute, Boston, MA, Rodger Tiedemann, PhD, ChB, MB, of Princess Margaret Cancer Centre, Toronto, ON, Yael Cohen, MD, of Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel,  and Eileen Boyle, MD, PhD, of NYU Langone, New York City, NY, have a fascinating discussion on using single-cell multiomics to better understand the mechanisms of drug resistance and response to therapy, drawing focus on the impact of chromosome 1q copy number alterations on patient outcomes, as well as on signatures of drug resistance in primary refractory patients, and on how interactions between tumor cells and the tumor microenvironment can predict response to treatment. This discussion took place at The International Workshop on Myeloma 2022, held in Scottsdale, AZ.

Recent advances in amyloidosis treatment

Amyloidosis is a disease that results from the accumulation of a toxic, insoluble protein called amyloid in various tissues and organs, which eventually leads to organ failure. Amyloidosis can be acquired or hereditary, and occurs when protein misfolding turns soluble precursor proteins into insoluble fibrils. There are four main types of amyloidosis: light chain (AL) amyloidosis, AA amyloidosis, ATTR amyloidosis, and AB2M amyloidosis. Amyloidosis remains a challenging disease to diagnose and treat, although recent advances and data from clinical trials provide promising future therapeutic strategies.

In this exclusive podcast, Efstathios Kastritis, MD, University of Athens School of Medicine, Athens, Greece, Vaishali Sanchorawala, MD, Boston University School of Medicine, Boston, MA, and Maria Moscvin, MD, Brigham and Women’s Hospital, Boston, MA, discuss treatment approaches and clinical trial updates to bring you the latest in this field. This interview took place at the 63rd ASH Annual Meeting and Exposition Congress, Atlanta, GA, 2021.

ASH 2021: a deep dive into ALL immunotherapy

Various forms of immunotherapy represent a novel treatment option, especially for patients who progress from conventional chemotherapy hematopoietic stem-cell transplantation (HSCT). Chimeric antigen receptor (CAR) T-cell therapy consists of modified T cells from patients that target antigens specific to cancer cells. Six CAR T-cell therapies have currently been approved by the FDA, with tisagenlecleucel and brexucabtagene autoleucel approved for B-cell acute lymphoblastic leukemia (B-ALL).

Tune into this podcase as Nitin Jain, MD, University of Texas MD Anderson Cancer Center, Houston, TX, delves into the latest updates in CAR T-cell therapies for B-ALL, including exciting results from the  Phase I BALLI-01 trial (NCT04150497) of UCART22 and a Phase I/IIa trial of PBCAR0191 (NCT03666000). Dr Jain additionally presents preliminary results from a Phase I/II trial of ADCT-602 (NCT03698552), an antibody drug conjugate composed of an anti-CD22 antibody and a pyrrolobenzodiazepine (PBD) dimer cytotoxin. This interview took place at the 63rd ASH Annual Meeting and Exposition Congress, Atlanta, GA, 2021.

ASH 2021: what did ASH 2021 mean for MDS?

With high rates of relapse in patients with myelodysplastic syndromes (MDS), there is a great unmet need for novel treatments that are effective and tolerable, despite the heterogeneous nature of MDS. A recent shift in personalized medicine has resulted in a number of clinical trials investigating the combination of hypomethylating agents with novel therapies which likely have a significant impact on the standard of care in MDS. For patients who fail conventional chemotherapy and autologous stem cell transplantation, chimeric antigen receptor (CAR) T-cell therapy and other immunotherapies represent promising therapies.

In this exclusive podcast, David Sallman, MD, Moffitt Cancer Center, Tampa, FL, and Andrew Brunner, MD, Massachusetts General Hospital, Boston, MA, discuss the limitations of current standards of care for MDS and explore emerging treatment targets and strategies for this condition, including drug combinations and cell therapies, especially in TP53-mutated MDS. This interview took place at the 63rd ASH Annual Meeting and Exposition Congress, Atlanta, GA, 2021.

ASH 2021: novel developments in MPNs

The JAK-STAT pathway plays a pivotal role in the pathogenesis of myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis and JAK 1/2 inhibitors such as ruxolitinib have been vital in improving patient survival. The recent approval of ropeginterferon, an interferon therapy for patients with polycythemia vera, and investigational combination therapies in myelofibrosis represent a new generation of therapies that aim to treat MPNs.

In this podcase, Ruben Mesa, MD, UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX, and Naveen Pemmaraju, MD, University of Texas MD Anderson Cancer Center, Houston, TX, share valuable insights on MPNs, including the use of LSD1 inhibitor IMG7289 and ropeginterferon in the second line setting, as well as updates in the treatment landscape of polycythemia vera and myelofibrosis. This interview took place at the 63rd ASH Annual Meeting and Exposition Congress, Atlanta, GA, 2021.

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.