Blood Podcast

In this week's episode, Blood editor Dr. Laura Michaelis interviews author Dr. Taylor Brooks on his latest paper published in volume 146 issue 18 of Blood Journal. The conversation discusses outcomes of bispecific antibodies (epcoritamab or glofitamab) in treating aggressive B-cell lymphoma in a study with 245 patients. Findings show a tentative way forward in treatment for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Featured Article:

• Real-world outcomes of patients with aggressive B-cell lymphoma treated with epcoritamab or glofitamab

In this Review Series episode, Associate Editor Dr. Philippe Armand speaks with multiple authors about what it might look like to improve treatments follicular lymphoma, a disease that has been put on the backburner of innovation due to its generally treatable nature. Dr. Armand discusses "Treatment of relapsed and refractory follicular lymphoma: which treatment for which patient for which line of therapy?" with author Dr. Carla Casulo,  "The future of follicular lymphoma management: strategies on the horizon” with author Dr. Sarah C. Rutherford, and "An updated understanding of follicular lymphoma transformation” with Dr. Erin M. Parry.

Find the whole review series on follicular lymphoma in volume 146 issue 15 of Blood Journal.  

In this week's episode of the Blood Podcast, Associate Editor Dr. James Griffin interviews Drs. Binod Dhakal and Ruben Bierings about their respective papers published in this week's issue of Blood. Dr. Dhakal presents his study on using talquetamab, a bispecific antibody, as a bridging therapy before BCMA-targeted CAR T-cell therapy in multiple myeloma patients, showing promising results with high response rates and manageable toxicities. Next, Dr. Bierings identified patients with genetic variants in the guanine exchange factor MAP kinase–activating death domain (MADD) that impair VWF secretion from endothelial cells and possibly cause VWD type 1. 

Featured Articles

• A novel cause of type 1 von Willebrand disease: impaired exocytosis of Weibel-Palade bodies due to biallelic MADD variants
  Sophie Hordijk, Stijn A. Groten, Petra E. Bürgisser, Sebastiaan N. J. Laan, Georg Christoph Korenke, Tomáš Honzík, Diane Beysen, Frank W. G. Leebeek, Paul A. Skehel, Maartje van den Biggelaar, Tom Carter, Ruben Bierings
• Sequential targeting in multiple myeloma: talquetamab, a GPRC5D bispecific antibody, as a bridge to BCMA CAR-T therapy
  Binod Dhakal, Othman S. Akhtar, David Fandrei, Alexandria Jensen, Rahul Banerjee, Darren Pan, Shambavi Richard, Reed Friend, Matthew Rees, Patrick Costello, Mariola Vazquez Martinez, Oren Pasvolsky, Charlotte Wagner, James A. Davis, Omar Castaneda Puglianini, Ran Reshef, Aimaz Afrough, Danai Dima, Manisha Bhutani, Omar Nadeem, Ricardo Parrondo, Ciara Freeman, Lekha Mikkilineni, Shahzad Raza, Larry D. Anderson Jr, Prashant Kapoor, Hitomi Hosoya, Saurabh Chhabra, Ariel Grajales-Cruz, Mahmoud Gaballa, Shonali Midha, Melissa Alsina, Douglas Sborov, Krina Patel, Yi Lin, Christopher Ferreri, Nico Gagelmann, Anupama Kumar, Doris Hansen, Andrew Cowan, Luciano J. Costa, Maximilian Merz, Surbhi Sidana

In this Spotlight series episode on Acute Myeloid Leukemia, Blood Editor, Dr. Selina Luger interviews Drs. Laura Michaelis and Alexander Perl on their paper in the series titled “The fit older adult with acute myeloid leukemia: clinical challenges to providing evidence-based frontline treatment”. The conversation explores challenges in treating AML across different patient populations. They also focus on treatment approaches for fit older adults with AML, highlighting the need for less toxic therapies and ongoing randomized trials to better understand treatment efficacy.

See the full spotlight series on Acute Myeloid Leukemia in Volume 145 Issue 24 of Blood journal. 

In this week's episode we’ll learn more about a study comparing busulfan-melphalan with melphalan alone as the conditioning protocol for newly diagnosed, transplant-eligible multiple myeloma; then we will discuss data on how three-dimensional transcriptomics can reveal complex interactions between plasma cells and bone marrow microenvironments.

Featured Articles

• High-dose busulfan-melphalan vs melphalan and reinforced VRD for newly diagnosed multiple myeloma: a phase 3 GEM trial
• Profiling the spatial architecture of multiple myeloma in human bone marrow trephine biopsy specimens with spatial transcriptomics
• Preclinical advances in glofitamab combinations: a new frontier for non-Hodgkin lymphoma

In this How I Treat podcast episode, Laura Michaelis, MD interviews Sung-Yun Pai, MD about their recently published article in Blood journal "How I treat Wiskott-Alrich syndrome". They highlight recent updates in treatment, including new risk-benefit calculations due to safer treatments and longer follow-ups. Challenges include late diagnosis, lack of well-matched donors, and limited gene therapy availability. They emphasize the importance of early referral to specialized centers and the need for discussions about curative intent therapies, including transplant and gene therapy. The conversation also covers the complexities of gene therapy, such as the need for better conditioning agents and the challenges of achieving full correction in all cell types.

In this week's episode we'll learn about targeting the tissue factor pathway inhibitor with a monoclonal antibody to rebalance HEMOSTASIS in hemophilia A and B. In the phase 3 BASIS trial, the monoclonal antibody marstacimab reduced bleeding events, and was generally well tolerated, with no unanticipated side effects. After that: matched-donor allogeneic CD19 CAR-T for adult B-ALL. Given after allogeneic transplantation, CAR-donor lymphocyte infusion after lymphodepleting chemotherapy was associated with favorable efficacy and a tolerable safety profile. Finally: a new prognostic index for mycosis fungoides and Sézary syndrome. Comprised of four prognostic factors, the “CLIPI” could enable more personalized treatment of cutaneous lymphomas, identifying patients who may benefit from intensified treatment.

Featured Articles

• Marstacimab prophylaxis in hemophilia A/B without inhibitors: results from the phase 3 BASIS trial
• Matched donor allogeneic CAR-T for adult B-ALL: toxicity, efficacy, repeat dosing, and the importance of lymphodepletion
• A new prognostic index (CLIPI) for advanced cutaneous lymphoma enables precise patient risk stratification

In this week's episode, we’ll learn more about relationships between Epstein-Barr virus genomic variants and human diseases, including hematological malignancies; the presence and timing of somatic GATA1 mutations and their relationship to a Down syndrome-specific form of leukemia; and new definitions for high-risk multiple myeloma that emphasize the presence of two or more high-risk cytogenetic abnormalities.

Featured Articles:

• Association of Epstein-Barr virus genomic alterations with human pathologies
• Clinical significance of preleukemic somatic GATA1 mutations in children with Down syndrome
• Biallelic antigen escape is a mechanism of resistance to anti-CD38 antibodies in multiple myeloma

In this Review Series episode, Associate Editor Dr. Hervé Dombret speaks with Dr. Mark Litzow about the latest immunotherapy advances for Acute Lymphoblastic Leukemia (ALL). The discussion highlights innovative treatments like blinatumomab and inotuzumab, which are showing remarkable success in clinical trials, including an 85% three-year survival rate and over 90% complete remission in elderly patients. Researchers are focusing on reducing chemotherapy intensity, developing personalized treatment approaches, and identifying optimal immunotherapy strategies for different ALL subtypes. The conversation underscores a promising shift towards more targeted, less toxic treatments that could significantly improve patient outcomes across various age groups and disease characteristics. These emerging therapies represent a potential paradigm shift in ALL treatment, offering hope for more effective and less aggressive therapeutic interventions.

Read Dr. Litzow's paper “Incorporation of immunotherapy into frontline treatment for adults with B-cell precursor acute lymphoblastic leukemia” or find the whole review series on acute lymphoblastic leukemia in volume 145 issue 14 of Blood Journal. 

In this week's episode we'll learn about Azacitidine in VEXAS syndrome. Treatment can provide responses in patients with this complex autoinflammatory disorder. But relapse rates were high, so long-term therapy may be required to maintain disease control. After that: A step forward in precision blood matching. High-throughput array genotyping enables extended matching to reduce antibody formation. The results show the potential for reducing harm in regularly transfused patients. Finally, identifying a new vulnerability in TP53-mutated AML. Loss of the tumor suppressor BAP1 defines a unique subtype of TP53-mutated de novo AML. BAP1 loss also confers sensitivity to BCL-xL inhibitors in vivo, opening a new therapeutic avenue.

Featured Articles

• Efficacy and safety of azacitidine for VEXAS syndrome: a large-scale retrospective study from FRENVEX
• Array genotyping of transfusion-relevant blood cell antigens in 6946 ancestrally diverse study participants
• Loss of BAP1 defines a unique subtype of TP53-mutated de novo AML and confers sensitivity to BCL-xL inhibitors