Blood Podcast Summary

Episode: "VTE Risk Model in Children and a Novel Tri-specific T-cell-engager for MM"
Host: Dr. Laurie Sen (Associate Editor, Blood)
Date: February 19, 2026
Podcast: American Society of Hematology – Conversations with Blood Authors

Episode Overview

This episode features in-depth conversations with leading researchers about two significant studies recently published in Blood. Dr. Julie Jaffre discusses the multi-site validation of a thrombosis risk model for critically ill children (CHAT ICU model), while Dr. Ulrike Philippar highlights a novel tri-specific T-cell engager, Romantomig, targeting multiple antigens in multiple myeloma (MM) models. Both segments explore the clinical importance, experimental details, and potential impact of these advances in hematology.

Segment 1: Multi-site Validation of a Venous Thrombosis Risk Model in Critically Ill Children

Guest: Dr. Julie Jaffre, Rady Children’s Hospital & UC San Diego
Original Paper: "Multi Site Validation of a Venous Thrombosis Risk Model in Critically Ill Children through the CHAT Consortium"
Timestamps: 00:26–09:08

Clinical Background and Need

• Rising VTE in Pediatric Patients:
  • Hospital-associated VTE rates in children have increased significantly—by about 120% over the past decade, affecting all hospital units, with the pediatric ICU showing the highest rates.
  • Symptomatic clots occur in about 2% of PICU admissions; up to 16% may develop asymptomatic clots if central venous lines are present.
  • (Dr. Jaffre, 01:05):

    "Rates of VTE... have been going up for the last really couple of decades... We see rates now going up by about 120% over the last 10 years."

• Gap in Prevention:
  • Effective prevention in children still lags behind adult protocols.

Development of the CHAT ICU Risk Model

• Origin:
  • The CHAT Consortium began with 8 centers (now 69) aiming to identify and validate risk factors for thrombosis in hospitalized children.
• Identified Risk Factors:
  • Five main risk factors:
    1. Immobility (Braden score)
    2. New infection / inflammation
    3. Congenital heart disease
    4. ICU stay ≥ 3 days
    5. Central venous catheter
  • (Dr. Jaffre, 02:30):

    "We created a risk model... five main risk factors. So things like being immobile... new infection... congenital heart disease... three or more days in the ICU... and having a central venous catheter."

Study Design & Population

• Prospective, Multi-center Validation:
  • Despite the pandemic, 32 centers prospectively validated the risk model, enrolling over 4,500 PICU patients via chart review.
  • Risk factors were assessed within the first 24 hours of ICU admission, and patients were followed for development of VTE during and after hospitalization (to 30 days).
  • (Dr. Jaffre, 03:25):

    "We were able to enroll over 4,500 patients, which was a pretty fantastic feat in pediatric research."

Main Findings

• Validation of Predictive Utility:
  • Risk scores were created by weighting each risk factor (some scored 1, others 2).
  • VTE incidence:
    • 1 risk factor: 1% risk
    • 5–6 risk factors: 17% risk
    • All risk factors: up to 30% risk!
  • The model can be used for real-time risk stratification of PICU patients.
  • (Dr. Jaffre, 05:14):

    "The risk of actually developing a clot with one of those five risk factors was 1%. But once you get up to five, six risk factors, that is going up to 17%...even 30% if you have all of the risk factors."

  • Emphasizes next steps: developing strategies for safe and effective VTE prevention in children.

Limitations and Next Steps

• Does Not Predict Bleeding Risk:
  • The model doesn't account for bleeding risk, which is critical when considering prophylactic anticoagulation.
  • Existing studies show low bleeding risk with prophylactic anticoagulation in children, but ICU patients are a higher-risk group.
  • Future goal: develop complementary models for both thrombosis and bleeding risks.
  • (Dr. Jaffre, 07:29):

    "Most clinicians have been hesitant to start prophylactic anticoagulation because of that potential risk of bleeding... one day we will have a CHAT bleeding model."

Notable Quotes

• (Dr. Jaffre, 07:29):

  "What a person needs to do is not only apply the CHAT risk model, but hopefully one day we will have a CHAT bleeding model and we can put the thrombosis CHAT model and the bleeding CHAT model together to find the perfect patient..."

Key Segment Timestamps

• [01:05] Pediatric VTE background/rates
• [02:30] Risk factor identification
• [03:25] Study design & patient enrollment
• [05:14] Model validation & risk stratification
• [07:29] Limitations: Bleeding risk & future directions

Segment 2: A Novel Tri-specific T-cell Engager (Romantomig) for Multiple Myeloma

Guest: Dr. Ulrike Philippar, Johnson & Johnson Innovative Medicine
Original Paper: "A novel T cell engaging trispecific antibody targeting BCMA, GPRC5D and CD3 in multiple myeloma models"
Timestamps: 10:14–15:59

Challenges of Current BCMA/GPRC5D Bispecifics

• Response Rates & Resistance:
  • Both BCMA-CD3 and GPRC5D-CD3 bispecific antibodies have improved patient outcomes but face limitations due to disease heterogeneity and resistance.
  • Clonal variation means some myeloma cells express only BCMA or GPRC5D; after therapy, antigen downregulation or gene deletion can cause therapeutic escape.
  • (Dr. Philippar, 10:31):

    "There's a heterogeneity... clones that express BCMA and GPRC5D but then there's also clones that only express BCMA or GPRC5D... resistance... comes through downregulation of a tumor associated antigen."

Rationale for Trispecific Targeting

• Addressing Tumor Heterogeneity and Resistance:
  • Designing Romantomig to engage both BCMA and GPRC5D (plus CD3) aims to prevent escape via single antigen loss, increase response rates, and improve durability.
  • (Dr. Philippar, 12:08):

    "The rationale was to have one molecule that is addressing the heterogeneity... also durability and hopefully prevention of resistance."

Key Experimental Findings

• Preclinical Efficacy Across Models:
  • In vitro, Romantomig effectively kills multiple myeloma cell lines expressing either or both antigens.
  • Knockdown and knockout experiments demonstrate activity even if only one target is present.
  • Experiments with patient-derived samples confirmed efficacy across variable antigen expression.
  • In vivo mouse models with both BCMA- and GPRC5D-positive tumors showed shrinkage of both with Romantomig—superior to using separate bispecifics.
  • (Dr. Philippar, 12:41):

    "We have shown that ramantamib can efficiently bind to... cell lines... lead to cytotoxicity... and T cell activation... both tumors shrink, so we see very potent efficacy if one of the targets is expressed..."

Clinical Implications and Future Directions

• Potential Post-bispecific Therapy:
  • Romantomig shows early activity even in patients refractory to prior BCMA or GPRC5D-targeting therapies, depending on resistance mechanism.
  • Early clinical data: 100% overall response rate, with deeper responses over time.
  • Improved safety profile supports outpatient administration with a single step-up dose.
  • (Dr. Philippar, 15:24):

    "Romantamig demonstrated a favorable safety profile compared with BCMA or GPRC5D targeting bispecific antibodies, which is leading to a convenient single step up dose."

Distinguishing Trispecific from Combination Therapy

• More than Just Two Bispecifics:
  • The trispecific format enables single-agent treatment for tumors expressing either antigen, potentially offering advantages in efficacy, safety, and logistics versus combining separate bispecifics.

Notable Quotes

• (Dr. Philippar, 12:08):

  "The rationale was to have one molecule that is addressing the heterogeneity, so leading to higher overall response rates but also durability and hopefully prevention of resistance..."

• (Dr. Philippar, 15:24):

  "The early overall response rate for Romantamig were 100% and responses continue to deepen..."

Key Segment Timestamps

• [10:31] Limitations of bispecifics & resistance mechanisms
• [12:08] Rationale for trispecific design
• [12:41] Experimental findings
• [14:37] Post-bispecific therapy considerations
• [15:24] Safety, outpatient use, and trispecific vs. combo therapy

Conclusion & Key Takeaways

• For Pediatric VTE:

  • The CHAT ICU model enables improved risk stratification in critically ill children, setting the stage for safer, targeted thromboprophylaxis. Future research should focus on integrating bleeding risk models.

• For Multiple Myeloma:

  • Trispecific antibody Romantomig represents a promising new strategy to overcome tumor heterogeneity and resistance seen with current bispecific therapies, with early data suggesting potent efficacy and favorable safety.

For Further Reading

• Explore both featured studies in full at bloodjournal.org.