DECODE: CRS | Ametris

Introduction

Patient access to CAR-T and T‑cell engager (TCE) therapies remains limited despite their transformative clinical potential. A key bottleneck is Cytokine Release Syndrome (CRS), a frequent but increasingly manageable inflammatory response associated with CAR‑T and TCEs. Concern over CRS severity has driven highly conservative care models, requiring inpatient administration, specialized centers, and intensive monitoring. As a result, CRS functions less as a safety issue and more as a system‑level barrier that restricts where and how therapy can be delivered.

Expanding access to immunotherapy depends on de‑risking CRS in outpatient and community settings, enabling decentralized care models, lower cost of delivery, and broader physician participation. Technologies and approaches that improve CRS predictability, early detection, and standardized management are critical enablers of scale. By reducing uncertainty around adverse event management, they unlock outpatient administration, increase center capacity, and significantly expand the addressable patient population.

The Problem

CRS remains a significant clinical barrier to expanding access to CAR-T and bispecific TCE immunotherapies.

Several key challenges limit progress:

Heterogeneity across therapies: CRS presents differently across immunotherapy classes, individual drugs, and indications, making it difficult to generate evidence that is both robust and broadly applicable.
Variability in grading and monitoring: Intensive monitoring requirements restrict many therapies to specialized centers.
Operational burden: Intensive monitoring requirements restrict many therapies to specialized centers.
Access constraints: Community providers often face uncertainty in managing adverse events, limiting the number of patients who can safely receive treatment.
Capacity and cost pressures: Without standardized protocols for detecting and managing CRS, health systems face higher costs and constrained capacity for therapies that could otherwise be delivered in outpatient settings.

These challenges are not confined to a single therapy or sponsor, but rather they are a shared constraint across the immunotherapy ecosystem. A coordinated, cross-sector solution is needed to generate clinically meaningful evidence that satisfies regulatory oversight and is applicable across modalities.

The Solution

DECODE CRS

Pre-Competitive, System-Level Approach to Accelerate Immunotherapy Access

Building on DiMe’s original CRS digital measures work, DECODE CRS combines Ametris’ expertise in continuous sensor-based data collection and DiMe’s cross-sector leadership with global immunotherapy development experience from leading biopharma sponsors.

Workstream #1:

Through structured collaboration, members will align on clinical, commercial, and regulatory needs and success criteria for CRS monitoring products, including:

Interviews with patients, clinicians, and investigators to define user needs, workflow fit, and usability criteria
Workshops with payors, regulators, and health systems to evaluate utility, reimbursement, and adoption
Best practices for objective CRS grading, adverse event adjudication, and precise data collection guidelines
Standardized protocols and tools needed for widespread community clinic adoption. This standardization requires a consensus amongst experts in how adverse events are defined.

Collaboration from the first workstream will inform the largest prospective study of its kind focused on developing scalable solutions to increase immunotherapy access in community settings, which will be carried out as part of workstream 2.

Workstream #2:

Collect a high-quality dataset with approved immunotherapies to develop a CRS early warning model with this effort informed by workstream 1.

Prospective study with at least 150 patients on approved CAR-T and TCE immunotherapies to build a robust real-world dataset
Model development and validation for early CRS detection. Analysis of model generalizability across modalities and future sample size requirements for different intended uses
Care providers need guidance and alerting tools to aid in the standardization of adverse event management. This guidance and these tools are data-driven products that require this unique, first-in-kind data gathering effort.

The Impact

DECODE CRS aims to develop a clinically appropriate, regulatory-ready, and commercially viable monitoring solution to enable:

Expanded access to CAR-T and TCE treatments beyond specialized cancer centers
Safer outpatient immunotherapy delivery
Reduced variability in adverse event detection and management
Lower system-wide development and operational costs
Improved patient outcomes through earlier detection and intervention
Less burden on healthcare systems while increasing capacity

DECODE CRS seeks to accelerate progress at a pace and level of rigor that individual efforts cannot achieve alone.

Please Check Back for Regular Updates

Find more information below about how to become involved in the project and access related resources.

Become a Partner

Ametris and DiMe continue to welcome additional partners to the DECODE CRS Coalition.

Participation Provides the Opportunity to:

Influence clinical and research direction for defining, collecting, and adjudicating CRS data
Contribute to the development of broadly applicable evidence standards
Evaluate reimbursement and real-world feasibility strategies
Align early with regulators, payors, clinicians, and patient representatives
Help define scalable models for community and rural care settings
Workstream 2 partners have access to a first-in-kind immunotherapy treatment dataset consisting of wearable data as well as patient outcome-related data for internal analysis. A CRS monitoring algorithm that results from these data, as well as participation in health authority interactions, is provided along with this dataset.

CRS is a shared barrier to immunotherapy access. Through pre-competitive collaboration, we can create shared solutions that expand safe, equitable access to life-saving immunotherapies.

Case Studies and Related Resources

White Paper

Bringing CAR-T and TCE Care Closer to Home: An Adjudication Framework and Feasability Assessment for Outpatient CRS Monitoring

Webinar

Overcoming Treatment Barriers: How DHTs can Facilitate Widespread Outpatient Immunotherapy Treatments

Blog

The Pathway to a Digital Health Solution for Cytokine Release Syndrome Detection and Prediction

Flyer

Cytokine Release Syndrome Monitoring

Digital Endpoint Guide

Oncology

DiME CRS

De-risking Cytokine Release Syndrome: Digital Measures Development Project Home