PO40 | RADAR, UK-MRA MYELOMA XV - COMPARING MRD-GUIDED TREATMENT ESCALATION AND DE-ESCALATION STRATEGIES IN PATIENTS WITH NEWLY DIAGNOSED MYELOMA SUITABLE FOR STEM CELL TRANSPLANTATION: THROMBOPROPHYLAXIS SUBGROUP STUDY PROTOCOL

Z. Sayar, on behalf of the RADAR Investigators | Whittington Health NHS Trust and Royal Free Hospital, London, UK

Background. The Risk-Adapted therapy Directed The Response (RADAR) trial compares treatment escalation and de-escalation strategies in newly diagnosed patients with multiple myeloma (NDMM) suitable for transplant. Thromboprophylactic (TP) guidelines risk stratify patients as high venous thromboembolism (VTE) risk (receive low-molecular-weight heparin [LMWH]) or standard risk of VTE (receive aspirin) (Palumbo, A. 2008). The use of direct oral anticoagulants (DOACs) has been adopted in some UK centers as an alternative to LMWH (Sayar, Z. 2022). In the Myeloma IX trial, VTE occurred in 15.2% of patients receiving treatment. In the Myeloma XI trial, at least one thrombotic event occurred in 13.7% of patients receiving treatment (VTE 12.2%, arterial thrombosis 1.8%) (Bradbury, CA 2020). Myeloma chemotherapy regimens evolve rapidly without contemporaneous knowledge of thrombotic risk associated with them.

Aims. A TP subgroup in the RADAR trial aims to understand the thrombotic risk of chemotherapy regimens used to treat NDMM. It aims to investigate whether DOACs are a suitable alternative to LMWH for TP.

Materials and Methods. The UK-MRA RADAR study is a national, multi-center, risk-adapted, response-guided, multi-arm, multi-stage phase II/III trial that will recruit 1400 patients. The RADAR protocol states TP choice is based on assessment of the patient’s underlying risks, clinical status, and local practice. The trial opened to recruitment in May 2021 (due to close in May 2026) with the TP subgroup amendment made in June 2024.

Outcomes/Analysis. The hypothesis is DOACs are non-inferior to LMWH as primary TP in patients at high risk of thrombosis with myeloma receiving outpatient chemotherapy. The primary efficacy outcome is the first episode of objectively documented venous or arterial thromboembolism. This will be categorized according to the TP agent prescribed, chemotherapy regimen received, and adjusted for demographic covariates and disease stage. The main safety outcome is bleeding as defined by the ISTH (Schulman, S. 2005). This will be categorized according to the TP agent prescribed. This novel and large data set will contribute to our understanding of which TP agents are prescribed, risk of thrombosis with different chemotherapy and TP regimens and bleeding events.

Conclusions. To our knowledge, this is the first TP subgroup of a myeloma trial collecting data contemporaneously, thus offering information on thrombosis risk and prevention in line with the chemotherapy agent.