Key Clinical Summary 

• Initial UK RADAR trial results show 88.1% of transplant-eligible, newly diagnosed double-hit multiple myeloma patients remained progression-free at 18 months following Isa-VRDc induction, ASCT, consolidation, and IsaR maintenance. 
• The regimen achieved deep responses, including ≥VGPR rates up to 96.2% and MRD negativity near 70% post-transplant. 
• Safety findings were consistent with intensive therapy, with infections as the most common serious adverse events. 

Early findings from the UK Myeloma Research Alliance (UKMRA) RADAR trial demonstrate that a risk-adapted pathway using isatuximab, bortezomib, lenalidomide, dexamethasone, and cyclophosphamide (Isa-VRDc) can achieve high progression-free survival (PFS) in newly diagnosed, transplant-eligible patients with double-hit ultra-high-risk multiple myeloma. The prospective national phase II/III study evaluates intensified therapy across induction, consolidation, and maintenance. 

Study Findings  

RADAR enrolled 70 high-risk participants (median age 60 years) between September 2022 and September 2023, all with ≥2 high-risk cytogenetic abnormalities (HRCA), including t(4;14), t(14;16), t(14;20), del(17p), del1p, or gain(1q). Eight participants carried ≥3 HRCA. Of the 69 patients initiating induction, 68 completed all 4 cycles, and 61 proceeded to autologous stem cell transplant (ASCT). Treatment adherence exceeded 90% across induction, consolidation, and maintenance. 

Among 67 evaluable patients, 59 were alive and progression-free at 18 months (88.1%; 95% CI 77.8–94.7%), surpassing the trial’s predefined Green threshold for success and outperforming historical controls from Myeloma XI. Response depth increased along the treatment continuum: ≥VGPR rates were 82.9% post-induction, 87.5% post-ASCT, and reached 96.2% and 85.7% at 6 and 12 months after consolidation. 

MRD negativity rose from 26.2% post-induction to 69.5% post-ASCT, with sustained negativity in 66.7% of evaluable patients 12 months into consolidation. Safety analyses showed grade 3–4 toxicities in 63.8% of patients. Serious adverse events occurred in 68.1%, largely infections (42.4%), including 31 grade ≥3 events. 

Investigators concluded that Isa-VRDc induction followed by Isa-VRD consolidation and IsaR maintenance is feasible, deliverable, and capable of producing deep, durable responses in ultra-high-risk myeloma. 

Clinical Implications 

Double-hit myeloma remains one of the most challenging disease subsets, with outcomes significantly inferior to those with standard-risk or single-HRCA disease. The RADAR results offer encouraging evidence that intensifying frontline therapy may improve disease control, MRD negativity rates, and early PFS benchmarks. 

For clinicians, these findings suggest Isa-VRDc may help close the survival gap for genetically high-risk patients when delivered in a structured, multi-phase approach with ASCT. The regimen’s high deliverability and consistent response deepening signal a potential role for this strategy in future risk-adapted treatment algorithms. However, the substantial rate of serious infections highlights the need for vigilant supportive care and monitoring. 

Conclusion 

Initial RADAR trial data demonstrate that Isa-VRDc induction followed by consolidation and maintenance yields high PFS and deep, sustained responses in double-hit myeloma. Continued follow-up will determine long-term durability and inform its role in future high-risk treatment pathways. 

Reference 

Ramasamy K, Royle K, Cicero R, et al. Double hit ultra-high risk myeloma treated with isatuximab, bortezomib, lenalidomide, dexamethasone and cyclophosphamide (Isa-VRDc) induction and isa-VRD consolidation: Initial results of the UK myeloma research alliance (UKMRA) RADAR trial in newly diagnosed transplant eligible patients. Presented at: ASH 2025; December 6-9, 2025; Orlando, Florida.