This study will describe the use of triplet therapy with daratumumab, lenalidomide and dexamethasone (DRd) in the treatment of for transplant ineligible (TIE) untreated myeloma outside of clinical trials and assess the associated clinical outcomes.

Triplet therapy with daratumumab, lenalidomide and dexamethasone (DRd) for transplant ineligible (TIE) untreated myeloma patients (MAIA) was reported in 2019. NICE approved this in September 2023 and since this time DRd has become the standard of care regimen for TIE patients with newly diagnosed multiple myeloma in the UK. Although there are reports of real world experience (RWE) of DRd efficacy in relapsed setting, there are no RWE reports of DRd efficacy and outcomes from the UK where it is used in the upfront setting and very limited data from Europe. Moreover, UK clinicians often adopt a pragmatic dose adjustment approach, particularly in the dosing of lenalidomide (escalation and de-escalation) with steroid tapering. As well as reducing short-term toxicities, this approach may lead to longer term benefits by reducing long-term steroid adverse effects such as steroid-induced diabetes, help ameliorate immune paresis and reduce infection risk.

However, there is very limited data on the efficacy and outcomes of this practice. In particular, there is no published RWE on the impact of pre-emptive dose modifications on tolerability and efficacy in frail patients, the cohort in which the highest treatment discontinuation rates were observed in the MAIA trial. It is also perceived that patients with comorbidities, which would have been excluded in MAIA cohort, are benefiting from this flexible approach in real world practice, especially people with chronic kidney disease and other comorbidities. A proportion of patients initially deemed fit for autologous stem cell transplantation (received D-VTD as induction) are also receiving DRd if they fail to receive a transplant. These patients were not represented in the MAIA study and the outcomes following de-escalation from D-VTD to DRd are unknown.

Inclusion Criteria:

• Age ≥18 years
• Diagnosis of NDMM
• Not eligible for autologous stem cell transplant at diagnosis
• Received frontline DRd treatment following NICE approval (post-September 2023)
• Minimum 3 months of follow-up data available

Exclusion Criteria:

• Participation in an interventional clinical trial for first-line therapy
• Insufficient treatment or follow-up data for analysis
• DRd used in relapsed/refractory setting rather than newly diagnosed disease

Sites participating in this study will be those who have prescribed DRd for newly diagnosed transplant ineligible patients since this triple combination was reimbursed for use in the UK healthcare system in 2023.

Within the study, data will be collected from the medical records of adult patients aged ≥18 years with ND MM, who are ineligible for transplant and who have received at least one dose of DRd outside of clinical trials.

To be eligible for inclusion in the study, the date of the first dose should be:

• on or before 31 December 2024, between September 2023 to 31 December 2024 (first data cut)
• on or before 31 December 2025, between September 2023 and 31 December 2025 (second data cut)

Data will be analysed in Q1 2026 to assess treatment outcomes at 12 months (to 31 December 2025) and in Q1 2027 to assessment 12- and 24-months treatment outcomes.