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.
Study Type
OBSERVATIONAL
Enrollment
300
The Royal Wolverhampton NHS Trust
Wolverhampton, United Kingdom
Overall response rate (OOR) at 12 months
Proportion with partial response (PR) or better (per IMWG criteria).
Time frame: 12 months
Real-world dosing strategy for DRd - starting doses of Daratumumab, Lenalidomide and dexamethasone in cycle 1 and relative dose intensity at 12 months
% of patients who have had a dose adjustment in any of the DRD treatment components within the first 12 months of treatment
Time frame: 12 months
Progression -Free Survival (PFS) at 12 and 24 months
Time from first dose to documented disease progression or death (whichever first) Median time to disease progression or death
Time frame: 12 months and 24 months
Overall survival at 12 and 24 months
Time from first dose to death from any cause
Time frame: 12 months and 24 months
Very good partial response (VGPR)
Per IMWG response definitions (CR = negative immunofixation in serum \& urine + \<5% bone-marrow plasma cells; sCR adds normal free light-chain ratio and absence of clonal plasma cells).
Time frame: 24 months
Occurrence of severe infections
% of patients who have had a grade 3 or 4 infection within 12 or 24 months of starting treatment
Time frame: 12 months and 24 months from starting treatment
Treatment exposure /discontinuation (Treatment deliverability)
Median duration of treatment % treatment discontinuation before 12 and 24 months
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Time frame: 12 months and 24 months
Dosing practice and outcome difference between academic and DGH trusts
Time frame: 12 months and 24 months
Treatment setting
Proportion of patients receiving daratumumab in the community via an outreach service
Time frame: 12 months and 24 months