Myeloma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
The Royal Wolverhampton Hospitals NHS Trust
Johnson & Johnson
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (OOR) at 12 months | 12 months | Proportion with partial response (PR) or better (per IMWG criteria). |
| Real-world dosing strategy for DRd - starting doses of Daratumumab, Lenalidomide and dexamethasone in cycle 1 and relative dose intensity at 12 months | 12 months | % of patients who have had a dose adjustment in any of the DRD treatment components within the first 12 months of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression -Free Survival (PFS) at 12 and 24 months | 12 months and 24 months | Time from first dose to documented disease progression or death (whichever first) Median time to disease progression or death |
| Overall survival at 12 and 24 months | 12 months and 24 months | Time from first dose to death from any cause |
| Very good partial response (VGPR) | 24 months | 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). |
| Occurrence of severe infections | 12 months and 24 months from starting treatment | % of patients who have had a grade 3 or 4 infection within 12 or 24 months of starting treatment |
| Treatment exposure /discontinuation (Treatment deliverability) | 12 months and 24 months | Median duration of treatment % treatment discontinuation before 12 and 24 months |
| Dosing practice and outcome difference between academic and DGH trusts | 12 months and 24 months | — |
| Treatment setting | 12 months and 24 months | Proportion of patients receiving daratumumab in the community via an outreach service |
Countries
United Kingdom
Contacts
CONTACTTanweer Ahmed
CONTACTLorraine Jacques
PRINCIPAL_INVESTIGATORHannah Giles
University Hospital Birmingham NHS Foundation Trust
Outcome results
None listed