More efficient delivery of high-cost standard-of-care therapies in relapsed multiple myeloma using real-time feedback of patient-reported outcome measures: the MY-PROMPT-2 trial

Topic: 35. Quality of life and palliative care Background: Despite advances in treatment of multiple myeloma (MM), real-world data show that survival benefits achieved with newer therapies in clinical trials are not seen in clinical practice. Moreover, newer MM therapies with multiple combinations are more complex to deliver with challenging toxicities. Data from the Australian & New Zealand Myeloma and Related Diseases Registry (MRDR) show many patients stop therapy early, mainly for reasons not associated with disease response, and therefore, do not experience the potential survival benefit that optimal duration on therapy (DoT) affords. If treating clinicians are aware of emerging symptoms, thus informing timely intervention, DoT may be optimized, enhancing treatment effectiveness. Routine use of patient-reported outcome measures (PROMs), including feedback to treating clinicians, improves outcomes in non-hematological cancer populations, but has not been tested in MM. The pilot MY-PROMPT randomized controlled trial (RCT) showed real-time feedback of PROMs in MM was feasible and acceptable to patients and clinicians. MY-PROMPT-2 builds on this. Aims: To determine in patients with relapsed MM (RMM), receiving standard of care (SoC) lenalidomide (R), carfilzomib (K) or daratumumab (D)-based therapies, whether routine real-time PROMs feedback to clinicians at patient visits improves event-free survival (EFS: time from randomization to an event [permanent discontinuation of treatment, progression or death]) compared to patients on SoC alone. Methods: This parallel, non-blinded, multicenter Bayesian RCT, uses 1:1 allocation, stratified by 3 SoC regimens (R, K, or D-based) and age. There is provision for recruitment of 200 adults with RMM co-enrolled on the MRDR. Intervention: PROM results summary is fed back to clinicians at monthly visits for 12 months. PROMs used: • MyPOS: MM-specific, 30 item questionnaire on symptoms/ mood/ healthcare support • Additional regimen-specific questions (≤5) for common side effects of K, and D-based regimens ePROM system: REDCap-based for easy implementation in routine care. PROMs are emailed to intervention patients 1 week before clinic visits. Completion in clinic is possible. A summary of reported concerns is emailed to the clinician, patient and site staff, allowing delivery via multiple pathways. PROMs to compare health-related quality of life (EORTC QLQ-C30) and treatment satisfaction (TSQM-9) between groups are collected 3-monthly in both trial arms for 12 months. Novel statistical trial design: Once ≥60 events have been observed between the 2 arms, EFS monitoring comparing the intervention versus control arm, starts. Using pre-established criteria, if monitoring shows • the intervention arm is inferior to controls, the trial will be stopped. • the intervention arm is superior to controls, the Trial Management Committee can declare: ○ Proof of concept (i.e. publish) - if statistical thresholds are met or ○ Recommend further expansion of trial (subject to funding). Results: Recruitment has commenced at >2 sites and will be active at up to 15 sites. Summary/Conclusion: This is the first registry-based multicenter trial in patients with MM (and a first in blood cancer) to test the clinical benefit of real-time PROM reporting. The widely used ePROM platform facilitates translation into practice and the pragmatic design suits rare diseases allowing a smaller sample size to guide the decision to adopt real-time PROM reporting. Registry co-enrollment means potential benefits for MM patients at all MRDR sites in Australia & NZ. Findings could be translatable to other cancers, chronic diseases and disease registries. Keywords: Myeloma, Patient reported outcomes, Clinical trial, Treatment