Patient experience sub-study of a randomised UK multicentre Phase 2 trial of ASTX727 versus hydroxycarbamide/best supportive care in myelodysplastic (MDS)/myeloproliferative (MPN) overlap syndromes (AMMO)

Abstract

Abstract Introduction MDS/MPN Overlap Syndromes are haematological neoplasms with overlapping features of myeloid dysplasia and proliferation. They mostly affect older male adults. Comorbidities, notably cardiovascular, renal and inflammatory, are frequent and complicate therapeutic delivery. Clinical trials have thus been challenging to design and deliver. AMMO is a UK randomised phase 2 trial comparing the oral hypomethylating drug ASTX727 vs hydroxycarbamide/best supportive care (HC/BSC). We evaluated patient experience of being on the trial to establish support needs, identify barriers to participation and inform future trial modifications. Methods A qualitative sub-study with consenting patients was conducted in parallel to the interventional trial. Patients were interviewed at trial entry, end of cycle 6 (C6) and at 12months. Interviews were audio-recorded and transcribed verbatim. Reflective thematic analysis was performed independently by 2 researchers. Content analysis was applied to compare prevalence and burden of symptoms and side effects (SEs). Results In total 44 patients consented to the sub-study (ASTX727 arm=37; HC/BSC10 arm=10; 2 screen fails); with 79 interviews in total. Number of interviews per participant were 1 (n=18), 2 (n=17) or 3 (n=9). Timepoints were trial entry (n=23), C6 (n=34) and 12months (n=22). Reasons for non-completion included late referral to sub-study (n=30), lost to FU (n=19), declined/withdrew (n=13), died (n=10), screen fail (n=6) and otherwise not considered appropriate (n=2). Mean age of participants was 72, with 57% male, mirroring the main trial demographic. Preliminary analysis is situated within the 4 domains of the Person-Centred Care Framework: 1) Prerequisites: Staff were considered professionally competent, displaying skills needed to communicate/support effectively and accommodate individual needs. 2) Care environment: Patients noted good support from the clinical/trial teams and SEs were well managed. Patients consistently emphasised the importance of this, and for ease of contact with trial staff. 3) Person-centred processes: Appropriate information was mostly delivered to support informed decision-making. Coping mechanisms employed included acceptance and humour, with patients emphasising reliance on clinical and personal support. Many expressed anxiety initially regarding randomisation, hopeful to be allocated ASTX727. Those randomised to HC/BSC expressed disappointment/upset, but broad acceptance and recognition of its importance to trial design; all retained a feeling of contributing meaningfully to the trial. 4) Person-centred outcomes: Patients were largely satisfied with their care, expressing gratitude/admiration for clinical staff and management of issues. Although most were satisfied with information provision, some highlighted suboptimal areas. Notably, some felt explanations (and of proposed next steps) when approaching end of trial (C6) were insufficient. Complexities of randomisation were often misunderstood; several thought the HC/BSC arm included placebo or that the trial was blinded. As in the CTCAE-categorised toxicity report, patients frequently recognised low blood counts as an important SE and understood their implications (eg need for transfusions). Many did report having infections, exhibiting awareness of the risks and recommended precautions. Contrasting with the formal report, the most common/burdensome patient-reported SE (particularly at 12months) was fatigue, followed by nausea/vomiting. Many though self-reported no SEs. The financial impact of participation (eg travel costs) was a notable challenge highlighted by some; generally those living furthest from trial centres. Conclusion Substantial qualitative data were generated around patient experience participating in AMMO. Overall experience (on both arms) was positive, exceeding the expectations of many, especially those deriving clinical benefit. Most were grateful for the opportunity to participate, expressing a range of motivations including extending life expectancy, improving quality of life or to benefit future patients. Results highlight variation in support/information needs, with desire for more robust communication, especially around personal trial completion/next steps, a recurrent theme. Other areas identified as key to optimising patient experience included coping/support mechanisms and financial toxicities; reaffirming the importance of trial sponsors making provision for cost reimbursement.