P12 health-related quality of life in frail and intermediate-fit patients with newly diagnosed multiple myeloma treated with dose-adjusted melphalan-prednisone-bortezomib (mpv)

Background: Frailty in non-transplant eligible (NTE) newly diagnosed multiple myeloma (NDMM) patients is associated with toxicity which can negatively affect physical functioning and quality of life (QoL). Older patients may prefer QoL and physical independence over length of life, highlighting the importance of taking health-related (HR) QoL assessment into account for treatment guidance. Methods: The HOVON123 study (NTR4244) was a phase II trial in which 238 NTE-NDMM patients ≥75 years were treated with 9 dose-adjusted cycles MPV. Nine (3 functional; 6 symptom) subscales of two HRQoL instruments (EORTC QLQ-C30 and MY20) were obtained at baseline (T0), after 3 (T1) and 9 (T2) cycles of therapy, and 6 (T3) and 12 (T4) months after discontinuation of therapy in patients without progression. The presence of “tingling hands/feet” was used as a proxy for neuropathy. Differences in baseline HRQoL were analysed with independent t-tests and changes over time with linear mixed models. HRQoL changes and/or differences were reported only when both statistically significant (p<0.005, adjusted for multiple testing) and clinically relevant (>MID). Results: A total of 137 frail and 71 intermediate-fit patients were included in the HRQoL analysis, after exclusion of fit patients and patients whose frailty status or baseline HRQoL questionnaire was missing. Compliance was not materially different in both groups. Frail patients had an inferior HRQoL at baseline in the subscales global health status, physical functioning, fatigue and pain, compared with intermediate-fit patients. Both groups reported improvements in global health status and future perspective. In contrast to intermediate fit patients, frail patients improved in physical functioning, fatigue and pain over time. The improvements in global health status were reached earlier in frail patients (T1) compared with intermediate fit patients (T2), Figure 1. In both intermediate fit and frail patients there was an increase in neuropathy. All other subscales remained within MID ranges and/or were not statistically significant different from baseline. The improvement in global health status sustained after treatment completion (T3-T4) both for frail and intermediate fit patients. This also accounted for future perspective at T3, however, at T4 for intermediate fit patients only. In contrast, the improvement in all other HRQoL domains during treatment, lost clinical relevance and/or statistical significant difference during the TFI. The deterioration in neuropathy remained until T4 in frail patients, but not for intermediate fit patients, reversing at T4, Figure 1. Conclusion: HRQoL in frail patients is inferior as compared to intermediate fit patients at diagnosis. Importantly, treatment improved HRQoL, irrespective of frailty level, being more pronounced and occurring even faster in frail patients. Therefore, physicians should not withhold therapy in these patients because of their frailty status only.