Treatment sequences and drug costs from diagnosis to death in multiple myeloma.

Novel therapies for multiple myeloma (MM) have improved patient survival, but their high costs strain healthcare budgets. End-of-life phases of treatment are generally the most expensive, however, these high costs may be less justifiable in the context of a less pronounced clinical benefit. To manage drug expenses effectively, detailed information on end-of-life drug administration and costs are crucial. In this retrospective study, we analysed treatment sequences and drug costs from 96 MM patients in the Netherlands who died between January 2017 and July 2019. Patients received up to 16 lines of therapy (median overall survival: 56.5 months), with average lifetime costs of €209 871 (€3111/month; range: €3942-€776 185) for anti-MM drugs. About 85% of patients received anti-MM treatment in the last 3 months before death, incurring costs of €20 761 (range: €70-€50 122; 10% of total). Half of the patients received anti-MM treatment in the last 14 days, mainly fully oral regimens (66%). End-of-life treatment costs are substantial despite limited survival benefits. The use of expensive treatment options is expected to increase costs further. These data serve as a reference point for future cost studies, and further research is needed to identify factors predicting the efficacy and clinical benefit of continuing end-of-life therapy.

Ex vivo cultures and drug testing of primary acute myeloid leukemia samples: Current techniques and implications for experimental design and outcome.

New treatment options of acute myeloid leukemia (AML) are rapidly emerging. Pre-clinical models such as ex vivo cultures are extensively used towards the development of novel drugs and to study synergistic drug combinations, as well as to discover biomarkers for both drug response and anti-cancer drug resistance. Although these approaches empower efficient investigation of multiple drugs in a multitude of primary AML samples, their translational value and reproducibility are hampered by the lack of standardized methodologies and by culture system-specific behavior of AML cells and chemotherapeutic drugs. Moreover, distinct research questions require specific methods which rely on specific technical knowledge and skills. To address these aspects, we herein review commonly used culture techniques in light of diverse research questions. In addition, culture-dependent effects on drug resistance towards commonly used drugs in the treatment of AML are summarized including several pitfalls that may arise because of culture technique artifacts. The primary aim of the current review is to provide practical guidelines for ex vivo primary AML culture experimental design.

Quality of life gains in frail and intermediate-fit patients with multiple Myeloma: Findings from the prospective HOVON123 clinical trial.

BACKGROUND: Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. METHODS: The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID). RESULTS: 137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. CONCLUSION: HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.