Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.819256
Title: Optimising therapeutic outcomes of patients with haematological malignancies (multiple myeloma)
Author: Djebbari, Faouzi
ISNI:       0000 0004 9357 6948
Awarding Body: Kingston University
Current Institution: Kingston University
Date of Award: 2020
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Abstract:
Multiple myeloma (MM) is a haematological malignancy of plasma cells. It is caused by an uncontrolled proliferative behaviour of clonal B cells. Cancer Research UK reported around 5820 new cases each year (2% of all cases) making it the 19th most common cancer. MM remains an incurable disease with a relapsing and a remitting course. The 5-year and 10-year survival rates in England are reported to be 52.3% and 29.1% respectively. However, clinical outcomes have improved significantly in the last decade because of the increased availability of novel agents (oral and parenteral) in UK clinical practice, prescribed using one of two main strategies: fixed duration therapy (FDT) or continuous therapy (CT). These agents demonstrated their safety and efficacy in large phase 3 randomised clinical trials. Real-world data remains equally as important as clinical trials because it allows the myeloma community to understand the global variations in clinical practice, and reported outcomes of these therapies in the real-world. Advanced age, frailty and co-morbidities often exclude real-world patients from clinical trials. This created a gap in the literature about efficacy of novel therapies for those patients. A better understanding of outcomes in the real-world is, therefore, required. This introductory section presents my contribution to myeloma real-world research and to the optimisation of therapeutic outcomes of novel therapies used to treat this condition, through 6 different retrospective real-world studies and one large systematic review. KP1 of 272 bortezomib patients demonstrated that cumulative dose ≥50mg is associated with improved efficacy outcomes. KP2 of 30 carfilzomib patients demonstrated that this therapy is efficacious and has a reasonably good tolerability profile (comparable to ENDEAVOR trial). The study also demonstrated how dose attenuation should be considered early on in elderly patients or those with cardiac morbidities, to improve tolerability. KP3 of 59 DTPACE patients demonstrated that this intensive cytotoxic chemotherapy can be beneficial in extending time to next treatment (TTNT) if consolidated with an autologous stem cell transplant (ASCT). Conversely, it appears to be of less benefit in non-ASCTeligible patients, or those more heavily pre-treated. In KP4 which compared FDT (n=223) in the real-world to CT (n=253), FDT conferred inferior overall survival (OS), progression-free survival (PFS), and TTNT compared to CT. KP5 of 292 patients demonstrated that the median treatment-free interval (TFI) after 1st line therapy was 6.9 months and declined with subsequent treatment phases. The same trend was observed in the different age and co-morbidity subgroups. The large systematic review of evidence of non-standard dosing of 78 different oral anticancer agents (KP6 and KP7) identified 34 papers eligible for inclusion, of which two were myeloma studies and showed limited evidence: one for thalidomide and one for lenalidomide. In KP8 which investigated infection-morbidity in 200 elderly myeloma patients, a number of baseline clinical predictors of infective episodes were identified, such as raised baseline lactate dehydrogenase (LDH) levels, chronic obstructive pulmonary disease (COPD) and smoking history. In summary, this introductory section will describe the real-world outcomes of myeloma patients treated with a number of novel agents and using different modalities. This thesis will discuss strategies/recommendations to optimise outcomes of those therapies, and to improve tolerability.
Supervisor: El Nabhani, Shereen ; Modjtahedi, Helmout Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.819256  DOI: Not available
Keywords: multiple myeloma ; therapeutics ; real-world ; clinical outcomes
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