Real-world studies on B-cell malignancies

Abstract: Randomized controlled trials remain the preferred way of evaluating new treatments. However, in studies on malignancies, trial data may not always be sufficient to address the requirements of health care providers and regulatory agencies regarding recommendations as patients are strictly selected through inclusion- and exclusion criteria. Carefully collected data from consecutive, unselected patients from a well-defined area, without missing cases, will reveal the actual results in routine medical care. These real-world results often differ from results in clinical trials and may provide important additional information to data from clinical trials and serve as control for early non-randomized clinical studies of novel drugs. It is important to find optimal ways to use new high-cost cancer drugs not just for healthcare authorities but for the wider society. The aim of this thesis was to compile reliable real-world data in certain subgroups of patients with chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL), the two most common subgroups of lymphoid malignancies. The first study investigated the effectiveness and safety of 2nd line treatment in consecutive relapsed or refractory (R/R) CLL patients treated between 2003 and 2013 in the Stockholm region. In-depth analysis of each patient file was performed retrospectively. Despite access to new therapies no significant improvement in survival over time was demonstrated. These results highlighted the need for next generation targeted therapies in this patient group and constituted a relevant context for interpretation of and comparison with data obtained in clinical trials of new drugs. The second study was a nationwide study on consecutive CLL patients receiving 1st line therapy between 2007 and 2013. Baseline characteristics, treatment, outcome and toxicity were retrospectively extracted from each patient’s medical file. After a median follow-up of almost 5 years, median progression free survival (PFS) and overall survival (OS) were 24 and 58 months respectively, both significantly associated with type of treatment, del(17p), performance status, gender and age. Overall, there was no significant improvement in OS during the time period studied and importantly regional differences in outcome was observed. The study constitutes a large and unique material providing a context to evaluate the findings obtained in clinical trials of new drugs. The third study was an adjusted comparison between the Bruton tyrosine kinase inhibitor ibrutinib versus previous standard of care treatments in two cohorts of patients with R/R CLL. With multivariate regression modelling to adjust for differences in baseline prognostic factors, PFS and OS were significantly longer with ibrutinib than with previous standard of care regimens. The study describes a statistical approach to provide a preliminary comparison between treatments used in clinical routine and new drugs until comparisons from randomized clinical trials are available.In In the fourth study outcome of 1st line treatment in consecutive patients aged 80 years or older, diagnosed with DLBCL between 2000 and 2015 in the Stockholm region was evaluated. Retrospective data were collected from each individual patient file. Patients ≥ 85 years responded to and tolerated chemoimmunotherapy equally well as patients aged 80-84 years, highlighting that even very elderly patients benefit from active therapy provided that dose-adaption of chemotherapeutic drugs are performed.

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