Optimizing treatment sequencing in multiple myeloma: a novel model to predict survival outcomes

Over the past few years, many new treatments have been approved for patients with multiple myeloma (MM) and these have improved outcomes like response rates and survival. However, although patients usually respond to treatment initially, over time they typically relapse and often need multiple lines of subsequent treatment. There are a lot of treatments to choose from, but no data to guide physicians on what the most effective sequence of those treatments should be in order to maximize outcomes for individual patients. This remains an important unmet clinical need. We therefore developed a novel model to compare treatment sequences and their associated outcomes across different lines of MM treatment, from first-line through fourth-line therapy. The model uses data from individual patients who took part in clinical trials of daratumumab, as well as some data from indirect comparisons between other MM treatments. When using data representing clinical practice in Italy, the model showed that patients have the best clinical outcomes (overall survival and progression-free survival) when the most effective treatment is used first. We found that the optimal MM treatment sequences begin with first-line regimens containing daratumumab, which improve outcomes compared with alternative sequences. The model highlights the importance of starting with the most effective regimens and planning the optimal treatment sequence for individual patients.