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

Objective: Patients with multiple myeloma (MM) typically require multiple regimens and become harder to treat with each line of treatment. Furthermore, there is a lack of direct comparative clinical trial data to guide effective treatment sequencing. A novel model is described comparing alternative MM treatment sequences to optimize patient outcomes. Methods: The model compares treatment sequences and outcomes for adults with newly diagnosed transplant-eligible (TE) or transplant-ineligible (TIE) MM across four treatment lines (first-line [FL] to fourth-line [4L]). Inputs are derived from patient-level data from clinical trials and indirect treatment comparisons. We report a base case prediction using data representing clinical practice in Italy. Results: For FL TE, overall survival (OS) and progression-free survival (PFS) were greatest for FL regimens containing daratumumab; OS ranged from 11.80–18.10 years. PFS ranged from 4.82–13.42 years (FL) to 0.66–6.03 years (second-line [2L]), 0.81–1.76 years (third-line [3L]), and 0.69–0.72 years (4L). For FL TIE, OS rates were greater for treatment sequences with FL daratumumab vs. sequences with either 2L or no daratumumab (OS ranging from 5.95–10.61 years). PFS was greatest for FL daratumumab regimens in the TIE group, with PFS ranging from 2.12–7.48 years (FL), 0.53–4.73 years (2L), 0.63–1.17 years (3L), and 0.42 years (4L). Discussion: This novel model demonstrates that using the most effective treatment in FL optimizes treatment sequencing and clinical outcomes for patients. Conclusion: The optimal MM treatment sequences begin with daratumumab-containing regimens in FL and improve outcomes compared with alternative sequences. Plain language summary: 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. [ABSTRACT FROM AUTHOR]