Outcomes in patients with relapsed/refractory multiple myeloma with extramedullary disease: a meta-analysis.

Extramedullary disease (EMD), an aggressive form of multiple myeloma (MM), may require a multi-targeted treatment approach rather than standard MM therapies. While precise EMD treatment outcome estimates remain challenging given small clinical trial patient numbers, pooled estimates across studies may increase outcome precision. Meta-regression analyses used Bayesian multilevel, random-effects modeling of patients with and without EMD across nine historical clinical studies of standard treatment regimens, including daratumumab, for relapsed/refractory multiple myeloma (RRMM) from 2013 to 2019. EMD was defined as soft tissue plasmacytomas noncontiguous with bone (“true” EMD). Adjustments were performed to account for differences in baseline age, number of prior lines of therapy (LOT), and International Staging System (ISS) stage. Outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In patients with EMD (n = 158) versus without EMD (n = 2706), pooled ORR (95% credible interval) was 20.7% (11.7–33.9) versus 66.2% (53.0–77.4) with an odds ratio of 0.13 (0.09–0.20), pooled median PFS was 6.3 (4.2–9.5) versus 12.9 (8.8–18.8) months with a hazard ratio of 1.95 (1.63–2.32), and pooled median OS was 21.0 (15.9–27.9) versus 39.0 (31.0–48.5) months with a hazard ratio of 1.87 (1.53–2.26). Poorer outcomes in patients with versus without EMD were consistent following adjustment for age, number of prior LOT, and ISS stage. These results in patients with RRMM treated with standard treatment regimens confirmed notably worse outcomes in patients with versus without EMD, emphasizing continued unmet clinical need in this patient population.