Quantification of measurable residual disease in patients with multiple myeloma based on the IMWG response criteria

Stringent complete response (sCR) is defined as a deeper response than complete response (CR) in multiple myeloma. Whether achieving sCR correlates with better survival remains controversial. We evaluated the outcomes in patients with intact immunoglobulin multiple myeloma (IIMM) and light chain multiple myeloma (LCMM) who achieved a very good partial response (VGPR) or better. Multicolour flow cytometry was used to assess the depth of response. LCMM patients with sCR had significantly lower measurable residual disease (MRD) levels than those with CR (median MRD: 7.9 × 10–4 vs. 5.6 × 10–5, P < 0.01). Nonetheless, no significant difference was observed in MRD levels across the responses in groups of patients with IIMM (VGPR vs. CR: 3.5 × 10–4 vs. 7.0 × 10–5, P = 0.07; CR vs. sCR: 7.0 × 10–5 vs. 5.4 × 10–5, P = 0.81. In accordance with MRD levels, the median overall survival of patients with sCR was significantly longer (sCR, CR, VGPR; not reached, 41 months, and 58 months, respectively; VGPR vs. CR, P = 0.83; CR vs. sCR, P = 0.04) in LCMM, but not in IIMM (sCR, CR, VGPR; not reached, 41 months, and not reached, respectively; VGPR vs. CR, P = 0.59; CR vs. sCR; P = 0.10). Our results show that sCR represents a deeper response that correlates with longer survival in patients with LCMM, but not IIMM.

Resolving complex hierarchies in chemical mixtures: how chemometrics may serve in understanding the immune system

In this paper, we explore the ways in which manual sequential gating, machine learning and chemometrics compare, and show complementary strength in the analyses of the hierarchies of multicolour flow cytometry data, to resolve molecular and cell mixtures into insightful contributions to the immune system.