The present study investigated the prognostic relevance of CT-defined muscle quality parameters on OS and PFS in patients with MM undergoing autologous stem cell therapy. In short, the study could show some differences between survivors and non-survivors regarding skeletal muscle density, but this was not related to the OS and PFS analyses. Presumably, the patient sample of this single center study was too small to show a statistically significant effect of this body composition parameter on survival outcomes.

Body composition is an emerging area of research with extensive studies in several disease entities with overall promising results for additional risk stratification purposes provided by cross-sectional imaging (Wang and Bai 2012; Janssen 2011; Prado et al. 2008; Fielding et al. xxxx; Jang et al. 2020; Chianca et al. 2021; Pinto et al. 2022). Notably, sarcopenia and fat assessment have been shown to be prognostically relevant in several aspects of oncologic disease (Wang and Bai 2012; Janssen 2011; Prado et al. 2008; Fielding et al. xxxx; Jang et al. 2020; Chianca et al. 2021; Pinto et al. 2022). It should be emphasized that body composition assessment is a by-product of cross-sectional imaging that can be easily calculated and implemented into clinical routine without additional radiation exposure (Chianca et al. 2021; Pinto et al. 2022).

In particular, oncologic and hematologic patients are at risk for skeletal muscle wasting due to several factors, including prolonged bed rest and systemic inflammation (Zweegman et al. 2017; Fraz et al. 2019 May; Patel et al. 2020 Feb). In addition, MM patients often undergo whole-body CT or MRI (Rajkumar et al. 2014).

The importance of skeletal muscle area assessment in hematologic diseases was demonstrated in a recent meta-analysis (Surov and Wienke 2021 Mar). In the overall analysis, which pooled different hematologic diseases, sarcopenia was independently associated with lower OS with a reported HR = 1.94, CI 95% 1.30–2.90, p < 0.001 (Surov and Wienke 2021 Mar). However, most of the included studies included patients with lymphoma and leukemia, and only one study included patients with MM (Surov and Wienke 2021 Mar). Since then, more studies on MM have been published, but they have not yet been systematically pooled in another meta-analysis (Takeoka et al. 2016; Cunha Júnior et al. 2021; Umit et al. 2020 Nov; Tagliafico et al. 2022 Apr 1; Nandakumar et al. 2023 Feb 1; Surov et al. 2023 Dec). Takeoka reported negative results for the association between sarcopenia and overall survival in 56 patients (Takeoka et al. 2016). Similar results were published by Williams et al. in 142 MM patients (Williams et al. 2021 Jan).

In another recent study, da Cunha Júnior et al. evaluated 76 patients with MM using FDG-PET (Cunha Júnior et al. 2021). A key finding of this study was that visceral fat metabolic activity was strongly associated with overall survival with an HR of 13.36 (95% CI 3.12, 57.15, p < 0.001) in multivariate analysis (Cunha Júnior et al. 2021). However, skeletal muscle area and visceral fat area had no prognostic relevance for overall survival (Cunha Júnior et al. 2021).

However, in contrast to these studies, the prognostic relevance of muscle quality in MM patients is still unclear. This is important because in other disease entities, the superiority of muscle quality assessment over muscle surface quantity has been highlighted (Pinto et al. 2022). However, there are only few data available for hematologic diseases.

This is particularly controversial because in our patient cohort, surviving cases were found to have lower muscle density and consequently lower muscle quality than those who died. This is in contrast to other diseases where myosteatosis has been associated with a 75% higher mortality (Aleixo et al. 2020 Jan). The present contradictory results need to be clarified in other patient cohorts with MM.

It can be assumed that the change in muscle density throughout the patient's history may be more relevant than the status at the beginning of treatment.

Furthermore, it should be discussed that the identified HR of 2.48 for IMAC on PFS can be considered as an intermediate effect size, which probably did not reach statistical significance due to the small patient sample size (Flório et al. 2023 Feb).

The merit of the current study is the comprehensive investigation of muscle density cut-offs, which clearly demonstrated differences for prognostication. This study is the first to test the effect of different muscle quality cut-offs and to incorporate the effect of albumin as an important blood parameter with muscle quality defined by CT.

There are some statistical signals that the albumin gauge score might be relevant, which was not yet shown in the logistic regression analysis. Clearly, larger multicenter analyses are needed to harmonize the predominantly negative results regarding CT body composition in patients with MM.

Limitations of the present study must be acknowledged. First, the retrospective observational study design with possible inherent bias. Second, the patient sample is relatively small due to the single-center design. This also resulted in possible non-significance of our hazard ratios. In addition, the presented standard deviations are rather large, which is also an effect of the small sample size. Third, the measurements were performed by a single reader, which could lead to some reader bias. However, the region of interest was drawn in a standardized manner. Fourth, the time period of the study is rather long, which could lead to differences in survival due to potential differences in treatment. However, we could not further adjust for this fact.