The impact of sarcopenia in patients with multiple myeloma undergoing auto-HCT

Sarcopenia, defined as a reduction in muscle mass, occurs commonly in older adults and is correlated with chronic disease, fatigue, and falls; it has an overall poor clinical outcome. Given that multiple myeloma (MM) is a common hematological malignancy with a median age at diagnosis of 69 years, the risk of sarcopenia is increased for these patients. Sarcopenic obesity is the combination of sarcopenia and large amounts of fat mass, and is a prognostic factor for poor clinical outcomes.¹ Sarcopenic obesity has extensively been studied in solid tumors, but its effect in hematological cancers, particularly MM, is yet to be fully explored.  

A previous meta-analysis based on a large cohort showed that sarcopenia is an independent factor of overall survival (OS) that might significantly impact outcomes in oncology patients experiencing higher toxicities and treatment-related complications. When analyzing patients with hematological malignancies, sarcopenia was associated with lower OS in patients with diffuse large B-cell lymphoma who underwent treatment with chemotherapy. To date, published studies reporting on sarcopenia and survival in MM are scarce and contradictory.²

Therefore, Alexis Williams and colleagues¹ published in Bone Marrow Transplantation the results of a single-center, retrospective analysis that evaluated the impact of sarcopenia in patients with MM undergoing autologous hematopoietic cell transplantation (auto-HCT).

Method

Inclusion criteria

A total of 142 patients were included in the final analysis (Table 1). These patients

• had their first auto-HCT between January 2013–December 2017 and underwent a computerized tomography (CT) or positron emission tomography (PET) scan within 6 months of receiving their transplant
• were classified as sarcopenic: ≤ 80% high-density muscle
• were categorized as sarcopenic obese: sarcopenic with body mass index (BMI) ≥ 30 (Table 2)

Table 1. Patient characteristics¹

BMI, body mass index; HCT-CI, hematopoietic cell transplant-specific comorbidity index; ICU, intensive care unit; ISS, International Staging System; KPS, Karnofsky performance status; PR, partial response; VGPR, very good partial response *Any adverse event describes any patient experiencing a cardiovascular event, renal failure, respiratory failure, sepsis, or ICU transfer. Statistically significant value is indicated in bold font.
	Sarcopenia n = 72	No sarcopenia n = 70	p value
Median age at transplant (range)	63.3 (38.2–78.6)	59.7 (43.8–78.7)	0.7
Median BMI at transplant (range)	29.0 (21.5–46.1)	28.8 (17.8–40.8)	0.1
Time from diagnosis to transplant (range)	5.4 (0.7–30.2)	5.4 (3.3–27.6)	0.6
Stage (ISS), n (%)			0.5
ISS-I	25 (36.8)	22 (33.3)
ISS-II	27 (39.7)	25 (37.9)
ISS-III	16 (23.5)	19 (28.8)
Median HCT-CI, n (range)	1.0 (0.0–8.0)	1.0 (0.0–7.0)	0.7
KPS ≥ 90, n (%)	48 (66.7)	44 (62.9)	0.6
Pretransplant disease status, n (%)
≥ VGPR	44 (61.1)	37 (52.9)
≤ PR	28 (38.9)	33 (47.1)
Day 100 complications, n (%)
Any complication	24 (33.3)	15 (21.4)	0.3
Any adverse event002A p.	14 (19.4)	8 (11.4)	0.2
Cardiovascular event	9 (12.5%)	2 (2.9%)	0.03
Unplanned hospitalization	17 (23.6%)	11 (15.7%)	0.2

Results

• Sarcopenia was found in 72 patients (51%) with MM undergoing auto-HCT, and sarcopenic obesity was found in 32 patients (23%) (Table 2)
• The median follow-up was similar between patients with sarcopenia (27.2 months [range, 12.4–71.3]) and patients without sarcopenia (33 months [range, 12.8–74.3]) (p = 0.09)
• Sarcopenia was not associated with OS
• High BMI at the time of transplant translated to a worse OS: HR, 1.11; 95% CI, 1.02–1.22; p = 0.02
• There was no significant association between BMI at transplant and sarcopenia: HR, 0.94; 95% CI, 0.77–1.13; p = 0.50
• Sarcopenia, BMI at transplant, and age at transplant did not significantly affect progression-free survival
• Sarcopenia had a higher incidence of cardiovascular events in patients with MM who underwent auto-HCT, and accounted for 36% of all adverse events
  • Patients with sarcopenia had significantly more cardiac complications posttransplant (12.5%) vs patients without sarcopenia (2.9%), p = 0.03
  • There were no significant differences in any other event between patients with and without sarcopenia

Table 2. The BMI classifications of patients¹

BMI, body mass index *BMI ≥ 30 was classified as obese. †25 ≤ BMI < 30 classified as overweight. ‡18.5 ≤ BMI < 25 was classified as normal weight. §BMI < 18.5 was classified as underweight.
BMI classification	Patients (N = 142)
Obese, n (%)*	59 (42%)
Sarcopenic obesity, n (%)	32 (23%)
Overweight, n (%)†	56 (39%)
Normal weight, n (%)‡	26 (18%)
Underweight, n (%)§	1 (< 1%)

 Conclusion

In previous studies, sarcopenia has been associated with higher toxicities, complications, prolonged hospitalizations, overall frailty, and worse survival outcomes. Further investigations are needed to understand the underlying pathobiology of sarcopenia in patients with hematologic malignancies.

In this retrospective analysis, patients with MM undergoing auto-HCT with sarcopenia and sarcopenic obesity had a worse OS. Although auto-HCT is a curative option for patients with hematological cancers with a low rate of early posttransplant complications, this study shows that patients with MM and sarcopenia are still at great risk of cardiovascular complications.

Interestingly, sarcopenia is a modifiable clinical feature, and ongoing studies are evaluating different interventions to improve sarcopenia-related symptoms such as muscle mass, strength, and physical performance, and how these could be applied to patients with MM.