Assessment of Sarcopenia As a Measure of Frailty in Older Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Background:

Diffuse large B cell lymphoma (DLBCL) is a curable, yet aggressive lymphoma that occurs predominantly in older adults. The challenge in treating older patients is accurately identifying frailty, which confers increased vulnerability to adverse treatment outcomes. Sarcopenia, the loss of muscle mass, is independently associated with an increased risk of all-cause mortality, and may correlate with frailty. We aimed to assess the prevalence of baseline sarcopenia in older patients with relapsed/refractory (R/R) DLBCL, and its correlation with clinical outcomes.

Methods:

We conducted a retrospective cohort study of patients aged >60 years with R/R DLBCL treated at a Canadian cancer centre over the past 5 years from 2018 to 2022. Baseline sarcopenia measurements via skeletal muscle index, standardized uptake value, and skeletal muscle density were measured at the level of L3 vertebra on PET-CT scans done at time of diagnosis of R/R disease, before treatment initiation. The presence or absence of sarcopenia was defined using methodology outlined by van Vugt et al (Eur J Clin Nutr 2019), where Z-score was generated using L3 muscle reference data on sex matched subjects age ≥60. Z-score < - 3 was defined as sarcopenic. Patient and lymphoma characteristics, adverse events, and clinical outcomes were also collected and analyzed.

Results:

51 patients (34M/ 17F) with a median age of 72 (range 62 - 88) at R/R diagnosis were included. Forty-one (80%) patients were Stage III or IV, and 37 (73%) patients had a poor R-IPI score of 3 - 5. Patients received a median of 4 cycles of chemotherapy (range 1 - 8). Twenty-six (51%) patients received GDP-R, with 11 (22%) patients proceeding to autologous stem cell transplant. The prevalence of baseline sarcopenia was 49% (25/51), with a median Z-score of -2.88 (range -5.47 - -0.66). There was no significant association between sarcopenia and DLBCL stage, R-IPI, baseline ECOG score, or baseline BMI. There was no significant association between sarcopenia and chemotherapy regimen changes (i.e., dose decrease, drug or regimen discontinuation). There was no significant association between sarcopenia and occurrence of febrile neutropenia, infection requiring antibiotics, hospital or ICU admissions, bleeding complications, or transfusion requirements. There was also no significant difference in overall response rates (42% vs 62%), complete response rates (38% vs 57%), and overall survival (34% vs 36%) in the non-sarcopenic group compared to the sarcopenic group.

Conclusion:

There is a high prevalence of sarcopenia in patients with R/R DLBCL. Sarcopenia is becoming an increasingly recognized tool for risk stratification of frail patients to allow for individualization and optimization of various treatment intensities and options. This retrospective study serves as a historical control for our concurrent prospective study which incorporates both clinical frailty and sarcopenia assessments.

Phua:Roche: Research Funding; Sanofi: Honoraria, Other: Travel support; CSL: Honoraria, Other: Travel support; EusaPharma: Honoraria; AstraZeneca: Honoraria, Other: Travel support; Bayer: Honoraria; Octapharma: Honoraria, Other: Travel support; Recordati: Honoraria, Other: Travel support; FORUS Therapeutics: Honoraria, Other: Travel support; Beigene: Honoraria, Other: Travel support; Johnson & Johnson: Honoraria, Other: Travel support; Abbvie: Honoraria, Other: Travel support; Pfizer: Honoraria.