Investigators Document Muscle Loss During Immunochemotherapy for DLBCL

In a retrospective study of patients (N = 104) with newly diagnosed diffuse large B-cell lymphoma (DLBCL) with unfavorable disease features who were treated with a standard immunochemotherapy combination, approximately half experienced muscle loss. However, the authors of the study said the observed muscle loss was “detrimental only if very pronounced.”

In the study, investigators sought to understand how treatments for curable lymphoma affect the musculoskeletal system. They based their observations on measurable changes in the psoas, which is a flexor muscle extending from the lower back to the femur. “Factors that affect muscle loss are mostly related to immunochemotherapy and not disease features prior to therapy per se,” they concluded.

The investigators evaluated muscle loss in patients treated with etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride, and rituximab (R-DA-EPOCH).

The standard of care for DLBCL is the combination therapy rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), and with this, DLBCL is “curable in a majority of newly diagnosed patients,” the authors wrote. However, they said, “a substantial proportion” of patients with DLBCL who have aggressive disease or poor prognostic disease features “might benefit from more intensive therapeutic approaches.”

Previous studies have reported improved outcomes with the R-DA-EPOCH treatment regimen in these patients.

The authors noted that sarcopenia (muscle loss) or cancer-induced cachexia (weight loss, muscle wasting) at baseline have been associated with poorer outcomes in patients with various cancers including non-Hodgkin lymphoma; and skeletal muscle loss during chemotherapy has been associated with negative prognosis in gastrointestinal cancers.

To the authors’ knowledge, their study is the first to assess muscle mass dynamics during immunochemotherapy and prognostic associations in patients with lymphoid malignancies.

Investigators assessed the effect of R-DA-EPOCH immunochemotherapy on skeletal muscle mass by measuring psoas muscle area (PMA) in patients who had available baseline and end-of-treatment computed tomography scans.

The study included patients with unfavorable prognostic features who were treated with R-DA-EPOCH between 2005 and 2019. Unfavorable prognostic features were defined as “a very high proliferative index Ki-67+ ≥ 80% and/or International Prognostic Index (IPI) ≥ 2 points.” Ki-67 is a marker that is strongly associated with tumor cell proliferation and IPI helps to predict outcomes in patients with cancer.

“Small but Significant” Muscle Mass Loss

The authors reported that more than half (57.7%) of patients experienced muscle loss, and the mean loss was 5%. Median psoas area measurement was 1238 mm2 at baseline and 1099 mm2 at the end of treatment, “with a small but significant decline during the immunochemotherapy period.”

In their multivariate model, investigators identified the following as contributors to psoas muscle mass loss: higher body surface area (odds ratio [OR] 17.98 for each 1 m2), the number of cycles with required dose reduction (OR, 2.86, for each additional cycle), and worse response to therapy (OR, 3.09, for each response category increment).

They theorized that because R-DA-EPOCH is dosed according to body surface area, the association between body surface area and muscle loss could be “a consequence of higher delivered absolute drug doses.” Further, the number of cycles with required dose reduction could indicate “poor immunochemotherapy tolerance” or “weaker hematopoietic reserve” (bodily ability to produce blood cells), both of which could be important predictors of psoas muscle loss/improvement, they said.

Pronounced Muscle Loss and Survival

Median overall survival (OS) and progression-free survival (PFS) were not reached over the median 46-month follow-up of the study. The investigators found that PMA loss of 21% or greater, which occurred in 24% of patients, was associated with significantly worse OS and PFS.

These associations amounted to a significant, approximately 3-fold increase in the risk of death or progression after adjustment for age, sex, IPI score, and response to treatment. Lack of response to treatment (progressive or stable disease vs partial or complete remission) was also associated with poorer OS and PFS.

Also, the authors reported that baseline PMA parameters characteristic of more aggressive tumor behavior, body mass index, age, and gender did not predict loss of muscle mass during immunochemotherapy, based on study findings.

They concluded that “muscle mass loss occurs in approximately half of R-DA-EPOCH–treated [patients with] newly diagnosed DLBCL with unfavorable disease features, and if pronounced, this is associated with worse clinical outcomes independently of achieved response to therapy.” Because they found “profound negative prognostic implications” with pronounced muscle loss, “a question emerges whether active strategies aimed at muscle mass improvement like physiotherapy and intensive nutritional support might improve outcomes in this subgroup of patients.”

Reference

Lucijanic M, Huzjan Korunic R, Sedinic M, Kusec R, Pejsa V. More pronounced muscle loss during immunochemotherapy is associated with worse clinical outcomes in newly diagnosed patients with diffuse large B-cell lymphoma with unfavorable features. Ther Clin Risk Manag. 2021;17:1037-1044. doi:10.2147/TCRM.S323749