Splenic Enlargement and Bone Marrow Hyperplasia in Patients Receiving Trastuzumab-Emtansine for Metastatic Breast Cancer

Abstract

Background: An association between trastuzumab-emtansine (T-DM1) and splenic enlargement is reported in preclinical data, and has been noted anecdotally in patients receiving T-DM1 at our institution. Use of whole-body MRI examinations (WB-MRI) allows for detailed bone marrow assessment and semi-automated splenic volume calculations.

Objective: To retrospectively evaluate changes in splenic volume versus evidence of bone marrow hyperplasia and/or changes in portal venous pressure in patients receiving T-DM1 for metastatic breast cancer.

Patients and methods: Twelve metastatic breast cancer patients underwent 29 WB-MRIs before and during T-DM1 therapy. Splenic volume, portal vein diameter, bone marrow diffusion-weighted normalised signal intensity (nSI), quantitative water diffusivity (apparent diffusion coefficient, ADC) and fat fraction (rF%) were measured and correlated.

Results: Splenic volume increases were observed in 92% of patients. Mean splenic volume increased from 144 cm³ (95% CI 110-177 cm³) to 209 cm³ (95% CI 161-257 cm³) on T-DM1 therapy (p = 0.006). Splenic volume increases correlated with treatment duration (r² = 0.43). Bone marrow hyperplasia was evidenced by an increase in bone marrow nSI (3.5 to 4.8, p = 0.12), and decreases in rF% (64.3% to 57.3%, p = 0.12) and ADC (655 μm²/s to 543 μm²/s, p = 0.11). No changes to portal vein diameter were seen.

Conclusions: Previously unreported increases in splenic volume and bone marrow hyperplasia are observed on WB-MRI in patients on T-DM1 therapy. Caution must be applied to avoid misinterpreting T-DM1-induced bone marrow hyperplasia as diffuse disease progression in bone.