Plasma Cell precursor and Other Disorders
Category: Plasma Cell precursor and Other Disorders
The Impact of HER2-Directed Treatment on Monoclonal Protein (M-Protein) Levels in Patients with Concomitant Breast Cancer and Plasma Cell Disorders: A Case Series
Kristina Nasr, MD
Internal Medicine Resident
Cleveland Clinic Foundation/Internal Medicine Residency Program
We present a case series of two patients with concomitant breast cancer and plasma cell disorder who witnessed a reduction in their M protein while on HER 2 immunotherapies. Data were collected retrospectively from systematic chart reviews.
Results:
Patient 1: 79-year-old female with IgG kappa multiple myeloma (MM) (del 17p, t(4:14), del 13q) diagnosed in 2014 was started on lenalidomide but stopped shortly after due to side effects (SE). She was switched to Bortezomib and dexamethasone, discontinued in 2016 due to neuropathy, but achieved VGPR. Given age/comorbidities, she was observed until 2018 when rising M spike prompted Bortezomib restart, which was ineffective, leading to third-line treatment with Carfilzomib, pomalidomide, dexamethasone (KPD). P stopped due to suspected seizure. K continued until disease progression. Fourth-line single-agent daratumumab started with initial disease control switched to fifth-line Cyclophosphamide, Bortezomib, and dexamethasone, achieving VGPR. After HER2 + breast cancer diagnosis, myeloma treatment was held post cycle 3 on Jul, 2022. She completed 12 weeks of Paclitaxel/Trastuzumab by Nov, 2022, followed by Trastuzumab through Aug, 2023. Anastrozole started on Jan, 2023. During Paclitaxel/Trastuzumab treatment, she achieved serologic complete response with undetectable M protein. M protein remained undetectable until Apr, 2024, when recurrence was documented while off HER2 therapy. Therapy with daratumumab and pomalidomide was initiated.
Patient 2: 77-year-old female with IgG kappa MGUS ( >30 years) and HER2 + breast cancer was started on systemic treatment with Trastuzumab/Pertuzumab; chemotherapy portion of treatment declined. After mass progression, she transitioned to Trastuzumab Deruxtecan. She was switched back to Trastuzumab after 3 cycles due to SE. Dose-reduced ado-trastuzumab emtansine was initiated after disease progression. Interestingly, at time of diagnosis, her M protein concentration was 1.22 g/dL, kappa 38.3 mg/L, lambda 11.2 mg/L, k/l ratio 3.42. While on HER2 immunotherapy, M protein became undetectable in 18 months. During treatment, M protein reappeared at 0.25 g/dL, likely reflecting the drug itself-an antibody-while the k/l ratio remained normal.
Conclusions:
HER2 immunotherapy showed M protein reduction in both cases of plasma cell dyscrasia. A study by Uckun and Qazi found that patients with higher levels of ERBB2/HER2 in MM had poorer outcomes1. Further comparative analysis is needed to identify which patient subsets may benefit from HER2 testing. This case series highlights the potential role of HER2 as a biomarker in plasma cell dyscrasias and its utility in relapsed/refractory MM.