SBRT Plus Lenalidomide for Solitary Plasmacytoma: Phase II Trial

A Phase II Trial of Stereotactic Body Radiotherapy (SBRT) With Lenalidomide Maintenance for Solitary Plasmacytoma

Solitary Plasmacytoma (SP) is a rare malignant plasma cell tumor, including Solitary Bone Plasmacytoma (SBP) and Solitary Extramedullary Plasmacytoma (SEP). Radiotherapy is the preferred treatment for SP. Although the local response rate of SP after radiotherapy is as high as 86%, 55% of patients will experience disease progression within 5 years.

Stereotactic Body Radiation Therapy (SBRT), as a new technology for "precision radiotherapy," delivers a higher dose of radiation to the tumor site through a few short treatment sessions while maintaining low-dose exposure to surrounding normal tissues. This approach achieves good local tumor control and effectively reduces radiotherapy-related side effects, making it valuable for application in SP patients. Additionally, numerous preclinical studies have confirmed that SBRT has positive immunomodulatory effects.

Based on data published in the New England Journal of Medicine in 2013, lenalidomide-based immunomodulatory therapy significantly delays the progression of symptomatic myeloma with minimal toxicity in patients with smoldering multiple myeloma.

This study aims to assess the efficacy and safety of combining SBRT with lenalidomide in patients with SP, compared to conventional intensity-modulated radiotherapy. The goal is to extend progression-free survival (PFS) in newly diagnosed SP patients, reduce adverse reactions, and improve quality of life.

Inclusion Criteria:

• Patients with newly diagnosed solitary plasmacytoma (SP).
• Age between 18 and 80 years.
• Diagnosis of SP must meet the following four criteria:

Biopsy-confirmed plasmacytoma in bone or soft tissue. No evidence of clonal plasma cell proliferation in the bone marrow. No other lesions detected on whole-body imaging (whole-body PET-CT or MRI recommended) except for the primary solitary lesion.

No end-organ damage caused by plasma cell disease, including SLiM CRAB [excluding bone destruction caused by the SP itself.

Exclusion Criteria:

• Patients who are not suitable for radiotherapy or unable to receive SBRT due to technical limitations, such as patients with plasmacytoma in the extremities who cannot abduct the affected limb or maintain the treatment position due to pain.
• Eastern Cooperative Oncology Group (ECOG) performance status score greater than 2.
• Patients who meet the diagnostic criteria for multiple myeloma at the time of diagnosis: bone marrow biopsy showing more than 10% plasma cells, serum calcium level above 11.5 mg/dL, serum creatinine above 2 mg/dL, creatinine clearance rate below 40 mL/min, or hemoglobin below 10 g/dL.
• Patients with uncontrolled infectious comorbidities.
• Patients with other active malignancies.
• Pregnant or breastfeeding patients.
• Patients with a history or current pulmonary embolism.
• Patients with a history of autoimmune disease, even if it is controlled.
• Patients who are seropositive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) DNA > 1,000 copies/mL.
• Patients with myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, or severe uncontrolled arrhythmia.
• Patients with neuropathy Grade 2 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events.
• Patients with neutrophil count < 1×10^9/L, hemoglobin < 8 g/dL, or platelet count < 75×10^9/L.
• Patients with severely impaired liver or kidney function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN), total bilirubin > 1.5 × ULN, or estimated glomerular filtration rate (eGFR) < 40 mL/min.