Abstract
This manuscript reviews current advances in the use of radioimmunotherapy (RIT) for the treatment of B-cell non-Hodgkin’s lymphoma (NHL). RIT has been in use for more than 20 years and has progressed significantly with the discovery of new molecular targets, the development of new stable chelates, the humanization of monoclonal antibodies (MAbs), and the use of pretargeting techniques. Today, two products targeting the CD20 antigen are approved: 131I-tositumomab (Bexxar®), and 90Y-ibritumomab tiuxetan (Zevalin®). 131I-tositumomab is available in the United States, and 90Y-ibritumumab tiuxetan in Europe, the United States, Asia, and Africa. RIT can be integrated in clinical practice using non-ablative activities for treatment of patients with relapsed or refractory follicular lymphoma (FL) or as consolidation after induction chemotherapy in front-line treatment in FL patients. Despite the lack of phase III studies to clearly define the efficacy of RIT in the management of B lymphoma in the era of rituximab-based therapy, RIT efficacy in NHL has been demonstrated. In relapsing refractory FL and transformed NHL, RIT as a monotherapy induces around 30% complete response with a possibility of durable remissions. RIT consolidation after induction therapy significantly improves the quality of the response. Dose-limiting toxicity of RIT is hematological, depending on bone marrow involvement and prior treatment. Non-hematological toxicity is generally low. Different studies have been published assessing innovative protocols of RIT or new indications, in particular treatment in patients with aggressive lymphomas. High-dose treatment, RIT as consolidation after different therapeutic induction modalities, RIT in first-line treatment or fractionated RIT showed promising results. New MAbs, in particular humanized MAbs, or combinations of naked and radiolabeled MAbs, also appear promising. Personalized dosimetry protocols should be developed to determine injected activity.
Highlights
INTRODUCTIONB-cell non-Hodgkin’s lymphoma (NHL) can be classified into more than 25 histological subtypes according to World Health Organization (WHO)
There was no significant difference in the 4-year cumulative incidence of relapse/progression between Z-BEAM or totalbody irradiation (TBI) regimen (40.4 and 42.1%, respectively), whereas the non-relapse mortality was significantly higher in the TBI group (0% compared with 15.8% for TBI at 4 years), underlying the potentially lower toxicity of Z-BEAM
This study demonstrated that fractionated RIT with 90Y-epratuzumab achieved high rates of durable complete response (CR) with manageable toxicity in previously treated lymphoma patients
Summary
B-cell NHL can be classified into more than 25 histological subtypes according to World Health Organization (WHO). This hypothesis is challenged by other explanations such as a decreased sensing of DNA damage by ATM at low-dose-rate that results in decreased activation of the early DNA damage response and repair [12] Other effect such as reoxygenation of hypoxic cells during the irradiation and effects on tumor vessels have been proposed to explain the relatively high efficacy of RIT [10]. Promising results have been observed using 90Y-RIT in the consolidation setting in patients in partial response (PR) or complete response (CR) after induction therapy [14] Radionuclides such as 131I or 177Lu with shorter-range energy emissions should be more favorable in the setting of minimal residual disease (MRD). Personalized dosimetry protocols are proposed to better predict dose-effect relationships
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have