What is radioimmunotherapy?
Radioimmunotherapy (RIT) is an innovative cancer treatment that combines the power of radiation therapy with the precision of immunotherapy. It leverages the specificity of monoclonal antibodies to deliver radioactive isotopes directly to cancer cells, exploiting the immune system's ability to recognize and target unique proteins on the surface of malignant cells. By selectively directing radiation to the tumor site, this approach minimizes collateral damage to healthy tissues, providing a highly targeted and potent anti-cancer treatment.
The dual modality of radioimmunotherapy allows radiation to be delivered in small, concentrated doses, maximizing the therapeutic efficacy while reducing systemic exposure and side effects. While this treatment modality is predominantly used in managing certain hematologic cancers, such as non-Hodgkin lymphoma, ongoing research, and clinical trials actively explore ways to expand its applications to solid tumors, offering new hope for patients with a wide range of oncological conditions.
Background and first agent in radioimmunotherapy
The origins of radioimmunotherapy can be traced back to the 1980s when researchers began exploring monoclonal antibodies as delivery vehicles for radioisotopes. The first approved radioimmunotherapy agent was ibritumomab tiuxetan, which received FDA approval in 2002 for treating relapsed or refractory B-cell non-Hodgkin lymphoma. Zevalin, a combination of a monoclonal antibody targeting the CD20 antigen on B-cells and the radioactive isotope yttrium-90, offered a new therapeutic option for patients whose cancers had not responded to conventional therapies.
Following Zevalin, another agent called tositumomab, which used iodine-131 as the radioactive component, was introduced. However, despite demonstrating effectiveness, Bexxar was discontinued in 2014 due to low demand, leaving Zevalin as the primary radioimmunotherapy agent for non-Hodgkin lymphoma [Louvain Drug Research Institute, 2021].
Current radioimmunotherapy options and indications
Today, radioimmunotherapy is primarily used to treat hematologic cancers, especially B-cell non-Hodgkin lymphoma [Goto et al., 2024]. These RIT agent groups include:
- Ibritumomab tiuxetan is highly effective for relapsed or refractory B-cell non-Hodgkin lymphoma, including both follicular and transformed forms. Studies have shown response rates of 74% to 83%, with complete remission rates up to 15% in relapsed disease. Potential side effects include hematologic toxicity such as neutropenia, thrombocytopenia, and increased infection risk.
- Lutetium-177-labeled monoclonal antibodies - next-generation radioisotope - are being investigated for use in various cancers, including prostate cancer and neuroendocrine tumors. Lu-177 delivers beta radiation and has demonstrated promising results in neuroendocrine tumors, with response rates around 30% to 35%.
- Newer agents are in development for solid tumors, such as pancreatic cancer, ovarian cancer, and glioblastoma. Some of these RIT agents target cancer-associated antigens like HER2, EGFR, and VEGF.
While RIT's primary application remains in hematologic cancers, researchers are actively developing new RIT agents for a broader range of cancer types, including difficult-to-treat solid tumors.
Radioimmunotherapy for early- and late-stage cancers
For patients with early-stage B-cell non-Hodgkin lymphoma, RIT can be used as consolidation therapy after chemotherapy. In these cases, patients first receive chemotherapy to reduce the tumor burden. Then, they receive Zevalin to eliminate any remaining cancer cells. This approach has improved progression-free survival, especially in patients who achieve partial remission with chemotherapy.
For patients with advanced or refractory cancers, RIT is often used as a salvage therapy. In these cases, where the disease is resistant to other treatments, RIT offers a valuable option for disease control. For example, Zevalin has demonstrated a significant efficacy rate in patients with refractory follicular lymphoma, with long-term remission observed in a subset of these patients.
RIT is also being evaluated for use in patients with metastatic disease. The combination of targeted radiation and immune-mediated cancer destruction provides a multi-pronged attack on advanced-stage tumors, and ongoing clinical trials aim to improve response rates and expand RIT's applications in metastatic settings.
What's next? Novel options in radioimmunotherapy
The future of radioimmunotherapy involves the development of new radiolabeled agents and combination therapies [Journal of Nuclear Medicine, 2022].
- Alpha-particle emitters like actinium-225 and astatine-211 emit more powerful alpha particles that can damage cancer cell DNA more effectively and improve tumor destruction. These agents are currently in early clinical trials.
- Radioimmunoconjugates for solid tumors are aimed to expand radioimmunotherapy beyond blood cancers and apply it to solid tumors such as prostate, colorectal, and brain cancers. The challenge remains to deliver these agents effectively to solid tumor masses, but early studies have been promising.
- The combination of RIT with immune checkpoint inhibitors (pembrolizumab and nivolumab) is under investigation. The goal is that the tumor-killing radiation combined with the immune system activation from checkpoint inhibitors will improve overall treatment effectiveness.
Post-treatment prognosis after radioimmunotherapy
For patients treated with radioimmunotherapy, the prognosis can vary considerably depending on factors such as cancer type, stage, and individual patient characteristics.
In the case of non-Hodgkin lymphoma, patients with relapsed or refractory follicular lymphoma who undergo Zevalin treatment have demonstrated impressive results. These individuals have a median progression-free survival of approximately 18 months and an overall response rate of around 80%. Even more encouragingly, some patients have experienced remissions lasting for several years. However, the treatment is not curative in the majority of cases.
Similarly, radioimmunotherapy agents like Lu-177-labeled antibodies have shown significant promise in managing neuroendocrine tumors. While these treatments may not be curative, they can stabilize disease and even achieve partial remissions in many patients.