Harnessing the Energy: Development of Radioimmunotherapy for Patients with Non-Hodgkin’s Lymphoma

Abstract

Radioimmunotherapy (RIT) combines the use of targeted monoclonal antibodies with radionuclides for the treatment of non‐Hodgkin's lymphoma (NHL), taking advantage of its inherent radiosensitivity. A number of trials have shown significantly higher response rates and longer progression‐free survival times in patients treated with the CD20‐targeted radioimmunoconjugate yttrium‐90‐ibritumomab tiuxetan compared with the standard of care. Furthermore, these benefits have also been shown in heavily pretreated patients who relapsed or were resistant to rituximab. Currently, a number of different treatment regimens and strategies are available for the treatment of NHL patients. Therefore, in an attempt to minimize toxicity, maximize efficacy, and improve survival, it is crucial to appropriately select patients who are good candidates for individual treatment approaches. A strategy for patient selection has been developed, including the use of existing patient assessment tools, such as the Follicular Lymphoma International Prognostic Index, to determine the optimal regimen for patients with follicular lymphoma according to their disease characteristics and physical condition. Patients who are fit make ideal candidates for potentially curative regimens, which include induction chemotherapy with or without immunotherapy followed by RIT consolidation and, potentially, maintenance therapy. Patients who are considered “compromised” would also benefit from induction treatment and RIT consolidation, with a view to reducing the lymphoma burden and decreasing the risk for disease progression. “Frail” patients would be better suited to supportive therapy to control symptoms. This paper explores factors that should be considered when assessing whether a patient is a good candidate for treatment with RIT, and aids physicians in the selection of the most appropriate therapy for each patient group.

Radioimmunotherapy for Stem Cell Transplantation in Non-Hodgkin’s Lymphoma: In Pursuit of a Complete Response

“…RIT for NHL specifically targets cells expressing the CD20 antigen that is present exclusively on mature B cells and B-cell lymphomas [18]. Two agents are currently used for RIT of NHL [19] There is a strong rationale for using RIT as a part of preconditioning treatment for SCT. For example, total-body irradiation (TBI) has traditionally been integrated into transplant regimens for many NHL patients, with the exclusion of the elderly who are unable to tolerate its toxicity.…”

“…This is especially pertinent because the majority of patients with relapsed or refractory B-cell NHL are Ͼ60 years old, and yet are often denied potentially curative HDC and/or TBI and ASCT because of the risk for excessive treatmentrelated morbidity and mortality [20,21]. In contrast to TBI, and by virtue of its targeted activity, RIT (conventional and high dose) can be used in elderly patients with comorbidities undergoing SCT, making it appropriate as a pretransplant regimen for a wider patient population [19]; as such, a dramatic decrease in TBI-containing regimens has been observed in data from the European Group for Blood and Marrow Transplantation registry since 2000 [22,23]. In two studies, 90 Yibritumomab tiuxetan was used to treat patients with NHL who were not eligible for HDC-and/or TBI-containing therapies prior to ASCT.…”

Radioimmunotherapy in the Treatment of Malignancies

“…Это и легло в основу одного из перспективных направлений в лечении онкологических больных -радиоиммунотерапии (РИТ) [18,21,24].…”

“…Однако значимых различий в показателях общей выживаемости в обеих под-группах выявлено не было (р=0,6). При изучении I-тозитумомаба частота объективного ответа и достижения полных морфологических регрессий на проводимое лечение составила 65 и 38 % соот-ветственно [19,21,45].…”

Summary

“…Based on these data, the European Medicines Agency has approved the use of 90 Y-ibritumomab tiuxetan as consolidation therapy following remission induction in previously untreated patients with FL. Guidelines have been published that recommend the use of RIT (and in particular 90 Y-ibritumomab tiuxetan) in first-line consolidation therapy [5][6][7], especially for patients in whom a significant survival benefit and possible cure are feasible [8]. It remains to be seen whether 90 Y-ibritumomab tiuxetan has the potential to treat aggressive lymphomas; however, the data appear promising.…”