Radioimmunotherapy in Non-Hodgkin’s Lymphoma: Retrospective Adverse Event Profiling of Zevalin and Bexxar

Sachpekidis, Christos; Jackson, David B.; Soldatos, Theodoros

doi:10.3390/ph12040141

Cited by 33 publications

(37 citation statements)

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“…The cumulative incidence of myelodysplastic syndrome/secondary leukemia reported for patients enrolled in Zevalin and Bexxar clinical trials is 5% to 10%. 29 Since the majority of patients who received RIT had also received cytotoxic therapies, it is difficult to determine which of these treatments has primarily contributed to the occurrence of myelodysplastic syndrome and acute myeloid leukemia. However, continuous focus needs to be kept on this serious toxicity in patients treated with RIT, including 177 Lu-lilotomab satetraxetan.…”

Section: Discussionmentioning

confidence: 99%

Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

et al. 2020

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For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20–based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the “cold” anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

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Section: Discussionmentioning

confidence: 99%

Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

et al. 2020

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“…To this end, mAbs could be labeled with radioisotopes such as iodine-131 and yttrium-90 to deliver radioisotopes to target Introduction on Monoclonal Antibodies DOI: http://dx.doi.org/10.5772/intechopen.98378 cells. Iodine-131 and Yttrium-90 were used in the treatment of Hodgkin's disease and lymphoma [26]. Using radiolabeled mAbs was also shown in cancer diagnosis using a diagnostic imaging called immunoscintigraphy [27].…”

Section: Applications Of Monoclonal Antibodies: Therapeutic and Diagnostic Uses 41 Therapeutic Applications Of Mabs In Cancer Therapymentioning

confidence: 99%

Introduction on Monoclonal Antibodies

Sadeghalvad¹,

Rezaei²

2021

Monoclonal Antibodies

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Monoclonal antibodies (mAbs) are a group of antibodies produced by identical clones of B lymphocytes against a particular antigen. mAbs are identical in several properties such as protein sequence, antigen-binding site region, binding affinity for their targets, and identical downstream functional effects. These characteristics of mAbs highlight their differences with the polyclonal antibodies which have heterogenous activities and recognize different epitopes on an antigen. Murine mAbs was the first generation of mAbs developed by hybridoma technology however, because of their murine origin, they can trigger the anti-mouse antibody response in the host which could accelerate mAb clearance and undesirable allergic reactions upon repeated administration. This issue was resolved by developing engineering methods toward producing less immunologic chimeric or humanized antibodies. mAbs applications have become a novel way of targeting antigens in a wide variety of diseases such as autoimmunity, malignancies, and asthma. In addition, high specificity and high affinity binding properties of mAbs make them effective biological reagents in immunodiagnostic assays. They can be used in diagnosis of infectious diseases and detection of certain antigens or in serological assessments for detection of antibodies against a certain antigen. This chapter summarizes the general properties of mAbs, their production processes, and their important diagnostic and therapeutic applications.

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“…Antibodies were developed to target the intracellular histone in tumor necrosis region [10]. It was proved to be efficient because the antibody recognized nonviable zones principally in hypoxic areas of the tumor that compromise 30 % to 70 % of the tumor mass [8][9][10]. Normal tissues were well preserved due to the absence of necrosis [11][12][13].…”

Section: Schlussfolgerung Die Intrakranielle Brachytherapie Mitmentioning

confidence: 99%

“…Intracranial brachytherapy with radiolabeled monoclonal antibodies has been used in various of solid tumors, including lymphomas, lung cancer, myeloma, et al [8,9]. Antibodies were developed to target the intracellular histone in tumor necrosis region [10].…”

mentioning

confidence: 99%

Intracranial 131I-chTNT Brachytherapy in Patients with Deep-Seated Glioma: A Single-center Experience with 10-Year Follow-up from China

Zhao

Zhang

et al. 2021

Nuklearmedizin

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Objective The intracranial brachytherapy has been applied for decades, however, no results with long-term follow-up have been reported. This study investigated the long-term efficiency of intra-tumoral injection of 131I-chTNT in patients with deep-seated glioma. Method Thirty-five patients undergoing 131I-chTNT brachytherapy between December 2004 and May 2009 were enrolled. 131I-chTNT was injected at a dose of 1.5 mCi/cm3 at an interval of 1 month for consecutive 3 times. Serial ECT scan and MRI were performed during follow-up. Progression-free survival (PFS) and overall survival (OS) were analyzed. Adverse reactions were graded with WHO Toxicity Grading Scale for determining the severity of adverse events. Results ECT scan showed that enhanced accumulation of radioactive agents in the tumor lasted for more than 30 days. Three months after final injection, tumor complete remission (CR) was observed in 4 patients (11.4 %), partial remission (PR) in 11 cases (31.4 %), stable disease (SD) in 10 cases (28.6 %) and progressive disease (PD) in 10 cases (28.6 %). At 6-month, CR, PR, SD and PD were 2, 6, 12 and 15 respectively. After 10 years of follow-up, median progression-free survival (PFS) and overall survival (OS) were 5.4 and 11.4 months. One-year survival was 45.7 %, two and five-year survival was 8.6 %, ten-year survival was 5.7 %. Multivariate analysis showed that pathological grade and tumor diameter were independent prognostic factors for PFS and OS. Grade I–II adverse events occurred after drug injection, including nausea, fever, headache, hairloss and fatigue. Conclusion 131I-chTNT intracranial brachytherapy is efficient and safe for patients with deep-seated glioma. It is a reliable option for inoperable glioma patients.

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Radioimmunotherapy in Non-Hodgkin’s Lymphoma: Retrospective Adverse Event Profiling of Zevalin and Bexxar

Cited by 33 publications

References 36 publications

Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma

Introduction on Monoclonal Antibodies

Intracranial 131I-chTNT Brachytherapy in Patients with Deep-Seated Glioma: A Single-center Experience with 10-Year Follow-up from China

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