Zevalin (ibritumomab tiuxetan) / CASI, Servier, Mundipharma, Aurobindo, Assertio - LARVOL DELTA

Long term follow up of the response adapted FOLL12 trial for patients with advanced stage follicular lymphoma: A study by the fondazione italiana linfomi (FIL). (ASH 2025) - "Eligiblepatients were randomly assigned to receive ICT with either R-CHOP or R-Bendamustine followed bystandard RM or a response-adapted post-induction approach based on metabolic response andmolecular assessment of minimal residual disease (MRD)...Post induction therapy in the experimental armconsisted of: CMR and MRD- patients, observation; CMR and MRD+ (EOI or Follow up) 4 weekly rituximabuntil MRD- for up to 3 courses; no CMR, one dose of ibritumomab tiuxetan followed by standard RM...Also with the longer follow up standardRM was associated with improved PFS vs the response adapted approach but still no difference in termof OS was observed. While similar excellent results are achieved in terms of long term outcomes thechoice of initial ICT may result in different risks in terms of late events mainly represented by secondmalignancies, tFL and infections."

Clinical • IO biomarker • Metastases • Follicular Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Solid Tumor • BCL2

Real-world outcomes of Y90-ibritumomab tiuxetan (Zevalin) in low-grade B-cell non-Hodgkin lymphoma: A single-institution experience (ASH 2025) - "Y90-IT received FDA approval in 2002 for the treatment of relapsed or refractory low-grade,follicular, or transformed B-cell non-Hodgkin lymphoma (NHL), including in patients (pts) refractory torituximab. In this large, single-institution, real-world cohort, Y90-IT demonstrated high response rates and durablesurvival outcomes, particularly when used as first-line consolidation in low-grade B-cell NHL. Thesefindings reinforce its efficacy across a range of clinical scenarios. However, the observed incidence ofsecondary malignancies, especially MDS/AML, highlights the need for ongoing surveillance."

Clinical • Real-world • Real-world evidence • Acute Myelogenous Leukemia • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Non-Hodgkin’s Lymphoma

A Systematic Literature Review (SLR) and Meta-Analysis of Clinical Evidence of Second Line or Later (2L+) Treatments for Follicular Lymphoma (FL) in Adult Patients (ASH 2023) - "Eligible treatments included CAR T cell therapies (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel), T cell engagers (mosunetuzumab, glofitamab, epcoritamab, odronextamab), phosphatidylinositol 3-kinase (PI3K) inhibitors (copanlisib, duvelisib, idelalisib), HSCT, yttrium-90 (90Y) ibritumomab tiuxetan, tazemetostat, and conventional therapies (immunochemotherapies, single- or multiagent chemo- or immunotherapies, and alkylating agents). This SLR demonstrated an evolving FL treatment landscape, with new agents such as CAR T cell therapies and T cell engagers exhibiting potential for improving effectiveness of treatment for patients in 3L+, 4L+, and 2L+ POD24 populations."

Retrospective data • Review • Bone Marrow Transplantation • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Radioimmunotherapy with ⁹⁰Y-ibritumomab-tiuxetan in CD20-positive follicular lymphoma - a retrospective long-term analysis (DGHO 2025) - "Introduction: Although overall response rates of ≥ 80% are achieved in patients (pts) with advanced follicular lymphoma (FL) after first-line immunochemotherapy, cure is the exception. ⁹⁰Y-IT achieves excellent rates in long-term PFS and OS, especially as first-line consolidation in previously untreated FL pts. Prospective studies (e.g. in comparison to standard maintenance therapy with rituximab or obinutuzumab) are needed to better define the role of RIT in the modern treatment landscape for FL."

Retrospective data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • CD20

Extravasation of Therapeutic Radiopharmaceuticals: A Systematic Review and Management Proposal. (PubMed, J Nucl Med) - "Severe radiation-induced injuries were observed after radiosynoviorthesis or extravasation of large molecules (e.g., [90Y]Y-ibritumomab tiuxetan). To date, there have been no reported cases of radiation-induced damage after extravasation during peptide receptor radionuclide therapy or prostate-specific membrane antigen-targeted radiopharmaceutical therapy. This systematic review highlights the consequences of 39 documented cases of extravasation of therapeutic radiopharmaceuticals and offers a step-by-step management guide."

Journal • Dermatology • Pain

Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma (clinicaltrials.gov) - P3 | N=20 | Terminated | Sponsor: Mayo Clinic | Completed ➔ Terminated; drug supply issues

Trial termination • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • BCL2

Assessing the Clinical Effectiveness of Radioimmunotherapy with Combined Radionuclide/Monoclonal Antibody Conjugates in Cancer Treatment: Insights from Randomised Clinical Trials. (PubMed, Cancers (Basel)) - "Over the past two decades, RIT has been extensively researched, along with two RIT products-90Y-ibritumomab tiuxetan and 131I-tositumomab. Additionally, standardisation in outcome reporting and longer follow-up periods are essential for more accurate economic and clinical assessments. Overall, RIT represents a valuable therapeutic modality, yet its integration into cancer treatment regimens should be guided by further research aimed at mitigating toxicity and optimising combination strategies."

Journal • Review • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor

HIRA to remove…drugs from Group 2 anticancer list, update reimbursement criteria (Korea Biomedical Review) - "The drugs that will be deleted from the list of Group 2 anticancer drugs are enocitabine, exemestane, heptaplatin (non-reimbursed), ibritumomab tiuxetan (non-reimbursed), irinotecan, letrozole...Ibritumomab tiuxetan (brand name: Zevalin) will have its annotation removed entirely from the non-Hodgkin's lymphoma treatment regimen."

Reimbursement • Non-Hodgkin’s Lymphoma • Oncology

Safety and Efficacy of Ibritumomab Tiuxetan Versus Rituximab in Newly Diagnosed and Relapsed Patients With Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis (SOHO 2024) - "No significant differences were found in key outcomes between ibritumomab tiuxetan and rituximab maintenance in newly diagnosed NHL patients. However, rituximab showed higher CR/CRu rates in relapsed patients compared to ibritumomab. Higher incidence of neutropenia and thrombocytopenia in newly diagnosed NHL patients were observed with ibritumomab."

Retrospective data • Review • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

How Should We Risk Stratify and Tailor Therapy for Relapsed/Refractory Indolent Lymphoma? (SOHO 2024) - "However, given that not all patients have bone marrow biopsy evaluation as a part of their workup, this tool has less commonly been used in routine clinical workflow.7 FLEX is a newer risk-stratification tool that includes patients treated in the bendamustine era...It is well known that most patients with FL will experience relapse of their disease and that the length of progression-free survival (PFS) will decrease with each relapse.3,14 End-of-induction (EOI) PET was evaluated in the GALLIUM study, which compared obinutuzumab + chemotherapy to rituximab + chemotherapy for untreated FL...If patients had a non-CMR in the experimental arm on EOI PET, they received (90)Y ibritumomab tiuxetan and rituximab maintenance twice a month for 2 years...This study has had challenges with enrollment, and the results have not yet been published.22 Future Directions Looking ahead, integrating genomic predictors into clinical practice to enhance risk stratification and exploring..."

Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Oncology

The Rebirth of Radioimmunotherapy of Non-Hodgkin Lymphoma: The Phoenix of Nuclear Medicine? (PubMed, Semin Nucl Med) - "However, despite their therapeutic efficacy, Bexxar® was withdrawn from the market by the manufacturer in 2014 due to limited commercial demand and Zevalin® has had very limited to no availability of late. I-131 rituximab is used to a limited extent in Australia, India and other countries, as well. But has RIT of NHL been (perhaps prematurely) left for dead by many? Given the current great clinical and commercial interest in radiopharmaceutical therapies of cancer, notably PSMA and SSTR targeting agents in prostate and neuroendocrine cancers, can radioimmunotherapy of NHL-like the mythical Phoenix-now rise from its ashes in an even better form to fly higher, faster, farther and longer than before?"

Journal • Review • Endocrine Cancer • Hematological Malignancies • Lymphoma • Neuroendocrine Tumor • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • SSTR

Radioligand Therapy in Lymphoma: Past, Present, and Future. (PubMed, PET Clin) - "In the 1990s, preclinical trials evaluated radiolabeled immunotherapy with monoclonal antibodies (MoAbs) such as anti-CD20 agents labeled with Iodine-131 (Bexxar) or Yttrium-90 (Zevalin). This review will discuss the historical timeline of radioimmunotherapy, debate on advantages and difficulties, and explore trials. We will examine future directions of radioligand therapy in hemato-oncology, considering emerging molecules that may become the next theragnostic trend."

Journal • Review • Hematological Malignancies • Lymphoma • Oncology

Present and Future of Theranostic Radioisotopes in South Korea (SNMMI 2024) - "Established theranostic agents in current clinical use Clinical indication Diagnostic agent Therapeutic agent Hyperthyroidism or thyroid cancer 123I-iodide 131I-iodide Adrenergic tumors 123I-iobenguane 131I-iobenguane Bone metastases from prostate cancer 99mTc-MDP 223Ra chloride Non-Hodgkins lymphoma 111In-ibritumomab 90Y-ibritumomab Neuroendocrine tumors 68Ga-DOTATATE 177Lu-DOTATATE Prostate cancer 68Ga-DKFZPSMA-11 177Lu-DKFZPSMA-617 The key to achieving the success of theranostics technology is developing nuclear medicine technology and radiopharmaceuticals through enhancing the production of isotopes and developing new isotopes to supply the medical market by collaborating with large research facilities that are capable of producing isotopes. The key to achieving the success of theranostics technology is developing nuclear medicine technology and radiopharmaceuticals through enhancing the production of isotopes and developing new isotopes to supply the medical..."

Brain Cancer • CNS Disorders • Endocrine Cancer • Endocrine Disorders • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Neuroendocrine Tumor • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Solid Tumor • Thyroid Gland Carcinoma

Recent preclinical and clinical advances in radioimmunotherapy for non-Hodgkin's lymphoma. (PubMed, Explor Target Antitumor Ther) - "Two radioimmunoconjugates targeting CD20, yttrium-90 (90Y)-ibritumomab-tiuxetan (Zevalin) and iodine-131 (131I)-tositumomab (Bexxar), have been approved in the USA Food and Drug Administration (FDA) for treating relapsed/refractory indolent or transformed NHL in 2002 and 2003, respectively. Immuno-PET strategies targeting CD20 and other antigens are currently being developed. The theragnostic approach by immuno-PET will be useful in monitoring the treatment response."

Journal • Preclinical • Review • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: City of Hope Medical Center | Active, not recruiting ➔ Completed

Trial completion • Bone Marrow Transplantation • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD20

S1001 PET-Directed Therapy in Treating Patients With Limited-Stage Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P2 | N=159 | Completed | Sponsor: SWOG Cancer Research Network | Active, not recruiting ➔ Completed

Trial completion • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Systematic Review of Clinical Applications of Anti-CD20 Radioimmunotherapy for Lymphoma. (PubMed, Oncologist) - "In the 2 decades since its approval, anti-CD20 RIT continues to demonstrate efficacy, particularly with a proportion of patients maintaining long-term remissions. The combination of prolonged efficacy, tolerability, and treatment convenience makes RIT a reasonable alternative to other systemic therapies. It is recommended that further research on RIT should focus on biomarkers of long-term response, pretargeting, and sequencing of RIT in the treatment course."

IO biomarker • Journal • Review • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The asymptomatic follicular lymphoma (AFL) trial: single-agent rituximab immunotherapy versus 90Y-ibritumomab tiuxetan radioimmunotherapy (RIT) for patients with new, untreated follicular lymphoma. (PubMed, Leuk Lymphoma) - "Both agents are highly active for AFL. The 1-week treatment with RIT and sparing of T-cells make combination therapy with newer agents attractive."

Journal • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma (clinicaltrials.gov) - P3 | N=20 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed | Trial completion date: Jan 2026 ➔ Nov 2023

IO biomarker • Trial completion • Trial completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • B2M • BCL2

A Phase II Study of Allo-HCT for B-Cell NHL Using Zevalin, Fludarabine and Melphalan (clinicaltrials.gov) - P2 | N=41 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Jun 2023 ➔ Dec 2023

Trial completion date • Bone Marrow Transplantation • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • CD20

FIL FLAZ12: A Phase III Multicenter, Randomized Study Comparing RIT Vs ASCT in Patients With Relapsed/Refractory (FL) (clinicaltrials.gov) - P3 | N=159 | Active, not recruiting | Sponsor: Fondazione Italiana Linfomi - ETS | Trial completion date: Jan 2023 ➔ Jan 2024

Trial completion date • Bone Marrow Transplantation • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Transplantation

S1001 PET-Directed Therapy in Treating Patients With Limited-Stage Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P2 | N=159 | Active, not recruiting | Sponsor: SWOG Cancer Research Network | Trial completion date: Jun 2023 ➔ Oct 2023

Trial completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Yttrium-90 ibritumomab tiuxetan plus ATG/TLI for allogeneic hematopoietic cell transplantation in non-Hodgkin lymphoma. (PubMed, Bone Marrow Transplant) - No abstract available

Journal • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Results of a Phase II Trial of Allogeneic Hematopoietic Stem Cell Transplantation Using Y-Ibritumomab Tiuxetan (Zevalin) in Combination With Fludarabine and Melphalan in Patients With High-Risk B-Cell Non-Hodgkin's Lymphoma. (PubMed, Clin Lymphoma Myeloma Leuk) - P2 | "Addition of Zevalin to Flu/Mel is safe and effective in high-risk NHL and met the prespecific endpoint. Results were suboptimal in patients with DLBCL."

Combination therapy • Journal • P2 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

OUTCOME OF HIGH DOSE CHEMOTHERAPY PLUS AUTOLOGOUS STEM CELL TRANSPLANTATION (HDT-ASCT) IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA: EXPERIENCE OF A SINGLE ITALIAN INSTITUTION (ICML 2023) - "The majority of them (84%) have previously received purine analogues or Ibritumomab tiuxetan or both... This long term follow up analysis confirms that HDT-ASCT is a safe and effective treatment for R/R FL. The plateau of TTP curve suggests that this approach is potentially curative for a non-negligible subset of pts, that may become larger if the incorporation of novel agents in the induction therapy will reduce the occurrence of 2nd malignancies. This procedure is still competitive with chemo-free second line therapies, in particular for pts with more aggressive disease requiring therapy within 12 months and a POD24 after first line."

Clinical • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology