Bexxar (iodine I 131 tositumomab)

However, despite their therapeutic efficacy, Bexxar® was withdrawn from the market by the manufacturer in 2014 due to limited commercial demand and Zevalin® has had very limited to no availability of late.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?

P3, N=571, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Mar 2024 --> Mar 2025

SWOG S0016 was a phase III study that randomized 531 patients with advanced-stage FL to either 6 cycles ofR-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-RIT (CHOP + I133-tositumomab). Undetectable MRD status, as assessed by Clonoseq, predicts improved 5- and 10-yearPFS in patients with FL treated with chemoimmunotherapy. MRD assessment by NGS is a promising prognostictool in FL. Figure.

P2, N=16, Active, not recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Mar 2023 --> Sep 2024

SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with CHOP-RIT (CHOP + I133-tositumomab) in patients with FL. Despite a relatively high failure rate to detect trackable sequences using current technology (~29%), MRD assessment by NGS is a promising prognostic tool in FL. *co-senior authors

We assayed archival follicular B-cell non-Hodgkin lymphoma specimens from a completed clinical trial, Southwest Oncology Group S0016, a phase 3 randomized intergroup trial of CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) chemotherapy plus R-CHOP (rituximab-CHOP) compared with CHOP chemotherapy plus 131-iodine tositumomab (radioimmunotherapy [RIT]-CHOP). In summary, subclonal TP53 mutations are common in FL and are a distinct phenomenon from AICDA-mediated genetic heterogeneity. The absence of a detectable subclonal mutation in TP53 defined a population that particularly benefited from RIT.

P1/2, N=96, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

For instance, the theranostic armamentarium for the referring hematooncologist now includes Y-ibritumomab tiuxetan for refractory low-grade follicular lymphoma or transformed B-cell non-Hodgkin lymphoma, as well as I-tositumomab for rituximab-refractory follicular lymphoma. Moreover, the first interim results of the SIERRA phase III trial reported beneficial effects from the use of I-anti-CD45 antibodies (Iomab-B) in refractory or relapsed acute myeloid leukemia...As an integral part of the treatment plan, such radioligand therapy-mediated myeloablation also allows one to line up patients for stem cell transplantation, which leads to successful engraftment during the further treatment course. In this continuing education article, we provide an overview of the current advent of theranostics in hematooncology and highlight emerging clinical applications.

P1/2, N=96, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2022 --> Nov 2023 | Trial primary completion date: Nov 2022 --> Nov 2023

Other than that, a resistance mechanism to rituximab emerged by inducing a failure in the apoptosis mechanism...Here came the development of 90Y-ibritumomab tiuxetan and 131I-tositumomab. After it, humanized anti-CD20 emerged ofatumumab, IMMU106 (veltuzumab) in 2005, and ocrelizumab which are considered as second generation anti-CD20 and 3 generation anti-CD20 include AME-133v (ocaratuzumab), PRO131921 and GA101 (obinutuzumab). Also multiple other agents emerged targeting different surface cell antigens like CD52 (alemtuzumab), CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab], Brentuximab vedotin), CD40 (SGN-40), and CD79b (Polatuzumab). Other agents include MAB targeting T-Cells like mogamulizumab, Denileukin Diftitox and BiTEs or bispecific T cell engagers like Mosunetuzumab, Glofitamab, and Epcoritamab...Another important aspect in immunotherapy is the half-lives of the medication which is an important factor that can influence the evaluation of the response. The MAB treatment showed important benefit in the treatment of iNHL and it continuously shows how rapidly it can develop to provide optimum care and benefit to patients with iNHL.

In particular, two monoclonal antibodies raised against CD20, that is Zevalin (Y-ibritumomab-tiuxetan) and Bexxar (I-tositumomab) received FDA approval for the treatment of relapsing/refractory indolent or transformed NHLs...However, its use in the clinical setting is still debated and, in case of relapse after optimized rituximab-containing regimens, the efficacy of RIT at standard dosage is suboptimal...In contrast, dose-escalation clinical protocols require the assessment of radiopharmaceutical biodistribution and dosimetry before the therapeutic injection, as dose constrains for critical organs may be exceeded when RIT is administered at high activities. The aim of the present study was to review and discuss the internal dosimetry protocols that were adopted for non-standard RIT administration in the myeloablative setting before hematopoietic stem cell transplantation in patients with NHLs.

P1/2, N=96, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: Nov 2021 --> Nov 2022

P2, N=1, Terminated, Rush University Medical Center | N=20 --> 1 | Completed --> Terminated; Lack of accrual and interest in study