Treatment of Refractory Hodgkin's Lymphoma Patients With an Iodine-131–Labeled Murine Anti-CD30 Monoclonal Antibody

Schnell, Roland; Dietlein, Markus; Staak, Jan Oliver; Borchmann, Peter; Schomaecker, Klaus; Fischer, Thomas; Eschner, W.; Hansen, Hinrich P.; Morschhauser, Franck; Schicha, H.; Diehl, Volker; Raubitschek, Andrew; Engert, Andreas

doi:10.1200/jco.2005.09.098

Cited by 103 publications

(56 citation statements)

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“…An alternative strategy has been to arm mAbs with radionuclides. Radioimmunotherapy using 90 Y-anti-ferritin and 131 I-anti-CD30 antibodies has resulted in partial (PRs) and CRs in HL (12)(13)(14)(15). Deficiencies with these approaches reflect the lack of tumor specificity of ferritin-targeted antibodies and the small number of CD30-expressing Reed-Sternberg cells in the tumor.…”

mentioning

confidence: 99%

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

Janik

Morris

O’Mahony

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Despite significant advances in the treatment of Hodgkin's lymphoma (HL), a significant proportion of patients will not respond or will subsequently relapse. We identified CD25, the IL-2 receptor alpha subunit, as a favorable target for systemic radioimmunotherapy of HL. The scientific basis for the clinical trial was that, although most normal cells with exception of Treg cells do not express CD25, it is expressed by a minority of Reed-Sternberg cells and by most polyclonal T cells rosetting around Reed-Sternberg cells. Forty-six patients with refractory and relapsed HL were evaluated with up to seven i.v. infusions of the radiolabeled anti-CD25 antibody 90 Y-daclizumab. 90 Y provides strong β emissions that kill tumor cells at a distance by a crossfire effect. In 46 evaluable HL patients treated with 90 Y-daclizumab there were 14 complete responses and nine partial responses; 14 patients had stable disease, and nine progressed. Responses were observed both in patients whose Reed-Sternberg cells expressed CD25 and in those whose neoplastic cells were CD25 − provided that associated rosetting T cells expressed CD25. As assessed using phosphorylated H2AX (γ-H2AX) as a bioindicator of the effects of radiation exposure, predominantly nonmalignant cells in the tumor microenvironment manifested DNA damage, as reflected by increased expression of γ-H2AX. Toxicities were transient bone-marrow suppression and myelodysplastic syndrome in six patients who had not been evaluated with bone-marrow karyotype analyses before therapy. In conclusion, repeated 90 Y-daclizumab infusions directed predominantly toward nonmalignant T cells rosetting around Reed-Sternberg cells provided meaningful therapy for select HL patients.T reatment with combination chemotherapy, radiation, and hematopoietic stem cell transplantation has increased the disease-free survival in Hodgkin's lymphoma (HL) from less than 5% in 1963 to more than 80% at present (1-6). Recently the US Food and Drug Administration approved brentuximab vedotin for the treatment of relapsed HL (7). Furthermore the anti-PD1 agent pembrolizumab has shown promising results in classic HL (8). Nevertheless, a significant fraction of patients do not respond to treatment or subsequently relapse. To date more than 30 different mAb preparations directed toward antigens expressed by malignant Reed-Sternberg cells have been studied (6). These include mAbs linked to drugs or toxins targeting CD25 or CD30 expressed on Reed-Sternberg cells (6-11). Brentuximab vedotin, an anti-CD30 antibody drug conjugate, has induced a significant number of responses in refractory HL (7, 11). Although other antibody immunotoxins have demonstrated some clinical efficacy, they have yielded few complete responses (CRs) (6, 9, 10). An alternative strategy has been to arm mAbs with radionuclides. Radioimmunotherapy using 90 Y-anti-ferritin and 131 I-anti-CD30 antibodies has resulted in partial (PRs) and CRs in HL (12-15). Deficiencies with these approaches reflect the lack of tumor specificity of ferritin-targ...

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confidence: 99%

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

Janik

Morris

O’Mahony

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…In patients with HL and NHL, investigators attempted to bind CD30 to the toxin ricin or 131 I. However, the presence of side effects such as decreases in serum albumin, edema, and hypotension with the ricin, or severe hematotoxicity in the case of the Iodine-131-coupled antibody, dampened the enthusiasm for these types of treatments (42)(43)(44). In a seminal phase 1/2 study by Ansell and colleagues (45), it was shown that a fully human anti-CD30 immunoglobulin G1 monoclonal antibody (MDX-060) was well tolerated at concentrations up to 15 mg/kg in a mixed patient population, including patients with HL and ALCL.…”

Section: Cd30 Antibodiesmentioning

confidence: 99%

Novel Therapeutic Options in Anaplastic Large Cell Lymphoma: Molecular Targets and Immunological Tools

Merkel

Hamacher

Sifft

et al. 2011

Molecular Cancer Therapeutics

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Anaplastic large cell lymphoma (ALCL) is a CD30-positive, aggressive T-cell lymphoma, and about half of the patients with this disease harbor the t(2;5)(p21;q35) translocation. This chromosomal aberration leads to fusion of the NPM gene with the ALK tyrosine kinase, leading to its constitutive activation. To date, treatment options include polychemotherapy (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone), which is sometimes combined with radiation in the case of bulky disease, leading to remission rates of $80%. However, the remaining patients do not respond to therapy, and some patients experience chemo-resistant relapses, making the identification of new and better treatments imperative. The recent discovery of deregulated ALK in common cancers such as non-small cell lung cancer and neuroblastoma has reinvigorated industry interest in the development of ALK inhibitors. Moreover, it has been shown that the ALK protein is an ideal antigen for vaccination strategies due to its low expression in normal tissue. The characterization of microRNAs that are deregulated in ALCL will yield new insights into the biology of ALCL and open new avenues for therapeutic approaches in the future. Also, CD30 antibodies that have been tested in ALCL for quite a while will probably find a place in forthcoming treatment strategies.

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“…An approach that has been recently investigated is the conjugation of anti-CD30 antibody with a radioisotope, given that HL is typically a radiosensitive tumor [83]. Clinical experience with radioimmunotherapy in HL had previously centered upon polyclonal antiferritin antibodies conjugated to either 131 iodine or 90 yttrium.…”

Section: Radioimmunotherapymentioning

confidence: 99%

“…In the pilot study of anti-CD30 based radioimmunotherapy for relapsed/refractory HL, murine anti-CD30 antibody was conjugated to 131 iodine, as this approach permits dosimetry and biodistribution assessments [83]. The 22 patients were heavily pretreated; most had received radiation and autologous stem cell transplantation, and approximately one-third had relapsed within several months of first-line treatment.…”

Section: Radioimmunotherapymentioning

confidence: 99%

Immunotherapies for Hodgkin's lymphoma

Kasamon

Ambinder

2008

Critical Reviews in Oncology/Hematology

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Treatment of Refractory Hodgkin's Lymphoma Patients With an Iodine-131–Labeled Murine Anti-CD30 Monoclonal Antibody

Abstract: Treatment with (131)I-Ki-4 is effective but can be associated with severe hematotoxicity.

Cited by 103 publications

References 43 publications

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

Novel Therapeutic Options in Anaplastic Large Cell Lymphoma: Molecular Targets and Immunological Tools

Immunotherapies for Hodgkin's lymphoma

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Treatment of Refractory Hodgkin's Lymphoma Patients With an Iodine-131–Labeled Murine Anti-CD30 Monoclonal Antibody

Abstract: Treatment with (131)I-Ki-4 is effective but can be associated with severe hematotoxicity.

Cited by 103 publications

References 43 publications

90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

90Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

Novel Therapeutic Options in Anaplastic Large Cell Lymphoma: Molecular Targets and Immunological Tools

Immunotherapies for Hodgkin's lymphoma

Contact Info

Product

Resources

About

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma

⁹⁰Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma