Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome

I. Buchmann; R. G. Meyer; W. Herr; A. Helisch; P. Bartenstein

doi:10.1055/s-0038-1625714

Nuklearmedizin - NuclearMedicine, Inhaltsverzeichnis

Nuklearmedizin 2005; 44(03): 107-117
DOI: 10.1055/s-0038-1625714

Original Articles

Schattauer GmbH

Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome

Conceptual chancesRadioimmuntherapien zur Behandlung der akuten myeloischen Leukämie und des myelodysplastischen SyndromsKonzeptionelle Chancen

I. Buchmann

¹Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. P. Bartenstein)

,

R. G. Meyer

²III. Medizinische Klinik und Poliklinik (Hämatologie) (Direktor: Prof. Dr. C. Huber), Universitätsklinikum Mainz

,

W. Herr

²III. Medizinische Klinik und Poliklinik (Hämatologie) (Direktor: Prof. Dr. C. Huber), Universitätsklinikum Mainz

,

A. Helisch

¹Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. P. Bartenstein)

,

P. Bartenstein

¹Klinik und Poliklinik für Nuklearmedizin (Direktor: Prof. Dr. P. Bartenstein)

› Institutsangaben

Abstract

Summary

The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term diseasefree survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT.

This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.

Zusammenfassung

Die Prognose von Patienten mit akuter myeloischer Leukämie (AML) hat sich durch die Einführung aggressiver, konsolidierender Chemotherapien und der hämatopoietischen Stammzelltransplantation (SZT) wesentlich verbessert. Dennoch erreichen selbst nach Durchführung einer SZT nur 20-30% der Patienten mit AML ein langfristiges, krankheitsfreies Überleben. Die Hauptursache für das langfristige Therapieversagen ist das Rezidiv; doch auch die Toxizität der Chemotherapie und die Komplikationen der hämatopoietischen SZT beeinflussen die Mortalitätsrate signifikant. Sowohl im Kontext der primär tumorzellreduktiven Therapie als auch im Rahmen der Konditionierungstherapie vor SZT ist das wesentliche Therapieziel daher, einen ausgeprägten antileukämischen Effekt zur Reduktion der Rezidivrate zu erzeugen, ohne dabei die akute Toxizität und die spätere Komplikationsrate zu steigern.

Die Einbeziehung von Radioimmuntherapien in die Behandlungsstrategie bei der AML und beim myelodysplastischen Syndrom (MDS) ermöglicht die Applikation hoher spezifischer Dosen im hämatopoetischen Knochenmark und erzielt daher in hohem Maße den geforderten antileukämischen Effekt zur Reduktion der Rezidivrate. Durch die vergleichsweise geringe Dosis extramedullärer Organe und Gewebe bleibt die extramedulläre Toxizität gering.

Diese Übersicht stellt systematisch und kritisch wertend die aktuell eingesetzten Radionuklide und Immunkonjugate zur Behandlung der AML und des MDS vor und fasst den aktuellen Stand der Forschung zur primären Reduktion der leukämischen Blastenzahl einerseits sowie zur Konditionierung vor SZT andererseits zusammen.

Keywords

Radioimmuntherapy - haematology - leukaemia - transplantation

Schlüsselwörter

Radioimmuntherapie - Hämatologie - Leukämie - Transplantation

Volltext

Referenzen

Literatur
1 Behr TM, Behe M, Lohr M. et al. Therapeutic advantages of Auger electron- over beta-emitting radiometals or radioiodine when conjugated to internalizing antibodies. Eur J Nucl Med 2000; 27: 753-65.
2 Bennet JM, Catovsky D, Daniel MT. et al. French- American-British (FAB) co-operative group. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189-99.
3 Boiron JM, Lerner D, Pigneux A. et al. Allogeneic transplantation for patients with advanced acute leukemia: A single center retrospective study of 92 patients. Leuk Lymphoma 2001; 41: 285-96.
4 Buchholz HG, Herzog H, Forster GJ. et al. PET imaging with yttrium-86: Comparisons of phantom measurements acquired with different PET scanners before and after applying background subtraction. Eur J Nucl Med Mol Imaging 2003; 30: 716-20.
5 Buchmann I, Bunjes D, Kotzerke J. et al. Myeloablative radioimmunotherapy with Re-188-anti- CD66-Antibody for conditioning of high-risk leukemia patients prior to stem cell transplantation. Cancer Biother & Radiopharm 2002; 17: 151-63.
6 Buchmann I, Mutschler J, Steinbach G. et al. Myeloablative radioimmunotherapy with Re-188-anti- CD66-mAb before stem cell transplantation does not increase cytokine levels. J Nucl Med 2002; 43: S314P.
7 Buchmann I, Schulz A, Sparber M. et al. Myeloablative radioimmunotherapy with Re-188-anti- CD66-mAb in paediatric leukaemia patients: A phase I-trial. J Nucl Med 2002; 43: S37P.
8 Buchmann I, Kull T, Glatting G. et al. A comparison of biodistribution and biokinetics of ^99mTc-an- ti-CD66-mAb BW250/183 and ^99mTc-anti- CD45-mAb YTH24.5 with regard to suitability for myeloablative radioimmunotherapy. Eur J Nucl Med Mol Imaging 2003; 30: 667-73.
9 Bunjes D, Buchmann I, Duncker C. et al. Re- 188-labeled anti-CD 66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with highrisk acute myeloid leukaemia or myelodysplastic syndrome: results of a phase I-II study. Blood 2001; 98: 565-72.
10 Bunjes D. Re-188-labeled anti-CD66 monoclonal antibody in stem cell transplantation for patients with high-risk acute myeloid leukemia. Leukemia & Lymphoma 2002; 43: 2125-31.
11 Caron PC, Co MS, Bull MK. et al. Biological and immunological features of humanized M195 (anti- CD33) monoclonal antibodies. Cancer Res 1992; 52: 6761-7.
12 Caron PC, Jurcic JG, Scott AM. et al. A phase 1B trial of humanized monoclonal antibody M195 (anti-CD33) in myeloid leukemia: Specific targeting without immunogenicity. Blood 1994; 83: 1760-8.
13 Cassileth PA, Harrington DP, Applebaum FR. et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Eng J Med 1998; 339: 1649-56.
14 Forrer F. Nuklearmedizin: Lu-177-DOTA-Rituximab. Schweiz Med Forum 2003; 51/52: 1266-8.
15 Geissler F, Anderson SK, Venkatesan P. et al. Intracellular catabolism of radiolabeled anti-mu antibodies by malignant B-cells. Cancer Res 1992; 52: 2907-15.
16 Glatting G, Kull T, Blumstein NM. et al. Dosimetry with Re-188 labelled anti-CD66 antibodies: Does the measurement of a biodistribution 3 h p.i. suffice to predict the residence times?. Eur J Nucl Med 2004; 31: S473.
17 Griffiths GL, Govidan SV, Sgouros G. et al. Cytotoxicity with Auger electron-emitting radionuclides delivered by antibodies. Int J Cancer 1999; 81: 985-92.
18 Harris NL, Jaffe ES, Diebold J. et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the clinical advisory committee meeting – Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17: 3835-49.
19 Helisch A, Förster GJ, Reber H. et al. Pre-therapeutic dosimetry and biodistribution of ⁸⁶Y-DOTAPhe( 1)-Tyr(3)-octreotide versus ¹¹¹In-pentetreotide in patients with advanced neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004; 31: 1386-92.
20 Hill GR, Crawford JM, Cooke KR. et al. Total body irradiation and acute graft-versus-host disease: The role of gastrointestinal damage and inflammatory cytokines. Blood 1997; 8: 3204-13.
21 Hill GR, Krenger W, Ferrara JLM. et al. Cytokine Dysregulation in acute graft-versus-host disease. Hem 1997; 2: 423-34.
22 Holler E, Kolb HJ, Mittermüller J. et al. Modulation of acute graft-versus-host disease after alloge- neic bone marrow transplantation by tumor necrosis factor α (TNFα) release in the course of pretransplant conditioning: Role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNFα (MAK 195F). Blood 1995; 86: 890-9.
23 Jaffe ES, Harris NL, Stein H. et al. World Health Classification of Tumours: Pathology & Genetics. Tumours of Haematopoietic and Lymphoid Tissues. IARC Press; Lyon: 2001
24 Jowsey J, Rowland RE, Marshall JH. The deposition of the rare earths in bone. Radiation Res 1958; 8: 490-501.
25 Jurcic JG, Caron PC, Nikula TK. et al. Radiolabeled anti-CD33 monoclonal antibody M195 for myeloid leukemias. Cancer Res 1995; 55: S5908-10.
26 Jurcic JG, Divgi CCR, McDevitt MR. et al. Potential for myeloablation with yttrium-90-HuM195 (anti-CD33) in myeloid leukemia. Proc Annu Meet Am Soc Clin Oncol 2000; 19: 24.
27 Jurcic JG, Larson SM, Sgouros G. et al. Targeted α-particle immunotherapy for myloid leukemia. Blood 2002; 100: 1233-9.
28 Kaminski MS, Zasadny KR, Francis IR. et al. Radioimmunotherapy of B-cell lymphoma with I-131-anti-B1 (anti-CD20) antibody. N Engl J Nucl Med 1993; 329: 459-65.
29 Kaminski MS, Estes J, Zasadny KR. et al. Radioimmunotherapy with iodine-131 tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: Updated results and long-term follow-up of the University of Michigan experience. Blood 2000; 96: 1259-66.
30 Kotzerke J, Fenchel S, Guhlmann A. et al. Pharmacokinetics of ^99mTc-pertechnetate and 188Re-perrhenate after oral administration of perchlorate: option for subsequent care after the use of liquid 188Re in a balloon catheter. Nucl Med Comm 1998; 19: 795-801.
31 Matthews DC, Appelbaum FR, Eary JF. et al. Development of a marrow transplantation regimen for acute leukemia using targeted hematopoietic irradiation delivered by I-131-labeled anti- CD45 antibody, combined with cyclophosphamide and total body irradiation. Blood 1995; 85: 1122-31.
32 Matthews DC. Immunotherapy in acute myelogenous leukemia and myelodysplastic syndrome. Leukemia 1998; 12: S33-6.
33 Matthews DC, Appelbaum FR, Eary JF. et al. Phase I study of I-131-anti-CD45 antibody plus cyclophosphamide and total body irradiation for advanced acute leukemia and myelodysplastic syndrome. Blood 1999; 94: 1237-47.
34 Michel RB, Brechbiel MW, Mattes MJ. A comparison of 4 radionuclides conjugated to antibodies for single-cell kill. J Nucl Med 2003; 44: 632-40.
35 Miederer M, McDevitt MR, Sgouros G. et al. Pharmacokinetics, dosimetry, and toxicity of the targetable atomic generator, 225Ac-HuM195, in nonhuman primates. J Nucl Med 2004; 45: 129-37.
36 Möllenbeck J, Schweickert H. Krebstherapie mit dem kurzlebigen Strahler Bi-213. Nachrichten – Forschungszentrum Karlsruhe 2000; 32: 87-90.
37 Newland A. Progress in the treatment of acute myeloid leukaemia in adults. Int J Hematol 2002; 76: S253-8.
38 Nikula TK, Bocchia M, Curcio MJ. et al. Impact of the high tyrosine fraction in complemantarity determining regions: Measured and predicted effects of radioiodination on IgG immunoreactivity. Mol Immunol 1995; 32: 865-72.
39 Postema EJ, Raemaekers JM, Oyen WJ. et al. Final results of a phase I radioimmunotherapy trial using Re-186-epratuzumab for the treatment of patients with non-Hodgkin’s lymphoma. Clin Canc Res 2003; 9: S3995-4002.
40 Press OW, Eary JF, Applebaum FR. et al. Phase II trial of ¹³¹I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet 1995; 346: 336-40.
41 Pui CH, Evans WE. Acute lymphoblastic leukaemia. N Eng J Med 1998; 339: 605-15.
42 Reske SN, Bunjes D, Buchmann I. et al. Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation. Eur J Nucl Med 2001; 28: 807-15.
43 Scheinberg DA, Tanimoto M, McKenzie S. et al. Monoclonal antibody M195: A diagnostic marker for acute myelogenous leukemia. Leukemia 1989; 3: 440-5.
44 Schwartz MA, Lovett DR, Redner A. et al. Doseescalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias. J Clin Oncol 1993; 11: 294-303.
45 Sgouros G, Ballangrud AM, Jurcic JG. et al. Pharmacokinetics and dosimetry of an alpha-particle emitter labeled antibody: Bi-213-HuM195 (anti- CD33) in patients with leukemia. J Nucl Med 1999; 40: 1935-46.
46 Stabin MG. MIRDOSE: personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 1996; 37: 538-46.
47 Shih LB, Thorpe SR, Griffiths GL. et al. The processing and fate of antibodies and their radiolabels bound to the surface of tumor cells in vitro: A comparison of nine radiolabels. J Nucl Med 1994; 35: 899-908.
48 Witherspoon RP, Deeg HJ, Storer B. et al. Hematopoietic stem-cell transplantation for treatment-related leukemia or myelodysplasia. J Clin Oncol 2001; 19: 2134-41.
49 Witzig TE, White CA, Wiseman GA. et al. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin’s lymphoma. J Clin Oncol 1999; 17: 3793-803.