Hodgkin’s lymphoma in nuclear medicine: diagnostic and therapeutic aspects^[*]

Summary

Today, diagnostic and therapeutic strategies of Hodgkin lymphoma (HL) with positrone emission tomography and radioiummunotherapy include state-of-the-art nuclear medicine which require the cooperation between oncology and nuclear medicine. The benefit of FDG-PET in HL patients with residual tumor masses consists of its high negative predictive value in the therapy control of the disease. The concept of waitful watching in patients with PET-negative residual masses after BEACOPPchemotherapy will be evaluated in a large multicenter trial of the GHSG (German Hodgkin Study Group). Radioimmunotherapy has been performed in patients with CD20-positive Non-Hodgkin lymphoma for 10 years with promising results. HL is also an excellent target for immunotherapy due to the expression of antigens such as CD25 and CD30. Thus, a new radio-immunoconstruct consisting of the murine anti-CD30 antibody Ki-4 labeled with iodine-131 was developed for patients with relapsed or refractory HL.

Zusammenfassung

Da die Diagnostik und Therapie des Morbus Hodgkin neue Methoden und Ansätze (z.B. Positronenemissionstomographie, Radioimmuntherapie) integriert, ist die interdisziplinäre Zusammenarbeit zwischen Onkologie und Nuklearmedizin Voraussetzung. Bei der Therapiekontrolle des Hodgkin-Lymphoms (HL), insbesondere bei Nachweis von Restgewebe nach Chemotherapie, besitzt die FDG-PET einen hohen negativen Vorhersagewert. In einer Multizenterstudie der GHSG (Deutsche Hodgkin-Studiengruppe) wird das Konzept des kontrollierten Zuwartens im Falle von PET-negativem Restgewebe nach BEACOPP geprüft. Die Radioimmuntherapie findet bei CD20-positven Non-Hodgkin-Lymphomen seit 10 Jahren mit vielversprechenden Ergebnissen Anwen-dung. Auch HL bieten durch die Expression des CD25-und CD30-Antigens für die Immuntherapie einen hervorragenden Ansatz. Daher wurde ein neues Radioimmunkonstrukt aus einem murinen Anti-CD30 Antikörper (Ki-4), markiert mit Iod-131, entwickelt und bei Patienten mit rezidiviertem oder therapierefraktärem HL eingesetzt.

Keywords

Hodgkin lymphoma - PET - radioimmunotherapy - multicenter trial

Schlüsselwörter

Hodgkin-Lymphom - PET - Radioimmuntherapie - Multizenterstudie

^* Diese Arbeit ist Prof. Dr. Dr. h.c. Hundeshagen zum 75. Geburtstag gewidmet.

• Literatur

• 1 Agnarsson BA, Kadin ME. The immunopheno-type of Reed-Sternberg cells. A study of 50 cases of Hodgkin’s disease using fixed frozen tissues. Cancer 1989; 63: 2083-7.
• 2 Bangerter M, Moog F, Buchmann I. et al. Whole-body 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for accurate staging of Hodgkin’s disease. Ann Oncol 1998; 9: 1117-22.
• 3 Becherer A, Mitterbauer M, Jaeger U. et al. Positron emission tomography with [¹⁸F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation. Leukemia 2002; 16: 260-7.
• 4 Canellos GP. Residual mass in lymphoma may not be residual disease. J Clin Oncol 1988; 6: 931-3.
• 5 Coiffier B. How to interpret the radiological abnormalities that persist after treatment in non-Hodgkin’s lymphoma patients?. Ann Oncol 1999; 10: 1141-3.
• 6 Cremerius U, Fabry U, Neuerburg J. et al. Prognostic significance of positron emission tomography using fluorine-18-fluorodeoxyglucose in patients treated for malignant lymphoma. Nuklearmedizin 2001; 40: 23-30.
• 7 Cremerius U, Fabry U, Wildberger JE. et al. Pre-transplant positron emission tomography (PET) using fluorine-18-fluoro-deoxyglucose (FDG) predicts outcome in patients treated with high-dose chemotherapy and autologous stem cell transplantation for non- Hodgkin’s lymphoma. Bone Marrow Transplant 2002; 30: 103-11.
• 8 de Wit M, Bohuslavizki KH, Buchert R. et al. ¹⁸FDG-PET following treatment as valid predictor for disease-free survival in Hodgkin’s lymphoma. Ann Oncol 2001; 12: 29-37.
• 9 de Wit M, Bumann D, Beyer W. et al. Whole-body positron emission tomography (PET) for diagnosis of residual mass in patients with lymphoma. Ann Oncol 1997; 8 (Suppl. 01) 57-60.
• 10 DeVita Jr VT, Serpick AA, Carbone PP. Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Ann Intern Med 1970; 73: 881-95.
• 11 Dittmann H, Sokler M, Kollmannsberger C. et al. Comparison of ¹⁸FDG-PET with CT scans in the evaluation of patients with residual and recurrent Hodgkin’s lymphoma. Oncol Rep 2001; 8: 1393-9.
• 12 Engert A, Burrows F, Jung W. et al. Evaluation of ricin A chain-containing immunotoxins directed against the CD30 antigen as potential reagents for the treatment of Hodgkin’s disease. Cancer Res 1990; 50: 84-8.
• 13 Glenn LD, Kumar PP. The residual mediastinal mass following radiation therapy for Hodgkin’s disease. Am J Clin Oncol 1991; 14: 16-24.
• 14 Gribben JG, Freedman AS, Neuberg D. et al. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med 1991; 325: 1525-33.
• 15 Hoh CK, Glaspy J, Rosen P. et al. Whole-body FDG-PET imaging for staging of Hodgkin’s disease and lymphoma. J Nucl Med 1997; 38: 343-8.
• 16 Israel O, Front D, Lam M. et al. Gallium-67 imaging in monitoring lymphoma response to treatment. Cancer 1988; 61: 2439-43.
• 17 Jerusalem G, Beguin Y, Fassotte MF. et al. Whole-body positron emission tomography using ¹⁸F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin’s disease. Haematologica 2001; 86: 266-73.
• 18 Jerusalem G, Warland V, Najjar F. et al. Whole-body ¹⁸F-FDG PET for the evaluation of patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Nucl Med Commun 1999; 20: 13-20.
• 19 Jochelson M, Mauch P, Balikian J. et al. The significance of the residual mediastinal mass in treated Hodgkin’s disease. J Clin Oncol 1985; 3: 637-40.
• 20 Josting A, Katay I, Rueffer U. et al. Favorable outcome of patients with relapsed or refractory Hodgkin’s disease treated with high-dose chemotherapy and stem cell rescue at the time of maximal response to conventional salvage therapy (Dex-BEAM). Ann Oncol 1998; 9: 289-95.
• 21 Kaminski MS, Zasadny KR, Francis IR. et al. Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma. J Clin Oncol 1996; 14: 1974-81.
• 22 Kaminski MS, Zasadny KR, Francis IR. et al. Radioimmunotherapy of B-cell lymphoma with [¹³¹I]anti-B1 (anti-CD20) antibody. N Engl J Med 1993; 329: 459-65.
• 23 Kanzler H, Hansmann ML, Kapp U. et al. Molecular single cell analysis demonstrates the derivation of a peripheral blood-derived cell line (L1236) from the Hodgkin/Reed-Sternberg cells of a Hodgkin’s lymphoma patient. Blood 1996; 87: 3429-36.
• 24 Klimka A, Barth S, Matthey B. et al. An anti-CD30 single-chain Fv selected by phage display and fused to Pseudomonas exotoxin A (Ki-4(scFv)-ETA’) is a potent immunotoxin against a Hodgkin-derived cell line. Br J Cancer 1999; 80: 1214-22.
• 25 Kostakoglu L, Goldsmith SJ. Fluorine-18 fluorodeoxyglucose positron emission tomography in the staging and follow-up of lymphoma: is it time to shift gears?. Eur J Nucl Med 2000; 27: 1564-78.
• 26 Kostakoglu L, Yeh SD, Portlock C. et al. Validation of gallium-67-citrate single-photon emission computed tomography in biopsy-confirmed residual Hodgkin’s disease in the mediastinum. J Nucl Med 1992; 33: 345-50.
• 27 Lenhard Jr RE, Order SE, Spunberg JJ. et al. Isotopic immunoglobulin: a new systemic therapy for advanced Hodgkin’s disease. J Clin Oncol 1985; 3: 1296-1300.
• 28 Naumann R, Vaic A, Beuthien-Baumann B. et al. Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin’s disease and non-Hodgkin’s lymphoma. Br J Haematol 2001; 115: 793-800.
• 29 Nourigat C, Badger CC, Bernstein ID. Treatment of lymphoma with radiolabeled antibody: elimination of tumor cells lacking target antigen. J Natl Cancer Inst 1990; 82: 47-50.
• 30 Partridge S, Timothy A, O’Doherty MJ. et al. 2-Fluorine-18-fluoro-2-deoxy-D glucose positron emission tomography in the pretreatment staging of Hodgkin’s disease: influence on patient management in a single institution. Ann Oncol 2000; 11: 1273-9.
• 31 Pichler R, Maschek W, Hatzl-Griesenhofer M. et al. Clinical value of FDG PET using coincident gamma cameras in staging and restaging of malignant lymphoma—compared with convenitonal diagnostic methods. Nuklearmedizin 2000; 39: 166-73.
• 32 Press OW, Eary JF, Appelbaum 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.
• 33 Radford JA, Cowan RA, Flanagan M. et al. The significance of residual mediastinal abnormality on the chest radiograph following treatment for Hodgkin’s disease. J Clin Oncol 1988; 6: 940-6.
• 34 Rehwald U, Schulz H, Reiser M. et al. Treatment of relapsed CD20-positive Hodgkin’s lymphoma with the monoclonal antibody rituximab is effective and well tolerated: Results of a phase-II trial of the GHSG. Blood 2003; 101: 420-4.
• 35 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.
• 36 Reske SN, Kotzerke J. FDG-PET for clinical use. Results of the 3rd German Interdisciplinary Consensus Conference “Onko-PET III”, 21 July and 19 September 2000. Eur J Nucl Med 2001; 28: 1707-23.
• 37 Schnell R, Borchmann P, Staak JO. et al. Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin’s lymphoma. Ann Oncol. 2003 accepted
• 38 Schnell R, Dietlein M, Schomäcker K. et al. Radio-immunotherapy with a new Iodine-131-labeled antibody (¹³¹I-Ki-4) in patients with Hodgkin’s lymphoma. Onkologie 2002; 25: 507a.
• 39 Schnell R, Borchmann P, Schulz H. et al. Current strategies of antibody-based treatment in Hodgkin’s disease. Ann Oncol 2002; 13 (Suppl. 01) 57-66.
• 40 Schnell R, Linnartz C, Katouzi AA. et al. Development of new ricin A-chain immunotoxins with potent anti-tumor effects against human Hodgkin cells in vitro and disseminated Hodgkin tumors in SCID mice using high-affinity monoclonal antibodies directed against the CD30 antigen. Int J Cancer 1995; 63: 238-44.
• 41 Schnell R, Staak JO, Borchmann P. et al. A Phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin’s and non-Hodgkin’s lymphoma. Clin Cancer Res 2002; 8: 1779-86.
• 42 Setoain FJ, Pons F, Herranz R. et al. ⁶⁷Ga scintigraphy for the evaluation of recurrences and residual masses in patients with lymphoma. Nucl Med Commun 1997; 18: 405-11.
• 43 Sieber M, Engert A, Diehl V. Treatment of Hodgkin’s disease: results and current concepts of the German Hodgkin’s Lymphoma Study Group. Ann Oncol 2000; 11 (Suppl. 01) 81-5.
• 44 Spaepen K, Stroobants S, Dupont P. et al. Can positron emission tomography with [(18)F]-fluorodeoxyglucose after first-line treatment distinguish Hodgkin’s disease patients who need additional therapy from others in whom additional therapy would mean avoidable toxi-city?. Br J Haematol 2001; 115: 272-8.
• 45 Spaepen K, Stroobants S, Dupont P. et al. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([¹⁸F]FDG) after first-line chemotherapy in non-Hodgkin’s lymphoma: is [¹⁸F]FDG-PET a valid alternative to conventional diagnostic methods?. J Clin Oncol 2001; 19: 414-9.
• 46 Spaepen K, Stroobants S, Dupont P. et al. Early restaging positron emission tomography with (18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non- Hodgkin’s lymphoma. Ann Oncol 2002; 13: 1356-63.
• 47 Stein H, Mason DY, Gerdes J. et al. The expression of the Hodgkin’s disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 1985; 66: 848-58.
• 48 Stumpe KD, Urbinelli M, Steinert HC. et al. Whole-body positron emission tomography using fluorodeoxyglucose for staging of lymphoma: effectiveness and comparison with computed tomography. Eur J Nucl Med 1998; 25: 721-8.
• 49 Vriesendorp HM, Herpst JM, Germack MA. et al. Phase I-II studies of yttrium-labeled antiferritin treatment for end-stage Hodgkin’s disease, including Radiation Therapy Oncology Group 87-01. J Clin Oncol 1991; 9: 918-28.
• 50 Vriesendorp HM, Quadri SM, Wyllie CT. et al. Fractionated radiolabeled antiferritin therapy for patients with recurrent Hodgkin’s disease. Clin Cancer Res 1999; 5 (Suppl. 010) 3324s-9s.
• 51 Weihrauch MR, Dietlein M, Schicha H. et al. Prognostic significance of 18F-Flurordeoxyglucose positron emisison tomography in lymphoma. Leukemia Lymphoma. 2003 accepted
• 52 Weihrauch MR, Re D, Bischoff S. et al. Whole-body positron emission tomography using ¹⁸F-fluorodeoxyglucose for initial staging of patients with Hodgkin’s disease. Ann Hematol 2002; 81: 20-5.
• 53 Weihrauch MR, Re D, Scheidhauer K. et al. Thoracic positron emission tomography using ¹⁸F-fluorodeoxyglucose for the evaluation of residual mediastinal Hodgkin disease. Blood 2001; 98: 2930-4.
• 54 Wilder RB, DeNardo GL, DeNardo SJ. Radioimmunotherapy: recent results and future directions. J Clin Oncol 1996; 14: 1383-1400.
• 55 Witzig TE, Gordon LI, Cabanillas F. et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non- Hodgkin’s lymphoma. J Clin Oncol 2002; 20: 2453-63.