Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Current Hematologic Malignancy Reports
Erschienen in: Current Hematologic Malignancy Reports 1/2012

01.03.2012 | Acute Myelogenous Leukemia (EJ Feldman, Section Editor)

What Happened to Anti-CD33 Therapy for Acute Myeloid Leukemia?

verfasst von: Joseph G. Jurcic

Erschienen in: Current Hematologic Malignancy Reports | Ausgabe 1/2012

Einloggen, um Zugang zu erhalten

Abstract

CD33, a 67-kDa glycoprotein expressed on the majority of myeloid leukemia cells as well as on normal myeloid and monocytic precursors, has been an attractive target for monoclonal antibody (mAb)–based therapy of acute myeloid leukemia (AML). Lintuzumab, an unconjugated, humanized anti-CD33 mAb, has modest single-agent activity against AML but failed to improve patient outcomes in two randomized trials when combined with conventional chemotherapy. Gemtuzumab ozogamicin, an anti-CD33 mAb conjugated to the antitumor antibiotic calicheamicin, improved survival in a subset of AML patients when combined with standard chemotherapy, but safety concerns led to US marketing withdrawal. The activity of these agents confirms that CD33 remains a viable therapeutic target for AML. Strategies to improve the results of mAb-based therapies for AML include antibody engineering to enhance effector function, use of alternative drugs and chemical linkers to develop safer and more effective drug conjugates, and radioimmunotherapeutic approaches.
Literatur
1.
Sabbath KD, Ball ED, Larcom P, et al. Heterogeneity of clonogenic cells in acute myeloblastic leukemia. J Clin Invest. 1985;75:746–56.PubMedCrossRef
2.
Andrews RG, Takahashi M, Segal GM, et al. The L4F3 antigen is expressed by unipotent colony-forming cells but not by their precursors. Blood. 1986;68:1030–5.PubMed
3.
Simmons D, Seed B. Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells. J Immunol. 1988;141:2797–800.PubMed
4.
Taylor VC, Buckley CD, Douglas M, et al. The myeloid-specific sialic acid-binding receptor, CD33, associated with the protein-tyrosine phosphatases, SHP-1 and SHP-2. J Biol Chem. 1992;274:11505–12.CrossRef
5.
Angata T, Kerr SC, Greaves DR, et al. Cloning and characterization of human Siglec-11: a recently evolved signaling molecule that can interact with SHP-1 and SHP-2 and is expressed by tissue macrophages, including brain microglia. J Biol Chem. 2002;277:24466–74.PubMedCrossRef
6.
Gilloly DJ, Allen JM. The human high affinity IgG receptor (Fc gamma RI) signals through the immunoreceptor tyrosine-based activation motif (ITAM) of the gamma chain of Fc epsilon RI. Biochem Soc Trans. 1997;25:215S.
7.
Paul SP, Taylor LS, Stansbury EK, McVicar DW. Myeloid specific human CD33 is an inhibitory receptor with differential ITIM function in recruiting the phosphatases SHP-1 and SHP-2. Blood. 2000;96:483–90.PubMed
8.
Scheinberg DA, Lovett D, Divgi CR, et al. A phase I trial of monoclonal antibody M195 in acute myelogenous leukemia: specific bone marrow targeting and internalization of radionuclide. J Clin Oncol. 1991;9:478–90.PubMed
9.
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.PubMed
10.
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.PubMed
11.
Xu Y, Scheinberg DA. Elimination of human leukemia by monoclonal antibodies in an athymic nude mouse leukemia model. Clin Cancer Res. 1995;1:1179–87.PubMed
12.
Caron PC, Dumont L, Scheinberg DA. Supersaturating infusional humanized anti-CD33 monoclonal antibody HuM195 in myelogenous leukemia. Clin Cancer Res. 1998;4:1421–8.PubMed
13.
Feldman E, Kalaycio M, Weiner G, et al. Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-CD33 monoclonal antibody HuM195. Leukemia. 2003;17:314–8.PubMedCrossRef
14.
Vitale C, Romagnani C, Puccetti A, et al. Surface expression and function of p75/AIRM-1 or CD33 in acute myeloid leukemias: engagement of CD33 induces apoptosis of leukemic cells. Proc Natl Acad Science U S A. 2001;98:5764–9.CrossRef
15.
Balaian L, Zhong RK, Ball ED. The inhibitory effect of anti-CD33 monoclonal antibodies of AML cell growth correlates with Syk and/or ZAP-70 expression. Exp Hematol. 2003;5:363–71.CrossRef
16.
• Raza A, Jurcic JG, Roboz GJ, et al. Complete remissions observed in acute myeloid leukemia following prolonged exposure to lintuzumab: a phase 1 trial. Leuk Lymph 2009, 50:1336–1344. Therapy with the unconjugated anti-CD33 monoclonal antibody lintuzumab can produce CR in some patients with AML.
17.
Jurcic JG, Nimer SD, Scheinberg DA, et al. Prognostic significance of minimal residual disease detection and PML/RAR-alpha isoform type: long-term follow-up in acute promyelocytic leukemia. Blood. 2001;98:2651–6.PubMedCrossRef
18.
Jurcic JG, DeBlasio T, Dumont L, et al. Molecular remission induction with retinoic acid and anti-CD33 monoclonal antibody HuM195 in acute promyelocytic leukemia. Clin Cancer Res. 2000;6:372–80.PubMed
19.
Mulford DA, Maslak PG, Weiss MA, et al. Reducing standard postremission chemotherapy in acute promyelocytic leukemia with risk-adapted therapy. Blood (ASH Annual Meeting Abstracts) 2003, 102:Abstract 2287.
20.
Feldman EJ, Brandwein J, Stone R, et al. Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J Clin Oncol. 2005;23:4110–6.PubMedCrossRef
21.
• Lancet JE, Sekeres MA, Wood BL, et al. Lintuzumab and low-dose cytarabine compared to placebo and low-dose cytarabine in patients with untreated acute myeloid leukemia 60 years and older: results of a randomized, double-blinded phase 2b study. Blood (ASH Annual Meeting Abstracts) 2011, 118: Abstract 3613. The addition of lintuzumab to low-dose cytarabine failed to produce a survival benefit in older patients with AML.
22.
Sievers EL, Appelbaum FR, Spielberger RT, et al. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood. 1999;93:3678–84.PubMed
23.
Larson RA, Sievers EL, Stadtmauer EA, et al. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer. 2005;104:1442–52.PubMedCrossRef
24.
Bross PF, Beitz J, Chen G, et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res. 2001;7:1490–6.PubMed
25.
Wadleigh M, Richardson PG, Zahrieh D, et al. Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood. 2003;102:1578–82.PubMedCrossRef
26.
Rajvanshi P, Schulman H, Sievers E, et al. Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy. Blood. 2002;99:10–4.CrossRef
27.
Amadori S, Suciu S, Selleslag D, et al. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy: a phase II study of the EORTC and GIMEMA leukaemia groups (AML-19). Br J Haematol. 2010;149:376–82.PubMedCrossRef
28.
•• Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol 2011, 29:369–377. The addition of GO to conventional induction chemotherapy improves the outcomes of patients with a favorable karyotype and a subset of patients with intermediate-risk AML.
29.
•• Petersdorf S, Kopecky K, Stuart RK, et al. Preliminary results of Southwest Oncology Group Study S0106: an international intergroup phase 3 randomized trial comparing the addition of gemtuzumab ozogamicin to standard induction therapy versus standard induction therapy followed by a second randomization to post-consolidation gemtuzumab ozogamicin versus no additional therapy for previously untreated acute myeloid leukemia. Blood (ASH Ann Meeting Abstracts) 2009, 114:Abstract 790. The addition of GO to standard induction chemotherapy provided no improvement in patient outcomes and was associated with an increased early death rate.
30.
Brunnberg U, Mohr M, Noppeney R, et al. Induction therapy of AML with ara-C plus daunorubicin versus ara-C plus gemtuzumab ozogamicin: a randomized phase II trial in elderly patients. Ann Oncol 2011 Aug 2 (Epub ahead of print).
31.
Fernandez HF, Sun Z, Litzow MR, et al. Autologous transplantation gives encouraging results for young adults with favorable-risk acute myeloid leukemia, but is not improved with gemtuzumab ozogamicin. Blood. 2011;177:5306–13.CrossRef
32.
• Löwenberg B, Beck J, Graux C, et al. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 trial. Blood. 2010;115(13):2586–91. Postremission therapy with GO did not improve DFS or OS in patients with AML over 60 years of age after intensive induction chemotherapy.
33.
Stone RM, Moser B, Sanford B, et al. High dose cytarabine plus gemtuzumab ozogamicin for patients with relapsed or refractory acute myeloid leukemia: Cancer and Leukemia Group B study 19902. Leuk Res. 2011;35:329–33.PubMedCrossRef
34.
Chevallier P, Delaunay J, Turlure P, et al. Long-term disease-free survival after gemtuzumab, intermediate-dose cytarabine, and mitoxantrone in patients with CD33+ primary resistant or relapsed acute myeloid leukemia. J Clin Oncol. 2008;26:5192–7.PubMedCrossRef
35.
Martin MG, Augustin KM, Uy GL, et al. Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF. Am J Hematol. 2009;84:733–7.PubMedCrossRef
36.
Estey EH, Giles FJ, Beran M, et al. Experience with gemtuzumab ozogamicin (“Mylotarg”) and all-trans retinoic acid in untreated acute promyelocytic leukemia. Blood. 2002;99:4222–4.PubMedCrossRef
37.
• Ravandi F, Estey E, Jones D, et al. Effective treatment of acute promyelocytic leukemia with all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol 2009, 27:504–510. The combination of ATRA and ATO with GO in high-risk patients as initial therapy for APL is effective and safe and can substitute for chemotherapy-containing regimens.
38.
LoCoco F, Cimino G, Breccia M, et al. Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood. 2004;104:1995–9.CrossRef
39.
Aribi A, Kantarjian HM, Estey EH, et al. Combination therapy with arsenic trioxide, all-trans retinoic acid, and gemtuzumab ozogamicin in recurrent acute promyelocytic leukemia. Cancer. 2007;109:1355–9.PubMedCrossRef
40.
Middeldorf I, Galm O, Osieka R, et al. Sequence of administration and methylation of SOCS3 may govern response to gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with refractory or relapsed acute myelogenous leukemia (AML). Am J Hematol. 2010;85:477–81.PubMedCrossRef
41.
Walter RB, Boyle KM, Appelbaum FR, Bernstein ID, Pagel JM. Simultaneously targeting CD45 significantly increases cytotoxicity of the anti-CD33 immunoconjugate, gemtuzumab ozogamicin, against acute myeloid leukemia (AML) cells and improves survival of mice bearing human AML xenografts. Blood. 2008;111:4813–6.PubMedCrossRef
42.
Lapusan S, Vidriales MB, Thomas X, et al. Phase I studies of AVE9633, an anti-CD33 antibody-maytansinoid conjugate, in adult patients with relapsed/refractory acute myeloid leukemia. Invest New Drugs. 2011 Apr 26 (Epub ahead of print).
43.
Kersemans V, Cornelissen B, Minden MD, Brandwein J, Reilly RM. Drug-resistant AML cells and primary AML specimens are killed by 111In-anti-CD33 monoclonal antibodies modified with nuclear localizing peptide sequences. J Nucl Med. 2008;49:1546–54.PubMedCrossRef
44.
Appelbaum FR, Matthews DC, Eary JF, et al. The use of radiolabeled anti-CD33 antibody to augment marrow irradiation prior to marrow transplantation for acute myelogenous leukemia. Transplantation. 1992;54:829–33.PubMedCrossRef
45.
Burke JM, Caron PC, Papadopoulos EB, et al. Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advance myeloid leukemias. Bone Marrow Transplant. 2003;32:549–56.PubMedCrossRef
46.
Jurcic JG, Divgi CR, McDevitt MR, et al. Potential for myeloablation with yttrium-90-HuM195 (anti-CD33) in myeloid leukemia. Proc Am Soc Clin Oncol 2000, 9:Abstract 24.
47.
Jurcic JG, Larson SM, Sgouros G, et al. Targeted alpha particle immunotherapy for myeloid leukemia. Blood. 2002;100:1233–9.PubMed
48.
• Rosenblat TL, McDevitt MR, Mulford DA, et al. Sequential cytarabine alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia. Clin Cancer Res 2010, 16:5303–5311. This report offers proof-of-principle that following partial cytoreduction, targeted α-particle immunotherapy can produce remissions in patients with AML.
49.
McDevitt MR, Ma D, Lai LT, et al. Tumor therapy with targeted atomic nanogenerators. Science. 2001;294:1537–40.PubMedCrossRef
50.
Jurcic JG, Rosenblat TL, McDevitt MR, et al. Phase I trial of the targeted alpha-particle nano-generator actinium-225 (225Ac)-lintuzumab (anti-CD33; HuM195) in acute myeloid leukemia (AML). Blood (ASH Annual Meeting Abstracts) 2011, Abstract 768.
51.
Petrich T, Korkmaz Z, Krull D, et al. In vitro experimental 211At-anti-CD33 antibody therapy of leukaemia cells overcomes cellular resistance seen in vivo against gemtuzumab ozogamicin. Eur J Nucl Med Mol Imaging. 2010;37:851–61.PubMedCrossRef
52.
Natsume A, Niwa R, Satoh M. Improving effector functions of antibodies for cancer treatments: enhancing ADCC and CDC. Drug Des Devel Ther. 2009;3:7–16.PubMed
53.
Shields RL, Namenuk AK, Hong K, et al. High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem. 2001;276:6591–604.PubMedCrossRef
54.
Lazar GA, Dang W, Karki S, et al. Engineered antibody Fc variants with enhanced effector function. Proc Natl Acad Sci U S A. 2006;103:4005–10.PubMedCrossRef
55.
Dall’Acqua WF, Cook KE, Damschroder MM, et al. Modulation of the effector functions of a human IgG1 through engineering of its hinge region. J Immunol. 2006;177:1129–38.PubMed
56.
Natsume A, In M, Takamura H, et al. Engineered antibodies of IgG1/IgG3 mixed isotype with enhanced cytotoxic activities. Cancer Res. 2008;68:3863–72.PubMedCrossRef
57.
Doronina SO, Mendelsohn BA, Bovee TD, et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: Effects of linker technology on efficacy and toxicity. Bioconjug Chem. 2006;17:114–24.PubMedCrossRef
58.
Kovtun YV, Audette CA, Mayo MF, et al. Antibody-maytansinoid conjugates designed to bypass multidrug resistance. Cancer Res. 2010;70:2528–37.PubMedCrossRef
Metadaten
Titel
What Happened to Anti-CD33 Therapy for Acute Myeloid Leukemia?
verfasst von
Joseph G. Jurcic
Publikationsdatum
01.03.2012
Verlag
Current Science Inc.
Erschienen in
Current Hematologic Malignancy Reports / Ausgabe 1/2012
Print ISSN: 1558-8211
Elektronische ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-011-0103-0

Weitere Artikel der Ausgabe 1/2012

Current Hematologic Malignancy Reports 1/2012 Zur Ausgabe

Acute Myelogenous Leukemia (EJ Feldman, Section Editor)

Management of Refractory Acute Myeloid Leukemia: Re-induction Therapy or Straight to Transplantation?

Myeloproliferative Neoplasms (JJ Kiladjian, Section Editor)

Management of Myeloproliferative Neoplasms: From Academic Guidelines to Clinical Practice

Invited Commentary

Lessons from ALL-REZ BFM 90: Therapy for Childhood Leukemia Based on Timing and Site of Relapse

Myeloproliferative Neoplasms (JJ Kiladjian, Section Editor)

Role of TET2 Mutations in Myeloproliferative Neoplasms

Myeloproliferative Neoplasms (JJ Kiladjian, Section Editor)

Prognostication in Primary Myelofibrosis

Chronic Lymphocytic Leukemia (S O'Brien, Section Editor)

Can Prognostic Factors Be Used to Direct Therapy in Chronic Lymphocytic Leukemia?

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

23.04.2024 Medikamente in Schwangerschaft und Stillzeit Nachrichten

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise