Antibody Drug Conjugates (ADCs): Changing the Treatment Landscape of Lymphoma

Current Treatment Options in Oncology

Volumn 17, Issue 10, 2016, Pages

  Jagadeesh, Deepa ^a   Smith, Mitchell R ^a  

^a TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

Antibody drug conjugates (ADCs); Lymphoma

Indexed keywords

AGS 67E; BRENTUXIMAB VEDOTIN; CD19 ANTIGEN; CD22 ANTIGEN; CD30 ANTIGEN; CD37 ANTIGEN; CD79B ANTIGEN; COLTUXIMAB RAVTANSINE; CYCLOPHOSPHAMIDE; CYTOTOXIC AGENT; DENINTUZUMAB MAFODOTIN; DOXORUBICIN; HYDRAZONE DERIVATIVE; IMGN 529; INOTUZUMAB OZOGAMICIN; MONOCLONAL ANTIBODY; MOXETUMOMAB PASUDOTOX; PINATUZUMAB VEDOTIN; PLACEBO; POLATUZUMAB VEDOTIN; PREDNISONE; RITUXIMAB; UNCLASSIFIED DRUG; VEDOTIN; VINCRISTINE; ANTIBODY CONJUGATE; ANTINEOPLASTIC AGENT; TUMOR MARKER;

ANEMIA; ARTHRALGIA; ASTHENIA; AUTOLOGOUS STEM CELL TRANSPLANTATION; B CELL LYMPHOMA; BRONCHOSPASM; CHRONIC LYMPHATIC LEUKEMIA; CORNEA DISEASE; CORNEAL EPITHELIOPATHY; CUTANEOUS T CELL LYMPHOMA; DIARRHEA; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG WITHDRAWAL; EYE DISEASE; EYE TOXICITY; FEBRILE NEUTROPENIA; FOLLICULAR LYMPHOMA; HAIRY CELL LEUKEMIA; HEART FAILURE; HEMOLYTIC UREMIC SYNDROME; HODGKIN DISEASE; HUMAN; HYPERGLYCEMIA; HYPERTRANSAMINASEMIA; HYPOPHOSPHATEMIA; HYPOXIA; INFECTION; INTERNALIZATION; KERATOPATHY; LARGE CELL LYMPHOMA; LEUKOPENIA; LUNG DISEASE; LUNG EMBOLISM; LUNG INFECTION; LYMPHOMA; MANTLE CELL LYMPHOMA; MAXIMUM TOLERATED DOSE; MOTOR NEUROPATHY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; PERIPHERAL NEUROPATHY; PERIPHERAL T CELL LYMPHOMA; PROGRESSION FREE SURVIVAL; RECOMMENDED DRUG DOSE; RESPIRATORY FAILURE; REVIEW; SENSORY NEUROPATHY; SEPSIS; THROMBOCYTOPENIA; TUMOR REGRESSION; CLINICAL TRIAL (TOPIC); DRUG DEVELOPMENT; MOLECULARLY TARGETED THERAPY; MORTALITY; TREATMENT OUTCOME;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BIOMARKERS, TUMOR; CLINICAL TRIALS AS TOPIC; DRUG DISCOVERY; HUMANS; IMMUNOCONJUGATES; LYMPHOMA; MOLECULAR TARGETED THERAPY; TREATMENT OUTCOME;

EID: 84983684926     PISSN: 15272729     EISSN: 15346277     Source Type: Journal    
DOI: 10.1007/s11864-016-0428-y     Document Type: Review

References (67)

1. Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 000022(47):7359–68.
2. Przepiorka, D., et al., Gemtuzumab Ozogamicin. Journal of Clinical Oncology, 2013.
3. Petersdorf SH et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013;121(24):4854–60.
4. Castaigne, S., et al., Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet. 379(9825): p. 1508–1516.
5. Panowksi S et al. Site-specific antibody drug conjugates for cancer therapy. MAbs. 2014;6(1):34–45.
6. Chu YW, Polson A. Antibody-drug conjugates for the treatment of B-cell non-Hodgkin's lymphoma and leukemia. Future Oncol. 2013;9(3):355–68.
7. Peters, C. and S. Brown, Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep, 2015. 35(4).
8. McCombs JR, Owen SC. Antibody drug conjugates: design and selection of linker, payload and conjugation chemistry. AAPS J. 2015;17(2):339–51.
9. Ricart AD. Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin Cancer Res. 2011;17(20):6417–27.
10. Wright CW, Rumble JM, Duckett CS. CD30 activates both the canonical and alternative NF-κB pathways in anaplastic large cell lymphoma cells. J Biol Chem. 2007;282(14):10252–62.
11. Horie R et al. Ligand-independent signaling by overexpressed CD30 drives NF-kappaB activation in Hodgkin-Reed-Sternberg cells. Oncogene. 2002;21(16):2493–503.
12. Deutsch YE et al. CD30: an important new target in hematologic malignancies. Leuk Lymphoma. 2011;52(9):1641–54.
13. Muta H et al. CD30 signals integrate expression of cytotoxic effector molecules, lymphocyte trafficking signals, and signals for proliferation and apoptosis. J Immunol. 2000;165(9):5105–11.
14. Kumar A et al. A phase 1 dose-escalation study of XmAb®2513 in patients with relapsed or refractory Hodgkin lymphoma. Br J Haematol. 2015;168(6):902–4.
15. Francisco JA et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003;102(4):1458–65.
16. Sutherland MS et al. Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem. 2006;281(15):10540–7.
17. Younes A et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363(19):1812–21.
18. Younes A et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012;30(18):2183–9. The pivotal phase II trial that led to the approval of single agent brentuximab vedotin in relapsed/refractory Hodgkin lymphoma patients
19. Moskowitz CH et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;385(9980):1853–62. This is phase III randomized double-blinded study of brentuximab vedotin as maintenance therapy in relapsed/refractory Hodgkin lymphoma patients post autologous stem cell transplantation
20. Pro B et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30(18):2190–6. The pivotal study of single agent brentuximab vedotin that showed remarkable ORR of 86% in relapsed/refractory ALCL patients and led to its approval
21. Fanale MA et al. Brentuximab vedotin in the front-line treatment of patients with CD30+ peripheral T-cell lymphomas: results of a phase I study. J Clin Oncol. 2014;32(28):3137–43.
22. ORAL PRESENTATIONS. Hematological Oncology, 2013. 31(S1): p. 96–150.
23. Krathen M et al. Brentuximab vedotin demonstrates significant clinical activity in relapsed or refractory mycosis fungoides with variable CD30 expression. ASH Annual Meeting Abstracts. 2012;120(21):797.
24. Jacobsen ED et al. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015;125(9):1394–402.
25. Lajaunias F et al. Differentially regulated expression and function of CD22 in activated B-1 and B-2 lymphocytes. J Immunol. 2002;168(12):6078–83.
26. Moyron-Quiroz JE et al. Expression and function of CD22, a B-cell restricted molecule. Scand J Immunol. 2002;55(4):343–51.
27. Pfeifer M et al. Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes. Leukemia. 2015;29(7):1578–86.
28. Polson AG et al. Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma. Leukemia. 2010;24(9):1566–73.
29. Dijoseph JF et al. Therapeutic potential of CD22-specific antibody-targeted chemotherapy using inotuzumab ozogamicin (CMC-544) for the treatment of acute lymphoblastic leukemia. Leukemia. 2007;21(11):2240–5.
30. DiJoseph JF et al. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood. 2004;103(5):1807–14.
31. Advani A et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. J Clin Oncol. 2010;28(12):2085–93.
32. Ogura M et al. Phase I study of anti-CD22 immunoconjugate inotuzumab ozogamicin plus rituximab in relapsed/refractory B-cell non-Hodgkin lymphoma. Cancer Sci. 2012;103(5):933–8.
33. Fayad L et al. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol. 2013;31(5):573–83. The Phase I/II study of another ADC, inotuzumab ozogamicin that shows clinical efficacy in both follicular and diffuse large B cell lymphoma. This ADC is in late phase clinical trials and has more clinical efficacy data compared to other newer ADCs
34. Wagner-Johnston ND et al. A phase 2 study of inotuzumab ozogamicin and rituximab, followed by autologous stem cell transplant in patients with relapsed/refractory diffuse large B-cell lymphoma. Leuk Lymphoma. 2015;56(10):2863–9.
35. Chen AI et al. Final results of a phase I study of the anti-CD22 antibody-drug conjugate (ADC) DCDT2980S with or without rituximab (RTX) in patients (pts) with relapsed or refractory (R/R) B-cell non-Hodgkin’s lymphoma (NHL). Blood. 2013;122(21):4399.
36. Morschhauser F et al. Updated results of a phase II randomized study (ROMULUS) of polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed/refractory non-Hodgkin lymphoma. Blood. 2014;124(21):4457. The only randomized phase II study comparing 2 different ADCs, anti CD22 ADC PiV and the anti CD79b ADC polatuzumab vedotin (PoV), in combination with rituximab in both FL and DLBCL
37. Kreitman RJ, Pastan I. Immunoconjugates in the management of hairy cell leukemia. Best Pract Res Clin Haematol. 2015;28(4):236–45.
38. Alderson RF et al. CAT-8015: a second-generation pseudomonas exotoxin A-based immunotherapy targeting CD22-expressing hematologic malignancies. Clin Cancer Res. 2009;15(3):832–9.
39. Kreitman RJ et al. Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol. 2000;18(8):1622–36.
40. Kreitman RJ et al. Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. J Clin Oncol. 2005;23(27):6719–29.
41. Kreitman RJ et al. Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol. 2012;30(15):1822–8.
42. Dornan D et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009;114(13):2721–9.
43. Niiro H, Clark EA. Regulation of B-cell fate by antigen-receptor signals. Nat Rev Immunol. 2002;2(12):945–56.
44. Polson AG et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood. 2007;110(2):616–23.
45. Junutula JR et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol. 2008;26(8):925–32.
46. Palanca-Wessels MC et al. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study. Lancet Oncol. 2015;16(6):704–15.
47. Advani, R.H., et al., Two doses of polatuzumab vedotin (PoV, anti-CD79b antibody-drug conjugate) in patients (pts) with relapsed/refractory (RR) follicular lymphoma (FL): durable responses at lower dose level. ASCO Meeting Abstracts, 2015. 33(15_suppl): p. 8503.
48. Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 1995;18(5–6):385–97.
49. Anderson KC et al. Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation. Blood. 1984;63(6):1424–33.
50. de Rie MA et al. Regulatory role of CD19 molecules in B-cell activation and differentiation. Cell Immunol. 1989;118(2):368–81.
51. Del Nagro CJ et al. CD19 function in central and peripheral B-cell development. Immunol Res. 2005;31(2):119–31.
52. Blanc V et al. SAR3419: an anti-CD19-maytansinoid immunoconjugate for the treatment of B-cell malignancies. Clin Cancer Res. 2011;17(20):6448–58.
53. Younes A et al. Phase I multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/refractory B-cell lymphoma. J Clin Oncol. 2012;30(22):2776–82.
54. Ribrag V et al. A dose-escalation study of SAR3419, an anti-CD19 antibody maytansinoid conjugate, administered by intravenous infusion once weekly in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res. 2014;20(1):213–20.
55. Thieblemont C et al. Phase II study of anti-CD19 antibody drug conjugate (SAR3419) in combination with rituximab: clinical activity and safety in patients with relapsed/refractory diffuse large B-cell lymphoma (NCT01470456). Blood. 2013;122(21):4395.
56. Trneny, M., et al., Starlyte phase II study of coltuximab ravtansine (CoR, SAR3419) single agent: Clinical activity and safety in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL; NCT01472887. ASCO Meeting Abstracts, 2014. 32)(15_suppl): p. 8506.
57. Moskowitz CH et al. Interim analysis of a phase 1 study of the antibody-drug conjugate SGN-CD19A in relapsed or refractory B-lineage non-Hodgkin lymphoma. Blood. 2014;124(21):1741.
58. Moskowitz CH et al. A phase 1 study of denintuzumab mafodotin (SGN-CD19A) in relapsed/refactory B-lineage non-Hodgkin lymphoma. Blood. 2015;126(23):182.
59. van Spriel AB et al. A regulatory role for CD37 in T cell proliferation. J Immunol. 2004;172(5):2953–61.
60. Barrena S et al. Aberrant expression of tetraspanin molecules in B-cell chronic lymphoproliferative disorders and its correlation with normal B-cell maturation. Leukemia. 2005;19(8):1376–83.
61. Schwartz-Albiez R et al. The B cell-associated CD37 antigen (gp40-52). Structure and subcellular expression of an extensively glycosylated glycoprotein. J Immunol. 1988;140(3):905–14.
62. Pereira DS et al. AGS67E, an anti-CD37 monomethyl auristatin E antibody-drug conjugate as a potential therapeutic for B/T-cell malignancies and AML: a new role for CD37 in AML. Mol Cancer Ther. 2015;14(7):1650–60.
63. Deckert J et al. A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies. Blood. 2013;122(20):3500–10.
64. Beckwith KA et al. The CD37-targeted antibody-drug conjugate IMGN529 is highly active against human CLL and in a novel CD37 transgenic murine leukemia model. Leukemia. 2014;28(7):1501–10.
65. Stathis, A., et al., Preliminary findings from a phase I, multicenter, open-label study of the anti-CD37 antibody-drug conjugate (ADC), IMGN529, in adult patients with relapsed or refractory non-Hodgkin lymphoma (NHL). ASCO Meeting Abstracts, 2014. 32(15_suppl): p. 8526.
66. Deckert J et al. Preclinical mechanistic studies investigating neutrophil and lymphoid cell depletion by IMGN529, a CD37-targeting antibody-drug conjugate (ADC). Blood. 2014;124(21):3119.
67. Sawas A et al. A phase 1 study of the anti-CD37 antibody-drug conjugate AGS67E in advanced lymphoid malignancies interim results. Blood. 2015;126(23):3976.