Table Info

Table 2.

List of ADCs that have entered the clinical evaluation for lymphoma patients, sorted by their target and by their official name, if assigned, or by their common/alternative name

Target	Alias	Development codes	Linker	Payload	Payload target	Clinical stage^*	Orphan drug status (if any)^*	Development stage^*	Key AEs
CD19	Coltuximab ravtansine [111, 188]	SAR3419, huB4-DM	SPDB (C)	DM4	Microtubules	2	-	No on-going trials	IRR, ocular toxicity^±, gastrointestinal toxicity^†, peripheral neuropathy
	Denintuzumab mafodotin [112, 189]	SGN-CD19A, SGN-19A, hBU12-491	Maleimidocaproyl (NC)	MMAF	Microtubules	2	-	No on-going trials	Ocular toxicity^±
	Loncastuximab tesirine [113, 115, 121]	ADCT-402, RB4v1.2- SG-3249	Val-Ala (C)	PBD (SG3199)	DNA	Appr.	MCL, DLBCL	On-going trials	IRR, thrombocytopenia, neutropenia, cutaneous toxicity, edema/effusion
CD20	-	MT-3724 [190–193]	Ab directly fused to toxin	Shiga-like toxin-I A1	Ribosomes	2	-	No on-going n.a. trials
CD22	Inotuzumab ozogamicin [133, 194, 195]	CMC-544, PF-5208773, WAY-207294	4-(4-acetylphenoxy) butanoic acid (C)	Calicheamicin	DNA	2	Precursor cell lymphoblastic leukemia-lymphoma	On-going trials	IRR^‡, neutropenia, febrile, thrombocytopenia, anemia, gastrointestinal toxicity^†, hepatotoxicity^§, pancreatitis/ lipase elevation, veno-occlusive disease/sinusoidal obstruction syndrome, hemorrhagic events, tumor lysis syndrome
	Pinatuzumab vedotin [132, 149]	DCDT2980S, RG-7593, ACD22- VCMMAE, FCU-2703, RG-7593, RO-5541072	Val-Cit (C)	MMAE	Microtubules	2	-	No on-going trials	IRR^‡, neutropenia, peripheral neuropathy, gastrointestinal toxicity^†, hyperglycemia
	Moxetumomab pasudotox [136, 196]	RFB4[GTHW] , (dsFv)-PE38, HA22, CAT- 8015	-	Pseudomonas exotoxin A (PE38)	Protein synthesis	Appr.	HCL	On-going trials	IRR, gastrointestinal^†, edema, anemia, hypophosphatemia, headaches, hemolytic uremic syndrome, capillary leak syndrome
	Epratuzumab- cys-tesirine [135]	ADCT-602, Epratuzumab-cys-SG3249, hLL2-cys-PBD, hLL2-cys-SG3249	Val-Ala (C)	PBD (SG3199)	DNA	2	-	On-going trials	n.a.
	-	TRPH 222, CAT-02-106 [134, 140]	SMARTag (NC)	Maytansinoid	Microtubules	1	-	On-going trials	n.a.
CD25	Camidanlumab tesirine [155, 157, 158, 197, 198]	ADCT-301	Val-Ala (C)	PBD (SG3199)	DNA	2	-	On-going trials	IRR, gastrointestinal^†, anemia, hepatotoxicity, skin, edema, headache, immune system disorder and multiple cranial nerve palsy
CD30	Brentuximab vedotin [66, 68, 76, 199–202]	SGN-35, cAC10- vcMMAE	Val-Cit (C)	MMAE	Microtubules	Appr.	HL, ALCL, PTCL, CTCL	On-going trials	IRR^‡, gastrointestinal toxicity^†, neutropenia, thrombocytopenia, peripheral neuropathy, hyperglycemia, pancreatitis/ lipase elevation, pneumonitis, hepatotoxicity^§, JCV-induced progressive multifocal leukoencephalopathy
CD30	-	F0002-ADC, anti-CD30- MCC-DM1 [94]	SMCC (NC)	DM1	Microtubules	1	-	On-going trials	n.a.
CD37	Naratuximab emtansine [161, 162, 166]	Debio 1562, IMGN529	SPDB (C)	DM4	Microtubules	2	DLBCL	No on-going trials	IRR, gastrointestinal toxicity^†, febrile neutropenia, thrombocytopenia, tumor lysis syndrome
CD37	-	AGS67E [203, 204]	Maleimidocaproyl- Val-Cit-PABC (C)	MMAE	Microtubules	1	-	No on-going trials	n.a.
CD70	-	MDX-1203, BMS936561 [205, 206]	Val-Cit (C)	Duocarmycin (MED-2460)	DNA	1	-	No on-going trials	n.a.
	Vorsetuzumab mafodotin [207]	SGN-75, h1F6- mcMMAF	Val-Cit (C)	MMAE	Microtubules	1	-	No on-going trials	n.a.
	-	SGN-CD70A, SGN 70A [169]	Maleimidocaproyl 1 (NC)	MMAF	Microtubules	1	-	No on-going trials	n.a.
CD71	-	CX-2029, ABBV-2029 [20, 172]	Val-Cit (C)	MMAE	Microtubules	2	-	On-going trials	n.a.
CD79B	Polatuzumab vedotin [28, 96, 98, 149]	DCDS4501A, RG7596, anti-CD79B- VC-MMAE, RO-5541077	Val-Cit (C)	MMAE	Microtubules	Appr.	DLBCL	On-going trials	IRR^‡, gastrointestinal toxicity^†, febrile neutropenia, anemia, thrombocytopenia, peripheral neuropathy, edema
CD79B	Iladatuzumab vedotin [107]	DCDS0780A, RO7032005	Maleimidocaproyl- Val-Cit-PABC (C)	MMAE	Microtubules	1	-	No on-going trials	n.a.
CD205	-	MEN1309, OBT076 [174]	N-succinimidyl- 4-(2-pyridyldithio) butanoate (C)	DM4	Microtubules	1	-	On-going trials	n.a.
ROR1	Zilovertamab vedotin [177–179, 182]	VelosBio101, MK 2140, VLS-101	Maleimidocaproyl-Val-Cit-para-aminobenzoate (C)	MMAE	Microtubules	2	MCL	On-going trials	n.a.
ROR1	-	NBE-002 [180]	Sortase A-mediated SMAC-technology (NC)	PNU-159682	DNA	1	-	On-going trials	n.a.

based on http://adisinsight.springer.com and/or https://clinicaltrials.gov accessed in June 2022; -: none; ±: including corneal, extra corneal, and lacrimal disorders; †: including nausea, vomiting, and diarrhea; ‡: including headache, rash, back pain, vomiting, chills, nausea, dyspnea, pruritus, cough, and anaphylaxis; §: including liver enzyme and/or bilirubin elevation; AEs: adverse events; Ala: alanine; Alias: international nonproprietary name; Appr.: approved; C: cleavable; Cit: citrulline; DM1: maytansinoid, mertansine; DM4: maytansinoid, ravtansine; IRR: infusion-related reaction; MMAF: monomethyl auristatin F; MCL: mantle cell lymphoma; n.a.: data not available; NC: not cleavable; PABC: p-amino benzyloxycarbonyl; PBD: pyrrolobenzodiazepine; ROR1: receptor tyrosine kinase-like orphan receptor 1; SMCC: succinimidyl trans-4-(maleimidylmethyl)cyclohexane-1-carboxylate; SPDB: N-succinimidyl 4-(2-pyridyldithio)butyrate; Val: valine

Declarations

Author contributions

MB: data curation and writing – original draft; NL: data curation and writing – review & editing; CT: writing – review & editing; FS: writing – review & editing; PB: writing – review & editing; FB: data curation and writing – review & editing.

Conflicts of interest

Francesco Bertoni: institutional research funds from Acerta, ADC Therapeutics, Bayer AG, Cellestia, CTI Life Sciences, EMD Serono, Helsinn, ImmunoGen, Menarini Ricerche, NEOMED Therapeutics 1, Nordic Nanovector ASA, Oncology Therapeutic Development, Oncternal Therapeutics, PIQUR Therapeutics AG; consultancy fee from Helsinn, Menarini; expert statements provided to HTG; travel grants from Amgen, Astra Zeneca, Jazz Pharmaceuticals, PIQUR Therapeutics AG. The other authors have nothing to disclose.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Boni V, Sharma MR, Patnaik A. The resurgence of antibody drug conjugates in cancer therapeutics: novel targets and payloads. Am Soc Clin Oncol Educ Book. 2020;40:e58–74. [DOI] [PubMed]

do Pazo C, Nawaz K, Webster RM. The oncology market for antibody-drug conjugates. Nat Rev Drug Discov. 2021;20:583–4. [DOI] [PubMed]

Liu X, Gao W. Antibody–drug conjugates. In: Zhao Y, Shen Y, editors. Biomedical nanomaterials. John Wiley & Sons, Ltd; 2016. pp. 149–76. [DOI]

Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat Rev Clin Oncol. 2021;18:327–44. [DOI] [PubMed] [PMC]

Menon S, Parakh S, Scott AM, Gan HK. Antibody-drug conjugates: beyond current approvals and potential future strategies. Explor Target Antitumor Ther. 2022;3:252–77. [DOI] [PubMed] [PMC]

Khongorzul P, Ling CJ, Khan FU, Ihsan AU, Zhang J. Antibody-drug conjugates: a comprehensive review. Mol Cancer Res. 2020;18:3–19. [DOI] [PubMed]

Drews J. Paul Ehrlich: magister mundi. Nat Rev Drug Discov. 2004;3:797–801. [DOI] [PubMed]

Schwartz RS. Paul Ehrlich’s magic bullets. N Engl J Med. 2004;350:1079–80. [DOI] [PubMed]

Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–7. [DOI] [PubMed]

10.

Ponziani S, Di Vittorio G, Pitari G, Cimini AM, Ardini M, Gentile R, et al. Antibody-drug conjugates: the new frontier of chemotherapy. Int J Mol Sci. 2020;21:5510. [DOI] [PubMed] [PMC]

11.

Dubowchik GM, Walker MA. Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs. Pharmacol Ther. 1999;83:67–123. [DOI] [PubMed]

12.

Trail PA. Antibody drug conjugates as cancer therapeutics. Antibodies. 2013;2:113–29. [DOI]

13.

Orlandi R, Güssow DH, Jones PT, Winter G. Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989;86:3833–7. [DOI] [PubMed] [PMC]

14.

Tsuchikama K, An Z. Antibody-drug conjugates: recent advances in conjugation and linker chemistries. Protein Cell. 2018;9:33–46. [DOI] [PubMed] [PMC]

15.

Tolcher AW. The evolution of antibody-drug conjugates: a positive inflexion point. Am Soc Clin Oncol Educ Book. 2020;40:127–34. [DOI] [PubMed]

16.

Oberoi HK, Garralda E. Unmasking new promises: expanding the antigen landscape for antibody-drug conjugates. Clin Cancer Res. 2021;27:4459–61. [DOI] [PubMed]

17.

Herrera AF, Molina A. Investigational antibody-drug conjugates for treatment of B-lineage malignancies. Clin Lymphoma Myeloma Leuk. 2018;18:452–68.e4. [DOI] [PubMed]

18.

Chu Y, Zhou X, Wang X. Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress. J Hematol Oncol. 2021;14:88. [DOI] [PubMed] [PMC]

19.

Russler-Germain DA, Kahl BS. Recent advances in antibody-drug conjugates for lymphoma. Oncology (Williston Park). 2020;34:522–34. [DOI] [PubMed]

20.

Johnson M, El-Khoueiry A, Hafez N, Lakhani N, Mamdani H, Rodon J, et al. Phase I, first-in-human study of the probody therapeutic CX-2029 in adults with advanced solid tumor malignancies. Clin Cancer Res. 2021;27:4521–30. [DOI] [PubMed]

21.

Polson AG, Calemine-Fenaux J, Chan P, Chang W, Christensen E, Clark S, et al. Antibody-drug conjugates for the treatment of non–Hodgkin’s lymphoma: target and linker-drug selection. Cancer Res. 2009;69:2358–64. Erratum in: Cancer Res. 2010;70:1275. [DOI] [PubMed]

22.

Casi G, Neri D. Noninternalizing targeted cytotoxics for cancer therapy. Mol Pharm. 2015;12:1880–4. [DOI] [PubMed]

23.

Van Oss CJ. Hydrophobic, hydrophilic and other interactions in epitope-paratope binding. Mol Immunol. 1995;32:199–211. [DOI] [PubMed]

24.

Mahalingaiah PK, Ciurlionis R, Durbin KR, Yeager RL, Philip BK, Bawa B, et al. Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates. Pharmacol Ther. 2019;200:110–25. [DOI] [PubMed]

25.

Junutula JR, Flagella KM, Graham RA, Parsons KL, Ha E, Raab H, et al. Engineered thio-trastuzumab-DM1 conjugate with an improved therapeutic index to target human epidermal growth factor receptor 2–positive breast cancer. Clin Cancer Res. 2010;16:4769–78. [DOI] [PubMed]

26.

Junutula JR, Raab H, Clark S, Bhakta S, Leipold DD, Weir S, et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol. 2008;26:925–32. [DOI] [PubMed]

27.

Adhikari P, Zacharias N, Ohri R, Sadowsky J. Site-specific conjugation to cys-engineered THIOMAB™ antibodies. In: Tumey L, editor. Antibody-drug conjugates: methods and protocols. New York, NY: Springer US; 2020. pp. 51–69. [DOI] [PubMed]

28.

Dornan D, Bennett F, Chen Y, Dennis M, Eaton D, Elkins K, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood. 2009;114:2721–9. [DOI] [PubMed]

29.

Lyon RP, Bovee TD, Doronina SO, Burke PJ, Hunter JH, Neff-LaFord HD, et al. Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index. Nat Biotechnol. 2015;33:733–5. [DOI] [PubMed]

30.

Jain N, Smith SW, Ghone S, Tomczuk B. Current ADC linker chemistry. Pharm Res. 2015;32:3526–40. [DOI] [PubMed] [PMC]

31.

Lu J, Jiang F, Lu A, Zhang G. Linkers having a crucial role in antibody–drug conjugates. Int J Mol Sci. 2016;17:561. [DOI] [PubMed] [PMC]

32.

Sievers EL, Larson RA, Stadtmauer EA, Estey E, Löwenberg B, Dombret H, et al.; Mylotarg Study Group. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001;19:3244–54. [DOI] [PubMed]

33.

Gondi CS, Rao JS. Cathepsin B as a cancer target. Expert Opin Ther Targets. 2013;17:281–91. [DOI] [PubMed] [PMC]

34.

Mohamed MM, Sloane BF. Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer. 2006;6:764–75. [DOI] [PubMed]

35.

Caculitan NG, dela Cruz Chuh J, Ma Y, Zhang D, Kozak KR, Liu Y, et al. Cathepsin B is dispensable for cellular processing of cathepsin B-cleavable antibody–drug conjugates. Cancer Res. 2017;77:7027–37. [DOI] [PubMed]

36.

Akkapeddi P, Azizi SA, Freedy AM, Cal PMSD, Gois PMP, Bernardes GJL. Construction of homogeneous antibody-drug conjugates using site-selective protein chemistry. Chem Sci. 2016;7:2954–63. [DOI] [PubMed] [PMC]

37.

Tiberghien AC, Levy JN, Masterson LA, Patel NV, Adams LR, Corbett S, et al. Design and synthesis of tesirine, a clinical antibody-drug conjugate pyrrolobenzodiazepine dimer payload. ACS Med Chem Lett. 2016;7:983–7. [DOI] [PubMed] [PMC]

38.

Tiberghien AC, von Bulow C, Barry C, Ge H, Noti C, Collet Leiris F, et al. Scale-up synthesis of tesirine. Org Process Res Dev. 2018;22:1241–56. [DOI]

39.

Balendiran GK, Dabur R, Fraser D. The role of glutathione in cancer. Cell Biochem Funct. 2004;22:343–52. [DOI] [PubMed]

40.

Saito G, Swanson JA, Lee KD. Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. Adv Drug Deliv Rev. 2003;55:199–215. [DOI] [PubMed]

41.

Bargh JD, Isidro-Llobet A, Parker JS, Spring DR. Cleavable linkers in antibody-drug conjugates. Chem Soc Rev. 2019;48:4361–74. [DOI] [PubMed]

42.

Jeffrey SC, Andreyka JB, Bernhardt SX, Kissler KM, Kline T, Lenox JS, et al. Development and properties of β-glucuronide linkers for monoclonal antibody-drug conjugates. Bioconjug Chem. 2006;17:831–40. [DOI] [PubMed]

43.

Chen H, Lin Z, Arnst KE, Miller DD, Li W. Tubulin inhibitor-based antibody-drug conjugates for cancer therapy. Molecules. 2017;22:1281. [DOI] [PubMed] [PMC]

44.

Barreca M, Stathis A, Barraja P, Bertoni F. An overview on anti-tubulin agents for the treatment of lymphoma patients. Pharmacol Ther. 2020;211:107552. [DOI] [PubMed]

45.

Waight AB, Bargsten K, Doronina S, Steinmetz MO, Sussman D, Prota AE. Structural basis of microtubule destabilization by potent auristatin anti-mitotics. PLoS One. 2016;11:e0160890. [DOI] [PubMed] [PMC]

46.

Johansson MP, Maaheimo H, Ekholm FS. New insight on the structural features of the cytotoxic auristatins MMAE and MMAF revealed by combined NMR spectroscopy and quantum chemical modelling. Sci Rep. 2017;7:15920. [DOI] [PubMed] [PMC]

47.

Sokka IK, Ekholm FS, Johansson MP. Increasing the potential of the auristatin cancer-drug family by shifting the conformational equilibrium. Mol Pharm. 2019;16:3600–8. [DOI] [PubMed] [PMC]

48.

Park MH, Lee BI, Byeon JJ, Shin SH, Choi J, Park Y, et al. Pharmacokinetic and metabolism studies of monomethyl auristatin F via liquid chromatography-quadrupole-time-of-flight mass spectrometry. Molecules. 2019;24:2754. [DOI] [PubMed] [PMC]

49.

Anderl J, Faulstich H, Hechler T, Kulke M. Antibody-drug conjugate payloads. In: Ducry L, editor. Antibody-drug conjugates. Totowa, NJ: Humana Press; 2013. pp. 51–70. [DOI] [PubMed]

50.

Xi Z, Goldberg IH. 7.15 - DNA-damaging enediyne compounds. In: Barton SD, Nakanishi K, Meth-Cohn O, editors. Comprehensive natural products chemistry. Oxford: Pergamon; 1999. pp. 553–92. [DOI] [PubMed]

51.

Tietze LF, Schmuck K. Prodrugs for targeted tumor therapies: recent developments in ADEPT, GDEPT and PMT. Curr Pharm Des. 2011;17:3527–47. [DOI] [PubMed]

52.

Dokter W, Ubink R, van der Lee M, van der Vleuten M, van Achterberg T, Jacobs D, et al. Preclinical profile of the HER2-targeting ADC SYD983/SYD985: introduction of a new duocarmycin-based linker-drug platform. Mol Cancer Ther. 2014;13:2618–29. [DOI] [PubMed]

53.

Adams DJ, Dewhirst MW, Flowers JL, Gamcsik MP, Colvin OM, Manikumar G, et al. Camptothecin analogues with enhanced antitumor activity at acidic pH. Cancer Chemother Pharmacol. 2000;46:263–71. [DOI] [PubMed]

54.

Starodub AN, Ocean AJ, Shah MA, Guarino MJ, Picozzi VJ Jr, Vahdat LT, et al. First-in-human trial of a novel anti-Trop-2 antibody-SN-38 conjugate, sacituzumab govitecan, for the treatment of diverse metastatic solid tumors. Clin Cancer Res. 2015;21:3870–8. [DOI] [PubMed] [PMC]

55.

Antonow D, Thurston DE. Synthesis of DNA-interactive pyrrolo[2,1-c][1,4]benzodiazepines (PBDs). Chem Rev. 2011;111:2815–64. [DOI] [PubMed]

56.

Kumar A, White J, James Christie R, Dimasi N, Gao C. Chapter twelve - antibody-drug conjugates. In: Goodnow RA, editor. Platform technologies in drug discovery and validation. Academic Press; 2017. pp. 441–80. [DOI]

57.

Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, et al. A phase I study of ADCT-402 (loncastuximab tesirine), a novel pyrrolobenzodiazepine-based antibody-drug conjugate, in relapsed/refractory B-cell non-hodgkin lymphoma. Clin Cancer Res. 2019;25:6986–94. [DOI] [PubMed]

58.

Gregson SJ, Howard PW, Gullick DR, Hamaguchi A, Corcoran KE, Brooks NA, et al. Linker length modulates DNA cross-linking reactivity and cytotoxic potency of C8/C8’ ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimers. J Med Chem. 2004;47:1161–74. [DOI] [PubMed]

59.

Yaghoubi S, Karimi MH, Lotfinia M, Gharibi T, Mahi-Birjand M, Kavi E, et al. Potential drugs used in the antibody-drug conjugate (ADC) architecture for cancer therapy. J Cell Physiol. 2020;235:31–64. [DOI] [PubMed]

60.

Hallen HE, Luo H, Scott-Craig JS, Walton JD. Gene family encoding the major toxins of lethal Amanita mushrooms. Proc Natl Acad Sci U S A. 2007;104:19097–101. [DOI] [PubMed] [PMC]

61.

Hennessy EJ. Selective inhibitors of Bcl-2 and Bcl-xL: balancing antitumor activity with on-target toxicity. Bioorg Med Chem Lett. 2016;26:2105–14. [DOI] [PubMed]

62.

Figueroa-Vazquez V, Ko J, Breunig C, Baumann A, Giesen N, Pálfi A, et al. HDP-101, an anti-BCMA antibody-drug conjugate, safely delivers amanitin to induce cell death in proliferating and resting multiple myeloma cells. Mol Cancer Ther. 2021;20:367–78. [DOI] [PubMed]

63.

Wolska-Washer A, Robak T. Safety and tolerability of antibody-drug conjugates in cancer. Drug Saf. 2019;42:295–314. [DOI] [PubMed] [PMC]

64.

Gorczyca W. Phenotypic markers. 2nd ed. Flow cytometry in neoplastic hematology. London: CRC Press; 2010. pp. 81–110. [DOI] [PMC]

65.

Wahl AF, Klussman K, Thompson JD, Chen JH, Francisco LV, Risdon G, et al. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin’s disease. Cancer Res. 2002;62:3736–42. [PubMed]

66.

Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003;102:1458–65. [DOI] [PubMed]

67.

Hendriks D, Choi G, de Bruyn M, Wiersma VR, Bremer E. Chapter seven - antibody-based cancer therapy: successful agents and novel approaches. Int Rev Cell Mol Biol. 2017;331:289–383. [DOI] [PubMed]

68.

Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, 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;30:2183–9. [DOI] [PubMed] [PMC]

69.

Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, 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;30:2190–6. [DOI] [PubMed]

70.

Deng C, Pan B, O’Connor OA. Brentuximab vedotin. Clin Cancer Res. 2013;19:22–7. [DOI] [PubMed]

71.

Kuruvilla J, Ramchandren R, Santoro A, Paszkiewicz-Kozik E, Gasiorowski R, Johnson NA, et al.; KEYNOTE-204 investigators. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021;22:512–24. [DOI] [PubMed]

72.

Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, et al.; AETHERA Study Group. 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;385:1853–62. Erratum in: Lancet. 2015;386:532. [DOI] [PubMed]

73.

Moskowitz CH, Walewski J, Nademanee A, Masszi T, Agura E, Holowiecki J, et al. Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood. 2018;132:2639–42. [DOI] [PubMed]

74.

Prince HM, Kim YH, Horwitz SM, Dummer R, Scarisbrick J, Quaglino P, et al.; ALCANZA study group. Brentuximab vedotin or physician’s choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017;390:555–66. [DOI] [PubMed]

75.

Horwitz SM, Scarisbrick JJ, Dummer R, Whittaker S, Duvic M, Kim YH, et al. Randomized phase 3 ALCANZA study of brentuximab vedotin vs physician’s choice in cutaneous T-cell lymphoma: final data. Blood Adv. 2021;5:5098–106. [DOI] [PubMed] [PMC]

76.

Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, et al.; ECHELON-1 Study Group. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378:331–44. Erratum in: N Engl J Med. 2018;378:878. [DOI] [PubMed] [PMC]

77.

Straus DJ, Długosz-Danecka M, Connors JM, Alekseev S, Illés Á, Picardi M, et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021;8:e410–21. Erratum in: Lancet Haematol. 2022;9:e91. [DOI] [PubMed]

78.

Richardson NC, Kasamon YL, Chen H, de Claro RA, Ye J, Blumenthal GM, et al. FDA approval summary: brentuximab vedotin in first-line treatment of peripheral T-cell lymphoma. Oncologist. 2019;24:e180–7. [DOI] [PubMed] [PMC]

79.

Horwitz S, O’Connor OA, Pro B, Illidge T, Fanale M, Advani R, et al.; ECHELON-2 Study Group. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;393:229–40. Erratum in: Lancet. 2019;393:228. [DOI] [PubMed] [PMC]

80.

Herrera AF, Li H, Castellino SM, Rutherford SC, Davison K, Evans AG, et al. SWOG S1826: a phase III, randomized study of nivolumab plus AVD or brentuximab vedotin plus AVD in patients with newly diagnosed advanced stage classical hodgkin lymphoma. Blood. 2020;136:23–4. [DOI]

81.

Herrera AF, Moskowitz AJ, Bartlett NL, Vose JM, Ramchandren R, Feldman TA, et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018;131:1183–94. [DOI] [PubMed] [PMC]

82.

Ward JP, Thein J, Luo J, Wagner-Johnston ND, Cashen AF, Fehniger TA, et al. A phase I trial of brentuximab vedotin in combination with lenalidomide in relapsed or refractory diffuse large B-cell lymphoma. Blood. 2015;126:3988. [DOI] [PubMed] [PMC]

83.

Bartlett NL, Yasenchak CA, Ashraf KK, Harwin WN, Sims RB, Nowakowski GS. Brentuximab Vedotin in combination with lenalidomide and rituximab in subjects with relapsed or refractory diffuse large B-cell lymphoma (Dlbcl) (trial in progress). Hematol Oncol. 2021;39:345–6. [DOI]

84.

Reagan PM, Portell CA, Casulo C, Baran AM, Magnuson A, Barr PM, et al. A pilot study of brentuximab vedotin, rituximab and dose attenuated CHP in patients 75 years and older with diffuse large B-cell lymphoma. Blood. 2020;136:5–6. [DOI]

85.

Jagadeesh D, Knowles S, Horwitz SM. Frontline brentuximab vedotin and CHP (A+CHP) in patients with peripheral T-cell lymphoma with less than 10% CD30 expression (SGN35-032, trial in progress). Hematol Oncol. 2021;39:303–4. [DOI]

86.

Lynch RC, Cassaday RD, Smith SD, Fromm JR, Cowan AJ, Warren EH, et al. Dose-dense brentuximab vedotin plus ifosfamide, carboplatin, and etoposide (ICE) is highly active for second line treatment in relapsed/refractory classical hodgkin lymphoma: final results of a phase I/II study. Blood. 2020;136:16–8. [DOI]

87.

Barta SK, Feldman TA, DeSimone JA, Kim E, Devajaran K, Wiest D, et al. A phase I trial assessing the feasibility of romidepsin combined with brentuximab vedotin for patients requiring systemic therapy for cutaneous T-cell lymphoma. Blood. 2020;136:24–5. [DOI]

88.

Gong J, Guo F, Cheng W, Fan H, Miao Q, Yang J. Preliminary biological evaluation of 123I-labelled anti-CD30-LDM in CD30-positive lymphomas murine models. Artif Cells Nanomed Biotechnol. 2020;48:408–14. [DOI] [PubMed]

89.

Wang R, Li L, Duan A, Li Y, Liu X, Miao Q, et al. Crizotinib enhances anti-CD30-LDM induced antitumor efficacy in NPM-ALK positive anaplastic large cell lymphoma. Cancer Lett. 2019;448:84–93. [DOI] [PubMed]

90.

Wang R, Li L, Zhang S, Li Y, Wang X, Miao Q, et al. A novel enediyne-integrated antibody-drug conjugate shows promising antitumor efficacy against CD30⁺ lymphomas. Mol Oncol. 2018;12:339–55. [DOI] [PubMed] [PMC]

91.

Ryan M, Lyski R, Bou L, Meyer D, Jin S, Simmons J, et al. Abstract 2889: SGN-CD30C, a new CD30-directed camptothecin antibody-drug conjugate (ADC), shows strong anti-tumor activity and superior tolerability in preclinical studies. Cancer Res. 2020;80:2889. [DOI]

92.

Ryan M, Lyski R, Bou L, Heiser R, Grogan B, Meyer D, et al. SGN-CD30C, an investigational CD30-directed camptothecin antibody-drug conjugate (ADC), shows strong anti tumor activity and superior tolerability in preclinical studies. Blood. 2020;136:41–2. [DOI]

93.

Burke PJ, Hamilton JZ, Pires TA, Setter JR, Hunter JH, Cochran JH, et al. Development of novel quaternary ammonium linkers for antibody-drug conjugates. Mol Cancer Ther. 2016;15:938–45. [DOI] [PubMed]

94.

Shen Y, Yang T, Cao X, Zhang Y, Zhao L, Li H, et al. Conjugation of DM1 to anti-CD30 antibody has potential antitumor activity in CD30-positive hematological malignancies with lower systemic toxicity. MAbs. 2019;11:1149–61. [DOI] [PubMed] [PMC]

95.

Young RM, Shaffer AL 3rd, Phelan JD, Staudt LM. B-cell receptor signaling in diffuse large B-cell lymphoma. Semin Hematol. 2015;52:77–85. [DOI] [PubMed] [PMC]

96.

Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, et al. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2020;38:155–65. [DOI] [PubMed] [PMC]

97.

Sehn LH, Hertzberg M, Opat S, Herrera AF, Assouline S, Flowers CR, et al. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022;6:533–43. [DOI] [PubMed] [PMC]

98.

Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022;386:351–63. [DOI] [PubMed]

99.

Diefenbach C, Abrisqueta P, Gonzalez-Barca E, Panizo C, Arguinano Perez JM, Miall F, et al. Polatuzumab vedotin + rituximab + lenalidomide in patients (ts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (Dlbcl): primary analysis of a phase 1b/2 trial. Hematol Oncol. 2021;39:332–3. [DOI]

100.

Diefenbach C, Kahl B, Banerjee L, McMillan A, Ramchandren R, Miall F, et al. Polatuzumab vedotin (Pola) + obinutuzumab (G) and lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL): interim analysis of a phase Ib/II trial. J Clin Oncol. 2019;37:7505. [DOI]

101.

Diefenbach C, Budde E, Chavez J, Lossos IS, Mehta A, Dorritie K, et al. Promising clinical data from dose escalation in a phase Ib/II ongoing study of mosunetuzumab with polatuzumab vedotin for relapsed/refractory B-cell non-hodgkin’s lymphoma. Hematol Oncol. 2021;39:330–1. [DOI]

102.

Gritti G, Marlton P, Phillips TJ, Arthur C, Bannerji R, Corradini P, et al. Polatuzumab vedotin plus venetoclax with rituximab in relapsed/refractory diffuse large B-cell lymphoma: primary efficacy analysis of a phase Ib/II study. Blood. 2020;136:45–7. [DOI]

103.

Bannerji R, Yuen S, Phillips T, Arthur C, Isufi I, Marlton P, et al. Polatuzumab vedotin + obinutuzumab + venetoclax in patients with relapsed/refractory (R/R) follicular lymphoma (Fl): primary analysis of a phase 1b/2 trial. Hematol Oncol. 2021;39:169–70. [DOI]

104.

Strati P, Watson G, Horowitz SB, Nair R, Rodriguez MA, Steiner RE, et al. Clinical efficacy of polatuzumab vedotin in patients with relapsed/refractory large B-cell lymphoma after standard of care axicabtagene ciloleucel. Blood. 2020;136:16–7. [DOI]

105.

Polson AG, Yu SF, Elkins K, Zheng B, Clark S, Ingle GS, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood. 2007;110:616–23. [DOI] [PubMed]

106.

Spycher PR, Probst P, Bertrand R, Stark R, Santimaria R, Grabulovski D, et al. Abstract 1842: CD79b targeting ADC with superior pharmacokinetic profile and anti-tumor activity. Cancer Res. 2021;81:1842. [DOI]

107.

Herrera AF, Patel MR, Burke JM, Advani RH, Cheson BD, Sharman JP, et al. A phase I study of the anti-CD79b THIOMAB^TM-drug conjugate DCDS0780A in patients (pts) with relapsed or refractory B-cell non-hodgkin’s lymphoma (B-NHL). Blood. 2017;130:4129.

108.

Wang K, Wei G, Liu D. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Exp Hematol Oncol. 2012;1:36. [DOI] [PubMed] [PMC]

109.

Cooper LJN, Al-Kadhimi Z, DiGiusto D, Kalos M, Colcher D, Raubitschek A, et al. Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies. Blood Cells Mol Dis. 2004;33:83–9. [DOI] [PubMed]

110.

Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 1995;18:385–97. [DOI] [PubMed]

111.

Al-Katib AM, Aboukameel A, Mohammad R, Bissery MC, Zuany-Amorim C. Superior antitumor activity of SAR3419 to rituximab in xenograft models for non-Hodgkin’s lymphoma. Clin Cancer Res. 2009;15:4038–45. [DOI] [PubMed]

112.

Albertson TM, Sandalic L, Zhao B, Kostic A, Law CL. Abstract DDT01-04: SGN-CD19A: a novel Anti-CD19 antibody drug conjugate. Cancer Res. 2014;74:DDT01–4. [DOI]

113.

Zammarchi F, Corbett S, Adams L, Tyrer PC, Kiakos K, Janghra N, et al. ADCT-402, a PBD dimer-containing antibody drug conjugate targeting CD19-expressing malignancies. Blood. 2018;131:1094–105. [DOI] [PubMed]

114.

Hicks SW, Tarantelli C, Wilhem A, Gaudio E, Li M, Arribas AJ, et al. The novel CD19-targeting antibody-drug conjugate huB4-DGN462 shows improved anti-tumor activity compared to SAR3419 in CD19-positive lymphoma and leukemia models. Haematologica. 2019;104:1633–9. [DOI] [PubMed] [PMC]

115.

Linhares Y, Gandhi MD, Chung M, Adeleye J, Ungar D, Hamadani M. Safety and antitumor activity study evaluating loncastuximab tesirine and rituximab versus immunochemotherapy in diffuse large B-cell lymphoma. Blood. 2020;136:9–10. [DOI]

116.

Li Z, Wang M, Yao X, Li H, Li S, Liu L, et al. Development of novel anti-CD19 antibody-drug conjugates for B-cell lymphoma treatment. Int Immunopharmacol. 2018;62:299–308. [DOI] [PubMed]

117.

Hong EE, Erickson H, Lutz RJ, Whiteman KR, Jones G, Kovtun Y, et al. Design of coltuximab ravtansine, a CD19-targeting antibody-drug conjugate (ADC) for the treatment of B-cell malignancies: structure-activity relationships and preclinical evaluation. Mol Pharm. 2015;12:1703–16. [DOI] [PubMed]

118.

Coiffier B, Thieblemont C, de Guibert S, Dupuis J, Ribrag V, Bouabdallah R, et al. A phase II, single-arm, multicentre study of coltuximab ravtansine (SAR3419) and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. Br J Haematol. 2016;173:722–30. [DOI] [PubMed]

119.

Trněný M, Verhoef GEG, Dyer MJS, Yehuda DB, Patti C, Canales MA, 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). J Clin Oncol. 2014;32:8506. [DOI]

120.

Tarantelli C, Spriano F, Golino G, Gaudio E, Scalise L, Cascione L, et al. The antibody-drug conjugate (ADC) loncastuximab tesirine (ADCT-402) targeting CD19 shows strong in vitro anti-lymphoma activity both as single agents and in combination. Hematol Oncol. 2019;37:129–30. [DOI]

121.

Hamadani M, Radford J, Carlo-Stella C, Caimi PF, Reid E, O’Connor OA, et al. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2021;137:2634–45. [DOI] [PubMed] [PMC]

122.

Jain N, Stock W, Zeidan A, Atallah E, McCloskey J, Heffner L, et al. Loncastuximab tesirine, an anti-CD19 antibody-drug conjugate, in relapsed/refractory B-cell acute lymphoblastic leukemia. Blood Adv. 2020;4:449–57. [DOI] [PubMed] [PMC]

123.

Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22:790–800. [DOI] [PubMed]

124.

Moskowitz CH, Bastos-Oreiro M, Ungar D, Dautaj I, Kalac M. Safety and anti-tumor activity study of loncastuximab tesirine and durvalumab in diffuse large B-cell, mantle cell, or follicular lymphoma. Blood. 2019;134:2807. [DOI]

125.

Carlo-Stella C, Zinzani PLL, Janakiram M, Dia V, He X, Ervin-Haynes A, et al. Planned interim analysis of a phase 2 study of loncastuximab tesirine plus ibrutinib in patients with advanced diffuse large B-cell lymphoma (LOTIS-3). Blood. 2021;138:54. [DOI]

126.

Carlo-Stella C, Depaus J, Hess BT, Kingsley E, Zinzani PL, Ungar D, et al. A phase 2 randomized study of loncastuximab tesirine (lonca) versus (vs) idelalisib in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL) – LOTIS-6. Hematol Oncol. 2021;39:355–6. [DOI]

127.

Depaus J, Wagner-Johnston N, Zinzani PL, Phillips TJ, Maly J, Ferrari S, et al. Clinical activity of loncastuximab tesirine plus ibrutinib in non-Hodgkin lymphoma: updated LOTIS 3 phase 1 results. Hematol Oncol. 2021;39:325. [DOI]

128.

Carlo-Stella C, Linhares Y, Gandhi MD, Chung M, Adamis H, Ungar D, et al. Phase 3 randomized study of loncastuximab tesirine plus rituximab versus immunochemotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma – LOTIS-5. Hematol Oncol. 2021;39:342–3. [DOI]

129.

Fathi AT, Borate U, DeAngelo DJ, O’Brien MM, Trippett T, Shah BD, et al. A phase 1 study of denintuzumab mafodotin (SGN-CD19A) in adults with relapsed or refractory B-lineage acute leukemia (B-ALL) and highly aggressive lymphoma. Blood. 2015;126:1328. [DOI]

130.

Moskowitz CH, Fanale MA, Shah BD, Advani RH, Chen R, Kim S, et al. A phase 1 study of denintuzumab mafodotin (SGN-CD19A) in relapsed/refactory B-lineage non-hodgkin lymphoma. Blood. 2015;126:182. [DOI]

131.

Sullivan-Chang L, O’Donnell RT, Tuscano JM. Targeting CD22 in B-cell malignancies: current status and clinical outlook. BioDrugs. 2013;27:293–304. [DOI] [PubMed]

132.

Li D, Poon KA, Yu SF, Dere R, Go M, Lau J, et al. DCDT2980S, an anti-CD22-monomethyl auristatin E antibody-drug conjugate, is a potential treatment for non-Hodgkin lymphoma. Mol Cancer Ther. 2013;12:1255–65. [DOI] [PubMed]

133.

D DiJoseph JF, Dougher MM, Kalyandrug LB, Armellino DC, Boghaert ER, Hamann PR, et al. Antitumor efficacy of a combination of CMC-544 (inotuzumab ozogamicin), a CD22-targeted cytotoxic immunoconjugate of calicheamicin, and rituximab against non-Hodgkin’s B-cell lymphoma. Clin Cancer Res. 2006;12:242–9. [DOI] [PubMed]

134.

Maclaren AP, Levin N, Lowman H. Abstract 835: TRPH-222, a novel anti-CD22 antibody drug conjugate (ADC), has significant anti-tumor activity in NHL xenografts and reduces B cells in monkeys. Cancer Res. 2018;78:835. [DOI]

135.

Zammarchi F, Williams D, Havenith K, D’Hooge F, Howard PW, Hartley JA, et al. Abstract 637: preclinical activity of hLL2-PBD, a novel anti-CD22 antibody-pyrrolobenzodiazepine (PBD) conjugate in models of non-Hodgkin lymphoma. Cancer Res. 2015;75:637. [DOI]

136.

Bera TK, Onda M, Kreitman RJ, Pastan I. An improved recombinant Fab-immunotoxin targeting CD22 expressing malignancies. Leuk Res. 2014;38:1224–9. [DOI] [PubMed] [PMC]

137.

Yu SF, Zheng B, Go M, Lau J, Spencer S, Raab H, et al. A novel anti-CD22 anthracycline-based antibody-drug conjugate (ADC) that overcomes resistance to auristatin-based ADCs. Clin Cancer Res. 2015;21:3298–306. [DOI] [PubMed]

138.

Yu SF, Lee DW, Zheng B, del Rosario G, Leipold D, Booler H, et al. An anti-CD22-seco-CBI-dimer antibody-drug conjugate (ADC) for the treatment of non-Hodgkin lymphoma that provides a longer duration of response than auristatin-based ADCs in preclinical models. Mol Cancer Ther. 2021;20:340–6. [DOI] [PubMed]

139.

Su D, Chen J, Cosino E, dela Cruz-Chuh J, Davis H, Del Rosario G, et al. Antibody-drug conjugates derived from cytotoxic seco-CBI-dimer payloads are highly efficacious in xenograft models and form protein adducts in vivo. Bioconjug Chem. 2019;30:1356–70. [DOI] [PubMed]

140.

Hernandez-Ilizaliturri FJ, Flinn IW, Kuruvilla J, Assouline SE, Ulrickson ML, Christian BA, et al. A phase i pharmacokinetic (PK) and safety study of Trph-222 in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R NHL): dose-escalation results. Blood. 2020;136:41–2. [DOI]

141.

Ricart AD. Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin Cancer Res. 2011;17:6417–27. [DOI] [PubMed]

142.

DiJoseph JF, Armellino DC, Boghaert ER, Khandke K, Dougher MM, Sridharan L, et al. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood. 2004;103:1807–14. [DOI] [PubMed]

143.

Advani A, Coiffier B, Czuczman MS, Dreyling M, Foran J, Gine E, 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;28:2085–93. [DOI] [PubMed]

144.

Goy A, Forero A, Wagner-Johnston N, Christopher Ehmann W, Tsai M, Hatake K, et al. A phase 2 study of inotuzumab ozogamicin in patients with indolent B-cell non-Hodgkin lymphoma refractory to rituximab alone, rituximab and chemotherapy, or radioimmunotherapy. Br J Haematol. 2016;174:571–81. [DOI] [PubMed]

145.

Fayad L, Offner F, Smith MR, Verhoef G, Johnson P, Kaufman JL, 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;31:573–83. [DOI] [PubMed] [PMC]

146.

Pirosa MC, Zhang L, Hitz F, Novak U, Hess D, Terrot T, et al. A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas. Leuk Lymphoma. 2022;63:117–23. [DOI] [PubMed]

147.

Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, et al. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018;182:583–6. [DOI] [PubMed] [PMC]

148.

Advani RH, Lebovic D, Chen A, Brunvand M, Goy A, Chang JE, et al. Phase I study of the anti-CD22 antibody–drug conjugate pinatuzumab vedotin with/without rituximab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res. 2017;23:1167–76. [DOI] [PubMed] [PMC]

149.

Morschhauser F, Flinn IW, Advani R, Sehn LH, Diefenbach C, Kolibaba K, et al. Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019;6:e254–65. [DOI] [PubMed]

150.

Chandramohan V, Sampson JH, Pastan IH, Bigner DD. Chapter 10 - immunotoxin therapy for brain tumors. In: Sampson JH, editor. Translational immunotherapy of brain tumors. San Diego: Academic Press; 2017. pp. 227–60. [DOI]

151.

Kreitman RJ, Pastan I. Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin Cancer Res. 2011;17:6398–405. [DOI] [PubMed] [PMC]

152.

Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T, et al. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018;32:1768–77. [DOI] [PubMed] [PMC]

153.

Lin AY, Dinner SN. Moxetumomab pasudotox for hairy cell leukemia: preclinical development to FDA approval. Blood Adv. 2019;3:2905–10. [DOI] [PubMed] [PMC]

154.

Zammarchi F, Corbett S, Adams L, Mellinas-Gomez M, Tyrer P, Dissanayake S, et al. hLL2-Cys-PBD, a new site-specifically conjugated, pyrrolobenzodiazepine (PBD) dimer-based antibody drug conjugate (ADC) targeting CD22-expressing B-cell malignancies. Blood. 2016;128:4176. [DOI]

155.

Flynn MJ, Zammarchi F, Tyrer PC, Akarca AU, Janghra N, Britten CE, et al. ADCT-301, a pyrrolobenzodiazepine (PBD) dimer-containing antibody-drug conjugate (ADC) targeting CD25-expressing hematological malignancies. Mol Cancer Ther. 2016;15:2709–21. [DOI] [PubMed]

156.

Spriano F, Tarantelli C, Golino G, Gaudio E, Scalise L, Cascione L, et al. The anti-CD25 antibody-drug conjugate camidanlumab tesirine (ADCT-301) presents a strong preclinical activity both as single agent and in combination in lymphoma cell lines. Hematol Oncol. 2019;37:323–4. [DOI]

157.

Jabeen A, Huang S, Hartley JA, Van Berkel PH, Zammarchi F. Combination of camidanlumab tesirine, a CD25-targeted ADC, with gemcitabine elicits synergistic anti-tumor activity in preclinical tumor models. Blood. 2020;136:31–2. [DOI]

158.

Hamadani M, Collins GP, Caimi PF, Samaniego F, Spira A, Davies A, et al. Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. Lancet Haematol. 2021;8:e433–45. [DOI] [PubMed]

159.

Bertoni F, Stathis A. Staining the target: CD37 expression in lymphomas. Blood. 2016;128:3022–3. [DOI] [PubMed]

160.

Schaper F, van Spriel AB. Antitumor immunity is controlled by tetraspanin proteins. Front Immunol. 2018;9:1185. [DOI] [PubMed] [PMC]

161.

Deckert J, Park PU, Chicklas S, Yi Y, Li M, Lai KC, et al. A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies. Blood. 2013;122:3500–10. [DOI] [PubMed]

162.

Gaudio E, Tarantelli C, Arribas A, Cascione L, Kwee I, Rinaldi A, et al. Identification of anti-lymphoma biomarkers of response to the anti-CD37 antibody drug conjugate (ADC) IMGN529. Blood. 2016;128:4187. [DOI]

163.

de Winde CM, Veenbergen S, Young KH, Xu-Monette ZY, Wang XX, Xia Y, et al. Tetraspanin CD37 protects against the development of B cell lymphoma. J Clin Invest. 2016;126:653–66. [DOI] [PubMed] [PMC]

164.

Xu-Monette ZY, Li L, Byrd JC, Jabbar KJ, Manyam GC, Maria de Winde C, et al. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma. Blood. 2016;128:3083–100. [DOI] [PubMed] [PMC]

165.

Arribas AJ, Cascione L, Aresu L, Gaudio E, Rinaldi A, Tarantelli C, et al. Abstract 2853: development of novel preclinical models of secondary resistance to the anti-CD37 antibody drug conjugate (ADC) IMGN529/DEBIO1562 in diffuse large B-cell lymphoma (DLBCL). Proceedings: AACR Annual Meeting; 2018 Apr 14–18; Chicago, IL: Cancer Research; 2018. p. 2853. [DOI]

166.

Stathis A, Flinn IW, Madan S, Maddocks K, Freedman A, Weitman S, et al. Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study. Invest New Drugs. 2018;36:869–76. [DOI] [PubMed] [PMC]

167.

Jacobs J, Deschoolmeester V, Zwaenepoel K, Rolfo C, Silence K, Rottey S, et al. CD70: an emerging target in cancer immunotherapy. Pharmacol Ther. 2015;155:1–10. [DOI] [PubMed]

168.

Jacobs J, Zwaenepoel K, Rolfo C, Van den Bossche J, Deben C, Silence K, et al. Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer. Oncotarget. 2015;6:13462–75. [DOI] [PubMed] [PMC]

169.

Yang CY, Wang L, Pincus L, McCormick F, Gill R, Ai W. Abstract 4589: preclinical investigation of SGN-CD70A antibody-drug conjugate in T cell lymphomas. Cancer Res. 2017;77:4589. [DOI]

170.

Tannir NM, Forero-Torres A, Ramchandren R, Pal SK, Ansell SM, Infante JR, et al. Phase I dose-escalation study of SGN-75 in patients with CD70-positive relapsed/refractory non-Hodgkin lymphoma or metastatic renal cell carcinoma. Invest New Drugs. 2014;32:1246–57. [DOI] [PubMed]

171.

Phillips T, Barr PM, Park SI, Kolibaba K, Caimi PF, Chhabra S, et al. A phase 1 trial of SGN-CD70A in patients with CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma. Invest New Drugs. 2019;37:297–306. [DOI] [PubMed] [PMC]

172.

Singh S, DuPage A, Yang Weaver A, Sagert J, White C, Krimm M, et al. Abstract 2975: development of a probody drug conjugate (PDC) targeting CD71 for the treatment of solid tumors and lymphomas. Cancer Res. 2016;76:2975. [DOI]

173.

Johnson M, Rodon Ahnert J, Lakhani N, Sanborn RE, El-Khoueiry A, Hafez N, et al. P01.06 CX-2029, a probody drug conjugate targeting CD71 in patients with selected tumor types: PROCLAIM-CX-2029 dose expansion phase. J Thorac Oncol. 2021;16:S238. [DOI]

174.

Merlino G, Fiascarelli A, Bigioni M, Bressan A, Carrisi C, Bellarosa D, et al. MEN1309/OBT076, a first-in-class antibody-drug conjugate targeting CD205 in solid tumors. Mol Cancer Ther. 2019;18:1533–43. [DOI] [PubMed]

175.

Gaudio E, Tarantelli C, Spriano F, Guidetti F, Sartori G, Bordone R, et al. Targeting CD205 with the antibody drug conjugate MEN1309/OBT076 is an active new therapeutic strategy in lymphoma models. Haematologica. 2020;105:2584–91. [DOI] [PubMed] [PMC]

176.

Cui B, Widhopf GF, Prussak CE, Wu CCN, Sadarangani A, Zhang S, et al. Cirmtuzumab vedotin (UC-961ADC3), an anti-ROR1-monomethyl auristatin E antibody-drug conjugate, is a potential treatment for ROR1-positive leukemia and solid tumors. Blood. 2013;122:1637. [DOI]

177.

Mian YA, Widhopf GF II, Vo TT, Jessen K, Rassenti LZ, Kipps TJ. Development of cirmtuzumab antibody-drug conjugates (ADCs) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1). Blood. 2018;132:1862. [DOI]

178.

Wang M, Barrientos JC, Furman RR, Mei M, Barr PM, Choi MY, et al. VLS-101, a ROR1-targeting antibody-drug conjugate, demonstrates a predictable safety profile and clinical efficacy in patients with heavily pretreated mantle cell lymphoma and diffuse large B-cell lymphoma. Blood. 2020;136:13–4. [DOI]

179.

Jiang VC, Liu Y, McIntosh J, Jordan AA, Leeming A, Chen Z, et al. Targeting ROR1 using the antibody drug conjugate Vls-101 in aggressive mantle cell lymphoma. Blood. 2020;136:33. [DOI] [DOI]

180.

Tolcher AW, Meric-Bernstam F, McKean M, Beerli RR, Waldmeier L, Gebleux R, et al. NBE-002: a novel anthracycline-based antibody-drug conjugate (ADC) targeting ROR1 for the treatment of advanced solid tumors—a phase 1/2 clinical trial. J Clin Oncol. 2021;39:TPS1108. [DOI]

181.

Kipps TJ. ROR1: an orphan becomes apparent. Blood. 2022;140:1583–91. [DOI] [PubMed]

182.

Jiang VC, Liu Y, Jordan A, McIntosh J, Li Y, Che Y, et al. The antibody drug conjugate VLS-101 targeting ROR1 is effective in CAR T-resistant mantle cell lymphoma. J Hematol Oncol. 2021;14:132. [DOI] [PubMed] [PMC]

183.

Wang ML, Barrientos JC, Furman RR, Mei M, Barr PM, Choi MY, et al. Zilovertamab vedotin targeting of ROR1 as therapy for lymphoid cancers. NEJM Evidence. 2022;1:EVIDoa2100001. [DOI]

184.

Hartley-Brown M, Richardson P. Antibody-drug conjugate therapies in multiple myeloma—what’s next on the horizon? Explor Target Antitumor Ther. 2022;3:1–10. [DOI] [PubMed] [PMC]

185.

Lancman G, Richter J, Chari A. Bispecifics, trispecifics, and other novel immune treatments in myeloma. Hematology Am Soc Hematol Educ Program. 2020;2020:264–71. [DOI] [PubMed] [PMC]

186.

Sanchez L, Dardac A, Madduri D, Richard S, Richter J. B-cell maturation antigen (BCMA) in multiple myeloma: the new frontier of targeted therapies. Ther Adv Hematol. 2021;12:2040620721989585. [DOI] [PubMed] [PMC]

187.

Cohen AD. Myeloma: next generation immunotherapy. Hematology Am Soc Hematol Educ Program. 2019;2019:266–72. [DOI] [PubMed] [PMC]

188.

Kantarjian HM, Lioure B, Kim SK, Atallah E, Leguay T, Kelly K, et al. A phase II study of coltuximab ravtansine (SAR3419) monotherapy in patients with relapsed or refractory acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2016;16:139–45. [DOI] [PubMed] [PMC]

189.

Donaghy H. Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates. MAbs. 2016;8:659–71. [DOI] [PubMed] [PMC]

190.

Burnett CA, Hamlin P, Dabovic K, Higgins J, Persky DO. A phase 1/2 study of MT-3724 to evaluate safety, pharmacodynamics and efficacy of MT-3724 for the treatment of patients with relapsed or refractory diffuse large B cell lymphoma. Hematol Oncol. 2019;37:566. [DOI]

191.

Wang M, Jain P, Feng L, Badillo M, Graham V, Burnett C, et al. A phase 1 multicenter open-label study of escalating doses of the novel anti-CD20-targeting engineered toxin body MT-3724 in subjects with relapsed or refractory mantle cell lymphoma. Blood. 2020;136:34. [DOI] [DOI] [DOI] [DOI] [DOI]

192.

Higgins JP, Iberg A, Howard C, Willert E. Abstract 2060: combination of CD20 targeted engineered toxin body, MT-3724, with chemotherapy or IMiDs for the treatment of non Hodgkin’s lymphoma. Cancer Res. 2019;79:2060. [DOI]

193.

Tache J, Katz DA, Mazumder A, Peace D, Burnett C, Strack T, et al. Abstract PO-63: a phase 2a open-label study of MT-3724, a novel CD20-targeting engineered toxin body, in combination with lenalidomide (LEN) in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Blood Cancer Discovery. 2020;1:PO-63. [DOI]

194.

Kantarjian HM, DeAngelo DJ, Advani AS, Stelljes M, Kebriaei P, Cassaday RD, et al. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol. 2017;4:e387–98. [DOI] [PubMed]

195.

Jabbour EJ, DeAngelo DJ, Stelljes M, Stock W, Liedtke M, Gökbuget N, et al. Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE. Cancer. 2018;124:1722–32. [DOI] [PubMed]

196.

Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Robak T, le Coutre PD, et al.; Study 1053 investigators. Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial. J Hematol Oncol. 2021;14:35. [DOI] [PubMed] [PMC]

197.

Gaudio E, Tarantelli C, Cascione L, Spriano F, Golino G, Scalise L, et al. Analysis of Adct-602 pre-clinical activity in B-cell lymphoma models and identification of potential biomarkers for its activity. Blood. 2020;136:10–1. [DOI]

198.

Herrera AF, Carlo-Stella C, Collins GP, Maddocks KJ, Bartlett NL, Savage KJ, et al. Preliminary results of a phase 2 study of camidanlumab tesirine (Cami), a novel pyrrolobenzodiazepine-based antibody-drug conjugate, in patients with relapsed or refractory hodgkin lymphoma. Blood. 2020;136:21–3. [DOI]

199.

Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363:1812–21. [DOI] [PubMed]

200.

Carson KR, Newsome SD, Kim EJ, Wagner-Johnston ND, von Geldern G, Moskowitz CH, et al. Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: a report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project. Cancer. 2014;120:2464–71. [DOI] [PubMed] [PMC]

201.

Gandhi MD, Evens AM, Fenske TS, Hamlin P, Coiffier B, Engert A, et al. Pancreatitis in patients treated with brentuximab vedotin: a previously unrecognized serious adverse event. Blood. 2014;123:2895–7. [DOI] [PubMed] [PMC]

202.

Nademanee A, Sureda A, Stiff P, Holowiecki J, Abidi M, Hunder N, et al. Safety analysis of brentuximab vedotin from the phase III AETHERA trial in hodgkin lymphoma in the post-transplant consolidation setting. Biol Blood Marrow Transplant. 2018;24:2354–9. [DOI] [PubMed]

203.

Pereira DS, Guevara CI, Jin L, Mbong N, Verlinsky A, Hsu SJ, 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;14:1650–60. [DOI] [PubMed] [PMC]

204.

Sawas A, Savage KJ, Perez RP, Advani RH, Zaine JM, Lackey JM, et al. A phase 1 study of the anti-CD37 antibody-drug conjugate AGS67E in advanced lymphoid malignancies. Interim results. Hematol Oncol. 2017;35:49. [DOI]

205.

Thevanayagam L, Bell A, Chakraborty I, Sufi B, Gangwar S, Zang A, et al. Novel detection of DNA-alkylated adducts of antibody-drug conjugates with potentially unique preclinical and biomarker applications. Bioanalysis. 2013;5:1073–81. [DOI] [PubMed]

206.

Owonikoko TK, Hussain A, Stadler WM, Smith DC, Kluger H, Molina AM, et al. First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70. Cancer Chemother Pharmacol. 2016;77:155–62. [DOI] [PubMed]

207.

Oflazoglu E, Stone IJ, Gordon K, Wood CG, Repasky EA, Grewal IS, et al. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin Cancer Res. 2008;14:6171–80. [DOI] [PubMed]