Combinatorial Efficacy and Toxicity of an Engineered Toxin Body MT-3724 with Gemcitabine and Oxaliplatin in Relapsed or Refractory Diffuse Large B Cell Lymphoma

References

• Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood. 2006;107(1):265–276. doi:10.1182/blood-2005-06-2508.
   PubMed Web of Science ®Google Scholar
• Tedder TF, Engel P. CD20: a regulator of cell-cycle progression of B lymphocytes. Immunol Today. 1994;15(9):450–454. doi:10.1016/0167-5699(94)90276-3.
   PubMedGoogle Scholar
• Tedder TF, Streuli M, Schlossman SF, Saito H. Isolation and structure of a cDNA encoding the B1 (CD20) cell-surface antigen of human B lymphocytes. Proc Natl Acad Sci U S A. 1988;85(1):208–212. doi:10.1073/pnas.85.1.208.
   PubMed Web of Science ®Google Scholar
• Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–242. doi:10.1056/NEJMoa011795.
   PubMed Web of Science ®Google Scholar
• Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(19):3121–3127. doi:10.1200/jco.2005.05.1003.
   PubMed Web of Science ®Google Scholar
• Pfreundschuh M, Kuhnt E, Trümper L, Österborg A, Trneny M, Shepherd L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011;12(11):1013–1022. doi:10.1016/S1470-2045(11)70235-2.
   PubMed Web of Science ®Google Scholar
• Friedberg JW. Relapsed/refractory diffuse large B-cell lymphoma. Hematology Am Soc Hematol Educ Program. 2011;2011:498–505. doi:10.1182/asheducation-2011.1.498.
   PubMed Web of Science ®Google Scholar
• Coiffier B, Sarkozy C. Diffuse large B-cell lymphoma: R-CHOP failure-what to do? Hematology Am Soc Hematol Educ Program. 2016;2016(1):366–378. doi:10.1182/asheducation-2016.1.366.
   PubMed Web of Science ®Google Scholar
• Scott DW, Mottok A, Ennishi D, Wright GW, Farinha P, Ben-Neriah S, et al. Prognostic significance of diffuse large B-cell lymphoma cell of origin determined by digital gene expression in formalin-fixed paraffin-embedded tissue biopsies. J Clin Oncol. 2015;33(26):2848–2856. doi:10.1200/jco.2014.60.2383.
   PubMed Web of Science ®Google Scholar
• Hu S, Xu-Monette ZY, Tzankov A, Green T, Wu L, Balasubramanyam A, et al. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from the International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013;121(20):4021–4031;quiz 4250. doi:10.1182/blood-2012-10-460063.
   PubMed Web of Science ®Google Scholar
• Montoto S, Davies AJ, Matthews J, Calaminici M, Norton AJ, Amess J, et al. Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol. 2007;25(17):2426–2433. doi:10.1200/jco.2006.09.3260.
   PubMed Web of Science ®Google Scholar
• Crump M, Neelapu SS, Farooq U, Van Den Neste E, Kuruvilla J, Westin J, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017;130(16):1800–1808. doi:10.1182/blood-2017-03-769620.
   PubMed Web of Science ®Google Scholar
• Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184–4190. doi:10.1200/jco.2010.28.1618.
   PubMed Web of Science ®Google Scholar
• Corazzelli G, Capobianco G, Arcamone M, Ballerini PF, Iannitto E, Russo F, et al. Long-term results of gemcitabine plus oxaliplatin with and without rituximab as salvage treatment for transplant-ineligible patients with refractory/relapsing B-cell lymphoma. Cancer Chemother Pharmacol. 2009;64(5):907–916. doi:10.1007/s00280-009-0941-9.
   PubMed Web of Science ®Google Scholar
• 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(2):155–165. doi:10.1200/jco.19.00172.
   PubMed Web of Science ®Google Scholar
• Salles G, Duell J, González Barca E, Tournilhac O, Jurczak W, Liberati AM, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7):978–988. doi:10.1016/S1470-2045(20)30225-4.
   PubMed Web of Science ®Google Scholar
• 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(6):790–800. doi:10.1016/S1470-2045(21)00139-X.
   PubMed Web of Science ®Google Scholar
• Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020;7(7):e511–e522. doi:10.1016/S2352-3026(20)30120-4.
   PubMed Web of Science ®Google Scholar
• Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11(4):69. doi:10.1038/s41408-021-00459-7.
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Reagan PM, Miklos DB, et al. Comparison of 2-year outcomes with CAR T cells (ZUMA-1) vs salvage chemotherapy in refractory large B-cell lymphoma. Blood Adv. 2021;5(20):4149–4155. doi:10.1182/bloodadvances.2020003848.
   PubMed Web of Science ®Google Scholar
• Huang S, Jiang C, Zhang H, Bell T, Guo H, Liu Y, et al. The CD20-specific engineered toxin antibody MT-3724 exhibits lethal effects against mantle cell lymphoma. Blood Cancer J. 2018;8(3):33–33. doi:10.1038/s41408-018-0066-7.
   PubMedGoogle Scholar
• Huang S, Bell T, Liu Y, Guo H, Li C, Ahmed M, et al. Abstract 3651: Preclinical examination of the effects of MT-3724, an engineered toxin body targeting CD20, in mantle cell lymphoma. Cancer Res. 2017;77(13_Supplement):3651–3651. doi:10.1158/1538-7445.AM2017-3651.
   Google Scholar
• Willert EK, Robinson GL, Rajagopalan S, Brieschke B, Erdman J, Neill J, et al. Abstract 2477: engineered toxin bodies: a next-generation immunotoxin scaffold with novel immuno-oncology functionality. Cancer Res. 2015;75(15_Supplement):2477–2477. doi:10.1158/1538-7445.AM2015-2477.
   Google Scholar
• Rajagopalan S, Wirth R, Erdman J, Brieschke B, Null W, Liu J, et al. CD20-specific engineered toxin body demonstrates direct cell kill of multiple B-cell non-Hodgkin’s lymphoma types. Blood. 2013;122(21):5152–5152. doi:10.1182/blood.V122.21.5152.5152.
   Google Scholar
• Hamlin PA, Musteata V, Zodelava M, Park SI, Burnett C, Dabovic K, et al. Monotherapy activity with the first CD20-targeted immunotoxin, MT-3724, in subjects with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Blood. 2019;134(Supplement_1):4098–4098. doi:10.1182/blood-2019-129243.
   Google Scholar
• Fanale MA, Hamlin PA, Park SI, Persky DO, Higgins JP, Burnett C, et al. Safety and efficacy of anti-CD20 immunotoxin MT-3724 in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) in a phase I study. JCO. 2018;36(15_suppl):7580–7580. doi:10.1200/JCO.2018.36.15_suppl.7580.
   Web of Science ®Google Scholar
• Darvishi B, Farahmand L, Jalili N, Majidzadeh AK. Probable mechanisms involved in immunotoxin mediated capillary leak syndrome (CLS) and recently developed countering strategies. Curr Mol Med. 2018;18(5):335–342. doi:10.2174/1566524018666181004120112.
   PubMed Web of Science ®Google Scholar
• Baluna R, Vitetta ES. Vascular leak syndrome: a side effect of immunotherapy. Immunopharmacology. 1997;37(2-3):117–132. doi:10.1016/S0162-3109(97)00041-6.
   PubMed Web of Science ®Google Scholar
• Robinson GL, Rajagopalan S, Brieschke B, Erdman J, Neill J, Flores-Lefranc RE, et al. Abstract 1483: MT-3724, an engineered toxin body targeting CD20 for non-Hodgkin’s lymphoma. Cancer Res. 2016;76(14_Supplement):1483–1483. doi:10.1158/1538-7445.AM2016-1483.
   Google Scholar
• Hamlin PA, Musteata V, Park SI, Burnett C, Dabovic K, Strack T, et al. Safety and efficacy of engineered toxin body MT-3724 in relapsed or refractory B-cell non-Hodgkin’s lymphomas and diffuse large B-cell lymphoma. Cancer Res Commun. 2022;2(5):307–315. doi:10.1158/2767-9764.CRC-22-0056.
   Google Scholar
• Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–3068. doi:10.1200/jco.2013.54.8800.
   PubMed Web of Science ®Google Scholar
• Jeong G, Lee K, Lee I, Oh J, Kim D, Shin J, et al. Incidence of capillary leak syndrome as an adverse effect of drugs in cancer patients: a systematic review and meta-analysis. JCM. 2019;8(2):143. doi:10.3390/jcm8020143.
   Google Scholar
• De Pas T, Curigliano G, Franceschelli L, Catania C, Spaggiari L, de Braud F. Gemcitabine-induced systemic capillary leak syndrome. Ann Oncol. 2001;12(11):1651–1652. doi:10.1023/A:1013163831194.
   PubMed Web of Science ®Google Scholar
• Bajwa R, Starr J, Daily K. Gemcitabine-induced chronic systemic capillary leak syndrome. BMJ Case Rep. 2017;2017. doi:10.1136/bcr-2017-221068.
   PubMedGoogle Scholar
• Mertz P, Lebrun-Vignes B, Salem JE, Arnaud L. Characterizing drug-induced capillary leak syndromes using the World Health Organization VigiBase. J Allergy Clin Immunol. 2019;143(1):433–436. doi:10.1016/j.jaci.2018.09.001.
   PubMed Web of Science ®Google Scholar
• Administration UFaD. Prescribing information for gemcitabine. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020509s077lbl.pdf.
   Google Scholar
• Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b + myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005;11(18):6713–6721. doi:10.1158/1078-0432.Ccr-05-0883.
   PubMed Web of Science ®Google Scholar
• Fritz J, Karakhanova S, Brecht R, Nachtigall I, Werner J, Bazhin AV. In vitro immunomodulatory properties of gemcitabine alone and in combination with interferon-alpha. Immunol Lett. 2015;168(1):111–119. doi:10.1016/j.imlet.2015.09.017.
   PubMed Web of Science ®Google Scholar
• Tel J, Hato SV, Torensma R, Buschow SI, Figdor CG, Lesterhuis WJ, et al. The chemotherapeutic drug oxaliplatin differentially affects blood DC function dependent on environmental cues. Cancer Immunol Immunother. 2012;61(7):1101–1111. doi:10.1007/s00262-011-1189-x.
   PubMed Web of Science ®Google Scholar
• Hassan R, Broaddus VC, Wilson S, Liewehr DJ, Zhang J. Anti-mesothelin immunotoxin SS1P in combination with gemcitabine results in increased activity against mesothelin-expressing tumor xenografts. Clin Cancer Res. 2007;13(23):7166–7171. doi:10.1158/1078-0432.Ccr-07-1592.
   PubMed Web of Science ®Google Scholar
• Singh R, Zhang Y, Pastan I, Kreitman RJ. Synergistic antitumor activity of anti-CD25 recombinant immunotoxin LMB-2 with chemotherapy. Clin Cancer Res. 2012;18(1):152–160. doi:10.1158/1078-0432.CCR-11-1839.
   PubMed Web of Science ®Google Scholar
• Gujar SA, Clements D, Dielschneider R, Helson E, Marcato P, Lee PWK. Gemcitabine enhances the efficacy of reovirus-based oncotherapy through anti-tumour immunological mechanisms. Br J Cancer. 2014;110(1):83–93. doi:10.1038/bjc.2013.695.
   PubMed Web of Science ®Google Scholar
• Stojanovska V, Prakash M, McQuade R, Fraser S, Apostolopoulos V, Sakkal S, et al. Oxaliplatin treatment alters systemic immune responses. Biomed Res Int. 2019;2019:4650695. doi:10.1155/2019/4650695.
   PubMed Web of Science ®Google Scholar
• Kumar S, Mamuye A, Dabovic K, Wang J, Anand B, Yuet A, et al. 447 Interim results of a phase 1 study of the novel engineered toxin body TAK-169 in patients with relapsed or refractory multiple myeloma. J Immunother Cancer. 2021;9(Suppl 2):A475–A475. doi:10.1136/jitc-2021-SITC2021.447.
   Google Scholar
• Ramos HJ, Brieschke B, LeMar S, Dekker JD, Iberg A, Robinson GL, et al. Abstract 3366: in vivo efficacy of a PD-L1 targeted, antigen seeding engineered toxin body. Cancer Res. 2020;80(16_Supplement):3366–3366. doi:10.1158/1538-7445.AM2020-3366.
   Web of Science ®Google Scholar
• Wainberg ZA, Barve MA, Hamilton EP, Brenner AJ, Valdes F, Mita MM, et al. A phase I study of the novel immunotoxin, MT-5111, in subjects (subj) with HER-2 positive tumors: interim results. JCO. 2020;38(15_suppl):e15567–e15567. doi:10.1200/JCO.2020.38.15_suppl.e15567.
   Web of Science ®Google Scholar