OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 10 April 2019

• Reuben A. Hepatotoxicity of immunosuppressive drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2011, pp. 569-91.

  (Review of hepatotoxicity of monoclonal immunosuppressive agents written before the availability of mogamulizumab; "the biological immuno-suppressants are largely free from hepatotoxicity, with the exception of the TNF alpha antagonists").
• Wellstein A, Giaccone G, Atkins MB, Sausville EA. Pathway-targeted therapies: monoclonal antibodies, protein kinase inhibitors, and various small molecules. In, Brunton LL, Hilal-Danan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1203-36.

  (Textbook of pharmacology and therapeutics).
• https://www​.accessdata​.fda.gov/scripts/cder/daf/

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA scientific review of the new drug application for safety and efficacy; mentions that “hepatitis” was reported in 8% of 319 patients treated with mogamulizumab, but that there were no cases of hepatitis with jaundice and rates of ALT elevations were similar in comparator arms [19% vs 21% receiving vorinostat]).
• Ogura M, Ishida T, Hatake K, Taniwaki M, Ando K, Tobinai K, Fujimoto K, et al. Multicenter phase II study of mogamulizumab (KW-0761), a defucosylated anti-cc chemokine receptor 4 antibody, in patients with relapsed peripheral T-cell lymphoma and cutaneous T-cell lymphoma. J Clin Oncol 2014; 32: 1157-63. [PubMed: 24616310]

  (Among 37 patients with relapsed peripheral or cutaneous T-cell lymphoma treated with mogamulizumab, 35% had an objective response and side effects included lymphopenia [81%], skin rash [51%], fever [30%], infusion reactions [24%] and ALT elevations [22%] which were above 5 times ULN in only one subject [3%]).
• Nakano N, Kusumoto S, Tanaka Y, Ishida T, Takeuchi S, Takatsuka Y, Akinaga S, et al. Reactivation of hepatitis B virus in a patient with adult T-cell leukemia-lymphoma receiving the anti-CC chemokine receptor 4 antibody mogamulizumab. Hepatol Res 2014; 44: 354-7. [PubMed: 23601025]

  (65 year old woman with relapsed adult T-cell lymphoma [with anti-HBc without HBsAg or HBV DNA] developed reactivation of HBV 6 months after starting intermittent mogamulizumab therapy becoming HBsAg and HBV DNA positive [bilirubin not given, ALT 205 U/L, HBV DNA 7.8 million IU/mL], responding to entecavir therapy).
• Ifuku H, Kusumoto S, Tanaka Y, Totani H, Ishida T, Okada M, Murakami S, et al. Fatal reactivation of hepatitis B virus infection in a patient with adult T-cell leukemia-lymphoma receiving the anti-CC chemokine receptor 4 antibody mogamulizumab. Hepatol Res 2015; 45: 1363-7. [PubMed: 25753008]

  (72 year old man with adult T-cell lymphoma developed fatal reactivation of HBV [peak bilirubin ~31 mg/dL, ALT 3,080 U/L] shortly after starting mogamulizumab, having become HBsAg and HBV DNA positive before starting monoclonal antibody therapy after 8 previous cycles of cytotoxic chemotherapy).
• Totani H, Kusumoto S, Ishida T, Masuda A, Yoshida T, Ito A, Ri M, et al. Reactivation of hepatitis B virus (HBV) infection in adult T-cell leukemia-lymphoma patients with resolved HBV infection following systemic chemotherapy. Int J Hematol 2015; 101: 398-404. [PubMed: 25633779]

  (Among 24 patients with adult T cell lymphomas with antibody to HBV without HBsAg who received systemic chemotherapy, 3 [13%] developed HBV reactivation during prospective monitoring of HBV DNA levels, but none developed hepatitis having been promptly treated with entecavir; 2 of the 3 received mogamulizumab, the 3rd had undergone hematopoietic cell transplantation).
• Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, Dwyer KM, et al. Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma. Blood 2015; 125: 1883-9. [PMC free article: PMC4375715] [PubMed: 25605368]

  (Among 41 patients with cutaneous T-cell lymphoma treated with mogamulizumab, the objective response rate was 37% and adverse events included nausea [31%], fever [24%], infusion reactions [21%] and drug eruptions [17%]; no mention of ALT elevations or hepatotoxicity).
• Sugio T, Kato K, Aoki T, Ohta T, Saito N, Yoshida S, Kawano I, et al. Mogamulizumab treatment prior to allogeneic hematopoietic stem cell transplantation induces severe acute graft-versus-host disease. Biol Blood Marrow Transplant 2016; 22: 1608-14. [PubMed: 27220263]

  (Among 25 patients with acute T cell lymphoma treated with mogamulizumab before hematopoietic cell transplantation, graft-vs-host disease was more frequent and more severe than in patients who had not received mogamulizumab).
• Phipps C, Chen Y, Tan D. Lymphoproliferative disease and hepatitis B reactivation: challenges in the era of rapidly evolving targeted therapy. Clin Lymphoma Myeloma Leuk 2016; 16: 5-11. [PubMed: 26705677]

  (Review of reactivation of hepatitis B caused by targeted therapies of lymphoproliferative diseases; mentions two cases of HBV reactivation with reverse seroconversion during mogamulizumab therapy of adult T cell lymphomas).
• Kim YH, Bagot M, Pinter-Brown L, Rook AH, Porcu P, Horwitz SM, Whittaker S, et al.; MAVORIC Investigators. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol 2018; 19: 1192-204. [PubMed: 30100375]

  (Among 370 patients with refractory cutaneous T cell lymphoma treated with mogamulizumab or vorinostat, median progression-free survival was greater with the monoclonal antibody [7.7 vs 3.1 months], while adverse event rates were less except for infusion site reactions [24% vs 1%] and skin eruptions [24% vs 1%] while AST elevations occurred in 4% vs 7%, and there were no severe hepatic adverse reactions).
• Sato T, Coler-Reilly ALG, Yagishita N, Araya N, Inoue E, Furuta R, Watanabe T, et al. Mogamulizumab (anti-CCR4) in HTLV-1-associated myelopathy. N Engl J Med 2018; 378: 529-38. [PubMed: 29414279]

  (Among 21 patients with HTLV-1 associated myelopathy and adult T cell lymphoma treated with mogamulizumab, reduction in spasticity occurred in 79% of patients and infusions were well tolerated; 1 patient developed transient AST elevations above 5 times ULN which resolved rapidly upon stopping therapy).
• Miyagawa F, Yamamoto S, Miyao M, Nishikawa M, Ogawa K, Asada H. Predisposition to multi-drug hypersensitivity after administration of mogamulizumab. Eur J Dermatol 2018; 28: 526-8. [PubMed: 29952299]

  (59 year old woman with refractory adult T-cell leukemia-lymphoma developed a severe cutaneous reaction a few days after a third infusion of mogamulizumab, which resolved on stopping but recurred on two occasions when started on other medications without mogamulizumab).
• Bonnet P, Battistella M, Roelens M, Ram-Wolff C, Herms F, Frumholtz L, Bouaziz JD, et al. Association of autoimmunity and long-term complete remission in patients with Sézary syndrome treated with mogamulizumab. Br J Dermatol 2019; 180: 419-20. [PubMed: 30328116]

  (Two of 21 patients with refractory cutaneous T cell lymphomas treated with mogamulizumab developed autoimmune conditions (one with vitiligo and autoimmune hepatitis and one with hemolytic anemia) after successful treatment and long term complete responses with mogamulizumab).