New Data from MAVORIC Trial Sheds Light on Key Characteristics of Long-term POTELIGEO® (mogamulizumab-kpkc) Responders with Specific Subtypes of Cutaneous T-cell Lymphoma

BEDMINSTER, N.J., Dec. 6, 2020 /PRNewswire/ -- Kyowa Kirin, Inc., an affiliate of Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151) a global specialty pharmaceutical company, today announced data from two post-hoc analyses of the MAVORIC (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) trial. The first evaluated the clinical and demographic characteristics of mogamulizumab-treated patients based on their duration of overall response (ORR), while the second explored the characteristics of patients who experienced mogamulizumab-associated rash. The findings showed patients who achieved a long-term (> 12 months) response with mogamulizumab treatment were more likely to have Sézary syndrome (stage IVA1) or blood involvement compared to patients with an ORR of shorter duration. Further, among those who experienced treatment-related rash (n=44), the data show 80% were able to continue treatment for >6 months following the resolution of initial rash.

MAVORIC was a pivotal open-label, international, Phase 3, randomized controlled trial that evaluated the safety and efficacy of mogamulizumab versus standard-of-care vorinostat in patients with previously treated mycosis fungoides (MF), or Sézary syndrome (SS), the two most common types of cutaneous T-cell lymphoma (CTCL). It is the largest randomized study to compare systemic therapies in these subtypes of CTCL, a rare form of non-Hodgkin's lymphoma that can affect the skin, blood, lymph nodes and internal organs.

"Since CTCL is a chronic condition that is typically managed over time, how and when we sequence therapies is critical," said study author, Youn Kim, M.D., from the Stanford Cancer Center. "These data contribute to our understanding of mogamulizumab treatment in patients who have SS or advanced MF with blood involvement. Further, it shows that with proper evaluation and management of treatment-related rash, it may allow some patients to continue with treatment with durable responses."

Patient Characteristics of Long-term Responders to Mogamulizumab: Results from the MAVORIC Study (Abstract 2082)
The objective of this post-hoc analysis was to assess the clinical and demographic characteristics of MAVORIC cohorts who have ORRs of different duration following treatment with mogamulizumab. Based on a secondary data analysis as of March 19, 2018, patients were divided into four overlapping response cohorts based on minimum duration of overall response: ORR4 (response duration ≥4 months), ORR6 (≥6 months), ORR8 (≥8 months), ORR12 (≥12 months). Patients achieving ORR12 were considered long-term responders and were compared with the other ORR cohorts.

Among patients randomized to mogamulizumab (n=186), ORRs lasting ≥4, ≥6, ≥8, and ≥12 months were seen in 25.3%, 21.0%, 16.1%, and 10.8%, respectively. Mogamulizumab treatment resulted in significantly higher long-term overall response rates in both blood and skin measures compared to vorinostat. Responses in blood and skin lasting ≥6 months were seen in 49.2% and 27.4% of mogamulizumab-treated patients, respectively, compared with 5.6% and 7.5% with vorinostat. When compared with patients with shorter responses, patients who achieved long-term responses were more likely to have SS (stage IVA1) or blood involvement.

Characterization and Outcomes in Patients with Mogamulizumab-Associated Skin Reactions in the MAVORIC Trial (Abstract 1169)
The objective of this post-hoc analysis was to describe histopathological and other characteristics of mogamulizumab-associated rash in patients who were randomized to receive mogamulizumab during the MAVORIC study. As per protocol, biopsies of suspected rash were evaluated both by an on-site pathologist and sent for a blinded review at a central lab. Central lab assessments concluded that mogamulizumab-associated rash is heterogeneous in presentation. Differential diagnosis between on-site and central lab demonstrated difficulties in solely relying on standard histology (H and E stain) to differentiate disease from treatment-related rash. To avoid premature discontinuation, researchers advise establishing a close correlation of suspected drug rash with clinical features to differentiate from disease progression.

Among mogamulizumab-treated patients, 24% (44/184) reported treatment-emergent rash, the majority Grade 1/2, leading to discontinuation in 13 patients.¹ Patients who experienced mogamulizumab-associated rash were more likely to be diagnosed with SS (25/44, 56.8%) than MF (19/44, 43.2%). The proportion of patients with SS who responded to mogamulizumab and experienced rash (14/25, 56%) was significantly higher than the proportion of responders without rash (16/54, 30%) (P=0.02). Overall, 80% of patients (35/44) were able to continue treatment with a median duration of exposure of >6 months after resolution of their initial rash.

Please see POTELIGEO Indication and Important Safety Information below.

U.S. Indication
POTELIGEO (mogamulizumab-kpkc) injection for intravenous infusion is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior system therapy.

Important Safety Information

Warnings and Precautions:

• Dermatologic toxicity: Monitor patients for rash throughout the course of treatment. For patients who experienced dermatologic toxicity in Trial 1, the median time to onset was 15 weeks, with 25% of cases occurring after 31 weeks. Interrupt POTELIGEO for moderate or severe rash (Grades 2 or 3). Permanently discontinue POTELIGEO for life-threatening (Grade 4) rash or for any Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).
• Infusion reactions: Most infusion reactions occur during or shortly after the first infusion. Infusion reactions can also occur with subsequent infusions. Monitor patients closely for signs and symptoms of infusion reactions and interrupt the infusion for any grade reaction and treat promptly. Permanently discontinue POTELIGEO for any life-threatening (Grade 4) infusion reaction.
• Infections: Monitor patients for signs and symptoms of infection and treat promptly.
• Autoimmune complications: Interrupt or permanently discontinue POTELIGEO as appropriate for suspected immune-mediated adverse reactions. Consider the benefit/risk of POTELIGEO in patients with a history of autoimmune disease.
• Complications of allogeneic HSCT after POTELIGEO: Increased risks of transplant complications have been reported in patients who received allogeneic HSCT after POTELIGEO. Follow patients closely for early evidence of transplant-related complications.

Adverse Reactions:

• The most common adverse reactions (reported in ≥ 10% of patients) with POTELIGEO in the clinical trial were rash, including drug eruption (35%), infusion reaction (33%), fatigue (31%), diarrhea (28%), drug eruption (24%), upper respiratory tract infection (22%), musculoskeletal pain (22%), skin infection (19%), pyrexia (17%), edema (16%), nausea (16%), headache (14%), thrombocytopenia (14%), constipation (13%), anemia (12%), mucositis (12%), cough (11%), and hypertension (10%).

You are encouraged to report suspected adverse reactions to Kyowa Kirin, Inc. at 1-844-768-3544 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch/.

Please click here for full U.S. prescribing information.

About POTELIGEO (mogamulizumab-kpkc)
POTELIGEO is a humanized monoclonal antibody that recruits the body's own immune cells to kill CCR4+ (CC chemokine receptor 4) malignant T-cells.^2,3 CCR4 is overexpressed in Sézary syndrome and in mycosis fungoides at all stages.^4,5 POTELIGEO was produced using Kyowa Kirin's proprietary POTELLIGENT^® technology platform, which is associated with enhanced antibody-dependent cellular cytotoxicity.⁶

About Mycosis FungoidesSézary Syndrome
Mycosis fungoides and Sézary syndrome are the most common subtypes of cutaneous T-cell lymphoma.⁷ Most people with CTCL have MF (50%-70%), with some (~12%) experiencing rapid progression (or disease worsening) to advanced-stage MF.^7,8 In the early stages, many people only experience skin symptoms, which may include redness, rashes, and smaller patches.⁹ If skin symptoms progress, larger areas of the skin will be affected with more intense redness, scaling, and lesions.⁷ In some people, CTCL can spread to other parts of the body such as the blood and lymph nodes.¹⁰ SS is a rare (~3%), serious form of CTCL that affects the skin and blood with the most noticeable symptom being a red, itchy rash covering large portions of the body.^11,12 Sometimes, it can spread to the lymph nodes and internal organs.^11,12

About Kyowa Kirin
Kyowa Kirin commits to innovative drug discovery driven by state-of-the-art technologies. Kyowa Kirin focuses on creating new value in four therapeutic areas: nephrology, oncology, immunology/allergy and neurology. Under the Kyowa Kirin brand, the employees from 40 group companies across North America, Europe and Asia/Oceania unite to champion the interests of patients and their caregivers in discovering solutions wherever there are unmet medical needs. Since 2018, the company has received approval from the U.S. Food and Drug Administration for three first-in-class medicines. You can learn more about the business of Kyowa Kirin at kkna.kyowakirin.com.

¹ Kim YH, et al. Lancet Oncol. 2018;19(9):1192-204

² POTELIGEO package insert. Kyowa Kirin Inc., Bedminster, NJ USA.

³ Ishida T, Iida S, Akatsuka Y, et al. The CC chemokine receptor 4 as a novel-specific molecular target for immunotherapy in adult T-cell leukemia/lymphoma. Clin Cancer Res. 2004;10:7529-7539.

⁴ Ferenczi K, Fuhlbrigge RC, Pinkus J, et al. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119:1405-1410.

⁵ Kallinich T, Muche JM, Qin S, et al. Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides. J Invest Dermatol. 2003;121:1045-1052.

⁶ National Cancer Institute. Mogamulizamab. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/mogamulizumab. Accessed October 2020.

⁷ Cutaneous T-Cell Lymphoma. Leukemia & Lymphoma Society. https://www.lls.org/sites/default/files/file_assets/PS96_CTCL_Booklet_Final.pdf.   

⁸ Talpur R, Singh L, Daulat S, et al. Long-term Outcomes of 1,263 Patients with Mycosis Fungoides and Sezary Syndrome from 1982 to 2009. Clin Can Res. 2012;18(18):5051-5060. doi:10.1158/1078-0432.ccr-12-0604.

⁹ National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) - Primary Cutaneous Lymphomas. https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/primary_cutaneous.pdf.

¹⁰ Pulitzer M. Cutaneous T-cell Lymphoma. Clin in Laboratory Med. 2017;37(3):527-546. doi:10.1016/j.cll.2017.06.006.

¹¹ Willemze R, Cerroni L, Kempf W, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019;133(16):1703-1714. doi:10.1182/blood-2018-11-881268

¹² Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(6):1713-1722. doi:10.1182/blood-2007-03-055749.

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