Written by: Francine Foss, MD
Professor of Medicine (Hematology) and Dermatology
Director, Multidisciplinary T cell Lymphoma Program, Hematology; Scientific Leader, Lymphoma CRT
Yale Cancer Center
Content sponsored by Kyowa Kirin, Inc.
Dr. Foss is a paid consultant for Kyowa Kirin and was compensated for her contribution in drafting this article.
POTELIGEO® (mogamulizumab–kpkc), indicated for the treatment of adult patients with relapsed or refractory Mycosis Fungoides (MF) or Sézary Syndrome (SS) after at least one prior systemic therapy, is a first-in-class humanized monoclonal antibody (mAb) directed against CC chemokine receptor 4 (CCR4), a protein consistently expressed on cancerous cells seen in both MF and SS.1-3
POTELIGEO received FDA approval based on results of the MAVORIC trial, a randomized, open-label, phase 3 trial that compared its efficacy with that of an active comparator, vorinostat, in previously treated patients with relapsed or refractory MF or SS. In MAVORIC, patients receiving mogamulizumab (n=186) demonstrated efficacy superior to those receiving vorinostat (n=186) in the prespecified primary endpoint, with significantly longer progression-free survival (PFS) (7.6 vs 3.1 months; hazard ratio: 0.53, 95% CI [0.41, 0.69], P<0.001). For the secondary endpoint, overall response rate (ORR), significantly more patients achieved a response to mogamulizumab vs the comparator (28% vs 5%, P<0.001). When evaluated by disease compartment, response rates were higher with mogamulizumab compared with vorinostat in the blood (67% vs 18%), skin (42% vs 16%), and lymph nodes (15% vs 4%). The most common adverse reactions (reported in ≥20% of patients) were rash, infusion-related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection.4
The OMEGA study was a retrospective analysis of real-world patients receiving mogamulizumab in 14 centers throughout France. The full study-report article can be accessed at https://doi.org/10.1111/jdv.19134. A total of 122 patients were reviewed, 53 with MF and 69 with SS. All had been treated with mogamulizumab from February 2014 until March 2020.5 The OMEGA study contains information that is not included in the FDA-approved labeling for POTELIGEO; the study included 2 patients with SS in whom mogamulizumab was administered as a first-line therapy. OMEGA also reported a serious adverse reaction, vitiligo (3 patients [2.4%]), that was not captured in the MAVORIC trial. It is not known if there were variations from the FDA-approved labeling in the dosing schedule for any patients included in the study. Also, OMEGA differed from MAVORIC by defining treatment responses as complete or partial response (CR or PR) that occurred at any time, and for no prespecified duration post-initiation of mogamulizumab. In MAVORIC, by definition, treatment responses were required to be confirmed CR or PR at 2 or more consecutive assessments spaced at least 8 weeks apart.5
In the OMEGA study, key outcome measures were:
Primary endpoint: Best overall response rate (bORR)a
Secondary endpoints: bORR by compartment (skin, blood, lymph nodes, viscera)b and safety
Exploratory endpoint: PFS
a Percentage of patients achieving a global overall response (CR or PR) at any time and for no prespecified duration.
b Percentage of patients achieving a CR or PR in the specified compartment at any time and for no prespecified duration.
As shown in Figure 1, in the entire patient population, bORR was 58.7% (12.8% CR; 45.9% PR). In patients with SS, bORR was 69.5% (16.9% CR; 52.5% PR), and in patients with MF, bORR was 46.0% (8.0% CR; 38.0% PR). The median time to response under treatment (CR or PR) was similar according to disease subtype (3.1 months for patients with SS and MF; respective ranges: 01–25.0, and 0.3–44.3 months).5
Responses were seen across all involved disease compartments, as seen in Table 1.5
As seen in Figure 2, in the overall analysis population (n=122), the median PFS was estimated at 15.0 months (95% CI [9.0–50.8]). It was longer in patients with SS than in patients with MF (20.3 months [11.7–not reached] vs. 8.8 months [4.6–43.0]) but no significant difference between disease subtypes was shown (P= 0.0542).5
The percentage of patients who experienced a serious adverse reaction (AR) was consistent with MAVORIC (18.5% vs 20% in MAVORIC).1,2 Discontinuations of mogamulizumab due to ARs occurred in 15 patients (12.1%) rash was the most common reason for permanent discontinuation (9 patients; 7.3%). One patient discontinued due to thrombopenia and one patient discontinued due to an infusion-related reaction (0.8% each).5 The most common ARs can be seen in Table 2.
Limitations of the OMEGA study include its non-interventional and retrospective design, a patient population less selective than those in clinical trials, and overlap of 20 patients that were also part of the MAVORIC trial. The results are in line with efficacy and safety data demonstrated in the global clinical trial MAVORIC, and supports the effectiveness of mogamulizumab in real-world clinical practices.
INDICATION
POTELIGEO injection for intravenous infusion is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic 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%).
Please see the full Prescribing Information for POTELIGEO at www.poteligeohcp.com for additional information.
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/medwatch.
References:
1. Ferenczi K, et al. Increased CCR4 expression in cutaneous T cell lymphoma. J Invest Dermatol. 2002;119(6):1405-1410.
2. Yoshie O, et al. Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells. Blood. 2002;99(5):1505-1511.
3. Ishida T, et al. Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: its close association with skin involvement and unfavorable outcome. Clin Cancer Res. 2003;9(10 Pt 1):3625-3634.
4. POTELIGEO [package insert]. Kyowa Kirin Inc., Princeton, NJ USA.
5. Beylot-Barry M, Quereux G, Nardin C, et al. Effectiveness of mogamulizumab in patients with mycosis fungoides or Sézary syndrome: a multicentre, retrospective, real-world French study. J Eur Acad Dermatol Venereol. 2023;37(9):1777-1784.
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COMM-US-POT-0274 May 2024
