Mogamulizumab Improves Survival and Responses in Cutaneous T-cell Lymphoma With Blood Involvement

Lauren C. Pinter-Brown MD, FACP

Treatment with mogamulizumab-kpkc (Poteligeo) in adult patients with cutaneous T-cell lymphoma, including mycosis fungoides (MF) or Sézary syndrome (SS), demonstrated better outcomes in those who had higher levels of blood involvement at baseline assessment, according to results of a post-hoc analysis for the MAVORIC trial announced in a press release issued by Kyowa Kirin, Inc.¹

"Managing any type of cutaneous T-cell lymphoma can be complex as the initial presentation and treatment is focused on the skin but the disease can travel into the blood," said study author Lauren C. Pinter-Brown MD, FACP, Chao Family Comprehensive Cancer Center, University of California, Irvine, in a statement. "This latest analysis shows the need to be vigilant in monitoring a patient's blood so that the appropriate treatment can be used in patients with blood involvement to help improve outcomes."

MAVORIC was an open-label, international, randomized phase 3 study conducted at 61 medical centers in the United State, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the United Kingdom, Japan, and Australia. Patients aged 18 years or older with an ECOG performance score of 0 or 1 and adequate hematological, hepatic, and renal function were randomized 1:1 to receive either mogamulizumab at 1.0 mg/kg administered intravenously on a weekly basis for the first 28-day cycles, followed by days 1 and 15 of subsequent cycles or vorinostat at a dose of 400 mg daily. There was a total of 372 patients in the study.²

The post hoc analysis of outcomes of patients with cutaneous T-cell lymphoma stratified by blood classification showed superior progression-free survival (PFS) with mogamulizumab (7.7 months vs 3.1 months, respectively; P < .0001), compared with the vorinostat arm, per investigator assessment. The result was considered to be significant in patients with any blood involvement (B1 and B2 levels).¹

Mogamulizumab also demonstrated significant improvement in response compared with the control group. The objective response rate (ORR) observed with the experimental agent in the post hoc analysis was 28.0% versus 4.8% with vorinostat (P < .0001). The difference in time-to-next-treatment was also significantly longer for patients treated with mogamulizumab compared with those who received vorinostat. At the B1 level, mogamulizumab showed a 12.63-month time-to-next treatment and for vorinostat, it was 3.07 months (P =. 0018). At level B2 the time-to-next treatment observed with mogamulizumab was 13.07 versus 3.53 months with vorinostat (P < .0001).

Skin improvement was assessed during the post-hoc analysis using the modified Severity-Weighted Assessment Tool. Among those treated in the mogamulizumab arm, 43.5% showed a ≥50% improvement in skin response compared with 22.0% of the vorinostat arm. Moreover, patients with B1 level involvement treated with mogamulizumab showed a higher rate of skin improvement (45.2%) in comparison with the vorinostat population (56.0%). Only 25.0% of the patients with B0 involvement had skin improvement. Overall improvement of 100% was seen in 17.6% of the mogamulizumab-treated patients with B1 level involvement compared with 3.2% in the B2 level patients.

The safety portion of the analysis showed that the 2 treatment arms had similar treatment-emergent adverse events regardless of blood involvement.

In the primary analysis of the MAVORIC study, mogamulizumab also significantly improved PFS versus vorinostat n patients with cutaneous T-cell lymphoma. In the mogamulizumab arm, the median PFS was 7.7 months (95% CI, 5.7-10.3) versus 3.1 months (95% CI, 2.9-4.1) in the vorinostat group (HR, 0.53; 95% CI, 0.41-0.69; stratified log-rank P < .0001). Investigators concluded that the treatment could be a new treatment option for the patient population, especially for those with the MF and SS subtypes.² The post-hoc analysis further demonstrated this point.¹

"Insights from this MAVORIC analysis drive home the importance of identifying and closely monitoring for blood involvement in patients with either MF or SS, to ensure treatment approaches are tailored as the disease evolves," said Eslie Dennis, MD, SVP, chief medical officer at Kyowa Kirin Inc, in the press release. "These data demonstrate Poteligeo provides benefit over vorinostat in all patients with this rare cancer, particularly for patients with blood involvement who are thought to have a worse prognosis."

_References:

_{1. New publication offers insight into Poteligeo® (mogamulizumab-kpkc) treatment response in cutaneous t-cell lymphoma patients with varying levels of blood involvement. News release. Kyowa Kirin, Inc. July 22, 2021. Accessed July 23, 2021. https://prn.to/3kUL1su}

_{2. Kim YH, Bagot M, Pinter-Brown L, et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(9): 1192-1204. doi: 10.1016/S1470-2045(18)30379-6}