Concomitant Steroids and Mogamulizumab Lead to Greater Response Rate in MF/SS, Suggests Benefit for Real-World Use

Larisa Geskin, MD

Responses were improved for patients receiving treatment with mogamulizumab (Poteligeo) with the use of concomitant topical steroids compared with the overall study population in the phase 3 MAVORIC study of patients with mycosis fungoides (MF) or Sézary syndrome (SS), according to the results of a post hoc analysis of the study.1

“It appears that concomitant use of topical steroids and mogamulizumab may produce better responses, but at least they don't hamper the responses to mogamulizumab and can safely be used for this patient population,” said Larisa Geskin, MD, when presenting the findings from the analysis on September 10 during the eighth annual meeting of the Society of Hematologic Oncology. Geskin, Associate Professor of Dermatology and Director of the Comprehensive Skin Cancer Center at the Division of Cutaneous Oncology in the Department of Dermatology at Columbia University Medical Center, suggested that this was likely to reflect real-world outcomes as the majority of patients with MF or SS receive corticosteroids.

Mogamulizumab is a first-in-class defucosylated monoclonal antibody that is directed against CCR4, which is highly expressed on malignant T cells in cutaneous T-cell lymphomas (CTCLs).

The open-label, randomized, international MAVORIC trial sought to compare the safety and efficacy of mogamulizumab in comparison with vorinostat (Zolinza) in adult patients with relapsed or refractory MF or SS subtypes of CTCL (NCT01728805).

Patients who had stage IB to IVB MF or SS and who had failed at least 1 prior systemic therapy were eligible to enroll in the trial, excluding patients with large cell transformation. These patients were randomized 1:1 to either mogamulizumab (n = 186), administered at 1.0 mg/kg intravenously weekly for the first 5 weeks and every 2 weeks thereafter, or vorinostat (n = 186) at 400 mg orally daily. Patients in the control arm who had progressive disease were allowed to cross over to the investigational arm.

The median age of patients was 64 years in the mogamulizumab arm and 65 years in the vorinostat arm; the majority of patients were male (59% and 58%, respectively), had MF (56% and 53%), stage IVA1 disease (39% and 44%), an ECOG performance status of 0 (57% and 56%), and had received 3 (range, 2-5) prior lines of systemic therapy.2

Those who were on stable low doses of corticosteroids for at least 4 weeks prior to the first study visit were allowed to continue on steroids, although the investigators tried to taper the patients down to the lowest tolerated dosage of the steroids.

Concomitant corticosteroid use was reported in 68% of patients in the mogamulizumab arm compared with 66% in the vorinostat arm, which Geskin noted is probably a reflection of true clinical practice for patients with MF/SS. Ninety-eight percent of patients receiving steroids were administered topical corticosteroids and 2% were systemic. The steroid potency was high in 44% of patients and low or intermediate in 23%, with the rates being similar between the 2 arms.1,2 

“That is related to a severe itching/pruritus that these patients experience—[that's] a major quality-of-life issue for these patients and we could not not provide that relief during the clinical trial,” Geskin commented.

In the primary analysis, mogamulizumab showed an overall benefit in survival in terms of a median progression-free survival (PFS) of 7.7 months (95% CI, 5.7-10.3) versus 3.1 months (95% CI, 2.9-4.1) with vorinostat (HR, 0.53; 95% CI, 0.41-0.69; stratified log-rank P <.0001).2

The overall response rate (ORR) with mogamulizumab was 28% (95% CI, 21.6%–35.0%) compared with 5% with vorinostat treatment (95% CI, 2.2%-9.0%) (risk ratio, 23.1; 95% CI, 12.8-33.1; P <.0001).

Adverse events with mogamulizumab in the study were most commonly infusion-related reactions (33%) and drug eruption (24%).

Investigators sought to discover in a post hoc analysis if the use of concomitant steroids in some of the study population had an impact on the safety and efficacy of the investigational agent.

Among the 127 patients in the mogamulizumab arm who continued to receive steroid treatment, the median PFS was 9.4 months compared with 3.1 months in the 122 patients who received steroids and vorinostat (P <0.0001).1

Additionally, the ORR was 37.0% with mogamulizumab and concomitant steroids versus 3.3% with vorinostat and steroids.

“Corticosteroid treatment is a backbone of CTCL therapy, and the increased efficacy observed with the combination of mogamulizumab and steroids is likely reflective of what would be observed with real-world use,” Geskin and her co-authors wrote in their poster.

ORR in skin and blood compartments also showed slight differences with the addition of steroids to mogamulizumab compared with what was seen in the intention-to-treat (ITT) population. The blood ORR was 73.4% with concomitant steroids versus 68.0% overall for patients who received mogamulizumab; whereas with vorinostat the blood ORR was 19.6% with steroids and 15.6% overall. The skin ORR was 53.5% with mogamulizumab and concomitant steroids versus 3.3% with vorinostat and steroids (P <0.001), but overall in the ITT group, the skin ORR was 41.9% versus 15.6% with mogamulizumab and vorinostat, respectively.

“Topical steroids have no effect on the blood by themselves and we can clearly see there are responses observed in the blood in the intent-to-treat population and with concomitant topical steroids,” Geskin noted.

Among all patients treated with mogamulizumab, the biggest differences in ORR seen with concomitant steroid use was observed in earlier disease stages. In patients with stage IB MF or SS, the ORR was 20.0% overall versus 33.3% with the addition of steroids. For those with stage IIA MF or SS, the ORRs were 19.0% and 28.6% in the ITT and steroid groups, respectively. In patients with stage IIB disease, the ORR was 15.6% in the ITT group and 28.6% in the steroid group.

Differences were not as significant with later disease stages. Only 1 of 9 patients with stage IIIA disease responded to mogamulizumab who also happened to be receiving concomitant steroids. Among patients with stage IIIB MF or SS, the ORR was 30.8% overall and 30.0% among those who received corticosteroids. In patients with stage IVA disease, the ORR were 38.0% and 44.4% in the ITT and steroid groups, respectively. No patients with stage IVB disease responded to mogamulizumab.

Rates of treatment-emergent adverse events were similar with or without the use of concomitant steroids. Infusion-related reaction occurred in 34.6% of patients who also received corticosteroids and drug eruption was reported in 27.6% of those who had steroids. Other common adverse events with mogamulizumab with or without steroids included diarrhea (23.4% vs 25.2%, respectively), fatigue (23.4% vs 26.0%), pyrexia (16.8% vs 15.0%), and nausea (15.2% vs 18.1%).

_References:

_{1. Akilov O, Geskin L, Ito T, Dwyer K, Herr F, Musiek A. Impact of concomitant steroids on mogamulizumab efficacy in MAVORIC. Presented at: 2020 SOHO Virtual Annual Meeting; September 9-12, 2020. Abstract TCL-127.}

_{2. Kim YH, Bagot M, Pinter-Brown L, 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(9):1192-1204. doi:10.1016/S1470-2045(18)30379-6}