Background

In Europe, it is estimated that the annual incidence of cutaneous T-cell lymphoma (CTCL) is approximately 52 new cases per million, affecting around 240 people per million at any one time1. Mycosis fungoides (MF) and Sézary syndrome (SS) are rare, debilitating, and potentially life-threatening subtypes of CTCL2,3. A recent systematic review and meta-analysis of 16,953 patients globally found that MF and SS represented 62% and 3% of CTCLs, respectively4. In the phase 3 MAVORIC trial, mogamulizumab (KW-0761, Poteligeo®)* showed significant improvements over vorinostat in terms of progression-free survival, overall response, and patient-reported quality-of-life5. However, estimating a relative overall survival (OS) benefit using trial data is challenging given that over 70% of patients in MAVORIC switched from vorinostat to mogamulizumab following disease progression5. Using real-world evidence (RWE) from the Australian National Cutaneous Lymphoma Database (ANCLD) collected at the Peter MacCallum Cancer Centre, this study aims to better understand the predicted OS for advanced MF and SS patients treated with mogamulizumab or vorinostat.

Methods

To augment the MAVORIC trial data with RWE, we performed a comparative survival analysis of mogamulizumab versus vorinostat using a selected cohort of patients with MF and SS from the Peter MacCallum cancer patient registry. The ANCLD, established in 2010, collects diagnostic, clinical, pathological, treatment, and survival data for patients with a cutaneous T- or B-cell lymphoma diagnosis. As of August 2020, 843 MF and 127 SS patients were registered. The mogamulizumab treatment arm in MAVORIC was reweighted to represent the distribution of gender and CTCL subtype (MF/SS) as observed in the ANCLD in a matching-adjusted indirect comparison. Median OS with two-sided 95% confidence intervals (CI) for each data set was estimated using Kaplan-Meier survival analysis. A Cox proportional hazards model with treatment as covariate was used to assess the magnitude of treatment difference in OS; a hazard ratio and 95% CIs were calculated.

Results

Figure 1 depicts the comparison between the adjusted OS of patients receiving mogamulizumab in the MAVORIC trial (182 patients) and patients receiving vorinostat in the ANCLD (64 patients). Based on ANCLD distributions, 55% of patients had confirmed MF, 45% had SS and 58% were male in the weighted analysis. Median OS in the re-weighted MAVORIC mogamulizumab arm was 57.2 months (95% CI 44.3 - not reached). Median OS of patients from initiation of vorinostat treatment in the ANCLD was 40.0 months (95% CI 29.0-81.9). The hazard ratio of mogamulizumab versus vorinostat for advanced MF and SS patients was 0.679 (95% CI 0.452-1.021; p=0.063).

Conclusions

Assessing relative survival from trial data in rare diseases can be challenging due to small sample sizes, and in the case of MAVORIC, due to the high proportion of crossover (treatment switching). Using RWE such as cancer patient registries can supplement clinical trial evidence by providing survival data observed in clinical practice over longer time periods. Results from the MAIC using MAVORIC and ANCLD data suggest that mogamulizumab can improve OS in patients with pre-treated MF and SS, although the difference did not reach statistical significance probably due to the small patient numbers.

*Mogamulizumab is approved by the European Medicines Agency (EMA), the U.S Food and Drug Administration (FDA), and the Australian Therapeutic Goods Administration (TGA) for the treatment of adult patients with MF or SS who have received at least one prior systemic therapy6–8.

1. Orphanet. Prevalence of rare diseases: Bibliographic data. Published online January 2021.
2. Morales Suárez-Varela MM, et al. Dermatol Basel Switz. 2000;201(1):21-28.
3. Olsen E, et al. Blood. 2007;110(6):1713-1722.
4. Dobos G, et al. Cancers. 2020;12(10):1-14.
5. Kim YH, et al. Lancet Oncol. 2018;19(9):1192-1204.
6. EMA. Poteligeo: CHMP Summary of opinion1 (initial authorisation). Published online 20 September 2018. EMA/CHMP/598685/2018
7. FDA Approves Mogamulizumab-Kpkc for Mycosis Fungoides or Sézary Syndrome. Published online 8 August 2018.
8. POTELIGEO (mogamulizumab) 4 mg/mL concentrate for solution for infusion. Therapeutic Goods Administration Australian Prescription Medicine Decision Summary. Published online 15 Feb 2021.