Differences in Progression and Survival Among Black Patients with Mycosis Fungoides and Sézary Syndrome: A Multicenter Retrospective Analysis at Large Urban Medical Centers

Introduction Black (B) patients with Mycosis fungoides and Sézary Syndrome (MF/SS) have inferior survival and distinct clinical presentations, including many high risk features compared to White patients. We sought to characterize clinical differences in presentation, treatment, and outcomes to identify drivers of disparities among B patients with MF/SS.

Methods We performed a retrospective review of 1,197 patients with MF/SS seen between 2010 and 2021 at 7 academic institutions in the United States that serve populations with large numbers of Blacks and minorities. Patients with a confirmed histopathologic diagnosis of MF or SS on internal or external review and consistent follow up were eligible for inclusion. The primary objective was to assess differences in clinical characteristics and survival between B and non-Black (NB) patients. Clinical variables included demographics, insurance, TNMB stage at diagnosis and highest stage. Descriptive analysis was performed for each variable. Comparison between B and NB patients utilized ANOVA for numerical covariates and Chi-square test or Fisher's exact test for categorical covariates. Kaplan-Meier curves for OS were generated, and subgroups were analyzed separately by Cox Proportional hazards model.

Results Self-reported race among the cohort was 508 (42.4%) Black, 638 (53.3%) White, and 51 (4.4%) were other races (14 Asian, 14 Hispanic, 2 American Indian or Alaska Native, 21 unknown). 295 patients (25.9%) progressed to a higher stage during their treatment course. The median survival of the whole cohort (n=1,045, 152 had implausible or missing survival data) was 18.3 years, (95% CI: 12.3-22.2).

B patients were younger (median 51 years in B vs. 63 in NB, p<0.001), more often female (55.9% in B; 37.9% in NB, p<0.001), and had higher rates of S. aureus bacteremia during their disease course (17.6% in B, vs. 7.9% in NB, p< 0.001, table 1A). There was no difference in insurance status (private, Medicare/Medicaid, or uninsured), comorbidities, or large cell transformation by racial group. There were differences in overall TNMB stage at diagnosis (p<0.001) and T- and N-stage at diagnosis by racial group (p<0.001 for each), with Black patients generally presenting with a higher stage. There were also differences in highest stage reached (p<0.001), with different patterns of progression in the T (p<0.001) and N stage (p=0.005). Black patients had higher rates of T2b (plaque stage > 10% BSA, 11.1% vs. 21.8%), whereas NB patients had higher rates of T3 (tumor stage, 27.3% in NB vs. 17.5% in B). There were higher rates of stage progression among B vs. NB patients, p=0.025. Overall, 152 (23.4%) of NB patients progressed compared to 143 (29.3%) of B patients. The median survival for B patients was 13.1 years (95% CI 10.3, not reached) versus 21.3 years in NB patients (95% CI: 13.2, not reached), however this did not reach statistical significance in the overall cohort (figure 1B).

On univariate analysis, race and gender were not associated with survival, however on subgroup analysis among patients <age 60 at diagnosis, black race was associated with inferior survival (p=0.023, figure 1C). Other covariates associated with inferior survival included age (p<0.001), number of comorbidities (p< 0.001), insurance status (p<0.001), S. aureus bacteremia (p< 0.001), higher overall TNMB stage (p<0.001), higher individual T, N, M and B stage (p<0.001 for each), and clonal TCR in the blood (p<0.001 each). Hypopigmented MF (HMF) was associated with a lower risk of death (HR: 0.39 (0.23-0.66) p<.001). On multivariable Cox proportional hazard model, age at diagnosis, comorbidities, highest overall TNMB stage, and highest N stage remained statistically significant for survival.

Conclusions In one of the largest multicenter analyses in MF/SS, with the largest black CTCL population ever described, we found that black patients had distinct presentations, higher rates of progression, with inferior survival in the younger cohort compared to non-black patients. Future studies aiming to disentangle the specific contributions of competing and opposing risk factors affecting survival in Black patients, such as over-representation of HMF (favorable risk factor), higher rates of S. aureus bacteremia, different distributions in age, stage, and gender, and social determinants of heath, are currently ongoing. Additional analyses will be updated at the time of the presentation.

Allen:Kyowa: Consultancy, Honoraria; Daiichi Sanyko: Consultancy, Honoraria. Iyer:Salarius Pharmaceuticals, Inc.: Consultancy. Huen:kyowa: Consultancy. Greenwell:Stemline: Consultancy; Kyowa Kirin: Consultancy. Mehta:Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Affimed: Research Funding; fortyseven Inc./Gilead: Consultancy, Research Funding, Speakers Bureau; I-MAB: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Innate pharmaceuticals: Research Funding; Juno pharmaceuticals/BMS: Consultancy, Research Funding; Kite/Gilead: Consultancy, Research Funding; Merck: Research Funding; Roche-Genentech: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Norvartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Morphosys/Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Porcu:Viracta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi, Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; DrenBio: Consultancy; Teva: Honoraria, Research Funding; Ono: Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees; Loxo: Membership on an entity's Board of Directors or advisory committees. Lechowicz:ADC Therapeutics: Consultancy; Kyowa Kirin: Consultancy; EUSA Pharma: Consultancy; Secura Bio Inc: Consultancy.