Long-term outcomes and clinical phenotypes associated with best response to low dose alemtuzumab in cutaneous T-cell lymphoma

Abstract

Cutaneous T-cell lymphomas (CTCL) have in common malignant T-lymphocyte infiltration in the skin. Low dose alemtuzumab (LDA) appears to be an effective treatment for leukemic disease, but in the absence of clinical trials, there is need for improved characterization of patients with CTCL most likely to benefit. A retrospective cohort study of 38 patients with CTCL treated with LDA with at least 5 years' follow-up data was conducted. As a surrogate for a central memory T-cell (T_CM) clinical phenotype, we evaluated whether the absence of a history of papules, plaques, and tumors (PPT) predicts better global and skin response. Twenty-five (65.8%) patients responded to LDA (95% CI: 49-80%). Patients with a T_CM phenotype were more than eight times as likely to achieve a CR [OR: 8.2, 95% CI: 1.2-57.6]. CR rate in the skin was 81.8% in T_CM phenotype patients compared to 37.0% in patients with a history of PPT (resident memory T-cell phenotype, T_RM) [OR: 7.7, 95% CI: 1.4-42.7]. Three patients experienced any infection requiring systemic intervention. LDA monotherapy can safely produce exceptional response rates in those presenting with diffuse erythema but without a history of PPT.

Fig. 1. Cumulative incidence of death according to PPT.

The estimated incidence of death at 2 years was 24% and at 5 years was 47%, here illustrating no significant difference noted in survival in those with and without a history of PPT.

Fig. 2. Alemtuzumab neutralizing antibody assay with plasma of patient with endogenous neutralizing anti-alemtuzumab antibodies.

Flow cytometry was performed on healthy donor peripheral blood mononuclear cells (PBMC) incubated with Alexa Fluor 488-labeled alemtuzumab in the presence of healthy donor (no neutralizing antibodies) or CTCL patient plasma. Top panels: In the absence of plasma or with healthy donor plasma, >98% of CD3+ cells bind fluorescently labeled alemtuzumab. In the presence of positive control plasma with known neutralizing anti-alemtuzumab antibodies, 96.7% of CD3+ cells remain unbound by labeled alemtuzumab. Bottom panels: In the presence of increasing concentrations of test patient plasma (10–50%), CD3+ cells display decreasing binding of labeled alemtuzumab, indicating increasing concentration of anti-alemtuzumab neutralizing antibodies in the patient plasma.