Alemtuzumab (ALZ) Is an Effective Treatment for Both Primary and Relapsed Severe Paraneoplastic Pemphigus (PNP) Associated to B-Cell Chronic Lymphocytic Leukemia (CLL).

ALZ is a monoclonal antibody used in the treatment of a variety of lymphoproliferative diseases, primarily CLL. PNP is a severe mucocutaneous disease often associated with B-cell malignancies. Besides distinct clinical and histopathological features, a correct PNP diagnosis relies on the demonstration by direct immunofluorescence of intercellular and basement membrane IgG deposits in the affected tissue. PNP is often refractory to immunosuppressive drugs and has frequently a fatal outcome. We report three cases, where sustained remissions of both PNP and CLL were induced by ALZ. In two of these cases, ALZ was able to reinduce a sustained PNP remission at the reappearence of the disorder years after the primary treatment. In all cases, the PNP diagnosis was confirmed by immunofluorescence. A 68-year old male with a 4-year CLL history developed blisters and ulcers on the extremities and trunk and severe stomatitis. Despite immunosuppression with steroids, fludarabine, cyclophosphamide, ciclosporin A, and azathioprin, PNP exacerbated. A standard 12-weeks ALZ schedule was initiated. PNP lesions started to regress under the last weeks of treatment and resolved completely within a few further weeks. A bone marrow biopsy showed a morphological and flowcytometric CLL remission. Now, 30 months after ALZ, the patient is still in remission without evidence of either PNP or CLL activity. Almost a year after this first case, a 77-year old male with a 3-year CLL history, presented with severe mucocutaneous lesions of the lips, oro-esophageal cavity, penis and extremities. PNP was diagnosed and a standard 12-weeks ALZ schedule was initiated. As in the first case, the lesions began to regress during the last weeks of treatment and normalized within the subsequent 8 weeks. At present, 1½ year after ALZ, the patient is well displaying only discrete residual PNP activity (left tongue margin, and praeputium). In the third case, a 80-year old woman with a B-CLL diagnosed 4 years previously, a severe PNP involving skin (upper trunk and extremities) and mucosae (anal and vagina) developed in association with marked CLL progression. After some unsuccessful immunosuppressive attempts, alemtuzumab treatment was initiated. All PNP lesions disappeared within a few weeks.

Conclusion: ALZ should be considered as a treatment option in severe CLL-associated PNP.