Alemtuzumab (Campath-1H) in Patients with Erythrodermic Cutaneous T-Cell Lymphoma (E-CTCL): The Northwestern University Experience.

Treatment of advanced mycosis fungoides (MF)/Sezary syndrome (SS) remains difficult as virtually all pts become refractory to most standard therapies. The CD52 monoclonal antibody alemtuzumab is a new therapeutic option. We report from a clinical trial as well as clinical use in E-CTCL. Alemtuzumab was IV administered at a dose of 30 mg three times per week (t.i.w.) for 4 weeks (Dose 1 and 2: 3 mg and 10 mg, respectively) followed by SQ administration of 30 mg for an additional 8 weeks t.i.w. All pts received prophylactic treatment with TMP-SMZ, acyclovir, and fluconazole until immune reconstitution. 19 pts with E-CTCL have been treated to date. 15 pts have been enrolled into the study; while 4 pts who did not meet the pre-study criteria were treated off study (including second malignancy without recurrence diagnosed within 5 years prior study entry in 2 pts and living too remote from study center in 2 pts). Median age was 63 yrs, (39 to 88 years). Clinical stages were: 8 (42%) stage III; 10 (53%) stage IVA; 1 (5%) stage IVB. All pts were heavily pretreated with a median of 5 prior treatments. The ORR was 79% (15 pts.) with CR in 47% (9 pts) and PR in 32 % (6 pts) with effective clearing of circulating Sezary cells in 100%. Four pts (21%) developed PD with the development of cutaneous tumors in one patient despite complete clearing of circulating Sezary cells. Median response duration was 7 months (1–39 months). We have analyzed minimal residual disease (MRD) by PCR of γ/δ TCR after treatment in skin and/or blood samples in 11 pts who achieved CR and PR. MRD was detected in 8 pts with subsequent relapse in 5 pts after a median time of 6 months. Only 3 pts had negative blood samples tested with histologic evidence of cutaneous residual disease in 2 pts (PR). Patients remained in remission for 17, 4, and 5 months, respectively. Another patient with CR had negative skin, but a positive blood sample tested and relapsed after 3 months. The median overall survival of all pts. was 18 months (1–50 months). Ten pts (53%) have died, 7 (37%) attributable to MF. One patient developed a second B-cell lymphoma approximately 6 months after completing alemtuzumab. One patient died of aplastic anemia. None of the pts died of infectious complications. In general, treatment was well tolerated, with the majority of toxicities being Grade 2 in severity and transient. The major hematologic side effect was T-cell depletion (lymphopenia Grade 4) with infectious complications in 4 pts (including PICC line infection in 2 pts, and Herpes zoster infection and neck abscess formation in one pt each) and neutropenic fever in one patient without documented infection. 6 pts developed grade 3 or 4 leukopenia with prolonged cytopenias in 2 pts requiring withholding and/or discontinuation from treatment. No patient manifested reactivation of CMV infection. One patient developed a fungal otitis externa remote from study during the terminal phase of CTCL. In conclusion, alemtuzumab has shown impressive responses in patients with refractory E-CTCL and could be considered for first-line therapy. The persistence of MRD suggests that a longer duration of therapy or sequential use of other biologic agents may enhance responses or improve durability.