Combination therapy with alemtuzumab and pentostatin is effective and has acceptable toxicity in patients with T-lymphoid neoplasms

Abstract

7037 Background: The development of effective therapeutic strategies for T-lymphoid neoplasms has been difficult partly due to the paucity of clinical trials. These neoplasms are generally refractory to traditional chemotherapy regimens. Alemtuzumab and pentostatin have response rates of 50% to 65% when used individually to treat various T-cell leukemias and lymphomas. However, most responses are partial and of limited duration. Methods: We have treated 20 patients (pts) with T-lymphoid malignancies (11 T-PLL, 1 ATL, 1 PTCL, 2 T- ALL, 3 γd-T cell hepatosplenic lymphoma, 2 T-LGL) with a combination of alemtuzumab 30 mg IV, 3 times weekly for up to 3 months and pentostatin 4 mg/m2 weekly×4 followed by alternate weekly administration for up to 6 months. Prophylactic antibiotics were administered during the treatment and for 2 months after its completion. Results: The median age of pts was 57 yrs (range, 22 –79 yrs), median WBC was 43.9×109/L (range 0.6 –279.5 x109/L), and median serum β2M was 4.1 mg/L (range, 1.7 –10.8 mg/L). Four pts had splenomegaly, and 6 lymphadenopathy. Thirteen had prior therapy (median 2). Twelve pts have responded (10 CR, 2 PR) for an overall response rate of 60% (including 8 of 11 T-PLL, 1 of 1 ATL, 0 of 2 T-ALL, 2 of 3γd-T cell hepatosplenic lymphoma, 0 of 1 PTCL and 1 of 2 T-LGL). Monoclonal T-cell receptor chain gene rearrangements were detected by PCR in 18 pts and became negative in 5 of 7 evaluable pts in CR. Median response duration has not been reached (range, 0 to 78 weeks). 3 pts have proceeded to allogeneic stem cell transplant, 4 (1 with ATL, 2 with T-PLL, and 1 with T-LGL) have died from disease progression after a response, and 8 were refractory to therapy. Opportunistic infections included reactivation of CMV in 7 pts, reactivation of HSV in 1 pt, recurrence of pre-existing Serratia pneumonia in 1 pt and Aspergillus pneumonia in 2 pts. Unexplained, marked and sustained pancytopenia occurred in 2 pts. Other toxicities were mainly grade 1 and 2 and included nausea, fever, edema, and shortness of breath. Conclusions: The combination of alemtuzumab and pentostatin is feasible and effective in T-cell neoplasms. Although infections including CMV reactivation are a concern, they may be minimized with adequate prophylactic antibiotic therapy. No significant financial relationships to disclose.