Abstract
The prognosis of patients with aggressive mature T cell lymphoma is very poor. We wondered whether the addition of the anti-CD52 monoclonal antibody alemtuzumab to 2-weekly CHOP chemotherapy as 1st line treatment would result in acceptable toxicity, improved response, and outcome. In a multicenter phase II design, 20 patients were to receive 8 cycles of CHOP14 (d 1: cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, 2 mg max, and day 1–5 prednisone 100 mg; repeat at day 15). Alemtuzumab 30 mg subcutaneously was added at day 1, 5 and 10 of each cycle (total of 24 administrations). Valaciclovir, cotrimoxazol and fluconazol were given as prophylaxis for herpes viral, PCP and fungal infections, respectively; G-CSF was given to enhance neutrophil recovery. Blood products were irradiated. Monitoring for CMV (re)activation by PCR or pp65 antigenemia was mandatory. Between Nov 2005 and Oct 2007, 20 patients with newly diagnosed T-NHL were included by 10 different centers (55% male; median age 50, range 20 to 65 years; 19 stage III/IV; 11 IPI high/high-intermediate). T-NHL histologies were: peripheral T cell lymphoma NOS (n=10), angioimmunoblastic lymphoma (n=6), subcutaneous panniculitis-like lymphoma (n=3), enteropathy-associated T cell lymphoma (n=1). Patients received a median of 8 CHOP cycles, 85% received 6 or more. Response to treatment was: 12 CR, 6 PR (ORR 85%) and 2 NR. At a median follow-up of 18 months, 11 patients are still alive, 9 patients have relapsed; the median FFS is 20 months (range 2–25) and median OS is 23 months (5–29). Toxicity was considerable, with CMV reactivation in 7/20 patients; one patient developed CMV disease; hospital admissions because of (mostly neutropenic) fever occurred in 8 patients. However, none of these patients died from these adverse events. One patient died in CR, 5 months after treatment due to sepsis complicating an extensive varicella zoster infection. Three patients (two with peripheral T cell lymphoma, one with angioimmunoblastic lymphoma without initial EBV activity) developed an EBV-related lymphoproliferative disorder. These patients ultimately died of relapse T-NHL.
In conclusion, an intensive alemtuzumab-CHOP14 regimen is feasible and effective in aggressive T-NHL as far as response and early outcome are concerned. Toxicity, especially the high percentage of herpes viral reactivation including EBV-related lymphoproliferation requires careful monitoring.
Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials