Alemtuzumab Administered by Subcutaneous Route Is Less Effective Than Intravenous Route for First Line Therapy of T-Cell Prolymphocytic Leukaemia: Results of a Pilot Study (UKCLL05)

T-cell prolymphocytic leukaemia (T-PLL) is a rare aggressive post thymic lymphoid disorder with distinctive clinical and pathological features. It is resistant to conventional chemotherapy and has a short median survival of 7 months. Intravenous (IV) alemtuzumab is an effective and well tolerated therapy for this disease, inducing remission in 76% of patients in the relapsed and refractory setting and increasing median survival to 24 months in responders. The aim of this study was to determine the efficacy of subcutaneous (SC) administration of alemtuzumab in previously untreated T-PLL patients. After an initial week of dose escalation, patients were treated with a dose of 30 mg 3 times weekly. Patients could be switched to the IV route if they had local side effects or showed a lack of response. Nine patients were enrolled. Male: female ratio was 2:1; median age was 61 years. All cases were centrally reviewed and confirmed to have a diagnosis of T-PLL. Eight had an immunophenotype typical of T-PLL (CD2, CD3, CD4, CD5 and CD 7 positive). One patient was unusually CD7 negative and also did not have an abnormality of chromosome 14. Seven had a complex karyotype and 8 had chromosome 14 abnormalities. Patients were treated on trial for a median of 7 weeks (range 3–13 weeks); 55% required a change to IV treatment due to a lack of response. This resulted in an increase in overall response (OR) from 33% (1 complete response [CR], 2 partial response [PR]) to 44 %.(2 CR, 2 PR). Five patients required addition of pentostatin to alemtuzumab at a dose of 4 mg/m² IV weekly to augment response. This increased OR to 77% (1 additional CR and 2 PR). 5 patients had haemopoietic progenitor cell transplants (HPCT) as consolidation; 1 was autologous and 4 were allogeneic. Median overall survival was 20 months (range 1–26 months) and disease free survival was 12 months (range 0–20 months). The treatment was well tolerated; however 2 patients had skin reactions to the SC injections. One patient required treatment for CMV reactivation and 2 patients had grade 4 haematologic toxicity which was related to disease and not treatment. Four patients remain alive and well in CR with a follow up of between 12 and 23 months, of whom 3 had allogeneic HPCT. The study was terminated early as a data safety monitoring review felt that SC treatment was not efficacious and patients should not be offered SC treatment. This pilot study suggests that the SC route of administration of alemtuzumab is not as effective as IV in the treatment of T-PLL; our series of 16 patients receiving first line therapy with IV alemtuzumab has shown an OR of 94% with 88% CR. It is therefore advisable that IV treatment should be used. Pentostatin is an effective agent to augment response. Allogeneic HPCT should be used as consolidation therapy when possible.