Maintenance Therapy by Glivec® and Pegasys® in Patients with Philadelphia Positive Acute Lymphocytic Leukemia Not Eligible for Hematopoietic Stem Cell Transplantation.

We previously reported a 93% CR rate in patients with Philadelphia positive acute lymphoblastic leukemias (Ph+ ALL) treated with an imatinib (Glivec®) based induction (DIV regimen) (Rea et al. Leukemia, 2006;20:400–3). We decided to further confirm these results in a larger prospective cohort of patients and to evaluate the combination of imatinib and Pegasys® for patients in CR not eligible for hematopoietic stem cell transplantation (HSCT). Patients not previously exposed to imatinib and with resistant or refractory Ph+ ALL, lymphoid blast crisis CML (LBC CML) or with de novo Ph+ ALL and aged over 55y were eligible. The DIV regimen consisted in one IV injection of vincristine 2 mg combined with 2 days of dexamethasone 40 mg PO repeated weekly for 4 weeks as induction and then monthly for 4 months as consolidation. Imatinib was administered at 800 mg per day during the induction period and at 600 mg/d continuously with 6 mercaptopurine during consolidation. Patients in CR not eligible for HSCT were allocated to maintenance therapy consisting in weekly SC injection of Pegasys® 45 μg and continuous administration of imatinib 400 mg per day for 2 years. 54 patients (median age 62y, 22 to 83) were included (22 resistant or refractory Ph+ ALL, 3 relapsed Ph+ ALL, 4 LBC CML and 25 elderly Ph+ ALL). The median follow up was 18 months. The overall CR rate after induction was 85%. 42 patients were eligible for post consolidation therapy: 18 patients received HSCT (10 allogenic HSCT including 9 out of the 15 patients aged under 55y and 8 autologous HSCT). 18 out of 24 patients (75%) without HSCT started the maintenance therapy. Reasons for not being in maintenance were relapse in one case, septic death in 3 cases and toxicity in 2 cases. The interval from CR to HSCT was 5.8 months in median (2.6 to 11.3). The medain interval from CR to maintenance was 5.4 months (5.2 to 6.7). The median survival of the transplanted group of patients was 29.9 months compared to 27.9 months for patients treated with the maintenance schedule (p=0,98). Six patients (33%) relapsed in the HSCT group and 7 (38.8%) in the maintenance group. Grade 2 to 4 neutropenia and/or thrombocytopenia were observed in 33% of cases during maintenance therapy leading to transient interruption of Pegasys® injections. Extra haematological grade 3 to 4 toxicities were infrequent (1 papillary oedema and two infections). We confirm here the high CR rate obtained in Ph+ acute lymphocytic leukemias with the DIV regimen, without the need of intensive chemotherapy. Maintenance therapy with Pegasys® and imatinib represents an alternative approach for patients not eligible for HSCT and was associated with a median survival of 27.9 months in this study.