Imatinib Achieves High Rates of Complete Citogenetic Remission (CCR) in CML Patients Relapsed after Autografting anf IFN-α Therapy.

Background: Imatinib, a selective inhibitor of the bcr-abl tyrosine kinase, induces CCR in the majority of patients with CML in first chronic phase (CP). In the present study we addressed the question if such achievement of CCR can occur also in patients relapsed after autografting and IFN-α therapy.

Methods: from 1991 to 2001, 50 patients with early chronic phase were treated with hydroxyurea; subsequently, when WBC count was less than 10x10⁹/L, the patients were treated with idarubicin containing regimen (ICE/mini-ICE protocols), mobilization of diploid or prevalently diploid peripheral blood stem cells (PBSC) with G-CSF during the early phase of recovery after chemotherapy and high-dose therapy followed by autologous diploid PBSC previously collected and cryopreserved. After engraftment, the patients received maintenance therapy with IFN-α (3MU/three times weekly). From september 2000, Imatinib became available for CML patients relapsed after IFN-α treatment. From that time all patients who relapsed after autografting and IFN-α received rescue therapy with Imatinib at 400 mg/daily for CP (Novartis protocol CSTI-106) and 600 mg/daily for accelerated phase (AP) (Novartis protocol-Italian Cooperative Study Group CSTI-003). Imatinib was given to 22 patients cytogenetically relapsed in CP and to 1 patient evoluted in AP.

Results: At the time of analysis (July 31, 2004), the median treatment duration with Imatinib was 32 months (range, 1 to 47). Four patients stopped Imatinib between 9 and 12 months for no response/progression. The patient in AP died of heart failure one month after starting Imatinib; since this patient have had previous history of cardiac failure, it is not clear if this event should be correlated with Imatinib therapy; two other patients died for progression. Imatinib induced major cytogenetic responses in 16/23 patients (70%) of whom 14/23 achieving CCR (61%). At a median follow up of 36 months the PFS and OS were 78% and 87%, respectively. Grade ≥III hematological toxicity occurred in 5 patients; this toxicity resolved with temporary discontinuation of the treatment.

Conclusion: Imatinib is an effective therapy for CP-CML patients who relapsed after autografting and IFN-α. The high rate of sustained haematological and cytogenetic responses achieved with Imatinib were associated to a favourable and manageable toxicity profile.