Interferon-Alpha (IFN-a) Is Able To Maintain Complete Molecular Response (CMR) In Chronic Myeloid Leukemia (CML) Patients Who Maintain Undetectable disease After Imatinib (IM) Discontinuation

Cytotoxic lymphocytes (CTLs) which recognize distinct antigenic peptides on CML cells, contributed greatly to the eradication of leukemic cells after allografting. Previously, BCR-ABL specific peptides and the PR1 non-apeptide, were found to elicit a CML-specific CTL response. PR1 is a peptide derived from myeloblastin (MBN), also known as proteinase 3. MBN is abundantly expressed in azurophil granules of normal myeloid cells and is substantially overexpressed in certain immature myeloid leukemia cells where it may be important for the maintenance of a leukemic phenotype. PR1-specific CTLs (PR1-CTLs) lyses and inhibits the proliferation of CML cells but not of normal myeloid precursors. The association between the emergence of PR1-CTLs and the response to IFN-a in vivo strongly implied that IFN-a can induce remissions via induction of a CML-specific PR1-CTLs response. Therefore IFN-a, given to CML patient with undetectable disease achieved with IM, might enable its discontinuation.

Ten consecutive CML patients, who were in stable CMR for at least one year after IM therapy, discontinued IM and received IFN-a. This drug was given at the dose of 3M/U/m² weekly. The median duration of IM therapy before discontinuation was 60 (range, 31-76) months. At a median follow-up of 40 months (range, 26-58 months), five patients still have undetectable level of BCR-ABL transcript. Five patients relapsed at a median of 8 months (range, 3 – 11 months) but all except one, achieved a new CMR after reintroduction of IM. Grade 2 intolerance (muscle pain, fever) to IFN-a developed in 6/10 patients. The details of patients characteristics will be discussed during the presentation. These preliminary results demonstrate that treatment with low dose IFN-a offered to CML patients with undetectable disease is feasible and this approach may become an attractive alternative to TKI discontinuation alone.