Sustained Complete Molecular Response (CMR) with Interferon-alpha Maintenance After Induction with Imatinib In Chronic Myeloid Leukemia (CML) Patients.

Abstract 4486

Cytotoxic lymphocytes (CTLs) which recognize distinct antigenic peptides on CML cells, contributed greatly to the cure after allografting. Previously, BCR-ABL specific peptides and the PR1 non-apeptide, were found to elicit a CML-specific CTL response (Molldrem, 1996/1997; Bocchia 1996, Clark 2001). 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 (Molldrem et al, 2000).

Recent data demonstrating a failure of IM to kill cell cycle-arrested CML precursors advice us to be attentive to arising escape mechanisms of even chronic phase CML; therefore IFN-a, given to CML patient with undetectable disease achieved with IM, might enable its discontinuation.

We have treated until now 8 CML patients who achieved stable CMR for at least one year after IM therapy. These patients discontinued IM and started IFN-a at the dose of 3–9 M/U/m² weekly (median 6 M/U/m²). The median duration of IM therapy was 60 (range, 31–76) months before IM discontinuation. At a median follow-up of 16 months (range, 9–24 months) after discontinuation of IM, five patients still have an undetectable level of BCR-ABL transcript under IFN-a. Grade 2 intolerance (muscle pain, fever) to IFN-a developed in 5/8 patients. The details of patients characteristics will be discussed during the presentation. These preliminary results demonstrate that treatment with low dose IFN-a in CML patients with undetectable disease is feasible and this approach may become an attractive alternative to lifelong TKI therapy.