Imatinib has marked antileukemic activity in advanced
Philadelphia chromosome-positive
acute lymphoblastic leukemia (Ph+ALL), but secondary resistance develops rapidly, reflecting the limitations of single-agent
therapy. Experimental data suggest that
interferon-alpha (IFN-alpha) enhances the antileukemic activity of
imatinib. We therefore examined combined
imatinib and low-dose IFN-alpha in six patients with Ph+ALL who were ineligible for
stem cell transplantation. All patients had received
imatinib for 0.5-4.8 months prior to IFN-alpha, for relapsed (n=3) or refractory (n=1) Ph+ALL or as an alternative to
chemotherapy following severe treatment-related toxicity (n=2). Five patients were in hematologic remission (CR) with
minimal residual disease (MRD+), one patient was refractory to
imatinib. Four of the five MRD+ patients are alive in CR after a median
treatment duration of 20 (11-21) months. Two of these patients are in continuous CR 21 months after
imatinib was initiated, while the other two patients experienced an isolated meningeal relapse that was successfully treated with additional intrathecal
chemotherapy. Sustained molecular remissions were achieved in three patients and are ongoing 13 and 10.5 months after central nervous system (CNS) relapse and 6 months after starting concurrent IFN-alpha and
imatinib, respectively. Marrow relapse occurred in one of the five MRD+ patients. Combination treatment was associated with a complete marrow response of 5 months duration in the
imatinib-refractory patient.
Imatinib combined with low-dose IFN-alpha may achieve prolonged hematologic and molecular remissions in a subset of patients with advanced Ph+ALL, who are not candidates for allogeneic SCT. CNS prophylaxis is necessary and may enhance the antileukemic activity of
imatinib and IFN-alpha.