Purpose: Despite advances in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), outcomes for relapsed/refractory (R/R) disease remain poor. Preclinical studies suggest that the combination of the CDK4/6 inhibitor palbociclib and dexamethasone may be effective in targeting leukemic cell growth. We conducted a phase I study of escalating doses of palbociclib in combination with dexamethasone in adults with R/R B-ALL.
Methods: Cycle 1 consisted of single agent palbociclib given for 7 days and continued for 28 additional days in combination with dexamethasone 20 mg daily. Palbociclib dosing began at 100 mg daily. Patients with a response were eligible for maintenance consisting of 1 week of palbociclib plus dexamethasone (20 mg daily × 2 days, 16 mg daily × 2 days, 12 mg daily × 2 days, 6 mg daily × 1 day), followed by 3 weeks of palbociclib alone. Safety, efficacy, and the expression of phospho-RB and c-MYB/BCL-2 were measured.
Conclusions: Seven patients were treated on study before it was closed early due to slow accrual. No dose limiting toxicities were identified. One patient had a complete response with incomplete hematologic recovery, suggesting possible efficacy of the treatment. Reduction in CD34+ cells, p-RB, c-MYB, and BCL-2 expression also suggested on-target therapy effects.
Keywords: Acute lymphoblastic leukemia; C-MYB; CDK4/6 inhibition; Dexamethasone; Palbociclib; Relapsed.
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