Phase II Study of Adding the Anti-PD-1 Pembrolizumab to Tyrosine Kinase Inhibitors in Patients With Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease

PRIMARY OBJECTIVES:

I. Assess the proportion of chronic myelogenous leukemia (CML) patients on stable-dose tyrosine kinase inhibitor (TKI) who convert to undetectable minimal residual disease (UMRD) (molecular response [MR]^4.5) during or within 2 years of initiating pembrolizumab therapy.

SECONDARY OBJECTIVES:

I. Among patients who have converted to UMRD (MR^4.5), assess the proportion of CML patients who maintain UMRD for 6 months and 12 months.

II. Among patients who have converted to UMRD (MR^4.5), assess the proportion of CML patients who discontinue their TKI.

III. Among patients who have converted to UMRD (MR^4.5), assess the proportion of CML patients who are UMRD and TKI-free at 2 years from first determined UMRD.

IV. Assess the proportion of CML patients who develop grade 3 or 4 immune related adverse events related to pembrolizumab treatment during the first 2 years after registration (not including grade 3 events that respond to corticosteroids and improve to grade 1 or less within 4 weeks).

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and dasatinib, imatinib mesylate, or nilotinib orally (PO) as clinically indicated per the treating physician. Treatment repeats every 21 days for up to 18 courses in the absence of disease progression or unacceptable toxicity. Patients with detectable MRD after course 18 continue pembrolizumab and dasatinib, imatinib mesylate, or nilotinib every 21 days for up to an additional 18 courses in the absence of disease progression or unacceptable toxicity. Patients with UMRD at any time before course 18 discontinue pembrolizumab after course 18 and continue dasatinib, imatinib mesylate, or nilotinib every 21 days for up to an additional 18 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 6 years from the date of registration.