Introduction: Chronic myeloid leukemia in myeloid blast phase (CML-MBP) is an aggressive and uncommon clinical entity with limited treatment options and poor prognosis. Although BCR::ABL1 tyrosine kinase inhibitors (TKIs) like dasatinib and ponatinib have transformed outcomes in chronic-phase CML (CML-CP), their impact in CML-MBP remains suboptimal. Prior studies suggest potential benefit from combining TKIs with intensive chemotherapy. Drawing on data from acute myeloid leukemia, we evaluated the combination of cladribine, idarubicin, and high-dose cytarabine (CLIA) with a TKI in patients with newly diagnosed or relapsed/refractory (R/R) CML-MBP.

Methods: Adults aged 18–65 with newly diagnosed (ND) or R/R CML-MBP and adequate organ function were eligible. CML-MBP was defined as ≥20% blasts in peripheral blood or bone marrow, or presence of extramedullary blast proliferation.Induction consisted of cladribine 5 mg/m² IV on days 1-5 and idarubicin 10 mg/m² IV on days 1-3. Two cytarabine doses were tested: CLIA-1 (1 g/m² IV days 1-5) and CLIA-2 (2 g/m² IV days 1-5). Responding patients proceeded to consolidation with 3 days of cladribine and cytarabine and 2 days of idarubicin. A BCR::ABL1 TKI started on day 1 and was given for 14 days during cycle 1 (starting on day 1), then continued uninterrupted starting cycle 2. Responses were assessed via bone marrow evaluation, flow cytometry, and PCR for BCR::ABL1 transcripts. Patients achieving remission were considered for allogeneic stem cell transplant (SCT).

Results: Thirteen patients have been treated: 7 (54%) in the frontline setting and 6 (46%) with R/R CML-MBP. Median age was 45 years (range, 32–61), and 54% were male. The majority were White (77%), with one patient each identifying as Black, Hispanic, and unknown; 92% were non-Hispanic. Ten patients (77%) received ponatinib, 2 (15%) received dasatinib, and 1 (8%) received bosutinib. Among frontline patients, 4 (57%) had prior TKI exposure for CML-CP, while 3 (43%) were TKI-naive. Extramedullary disease was found in 2 of 7 (28%) frontline patients and 3 of 6 (50%) R/R patients. Median bone marrow blast percentage at diagnosis was 28% (frontline, range 1-42%) and 35.5% (R/R, 0-57%). After one cycle, follow-up PCR was available in all 7 frontline patients (median 2.69%) and 4 of R/R patients (26.53%).

Among frontline patients, 6/7 (86%) achieved an overall response (CR/CRi/MLFS), including 4 (57%) CR/CRi. The one non-responding patient had hypocellular marrow with no recovery after cycle 1 and died of infection. 5/6 (83%) of patients with R/R disease achieved a response, including 3 (50%) CR. The median time to best response was 52.5 days (range, 20–84). 5 (38%) responding patients went on to receive SCT, 2 frontline and 3 R/R. The median overall survival (OS) was 13.1 and 8.3 months for frontline and R/R cohorts, respectively, with 1-year OS of 68.6% and 50%, respectively.

Eight of 13 patients (62%) experienced at least one adverse event, most commonly infections, febrile neutropenia, or laboratory evidence of renal or hepatic dysfunction. Three patients required hospitalization for infection-related complications. Non-infectious AEs were generally mild and often unrelated to study treatment. No unexpected or treatment-related deaths occurred.

Conclusion: The combination of CLIA and TKI was feasible and showed encouraging activity in patients with CML-MBP, particularly in the frontline setting. High rates of response were seen in both newly diagnosed and R/R patients, and 38% of patients proceeded to SCT. These results support further investigation of this regimen and highlight the importance of early post-remission strategies, including greater effort to bridge eligible patients to SCT to maximize the potential for durable remissions.

This content is only available as a PDF.
2025
Sign in via your Institution