Impact of frontline treatment approach on outcomes of myeloid blast phase CML.

Abstract

BACKGROUND:

The natural course of untreated chronic myeloid leukemia (CML) is progression to an aggressive blast phase. Even in the current era of BCR-ABL1 tyrosine kinase inhibitors (TKIs), the outcomes of blast phase CML remain poor with no consensus frontline treatment approach.

METHODS:

We retrospectively analyzed the response rates and survival outcomes of 104 consecutive patients with myeloid blast phase CML (CML-MBP) treated from 2000 to 2019 based on 4 different frontline treatment approaches: intensive chemotherapy (IC) + TKI (n = 20), hypomethylating agent (HMA) + TKI (n = 20), TKI alone (n = 56), or IC alone (n = 8). We also evaluated the impact of TKI selection and subsequent allogeneic stem cell transplant (ASCT) on patient outcomes.

RESULTS:

Response rates were similar between patients treated with IC + TKI and HMA + TKI. Compared to treatment with TKI alone, treatment with IC/HMA + TKI resulted in a higher rate of complete remission (CR) or CR with incomplete count recovery (CRi) (57.5% vs 33.9%, p < 0.05), a higher complete cytogenetic response rate (45% vs 10.7%, p < 0.001), and more patients proceeding to ASCT (32.5% vs 10.7%, p < 0.01). With a median follow-up of 6.7 years, long-term outcomes were similar between the IC + TKI and HMA + TKI groups. Combination therapy with IC/HMA + TKI was superior to therapy with TKI alone, including when analysis was limited to those treated with a 2nd/3rd-generation TKI. When using a 2nd/3rd-generation TKI, IC/HMA + TKI led to lower 5-year cumulative incidence of relapse (CIR; 44% vs 86%, p < 0.05) and superior 5-year event-free survival (EFS; 28% vs 0%, p < 0.05) and overall survival (OS; 34% vs 8%, p = 0.23) compared to TKI alone. Among patients who received IC/HMA + TKI, EFS and OS was superior for patients who received a 2nd/3rd generation TKI compared to those who received imatinib-based therapy. In a landmark analysis, 5-year OS was higher for patients who proceeded to ASCT (58% vs 22%, p = 0.12).

CONCLUSIONS:

Compared to patients treated with TKI alone for CML-MBP, treatment with IC + TKI or HMA + TKI led to improved response rates, CIR, EFS, and OS, particularly for patients who received a 2nd/3rd-generation TKI. Combination therapy with IC + TKI or HMA + TKI, rather than a TKI alone, should be considered the optimal treatment strategy for patients with CML-MBP.

• Authors: Kapil Saxena, Elias Jabbour, Ghayas Issa, Koji Sasaki, Farhad Ravandi, Abhishek Maiti, Naval Daver, Tapan Kadia, Courtney D DiNardo, Marina Konopleva, Jorge E Cortes, Musa Yilmaz, Kelly Chien, Sherry Pierce, Hagop Kantarjian, Nicholas J Short
• Journal: Journal of hematology & oncology (J Hematol Oncol) Vol. 14 Issue 1 Pg. 94 (06 15 2021) ISSN: 1756-8722 [Electronic] England
• PMID: 34130720 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Blast Crisis (pathology, therapy)
• Disease Progression
• Female
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (pathology, therapy)
• Male
• Middle Aged
• Protein Kinase Inhibitors (therapeutic use)
• Retrospective Studies
• Stem Cell Transplantation
• Survival Analysis
• Treatment Outcome
• Young Adult