TY - JOUR
T1 - Management and Outcomes of Blast Transformed Chronic Myelomonocytic Leukemia
AU - Hammond, Danielle
AU - Montalban-Bravo, Guillermo
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/10
Y1 - 2021/10
N2 - Purpose of Review: Despite recent advances in the treatment of de novo acute myeloid leukemia (AML), AML arising from antecedent chronic myelomonocytic leukemia (CMML) continues to have dismal outcomes. While the unique biological drivers of CMML and subsequent leukemic transformation (LT) have been revealed with advances in molecular characterization, this has not yet translated to the bedside. Here, we review these biologic drivers, outcomes with current therapies, and rationale avenues of future investigation specifically in blast phase CMML (CMML-BP). Recent Findings: CMML-BP outcomes are studied as an aggregate with more common categories of AML with myelodysplasia-related changes (AML-MRCs) or the even broader category of secondary AML (sAML), which illustrates the crux of the problem. While a modest survival advantage with allogeneic hematopoietic stem cell transplant exists, the difficulty is bridging patients to transplant and managing patients that require an allograft-sparing approach. Limited data suggest that short-lived remissions can be obtained employing CPX-351 or venetoclax-based lower intensity combination therapy. Promising future strategies include repurposing cladribine, exploiting the supportive role of dendritic cell subsets with anti-CD123 therapies, MCL-1 inhibition, dual MEK/PLK1 inhibition, FLT3 inhibition in RAS-mutated and CBL-mutated subsets, and immune therapies targeting novel immune checkpoint molecules such as the leukocyte immunoglobulin-like receptor B4 (LILRB4), an immune-modulatory transmembrane protein restrictively expressed on monocytic cells. Summary: The successful management of an entity as unique as CMML-BP will require a cooperative, concerted effort to design and conduct clinical trials dedicated to this rare form of sAML.
AB - Purpose of Review: Despite recent advances in the treatment of de novo acute myeloid leukemia (AML), AML arising from antecedent chronic myelomonocytic leukemia (CMML) continues to have dismal outcomes. While the unique biological drivers of CMML and subsequent leukemic transformation (LT) have been revealed with advances in molecular characterization, this has not yet translated to the bedside. Here, we review these biologic drivers, outcomes with current therapies, and rationale avenues of future investigation specifically in blast phase CMML (CMML-BP). Recent Findings: CMML-BP outcomes are studied as an aggregate with more common categories of AML with myelodysplasia-related changes (AML-MRCs) or the even broader category of secondary AML (sAML), which illustrates the crux of the problem. While a modest survival advantage with allogeneic hematopoietic stem cell transplant exists, the difficulty is bridging patients to transplant and managing patients that require an allograft-sparing approach. Limited data suggest that short-lived remissions can be obtained employing CPX-351 or venetoclax-based lower intensity combination therapy. Promising future strategies include repurposing cladribine, exploiting the supportive role of dendritic cell subsets with anti-CD123 therapies, MCL-1 inhibition, dual MEK/PLK1 inhibition, FLT3 inhibition in RAS-mutated and CBL-mutated subsets, and immune therapies targeting novel immune checkpoint molecules such as the leukocyte immunoglobulin-like receptor B4 (LILRB4), an immune-modulatory transmembrane protein restrictively expressed on monocytic cells. Summary: The successful management of an entity as unique as CMML-BP will require a cooperative, concerted effort to design and conduct clinical trials dedicated to this rare form of sAML.
KW - Allogeneic stem cell transplant
KW - Blast phase
KW - CPX-351
KW - Chronic myelomonocytic leukemia
KW - Secondary acute myeloid leukemia
KW - Venetoclax
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U2 - 10.1007/s11899-021-00643-3
DO - 10.1007/s11899-021-00643-3
M3 - Review article
C2 - 34499330
AN - SCOPUS:85114603666
SN - 1558-8211
VL - 16
SP - 405
EP - 417
JO - Current hematologic malignancy reports
JF - Current hematologic malignancy reports
IS - 5
ER -