Outcomes of patients with chronic myelomonocytic leukaemia treated with non-curative therapies: a retrospective cohort study

Pleyer, Lisa; Leisch, Michael; Kourakli, Alexandra; Padron, Eric; Maciejewski, Jaroslaw P.; Cirici, Blanca Xicoy; Kaivers, Jennifer; Ungerstedt, Johanna; Heibl, Sonja; Patiou, Peristera; Hunter, Anthony M.; Mora, Elvira; Geißler, Klaus; Dimou, Maria; Lorenzo, M.J.; Melchardt, Thomas; Egle, Alexander; Viniou, Athina-Nora; Patel, Bhumika J.; Arnán, Montserrat; Valent, Peter; Roubakis, Christoforos; Bernal, Teresa; Galanopoulos, Athanasios; Muñoz, Marı́a del Mar; Bonadies, Nicolas; Almeida, António; Čermák, Jaroslav; Jerez, Andrés; Montoro, María Julia; Cortés, Albert; Pita, Alejandro; Andrade, Bernardo López; Hellstroem-Lindberg, Eva; Germing, Ulrich; Sekeres, Mikkael A.; List, Alan F.; Symeonidis, Argiris; Sanz, Guillermo; Larcher-Senn, Julian; Greil, Richard

doi:10.1016/s2352-3026(20)30374-4

Cited by 36 publications

(28 citation statements)

References 30 publications

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“…Moreover, from informative patient records we saw that around half of the CMML patients younger than 60 years received intensive chemotherapy and part of them underwent stem cell transplantation. Results from an international cohort including 1653 CMML patients which were recently published showed that patients treated with intensive chemotherapy had a very poor survival with a median OS of only 11 months 12 . Furthermore, we cannot exclude a selection bias favouring referral of younger patients with more clinically aggressive disease by physicians in the community.…”

Section: Discussionmentioning

confidence: 92%

“…Results from an international cohort including 1653 CMML patients which were recently published showed that patients treated with intensive chemotherapy had a very poor survival with a median OS of only 11 months. 12 Furthermore, we cannot exclude a selection bias favouring referral of younger patients with more clinically aggressive disease by physicians in the community.…”

Section: Discussionmentioning

confidence: 99%

“…Hydroxyurea is often used to control myeloproliferation in CMML 9 . The cytidine analogues azacytidine (AZA) and decitabine (5‐aza‐2'‐deoxycytidine) have demonstrated some efficacy in delaying disease course in advanced CMML and were approved for the treatment of CMML 10‐12 …”

Section: Introductionmentioning

confidence: 99%

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Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia

Machherndl‐Spandl

Jäger

Barna

et al. 2021

European J of Haematology

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In older patients with chronic myelomonocytic leukaemia (CMML) and limited life expectancy due to age and or comorbidities, it is particularly important to consider the risk of transformation for individualised treatment decisions. There is limited information on potential differences between younger and older CMML patients regarding the cumulative risk of transformation as well as haematological, molecular and biologic characteristics. We analysed data from the Austrian Biodatabase for CMML (ABCMML) to compare these parameters in 518 CMML patients. Categorisation of patients into 3 age‐related groups: <60 years, 60‐79 years and ≥80 years, showed a significantly lower risk of transformation at higher age by competing risk analysis, with a 4‐year risk of 39%, 23% and 13%, respectively (P < .0001). The lower probability of transformation was associated with a lower percentage of blast cells in the peripheral blood (PB) of older patients. Furthermore, we provide a simple score based on age, PB blasts and platelet counts that allowed us to define subgroups of CMML patients with a different cumulative transformation risk, including a low‐risk group with a transformation risk of only 5%. Our findings may facilitate reasonable treatment decisions in elderly patients with CMML.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia

Machherndl‐Spandl

Jäger

Barna

et al. 2021

European J of Haematology

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“…The combination of TET2 mutation and ASXL1 wildtype predicted higher CR and better OS. A multicenter retrospective study including 949 non-selected, consecutive CMML patients investigated whether HMA provide a benefit in subgroups of CMML patients ( 119 ). Adjusted median OS for patients treated with HU versus HMA was 15.6 months as compared to 20.7 months; (p=0.0002).…”

Section: Treatment Of Cmmlmentioning

confidence: 99%

Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches

Geißler

2021

Front. Oncol.

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Numerous examples in oncology have shown that better understanding the pathophysiology of a malignancy may be followed by the development of targeted treatment concepts with higher efficacy and lower toxicity as compared to unspecific treatment. The pathophysiology of chronic myelomonocytic leukemia (CMML) is heterogenous and complex but applying different research technologies have yielded a better and more comprehensive understanding of this disease. At the moment treatment for CMML is largely restricted to the unspecific use of cytotoxic drugs and hypomethylating agents (HMA). Numerous potential molecular targets have been recently detected by preclinical research which may ultimately lead to treatment concepts that will provide meaningful benefits for certain subgroups of patients.

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“…MP CMML, blasts ≥10%, and higher risk CMML according to the CPSS, have significantly better outcomes with HMAs compared with hydroxyurea or chemotherapy, whereas patients with lower-risk disease i.e. MD CMML with <10% blasts and lower risk CPSS, do not benefit from HMA treatment ( 27 ). Although this study provides the only direct, real-life comparison of HMAs with other available treatments, its retrospective and multicenter nature raises concerns about the presence of treatment-selection bias that cannot be overcome with Cox’s models.…”

Section: Use Of Hypomethylating Agents In Cmmlmentioning

confidence: 99%

Approaching First-Line Treatment in Patients With Advanced CMML: Hypomethylating Agents or Cytotoxic Treatment?

Liapis

Kotsianidis

2021

Front. Oncol.

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Chronic myelomonocytic leukemia (CMML) is a rare clonal haematological malignancy bearing characteristics of both myelodysplastic syndromes and myeloproliferative neoplasms. It primarily affects older people (median age at diagnosis ~72 years). There are many challenges encountered in its treatment. One striking issue is the lack of strong clinical evidence from large randomized clinical trials for treating this disease. Another issue is that patients with CMML have highly variable outcomes with current treatments. Additional challenges include a wider application of current knowledge, an improved understanding of pathogenesis, development of new therapies, and management of refractory cases/disease progression. It is clear that there is still progress to be made. Here, we review the available first-line treatment options for advanced CMML. Emphasis has been placed on choosing between hypomethylating agents and cytotoxic treatments, on the basis on disease-specific and patient-specific characteristics. A proper selection between these two treatments could lead to a better quality of care for patients with CMML.

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Outcomes of patients with chronic myelomonocytic leukaemia treated with non-curative therapies: a retrospective cohort study

Cited by 36 publications

References 30 publications

Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia

Impact of age on the cumulative risk of transformation in patients with chronic myelomonocytic leukaemia

Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches

Approaching First-Line Treatment in Patients With Advanced CMML: Hypomethylating Agents or Cytotoxic Treatment?

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