Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity

Charles A. Schiffer, Jorge E. Cortes, Andreas Hochhaus, Giuseppe Saglio, Philipp Le Coutre, Kimmo Porkka, Satu Mustjoki, Hesham Mohamed, Neil P. Shah

Research output: Contribution to journalArticle

Abstract

BACKGROUND The proliferation of clonal cytotoxic T-cells or natural killer cells has been observed after dasatinib treatment in small studies of patients with chronic myeloid leukemia (CML). METHODS The incidence of lymphocytosis and its association with response, survival, and side effects were assessed in patients from 3 large clinical trials. Overall, 1402 dasatinib-treated patients with newly diagnosed CML in chronic phase (CML-CP), CML-CP refractory/intolerant to imatinib, or with CML in accelerated or myeloid-blast phase were analyzed. RESULTS Lymphocytosis developed in 32% to 35% of patients and persisted for >12 months. This was not observed in the patients who received treatment with imatinib. Dasatinib-treated patients in all stages of CML who developed lymphocytosis were more likely to achieve a complete cytogenetic response, and patients who had CML-CP with lymphocytosis were more likely to achieve major and deep molecular responses. Progression-free and overall survival rates were significantly longer in patients with CML-CP who were refractory to or intolerant of imatinib and had lymphocytosis. Pleural effusions developed more commonly in patients with lymphocytosis. CONCLUSIONS Overall, lymphocytosis occurred and persisted in many dasatinib-treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable.

Original languageEnglish (US)
Pages (from-to)1398-1407
Number of pages10
JournalCancer
Volume122
Issue number9
DOIs
StatePublished - May 1 2016

Fingerprint

Lymphocytosis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic Phase
Therapeutics
Dasatinib
Blast Crisis
Survival
Pleural Effusion
Cytogenetics
Natural Killer Cells
Disease-Free Survival
Survival Rate
Clinical Trials
Prospective Studies
T-Lymphocytes

Keywords

  • T-lymphocytes
  • chronic myeloid
  • dasatinib
  • killer cells
  • leukemia
  • lymphocytosis
  • natural

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Schiffer, C. A., Cortes, J. E., Hochhaus, A., Saglio, G., Le Coutre, P., Porkka, K., ... Shah, N. P. (2016). Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity. Cancer, 122(9), 1398-1407. https://doi.org/10.1002/cncr.29933

Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia : Effects on response and toxicity. / Schiffer, Charles A.; Cortes, Jorge E.; Hochhaus, Andreas; Saglio, Giuseppe; Le Coutre, Philipp; Porkka, Kimmo; Mustjoki, Satu; Mohamed, Hesham; Shah, Neil P.

In: Cancer, Vol. 122, No. 9, 01.05.2016, p. 1398-1407.

Research output: Contribution to journalArticle

Schiffer, CA, Cortes, JE, Hochhaus, A, Saglio, G, Le Coutre, P, Porkka, K, Mustjoki, S, Mohamed, H & Shah, NP 2016, 'Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity', Cancer, vol. 122, no. 9, pp. 1398-1407. https://doi.org/10.1002/cncr.29933
Schiffer, Charles A. ; Cortes, Jorge E. ; Hochhaus, Andreas ; Saglio, Giuseppe ; Le Coutre, Philipp ; Porkka, Kimmo ; Mustjoki, Satu ; Mohamed, Hesham ; Shah, Neil P. / Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia : Effects on response and toxicity. In: Cancer. 2016 ; Vol. 122, No. 9. pp. 1398-1407.
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AB - BACKGROUND The proliferation of clonal cytotoxic T-cells or natural killer cells has been observed after dasatinib treatment in small studies of patients with chronic myeloid leukemia (CML). METHODS The incidence of lymphocytosis and its association with response, survival, and side effects were assessed in patients from 3 large clinical trials. Overall, 1402 dasatinib-treated patients with newly diagnosed CML in chronic phase (CML-CP), CML-CP refractory/intolerant to imatinib, or with CML in accelerated or myeloid-blast phase were analyzed. RESULTS Lymphocytosis developed in 32% to 35% of patients and persisted for >12 months. This was not observed in the patients who received treatment with imatinib. Dasatinib-treated patients in all stages of CML who developed lymphocytosis were more likely to achieve a complete cytogenetic response, and patients who had CML-CP with lymphocytosis were more likely to achieve major and deep molecular responses. Progression-free and overall survival rates were significantly longer in patients with CML-CP who were refractory to or intolerant of imatinib and had lymphocytosis. Pleural effusions developed more commonly in patients with lymphocytosis. CONCLUSIONS Overall, lymphocytosis occurred and persisted in many dasatinib-treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable.

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