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Pleural effusion linked to first-line dasatinib molecular response


Oncol Rep 2016; Advance online publication

: Pleural effusion may be a positive sign during dasatinib treatment in patients with chronic phase chronic myeloid leukemia (CML–CP), suggests research published in Oncology Reports.

Analysis from the D-First study showed that 33% of 52 patients with newly diagnosed CML–CP developed pleural effusion within 18 months of beginning first-line tyrosine kinase inhibitor therapy, with 10 grade 1 and seven grade 2 cases reported.

Pleural effusion was significantly more common in patients aged 60 years or older than in younger patients, but gender, body weight, Sokal score and BCR–ABL1 transcript expression did not significantly predict likelihood of the adverse event.

Lymphocytosis per se was not associated with pleural effusion, the authors say. But CD56+ lymphocyte (natural killer cell) counts after 1 month of treatment were higher in patients who developed pleural effusion than those who did not, with a significant difference in the side-effect rate at 6, 12 and 18 months between patients who had a count of at least 428 per μL and those with a lower count.

The majority (75%) of the 51 patients who continued treatment for more than 1 month achieved a major molecular response (MMR; <0.1% BCR–ABL1IS) within 12 months of initiating dasatinib, and 59% had a deep molecular response (DMR; <0.0069% BCR–ABL1IS) within 18 months of treatment, say Noriyoshi Iriyama, from Nihon University School of Medicine in Tokyo, Japan, and co-authors.

MMR and DMR were assessed at 3, 6, 9, 12, 15, and 18 months; cumulative rates of MMR were higher in patients who developed pleural effusion than those who did not at all time points, with a significant difference in the rate of MMR by 3 months, becoming nonsignificant thereafter.

“We suggest that an immune response involving [natural killer] cells occurring as early as 1 month after dasatinib administration increases the incidence of [pleural effusion] for up to 18 months and likely promotes rapid tumor regression within 3 months,” the authors write.

They add that the cumulative rate of DMR was also consistently higher over the study in patients who experienced pleural effusion than those who did not, although the differences were not significant at any point.

“The DMR results suggest that the mechanism underlying [pleural effusion] development likely promotes only transient tumor regression in the first-line setting”, Iriyama et al say.

They conclude: “This study not only reveals a possible mechanism of [pleural effusion] development, but also suggests that, similar to previous studies, the occurrence of [pleural effusion] may be related to favorable outcomes in patients with CML-CP.”

By Lynda Williams, Senior medwireNews Reporter

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