RESUMEN
PURPOSE: To provide insights into the diagnosis and management of therapy-related myeloid neoplasms (t-MN) following PARP inhibitors (PARPi). EXPERIMENTAL DESIGN: In a French cancer center, we identified and described the profiles of 13 t-MN diagnosed among 37 patients with ovarian cancer referred to hematology consultation for cytopenia under PARPi. Next, we described these 13 t-MN post-PARPi among 37 t-MN post ovarian cancer according to PARPi exposure. Finally, we described 69 t-MN post-PARPi in a national cohort. RESULTS: From 2016 to 2021, cumulative incidence of t-MN was 3.5% (13/373) among patients with ovarian cancer treated with PARPi. At time of hematologic consultation, patients with t-MN had a longer PARPi exposure (9 vs. 3 months, P = 0.01), lower platelet count (74 vs. 173 G/L, P = 0.0005), and more cytopenias (2 vs. 1, P = 0.0005). Compared with t-MN not exposed to PARPi, patients with t-MN-PARPi had more BRCA1/2 germline mutation (61.5% vs. 0%, P = 0.03) but similar overall survival (OS). In the national cohort, most t-MN post-PARPi had a complex karyotype (61%) associated with a high rate of TP53 mutation (71%). Median OS was 9.6 months (interquartile range, 4-14.6). In multivariate analysis, a longer time between end of PARPi and t-MN (HR, 1.046; P = 0.02), olaparib compared with other PARPi (HR, 5.82; P = 0.003) and acute myeloid leukemia (HR, 2.485; P = 0.01) were associated with shorter OS. CONCLUSIONS: In a large series, we described a high incidence of t-MN post-PARPi associated with unfavorable cytogenetic and molecular abnormalities leading to poor OS. Early detection is crucial, particularly in cases of delayed cytopenia.
Asunto(s)
Neoplasias Primarias Secundarias , Neoplasias Ováricas , Femenino , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Carcinoma Epitelial de Ovario , Mutación , Mutación de Línea Germinal , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/epidemiologíaRESUMEN
We describe the use and value of a lenalidomide/bortezomib/dexamethasone regimen for the treatment of three patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN, a disease that lacks a consensus treatment). After five cycles of chemotherapy, we observed two complete responses and one clinical remission. Together with the encouraging literature data on the effects of lenalidomide and bortezomib on BPDCN cells, our results might prompt further investigations of this regimen's value in BPDCN.
