Treatment-free remission in FIP1L1-PDGFRA–positive myeloid/lymphoid neoplasms with eosinophilia after imatinib discontinuation

Abstract

FIP1L1-PDGFRA–positive myeloid/lymphoid neoplasms with eosinophilia (MLN-eo) are exquisitely sensitive to imatinib. Almost all patients achieve a complete molecular remission (CMR) by nested reverse transcription polymerase chain reaction, which can be maintained with low-dose imatinib (eg, 3 × 100 mg/wk). Because imatinib can be safely stopped in a substantial proportion of patients with BCR-ABL1–positive CML, we sought to analyze the clinical and molecular follow-up of 12 FIP1L1-PDGFRA–positive patients with MLN-eo in chronic phase who discontinued imatinib after achievement of a CMR. Median time of treatment and median time of CMR before imatinib discontinuation (last dose at 3 × 100 mg/wk, n = 8; or 100 mg/d, n = 4) were 80 (range, 43-175) and 66 (range, 37-174) months, respectively. A molecular relapse was observed in 4 patients after 10, 22 (n = 2), and 24 months. A second CMR was achieved in 3 patients after 3, 4, and 21 months. Eight patients (62%) are in ongoing CMR (median, 17 months; range, 3-71 months). Molecular relapse-free survival was 91% at 12 months and 65% at 24 months. No significant differences (eg, dose and duration of imatinib treatment or duration of CMR before imatinib discontinuation) were identified between patients with and without molecular relapse. Our data demonstrate that imatinib can be safely stopped in FIP1L1-PDGFRA–positive MLN-eo because of a high treatment-free remission at 12 and 24 months and because most patients achieve a rapid second CMR after restart of imatinib.

Epidemiology, clinical picture and long‐term outcomes ofFIP1L1‐PDGFRA‐positive myeloid neoplasm with eosinophilia: Data from 151 patients

“…Complete hematologic response (CHR) was defined as the normalization of the absolute eosinophil count. In the absence of validated criteria, and in line with previous studies reporting outcomes after IM discontinuation in F/P+ MN‐eo, 18‐20 complete molecular response (CMR) was defined as the disappearance of the F/P fusion gene by RT‐PCR or Q‐PCR (depending on the technical platforms of sites). After achieving remission (at least CHR, and CMR when searched for), relapse after IM discontinuation was defined as either (a) the recurrence of eosinophilia (with or without eosinophil‐related organ manifestations, with or without evidence of a new positive F/P test), but in the absence of an alternate cause to eosinophilia (hematologic relapse); (b) the recurrence of a new positive F/P test on peripheral blood occurring in a patient with previously documented CMR and without concomitant eosinophilia (isolated molecular relapse).…”

“…Robust epidemiological data are lacking, and the rates of F/P positivity among patients with unexplained eosinophilia are highly variable (ranging from 3 to 25%) depending mainly on the population studied 8,14,16,17 . Next, five small‐sample size studies showed conflicting results as to whether IM discontinuation was feasible, and no predictive factor of relapse has yet been reported 9,10,18‐20 . In this study, we aimed to perform a comprehensive analysis of the epidemiological, clinical features and treatment outcomes of F/P+ MN‐eo patients on a nationwide scale, and to identify predictors of relapse.…”

Successful Long-Term Control of the Syndrome of Episodic Angioedema With Eosinophilia (Gleich Syndrome) With Low-Dose Imatinib Mesylate and Prednisone

“…The most common of these is the FIP1L1-PDGFRA fusion, which is associated with nearly uniform beneficial clinical response to imitinab. 21 (2) Secondary or Reactive HES (HES R ), including lymphocyte-variant (L-HES), a subclass in which abnormal clones of T cells secrete large amounts of IL-5 resulting in hypereosinophilia. The broad group of HES R also encompasses various infectious diseases such as parasitic infestations, allergic disorders, chronic inflammatory, and autoimmune disorders.…”

“…30 HES patients with this gene fusion respond to small doses of imatinib mesylate, and after clinical and molecular remission has been achieved may be able to discontinue imatinib for an extended period of time. 21 …”

Update on CML-Like Disorders

“…10 MLN-eo is defi ned by the presence of fusion genes involving the tyrosine kinases PDGFRA, PDGFRB, FGFR1, or PCM1-JAK2. 1,11 These fusions are structurally and functionally analogous to BCR-ABL1 and it is perhaps unsurprising that many cases present with a disorder that can be considered as broadly CML-like. Other tyrosine kinase fusions such as ETV6-ABL1, BCR-JAK2, or those involving FLT3 would generally be classifi ed as CEL-NOS but again, they are typically associated with a CML-like phenotype.…”