Analysis of the Effectiveness of Maintenance Therapy By Imatinib in Patients with Pdgfra-Positive Neoplasm
Authors: Nemchenko Irina , Tsyba Nikolay , Chelysheva Ekaterina , Shukhov Oleg , Turkina Anna G 
Published: October 2019

Introduction: The effective therapy of PDGFRA- and PDGFRB-myeloid/lymphoid neoplasms with eosinophilia in the era of tyrosine kinase inhibitors (TKI) allows to achieve a complete hematologic response (CHR) and a molecular response (MR). The long-term duration of the MR makes it reasonable to evaluate the eligibility of various TKI maintenance regimens by analogy with Ph'-positive chronic myelogenous leukemia.

Objective: to evaluate the results of maintenance imatinib therapy in patients with PDGFRA-positive neoplasm.

Patients and Methods: Between November 2003 and March 2018, imatinib was used in 42 patients with a PDGFRA-positive neoplasm (male:female=40:2, median age 39 years).

The initial dose of imatinib was 100 mg per day. CHR was considered as normalization of complete blood counts and disappearance of clinical symptoms and complaints caused by to the disease. The MR was estimated by the qualitative RT-PCR method. The achievement of MR was noted in case of the absence of FIP1L1-PDGFRA transcript expression in bone marrow/peripheral blood cells.

The preservation of stable CHR and stable MR was the indication for switching to a maintenance (supportive) regimen. The frequency of imatinib use during the maintenance regimen was reduced from 100 mg daily to 100 mg every other day or 100 mg twice a week. All patients receiving imatinib within a reduced dose regimen underwent regular clinical and laboratory monitoring.

Results:

CHR was obtained in 95% (40/42) of patients. The MR was evaluated in 37 patients. The MR achievement was obtained in 87% (32/37) patients.

The reduction of the frequency of imatinib intake according to the above scheme was carried out in 1(53%) 7 out of 32 patients with stable CHR and MR at different time points after the therapy start. Patients who received imatinib in a supportive regimen were conditionally divided into 2 groups.

The first group included 13(77%) patients in whom CHR was maintained; the repetitive molecular tests in 11 patients of this group confirmed the preservation of MR. The median follow-up of patients before transfer to a supportive regimen was 30 months (from 12 to 65 months). The median duration of the maintenance regimen at the time of presentation was 29 months (1.5 months to 99 months).

The second group included 4(23%) of 17 patients with the loss of response to treatment during the maintenance regimen. The duration of imatinib therapy in the full-dose regimen prior to switch to a supportive regimen was 8, 13, 21 and 26 months and it was significantly less than in the first group of patients. The loss of MR and CHR was observed in 2 patients during the first 5 months after the change of the therapy regimen. Only a loss of MR without CHR loss was observed in the other 2 patients 3 and 11 months after the dose reduction of imatinib.

Conclusions:

Preserving a stable CHR and MR in patients with PDGFRA-positive neoplasm receiving imatinib makes it possible to transfer the patients to a maintenance regimen of imatinib 100 mg twice a week. We suggest that a continuous imatinib use in a dose 100 mg daily for at least 3 years is necessary in order to have a stable CHR and MR and to be eligible for switching to a supportive treatment regimen.

Disclosures

Chelysheva: Novartis: Other: provided consultations and performed lectures; Bristol Myers Squibb: Other: provided consultations and performed lectures; Fusion Pharma: Other: provided consultations . Shukhov:Novartis: Other: provided consultations and performed lectures ; Bristol Myers Squibb: Other: provided consultations and performed lectures . Turkina:Novartis: Other: provided consultations; Bristol Myers Squibb: Other: provided consultations; Phizer: Other: provided consultations; Fusion Pharma: Other: provided consultations.