Thalidomide in Advanced Mastocytosis. Results from an Open-Label, Multicentric, Phase II Study
Authors: Gruson Berengere , Lortholary Olivier , Canioni Danielle , Chandesris marie-Olivia , Lanternier Fanny , Grosbois Bernard , Livideanu Cristina , Lamy Thierry , Sevestre Henri , Larroche Claire , Esparcieux Aurélie , Chaby Guillaume , Marolleau Jean Pierre , Hermine Olivier , Damaj Gandhi 
Published: October 2019

Abstract
Abstract 1754

Background:
Mastocytosis is characterized by the abnormal accumulation of mast cells in various tissues responsible for organ failure and/or systemic symptoms that can be disabling and alter the quality of life (QOL). Beside symptomatic treatments, cytoreductive drugs such as a-interferon, purine analogs and to a less extent imatinib mesylate (in case of c-kit mutation other than D816V) and masatinib were shown to be effective but rare complete or long-term remissions were obtained. Thalidomide is an anti-angiogenic immuno-modulatory and anti-inflammatory drug that has preliminary been shown to have an activity in aggressive systemic mastocytosis (ASM) (Damaj et al, BJH 2008). We report the result of a multicentric, open-label, phase II study using thalidomide as a single agent in advanced SM (NCT00769587).

Patients and Methods:
Twenty patients (pts) were enrolled (1 missing data): smoldering systemic (SSM, n=9), ASM (n=6) and with an associated clonal hematologic non mast cell lineage disease (SM-AHNMD, n=4). Infiltrated organs were bone marrow (n=16), skin (n=14), splenomegaly (n=10), hepatomegaly (n=6), intestinal tract (n=6), lymph nodes (n=1). Median serum tryptase level at inclusion was 83.4 ng/L (range 5.3–775) and all patients except one carried the c-kit D816V mutation. Patients presented with anemia (n=6), thrombocytopenia (n=6) and neutropenia (n=1). Four patients were excluded, 1 for missing data and 3 were not evaluable. Thalidomide was administered orally at a starting dose of 50 mg/day and was progressively increased up to 200 mg/day or appearance of side effects. The duration of treatment was 6 months (1 cycle= 1 month). Responder patients may continue on thalidomide for a maximum of 12 months or progression. Primary objective was to determine the effective response rate by assessing the tumor burden. Secondary objectives were to assess the tolerance of thalidomide and to evaluate the QOL, depression (Hamilton score), pruritis, and handicap (Afirmm V2 score) related to mast cell disease.

Results:
Sixteen pts [7 males, 9 females; median age 65 years (range 43–76)] who received at least one cycle of thalidomide were analyzed.
The median number of thalidomide cycles was 6 (range 1–20) and the median dose received was 100mg/d. Partial response was obtained in 9 pts (56%), 4 pts remained stable (25%) and 3 pts progressed (19%). Pruritis score decreased significantly from 6.5 (95% CI 4.74–12.26) to 4 (95% CI 0–5.25) (p=0.03); the Afirmm score tended to improve from 116.5 (95% CI 55.0–168.3) to 92.5 (95% CI 37.4–131.2) (p=0.38) with no improvement of QoL and Hamilton scores, median tryptase level or cytopenia. Skin infiltration disappeared only in 2 of 14 patients concerned. Treatment discontinuation was due to failure in 4 pts, side effect in 2 pts and patient's decision in 2. Thalidomide was continued in five pts as a maintenance therapy for a median duration of 6 mo (4–14). The most relevant toxicities (grade 3–4) consisted in peripheral neuropathy (12.5%) and myelosuppression (18.7%).

Conclusions:
Thalidomide is an acceptable and effective treatment in advanced SM.

Disclosures:
No relevant conflicts of interest to declare.