ASCITES - A MANIFESTATION OF AGGRESSIVE SYSTEMIC MASTOCYTOSIS - CAN SUCCESSFULLY BE TREATED WITH MIDOSTAURIN (PKC412)
(Abstract release date: 05/19/16)
EHA Library. Dybedal I. 06/09/16; 134924; PB2024
Dr. Ingunn Dybedal
Contributions
Contributions
Abstract
Abstract: PB2024
Type: Publication Only
Background
Systemic mastocytosis (SM) is a myeloproliferative neoplasia caused by uncontrolled proliferation and accumulation of pathological mast cells in one or more extracutaneous organs. The 2008 WHO classification divides SM into several subtypes including aggressive SM (ASM) with at least one “C finding.” Among the four different “C findings” is palpable hepatomegaly with impairment of liver function, ascites and/or portal hypertension. Midostaurin (PKC412) is a new and so far not approved drug shown to have a strong inhibitory activity on neoplastic human mast cells carrying the D816V KIT mutation and with an acceptable side-effect profile.
Aims
The primary objective was to assess the clinical effect of PCK412 on ascites in patients with ASM. The secondary objective was to study the effects of PCK412 on other symptoms and findings in ASM patients.
Methods
All our patients with ASM and ascites were receiving midostaurin on a “compassionate use program” provided by Novartis. The 4 patients were ≥ 18 years and had a verified ASM according to the 2008 WHO classification. Liver biopsies, demonstrating mast cell aggregates, were performed in two of the patients. Portal hypertension was verified by abdominal ultrasound. All the patients had ascites and carried the D816V KIT mutation. The effect of PKC412 on ascites was evaluated by means of clinical examination, abdominal computed tomography and/or abdominal ultrasound.
Results
In all of the patients, PKC412 had a significant clinical effect on ascites. From having a need of pleuracentesis weekly or every second week, all of they became independent of pleuracentesis. Their quality of life enhanced dramatically. The patient with the most frequent need of pleuracentesis nearly died by peritonitis probably associated to all his interventions. The initial dosage of midostaurin was 100 mg twice daily. Two of the patients, further confirmed the efficacy of midostaurin by revealing relapse of ascites after having stopped with midostaurin because of sickness. In both cases the production of ascites ceased, and the need of pleuracentesis ended by reintroducing PKC412.
Conclusion
In all these patients with ASM, midostaurin had an excellent effect on ascites. Although this material is very small, all 4 out of 4 patients with ASM and ascites responded and became independent of paracentesis. The correlation between relapse of ascites when stopping midostaurin and disappearing when the medication was reintroduced, strongly supports a positive effect on ascites, which is a clinical finding that troubles many patients with ASM. It became nearly fatal for one patient in our material. In order to validate a significant effect of PCK412 on ascites in patients with ASM, studies on a larger population is needed.
Session topic: E-poster
Keyword(s): PKC412, Systemic mastocytosis
Type: Publication Only
Background
Systemic mastocytosis (SM) is a myeloproliferative neoplasia caused by uncontrolled proliferation and accumulation of pathological mast cells in one or more extracutaneous organs. The 2008 WHO classification divides SM into several subtypes including aggressive SM (ASM) with at least one “C finding.” Among the four different “C findings” is palpable hepatomegaly with impairment of liver function, ascites and/or portal hypertension. Midostaurin (PKC412) is a new and so far not approved drug shown to have a strong inhibitory activity on neoplastic human mast cells carrying the D816V KIT mutation and with an acceptable side-effect profile.
Aims
The primary objective was to assess the clinical effect of PCK412 on ascites in patients with ASM. The secondary objective was to study the effects of PCK412 on other symptoms and findings in ASM patients.
Methods
All our patients with ASM and ascites were receiving midostaurin on a “compassionate use program” provided by Novartis. The 4 patients were ≥ 18 years and had a verified ASM according to the 2008 WHO classification. Liver biopsies, demonstrating mast cell aggregates, were performed in two of the patients. Portal hypertension was verified by abdominal ultrasound. All the patients had ascites and carried the D816V KIT mutation. The effect of PKC412 on ascites was evaluated by means of clinical examination, abdominal computed tomography and/or abdominal ultrasound.
Results
In all of the patients, PKC412 had a significant clinical effect on ascites. From having a need of pleuracentesis weekly or every second week, all of they became independent of pleuracentesis. Their quality of life enhanced dramatically. The patient with the most frequent need of pleuracentesis nearly died by peritonitis probably associated to all his interventions. The initial dosage of midostaurin was 100 mg twice daily. Two of the patients, further confirmed the efficacy of midostaurin by revealing relapse of ascites after having stopped with midostaurin because of sickness. In both cases the production of ascites ceased, and the need of pleuracentesis ended by reintroducing PKC412.
Conclusion
In all these patients with ASM, midostaurin had an excellent effect on ascites. Although this material is very small, all 4 out of 4 patients with ASM and ascites responded and became independent of paracentesis. The correlation between relapse of ascites when stopping midostaurin and disappearing when the medication was reintroduced, strongly supports a positive effect on ascites, which is a clinical finding that troubles many patients with ASM. It became nearly fatal for one patient in our material. In order to validate a significant effect of PCK412 on ascites in patients with ASM, studies on a larger population is needed.
Session topic: E-poster
Keyword(s): PKC412, Systemic mastocytosis
Abstract: PB2024
Type: Publication Only
Background
Systemic mastocytosis (SM) is a myeloproliferative neoplasia caused by uncontrolled proliferation and accumulation of pathological mast cells in one or more extracutaneous organs. The 2008 WHO classification divides SM into several subtypes including aggressive SM (ASM) with at least one “C finding.” Among the four different “C findings” is palpable hepatomegaly with impairment of liver function, ascites and/or portal hypertension. Midostaurin (PKC412) is a new and so far not approved drug shown to have a strong inhibitory activity on neoplastic human mast cells carrying the D816V KIT mutation and with an acceptable side-effect profile.
Aims
The primary objective was to assess the clinical effect of PCK412 on ascites in patients with ASM. The secondary objective was to study the effects of PCK412 on other symptoms and findings in ASM patients.
Methods
All our patients with ASM and ascites were receiving midostaurin on a “compassionate use program” provided by Novartis. The 4 patients were ≥ 18 years and had a verified ASM according to the 2008 WHO classification. Liver biopsies, demonstrating mast cell aggregates, were performed in two of the patients. Portal hypertension was verified by abdominal ultrasound. All the patients had ascites and carried the D816V KIT mutation. The effect of PKC412 on ascites was evaluated by means of clinical examination, abdominal computed tomography and/or abdominal ultrasound.
Results
In all of the patients, PKC412 had a significant clinical effect on ascites. From having a need of pleuracentesis weekly or every second week, all of they became independent of pleuracentesis. Their quality of life enhanced dramatically. The patient with the most frequent need of pleuracentesis nearly died by peritonitis probably associated to all his interventions. The initial dosage of midostaurin was 100 mg twice daily. Two of the patients, further confirmed the efficacy of midostaurin by revealing relapse of ascites after having stopped with midostaurin because of sickness. In both cases the production of ascites ceased, and the need of pleuracentesis ended by reintroducing PKC412.
Conclusion
In all these patients with ASM, midostaurin had an excellent effect on ascites. Although this material is very small, all 4 out of 4 patients with ASM and ascites responded and became independent of paracentesis. The correlation between relapse of ascites when stopping midostaurin and disappearing when the medication was reintroduced, strongly supports a positive effect on ascites, which is a clinical finding that troubles many patients with ASM. It became nearly fatal for one patient in our material. In order to validate a significant effect of PCK412 on ascites in patients with ASM, studies on a larger population is needed.
Session topic: E-poster
Keyword(s): PKC412, Systemic mastocytosis
Type: Publication Only
Background
Systemic mastocytosis (SM) is a myeloproliferative neoplasia caused by uncontrolled proliferation and accumulation of pathological mast cells in one or more extracutaneous organs. The 2008 WHO classification divides SM into several subtypes including aggressive SM (ASM) with at least one “C finding.” Among the four different “C findings” is palpable hepatomegaly with impairment of liver function, ascites and/or portal hypertension. Midostaurin (PKC412) is a new and so far not approved drug shown to have a strong inhibitory activity on neoplastic human mast cells carrying the D816V KIT mutation and with an acceptable side-effect profile.
Aims
The primary objective was to assess the clinical effect of PCK412 on ascites in patients with ASM. The secondary objective was to study the effects of PCK412 on other symptoms and findings in ASM patients.
Methods
All our patients with ASM and ascites were receiving midostaurin on a “compassionate use program” provided by Novartis. The 4 patients were ≥ 18 years and had a verified ASM according to the 2008 WHO classification. Liver biopsies, demonstrating mast cell aggregates, were performed in two of the patients. Portal hypertension was verified by abdominal ultrasound. All the patients had ascites and carried the D816V KIT mutation. The effect of PKC412 on ascites was evaluated by means of clinical examination, abdominal computed tomography and/or abdominal ultrasound.
Results
In all of the patients, PKC412 had a significant clinical effect on ascites. From having a need of pleuracentesis weekly or every second week, all of they became independent of pleuracentesis. Their quality of life enhanced dramatically. The patient with the most frequent need of pleuracentesis nearly died by peritonitis probably associated to all his interventions. The initial dosage of midostaurin was 100 mg twice daily. Two of the patients, further confirmed the efficacy of midostaurin by revealing relapse of ascites after having stopped with midostaurin because of sickness. In both cases the production of ascites ceased, and the need of pleuracentesis ended by reintroducing PKC412.
Conclusion
In all these patients with ASM, midostaurin had an excellent effect on ascites. Although this material is very small, all 4 out of 4 patients with ASM and ascites responded and became independent of paracentesis. The correlation between relapse of ascites when stopping midostaurin and disappearing when the medication was reintroduced, strongly supports a positive effect on ascites, which is a clinical finding that troubles many patients with ASM. It became nearly fatal for one patient in our material. In order to validate a significant effect of PCK412 on ascites in patients with ASM, studies on a larger population is needed.
Session topic: E-poster
Keyword(s): PKC412, Systemic mastocytosis
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