Analysis Of The Efficacy And Safety Of Ruxolitinib In Patients With Myelofibrosis

ObjectiveTo evaluate the efficacy and safety of ruxolitinib in the treatment of patients with myelofibrosis.MethodsWe retrospectively analyzed the clinical data of 52 patients with myelofibrosis in our hospital from January 1,2018 to August 30,2019.21 males(40.4%)and 31 females(59.6%)were evaluated,and the median age of our samples was 58.5(26?73)years old.Among our sample patients,2 cases were Pre-PMF(3.9%),40 cases were Overt-PMF(76.9%),5 cases were Post-PV MF(9.6%),and 5 cases were Post-ET MF(9.6%).All patients with primary myelofibrosis(PMF)were confirmed according to the 2016 WHO diagnostic criteria.All Post-PV MF and Post-ET MF patients met the 2008 IWG-MRT diagnostic criteria.Patients were divided into 2 groups.The ruxolitinib therapy group contained 33 patients(63.5%)that were acceptable to ruxolitinib therapy and the best availabletherapy group was formed by 19 patients(36.5%)that did not accept to ruxolitinib therapy but are open to alternative approaches.During the treatment period,the clinical data including the improvement of systemic symptoms,spleen retraction,and variations in blood routine of the two groups of patients were observed and the clinical characteristics,curative effect,survival status and adverse reactions of two groups were compared statistically.According to the different therapeutic effects of rucotinib group,the relevant factors that may affect the efficacy of rucotinib were analyzed.Results1.Baseline characteristics:No statistical difference was found between the ruxolitinib therapy group(N=33 cases)and the best availabletherapy group(N=19 cases)in terms of their ages,genders,types of disease,DIPSS stratification,driving type of genetic mutations,bone marrow fibrosis grades,presence of hepatomegaly or not and peripheral blood cell count,etc.However,the median value of MPN-10 before treatment was greater in the ruxolitinib therapy group than that in the best available therapy group(27 points vs 16 points,U=143,P=0.001),and the median length of the subcostal spleen before treatment was larger than that in the best availabletherapy group(8cm vs 4.5cm,U=170.5,P=0.006).Therefore,the systemic symptoms and splenomegaly in the ruxolitinib group of patients were clearly more severe than those in the best availabletherapy group.2.Symptom relief:The overall score of MPN-10 in ruxolitinib therapy group was larger than that in the best availabletherapy group(P=0.039)after treatment.We found that the improvement ratios of both abdominal TSS and cytokine TSS in the ruxolitinib group was higher than those in the best availabletherapy group(X2=14.11,P<0.001 for abdominal TSS and X2=4.52,P=0.034 for cytokine TSS).The score of various symptoms in patients in ruxolitinib therapy group had declined in several different degrees compared with the same symptoms before therapy.Seven symptom scores including early satiety,abdominal discomfort,poor mobility,inattention,skin itching,fever,and weight loss had decreased by>50%.On the contrary,only four symptoms(fatigue,inattention,night sweats,and itching)of the best availabletherapy group were lower than before,and only the inattention score had dropped by 50%.According to the different curative effects in the patients of the ruxolitinib group,related factors that may affect the treatment of ruxolitinib were analyzed by comparing the following two groups:the dominant group(18 cases whose decline in MPN-10 were ?50%)and the control group(11 cases whose decline in MPN-10 were<50%).Additionally,we found that driving type of genetic mutations and the dose of ruxolitinib can affect the curative effect by univariate analysis.Furthermore,multifactor analysis the phenomenon that the dose of ruxolitinib can affect curative effect(OR=16.0,P=0.035)by multifactor analysis.In other words,the symptoms of the patients who took a higher dose(?10mg bid)were relieved more obviously,whose probability of symptom relief was 16 times higher than the patients who took a lower dose(<10 mg bid).3.Spleen size change:The median length of the subcostal spleen decreased by 2 cm after treatment(Z=-2.953,P=0.003),while the median length of the subcostal spleen of the best availabletherapy group increased by 0.5 cm after treatment(Z=-1.941,P=0.052).Furthermore,considering the proportion of patients with subcostal splenic length?35%reduction as the evaluation standard,we discovered that the effect of the ruxolitinib therapy group was more notable than the best availabletherapy group(P=0.016)in terms of splenic contraction.On the basis of different splenic contraction effects in ruxolitinib therapy group,spleen shrinkage of at least 35%was treated as the dominant group for splenic contraction(18 cases),and splenic contraction<35%was regarded as the control group(11 cases).It had been discovered that the reductions in splenomegaly in patients who took a dose of ruxolitinib?10 mg bid was more dramatic than patients who took a dose<10 mg bid(P=0.026)by univariate analysis.4.Survival status:The median follow-up time was 23.2 months.The 3-year overall survival(OS)of all patients was(81.5±7.2)%,and the 3-year event-free survival(EFS)of all patients was(77.5 ± 7.5)%.The 3-year OS rate of patients in the ruxolitinib therapy group and the best availabletherapy group were(78.2±8.9)%and(94.7±5.1)%(P=0.534).The 3-year EFS of patients in those two groups were(75.3±9.1)%and(89.5 ± 7.0)%(P=0.826).5.Adverse effects:During follow-up,31 out of 33(93.9%)patients had encountered adverse incidents.Hematological adverse responses found among them were anemia and thrombocytopenia.Non-hematological adverse effects discovered included hair loss,dizziness,bloating,bloating,shingles,edema,increase of blood sugar level,gums bleeding,nausea,pneumonia,insomnia.16 out of 19 patients(84.2%)in the best available therapy group had confronted negative incidents.Hematological adverse reactions observed contained anemia and thrombocytopenia.Non-hematological incidents recorded were fatigue,rash,tremor,muscle pain,insomnia,increase of transaminases level,gastrointestinal bleeding and blacknails.The patients in two groups exhibited enough tolerance to adverse reactions,and drug withdrawal was rare among them.ConclusionCompared with the best availabletherapy,although ruxolitinib therapy of MPN-MF has negative side effects such as controllable anemia and thrombocytopenia,itis able to reduce the enlargement of the spleen and improve systemic symptoms significantly and has a clinically acceptable safety profile and shows enough efficacy.Additionally,we found that the dose of ruxolitinib can affect the curative effect by univariate and multivariate analysis.Treating patients with higher dose of ruxolitinib(?10mg bid)is more effective in alleviating systemic symptoms and reducing spleen size.