ML-9 TREATMENT OUTCOMES OF TIRABRUTINIB FOR RELAPSED AND REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA IN A SINGLE INSTITUTE
Fumiharu OhkaJunya YamaguchiKazuya MotomuraKazuhito TakeuchiYuichi NagataSachi MaedaTomohide NishikawaYuji KibeHiroki ShimizuRyuta Saito
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Abstract Recent clinical studies improved prognosis of primary central nervous system lymphoma (PCNSL) using multiple treatment reagents combined with radiation therapy. However, for recurrent and refractory cases after treatment with regimen consisting of multiple reagents, potent effective treatment has not been established yet. Tirabrutinib, Bruton's tyrosine kinase inhibitor was introduced for treatment of recurrent and refractory PCNSL in Japan. However, case series study investigating the clinical outcome of PCNSL cases treated with tirabrutinib have not been reported yet excepting for phase I/II study of tirabrutinib. We treated nine recurrent and two refractory cases. In all of these cases, except for one case exhibiting severe skin rash in spite of cessation of administration of tirabrutinib, we obtained favorable overall response rate (CR or Cru=5 and PR=5) together with favorable progression free survival (median; 339 days). Five cases exhibited skin rash (CTCAE grade 3; n=2 and grade 2; n=3). Grade 3 or 2 skin rash were found on day 9 or 75 of tirabrutinib treatment, respectively. In one case, MYD88 mutations in ctDNA derived from blood plasma were turned to be negative after one week administration of tirabrutinib. Although adverse effects such as skin rash was frequently found, tirabrutinib is effective for recurrent or refractory PCNSL cases. Our data suggested that treatment response of tirabrutinib could be evaluated via evaluation of copy number analysis of MYD88 mutations in ctDNA of blood plasma.Keywords:
Refractory (planetary science)
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Abstract Background AIDS-related primary central nervous system lymphoma (AR-PCNSL) differs from immunocompetent-primary central nervous system lymphoma (IC-PCNSL) in certain features. The main objective of this study was to investigate the differences in clinicopathological features between AR-PCNSL and IC-PCNSL. Methods Thirty-seven AR-PCNSL patients and thirty IC-PCNSL patients were included. hematoxylin & eosin staining; immunohistochemical detection using CD20, Bcl-2, Bcl-6, p53, C-MYC, Ki67, and METTL3 antibodies; and Epstein–Barr encoding region (EBER) in situ hybridization were performed. Results All of the observed patients were classified as the DLBCL histological type. AR-PCNSL were younger (37.7 vs. 60.5 years) and had a higher likelihood of being male (86.5% vs. 63.3%) than non-AIDS patients were. Elevated LDH and low sugar content in cerebrospinal fluid (CSF) were more common among AR-PCNSL. The expression levels of METTL3, Bcl-2 and p53 expressions were significantly higher in AR-PCNSL patients than in PCNSL patients without AIDS. In contrast, AR-PCNSL patients exhibited lower levels of Bcl-6 expression. AR-PCNSL patients were more likely to be positive for EBER, accounting for 81.1% of these patients. Furthermore, we also found that the expression of METTL3 was lower in GCB-like DLBCL (n=7) than in ABC-like DLBCL (n=32) in AR-PCNSL ( p =0.041); however, in IC-PCNSL patients, the expression of METTL3 was not significantly different between GCB-like DLBCL and ABC-like DLBCL ( p =0.710). Conclusions Our study of Chinese AR-PCNSL and IC-PCNSL patients revealed new findings, indicating that METTL3, Bcl-2 and p53 were increased in AR-PCNSL patients compared to IC-PCNSL patients and that METTL3 was higher in ABC-like DLBCL patients than in GCB-like DLBCL in AR-PCNSL patients, suggesting a notable distinction in the pathological characteristics between PCNSL patients with or without AIDS.
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Objective To investigate the immunization status in children with measles rash. Methods Flow cytometry and ELISA was employed to investigate the changes of CD4+T,CD8+T,TL-2,TL-4,TL-6,TL-10 in early rash and after rash,and then compared with those in healthy children. Results CD4+T decreased,while CD8+T increased in early rash,and returned to normal after rash. TL-2 increased significantly in early rash(P0.01) ,and decreased after the rash,but still maintained high level(P0.05) . TL-4,TL-6 was low and increased immediately after the rash(P0.05) ,and TL-10 always maintained a high level in early rash and after rash(P0.05) . All the changes had no relation with gender and age,but in younger patients,the younger the patients,the greater CD4+T declined may be in the early rash. Conclusion There is the brief reversible immunosuppression in children with measles,TH1 dominates the early while TH2 plays an important role after rash. TL-10 plays an important regulatory role in children with measles immunization. Immune disorders may be more serious in younger patients
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Objective:To evaluate the relationship between erlotinib-induced skin rash and clinical outcome and explore the effective way to prevent skin rash.Methods:The data from 76 non-small cell lung cancer(NSCLC) patients who experienced erlotinib-induced skin rash from Dec 2005 to Sep 2008 were collected.All the patients were confirmed with NSCLC by pathological and cytological examination and received erlotinib 150 mg/d till they had progressive disease or intolerable adverse reaction.The severity of skin rash was recorded and graded according to National Cancer Institute-Common Toxicity Criteria(NCI-CTC).The therapeutic outcome of skin rash was observed.Results:The skin rash develops as early as 3 days after commencement of erlotinib therapy,with median onset at 8 days.Twenty-seven(35.5%) patients experienced grade 1 skin rash,44 patients(57.9%) had grade 2 and 5 cases(6.6%) had grade 3 skin rash.A statistically significant correlation was observed between skin rash and erlotinib therapy.The disease-controlling rate was 63.0% for grade 1 skin rash patients including 5 cases with partial remission and 12 cases with stable disease and 91.8% for grade 2/3 skin rash patients including 32 cases with partial remission and 13 cases with stable disease(P0.05).The median time to progression(TTP) and median overall survival(OS) were prolonged in patients experienced grade 2/3 skin rash compared with those in patients with grade 1 skin rash(TTP:5.1 months vs 9.7 months,P0.01;OS:10.0 months vs 14.6 months,P0.01).The skin rash was alleviated in 60 out of 76 patients(78.9%).Conclusion:Skin rash is a potent surrogate marker of favorable outcome in patients who received erlotinib treatment.It was tolerable to most patients.Appropriate therapy may be useful in decreasing the severity of skin rash.
Erlotinib Hydrochloride
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It is not uncommon for tuberculosis patients taking 3 or 4 kinds of antituberculous agents long-term to develop adverse effects such as rash or hepatic dysfunction.However,the frequency of rash is unclear because many cases are based on patients' self-reports.The purpose of this study was to clarify the incidence of rash caused by antituberculous agent as well as the relationship between rash and other factors such as other adverse effects,clinical test values and period of taking antituberculous agents until appearance of rash.We conducted a retrospective search of medical records for inpatients with tuberculosis at Tokyo Hospital from October 1,2004 to September 30,2006.There were 266 subjects and rash developed in 100 of them (38%).In most cases,the rash was only mild and easily controlled with antiallergics.However,rash was severe in 26 patients requiring the reduction or discontinuation of antituberculous agents.We noted no difference in rash occurrence rate among prescriptions for antituberculous agents and no relationship between rash and other factors was observed.These results indicate that the frequency of rash caused by antituberculous agents is high and that it is important to judge the severity of each case in order to perform appropriate treatment.
Discontinuation
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Objective To summarize the experience of identifying rash of the pediatric patients and improve the recognition rate of rash.Methods A total of 419 pediatric outpatients with rash were recruited.The characteristics of rash,accompanying symptoms,doctors diagnose and the status of identify triage wereanalyzed.Results The average accuracy of triage of rash Was 76.13%.11le accuracy of triage of rash in allersic skin diseases was 82.4% and in viral or bacterial infectious disases was 66.3%.The top five triage diseases were eczenma,acute urticaria,drug rash,chicken pox,hand,foot and mouth disease.Conclusions Since the pediatric patients'rash con be found in a vailety of diseases,triage nurses should carefully observe the performance and characteristics of the rash in order to prevent errors triage.
Key words:
Children; Rash; Triage
Triage
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The survival benefit from gemcitabine plus erlotinib was on average marginal for advanced pancreatic cancer (APC) patients. Skin rash developed shortly after starting treatment seemed to be associated with better efficacy and might be used to assist clinical decision-making, but the results across studies were inconsistent. Thus, we conducted a systematic review and meta-analysis.PubMed, Embase, Cochrane Central Register of Controlled Trials, three Chinese databases, and the abstracts of important conferences were searched for eligible studies. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and objective response. The random-effects model was used to pool results across studies if heterogeneity was substantial. Otherwise, the fixed-effect model was used.A total of 16 studies with 1,776 patients were included. Patients who developed skin rash during treatment had longer OS (8.9 vs 4.9 months, HR=0.57, 95% CI 0.50-0.64) and longer PFS (4.5 vs 2.4 months, HR=0.53, 95% CI 0.40-0.68) than those who did not. A dose- response relationship was also observed for both OS (HR=0.64 for grade-1 rash vs no rash and HR=0.46 for ≥grade-2 rash vs no rash) and PFS (HR=0.72 for grade-1 rash vs no rash and HR=0.43 for ≥grade-2 rash vs no rash).Skin rash was associated with better OS and PFS in APC patients treated with gemcitabine plus erlotinib. It might be used as a marker for efficacy to guide clinical decision-making toward a more precise and personalized treatment.
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Objective To evaluate the short-term effect and side effects of ICE regimen treating the patients with relapsed and refractory non-Hodgkin's lymphoma(NHL). Methods Twenty-five patients with relapsed and refractory NHL were treated with ICE regimen. Treatment was repeated every 3 weeks. Results The total effective rate was 76.0％ for 25 patients,The response rate(PR) was 60.0％. The main side effects were marrow suppression including of leucopenia and thrombocytopenia,no patients dead for toxic reactions of chemotherapy. Conclusion ICE regimen was a safe and effective salvage regimen for the patients with relapsed and refractory NHL.
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Lymphoma, non-Hodgkin; Chemotherapy
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Refractory (planetary science)
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Objective To observe the effect and toxicity of IPED regimen in treatment of refractory Non-Hodgkin's Lymphoma.Methods All 21 patients were treated over two cycles with IPED regimen. The IPED regimen was repeated every 28 days. The therapeutic effect was observed after treatment.Results 5 patients achieved complete remission(CR) ,10 partial remission(PR) 3 stable disease(SD),3 progression disease(PD). The overall response rate was 71.4%.The main side effects were myelosuppression and gastrointestinal reaction.Conclusion The IPED regimen is effective in the treatment of refractory Non-Hodgkin's lymphoma and it's toxicity is tolerable.
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Refractory (planetary science)
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