Partial Therapeutic Response Research Articles

Changes in therapeutic response, ocular manifestations of Graves' orbitopathy and quality of life during the first year after orbital radiotherapy.

The aim of our study was to assess the changes in the therapeutic response, ocular manifestations of GO and quality of life during the first year after OR. The study involved 26 consecutive patients with active moderate-to-severe GO indicated for OR, 18 females, mean age 57 ± 12.5. At baseline, all patients underwent comprehensive ocular examination and thyroid hormone and antibody testing. Then, OR was performed with a total dose of 20Gy, divided into 10 sessions of 2Gy each with concomitant oral intake of low-dose glucocorticoids. Therapeutic response and individual ocular manifestations were evaluated 1, 3, 6 and 12months after OR, and QoL-at 3, 6 and 12months by a disease-specific questionnaire. One month after OR, 61.6% of patients had a therapeutic response (full or partial). During the follow-up, the proportion of full-responders gradually increased up to 57.5% at 12months, while that of non-responders gradually decreased, reaching 11.5% at 12months. All individual ocular manifestations improved significantly 1-3months after OR. QoL related to visual functioning increased significantly at 6months, whereas QoL related to appearance improved significantly at 12months. The vast majority of our patients with active moderate-to-severe GO exhibited full or partial therapeutic response after OR. The initial effect on the therapeutic response and individual ocular parameters was evident as soon as 1-3months after the procedure. OR also has a beneficial effect on patients' QoL. NCT05775185/07.03.2023, retrospectively registered.

Novel Nonablative Radiofrequency Approach for the Treatment of Anal Incontinence: A Phase 1 Clinical Trial.

We aimed to describe the action, impact on quality of life, and side effects of perianal nonablative radiofrequency (RF) application in the treatment of anal incontinence (AI) in women. This was a pilot, randomized clinical trial conducted between January and October 2016. We enrolled women who consecutively attended the Attention Center of the Pelvic Floor (CAAP)with complaints of AI for more than six months. Nonablative RF was applied to the perianal region of the participantsusing Spectra G2 (Tonederm®, Rio Grande do Sul, Brazil). The reduced or complete elimination of the need for protective undergarments (diapers and absorbents) was considered a partial therapeutic response. Nine participants reported treatment satisfaction, while one reported dissatisfaction with the nonablative RF treatment of AI based on the Likert scale. No patientinterrupted treatment sessions because of adverse effects, although adverse effects occurred in six participants. However, the clinical and physical examination of the participants with burning sensations showed no hyperemia or mucosal lesions. This study showed a promising reduction of fecal loss, participant satisfaction with treatment, and improved lifestyle, behavior, and depression symptoms with minimal adverse effects.

Pathological complete response with nivolumab for recurrence of liver metastasis after gastrectomy of gastric cancer

BackgroundAdvanced gastric cancer has an unfavorable prognosis and poor curability. Immune checkpoint inhibitors, such as nivolumab, have recently emerged as a potential solution for this aggressive disease. However, there is a lack of established evidence on the clinical efficacy of these agents, particularly in the perioperative period for advanced gastric cancer patients who are unresectable, recurrent, or preoperative. Despite the limited data available, there have been rare cases of dramatic therapeutic effects. In this study, we present a successful case of nivolumab treatment along with surgery.Case presentationA 69-year-old female presented with pericardial discomfort and was diagnosed with advanced gastric cancer following upper gastrointestinal endoscopy. Laparoscopic distal gastrectomy with D2 lymph node dissection was performed, resulting in a final pathological diagnosis of Stage IIIA. The patient received postoperative adjuvant chemotherapy with oral S-1 therapy, but was found to have multiple liver metastases at 8 months postsurgery. Weekly paclitaxel and ramucirumab therapy was initiated, but the patient experienced adverse side effects, leading to the discontinuation of treatment. Nivolumab monotherapy was then administered for 18 cycles, resulting in a partial therapeutic response and PET–CT revealed a complete metabolic response. However, the patient developed a Grade 3 pemphigoid as an immune-related adverse event, leading to the cessation of nivolumab. The patient underwent laparoscopic partial hepatectomy. Postoperative pathology showed no residual tumor cells, indicating a complete response. At present, 25 months after surgery, the patient was alive without recurrence.ConclusionIn this report, we present a case of gastric cancer with liver metastatic recurrence, in which a complete pathological response was achieved with nivolumab treatment. Although determining whether surgical intervention is necessary following successful drug treatment can be challenging, PET–CT imaging may be useful in decision-making regarding surgical treatment.

Pervasive developmental disorders with a complex structure (epileptic seizures, catatonic, hallucinatory and manic symptoms, delirious episodes during life)

IntroductionThe significant clinical efficacy of lithium and lamotrigine in the described patients is consistent with the hypothesis that microdeletion of the SHANK3 gene may be associated with bipolar disorder.ObjectivesThe described phenotypes were characterized by intellectual disability, general speech underdevelopment, muscle hypotonia, and developmental dyspraxia. Their causal relationships with epileptic encephalopathy, schizophrenia, bipolar and hyperkinetic disorders have been analyzed.MethodsProspective studies of two patients with Phelan McDermid syndrome (22q13.3 microdeletions of the SHANK3 gene) within 10-12 years after genome scanning allowed describing the clinical polymorphism of developmental disorders. The sensitivity of psychotic symptoms to antipsychotic and mood stabilizer therapy has also been studied.ResultsManifest psychotic disorders in patients did not reveal an affinity for therapy with amisulpride, haloperidol, quetiapine, which demonstrated a partial therapeutic response to treatment with aripiprazole, which cast doubt on the possibility of qualifying psychotic symptoms in patients as the debut of schizophrenia. The partial therapeutic efficacy of combination therapy with aripiprazole and benzodiazepines (clonazepam/diazepam) qualified psychotic episodes in two patients with 22q13.3 syndrome as pediatric delirium. The significant clinical efficacy of lithium and lamotrigine in the described patients is consistent with the hypothesis that microdeletion of the SHANK3 gene may be associated with bipolar disorder.ConclusionsThe combination of lithium and lamotrigine may be recommended for the treatment of polymorbid mental disorders in patients with ASD and 22q13.3 syndrome. If lithium salts are poorly tolerated, a combination of lamotrigine and aripiprazole may be used to treat polymorbid mental disorders with confusion and catatonic symptoms in ASD.DisclosureNo significant relationships.

Neoadjuvant Chemotherapy for Breast Cancer: Evaluation by PET / CT

Abstract Background Breast cancer (BC)is the most commonly occurring cancer in women and the second most common cancer overall.An increase in the rate of breast preservation has come to be expected because of tumor reduction using neo-adjuvant chemotherapy (NAC) for locally advanced cancer and it is important to accurately determine the effects of NAC. Patients and Methods This study was conducted on 30 female patients with histopathologically confirmed breast cancer referred for a PET/CT scan aiming to demonstrate the role of 18F-FDG PET/CT in detecting the pathological response to NAC in BC patients. Results No statistically significant differences were found between the baseline number of lesions and that after three cycles of chemotherapy. Also, no statistically significant differences were found between the mean values of baseline and after three cycles of chemotherapy of both liver activity and size of right breast lesions. Meanwhile, the mean values of SUV of right and left breast lesions as well as the size of left breast lesions were significantly lower after three cycles of chemotherapy when compared to their baseline values. And no statistically significant differences were found between complete and partial therapeutic response in the right breast lesions as well as between complete and no therapeutic response in the left breast lesions as regards baseline SUV and SUV after 3 cycles of chemotherapy. Conclusion It can be concluded that FDG-PET/CT is useful for evaluation of neo-adjuvant chemotherapy for breast cancer. However, more studies are needed to validate the results of the current study.

Therapeutic Results in Patients with Hodgkin's Lymphoma Treated with Brentuximab Vedotin — Bulgarian Experience

Background: The introduction of Brentuximab Vedotin (BV) into clinical practice has improved the prognosis and survival of patients with Hodgkin's lymphoma, relapsed after stem cell transplantation or primary refractory disease. Aim: In patients with Hodgkin's lymphoma treated with Brentuximab Vedotin (BV), the overall response rate (ORR), type of response, event free survival (EFS) and the prognostic factors affecting them are analyzed. Patients and methods: Fourty-four (44) Hodgkin lymphoma patients treated with BV in 5 hematology clinics in Bulgaria were studied. The male / female ratio is 1.1 / 1, the mean age is 39.98 +/- 12.48. The most common histological variant is nodular sclerosis 31 (70.5%). In the II clinical stage there were 13 patients (29.5%), III - 16 (36.4%), IV -15 (34.1%). B-symptoms had 36 patients (81.8%), extranodal involvement - 17 (15.9%) and large mediastinal tumor mass - 14 (31.8%). All patients before treatment with BV received 4 (2-12) treatment lines, 50.0% -3 lines, 27.3% - 4 lines, and 9.1% > / = 5 lines. Stem cell transplantation was performed in 33 patients (75.0%), two of which were two autologous STCs, and in one auto/ allo SCT. Results: ORR is 60.0% (N=24) - complete response was achieved in 10 (25.0%) and partial in 14 (35.0%) patients. Stable disease was registered in 7 (17.5%) and progression in 9 (20,5%). Patients achieving at least a partial therapeutic response prior to commencement of BV treatment significantly improved their response at the end of treatment: 15 (62.5%) versus 9 (37.5%) with previous progression and stable disease (P < 0.05, R = + 0.496). PFS for the entire group is 10 months. The median survival (MS) was not reached by the end of the study. Age, sex, histological variant, clinical stage, number, type and outcome of previous treatment lines did not affect the duration of PFS. The only significant prognostic factor that determines a remarkably longer remission is the qualitative therapeutic response: in the CR + PR group, the median PFS is not reached by the time of the analysis, while in patients with stable disease and progression EFS is 7 months (P <0.001). Conclusion: BV is an effective drug with manageable toxicity. The results of the treatment of our patients confirm the accumulated international experience. An additional therapeutic response and prolonged progression-free survival give a chance to these previously doomed patients with Hodgkin's lymphoma. DisclosuresGoranova Marinova:Amgen: Consultancy, Honoraria; Roche: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Baxalta/Shire: Honoraria, Research Funding.

Role of diffusion weighted MRI in patients with hepatocellular carcinoma: prediction and assessment of response to trans-arterial chemoembolization

Aim: The study goal is to detect if apparent diffusion coefficient (ADC), a quantitative parameter of diffusion-weighted imaging (DWI), can recognize HCC post TACE residuals. Results were obtained by using MRI_DWI & ADC and were compared with those of Tri phasic-computed tomography (CT). patient and Methods MRI-DWI was performed to 20 patients with 24 HCC focal lesions before and 1month after TACE to calculate the ADC value of HCC. Patients were also evaluated with Tri phasic-CT after TACE. CT was performed within 1 month after TACE. Results: All patients under the study shows pretreatment restricted Diffusion weighted images with low ADC value. Mean ADC value before treatment was 1.14× 10¯³ ±0.29× 10¯³ and ranged from 0.819× 10¯³ to 2.48× 10¯³. 9 cases (45%) cases show post-TACE good therapeutic response with facilitated diffusion & mean ADC value 1.32×10¯³ with significant increase compared to pre-treatment values. 11 cases (55%) shows post-TACE partial or no therapeutic response with restricted diffusion & mean ADC value 1.18×10¯³. However, there was no statistical significant difference between ADC value of resolved and that of residual cases (P-value=0.067), DWI could predict the response of treatment as CT by 100%. All cases of Good therapeutic response had a facilitated diffusion, all cases of partial therapeutic response had a restricted diffusion but less than pretreatment and all cases with no therapeutic response had a restricted diffusion but more than pretreatment. Conclusion DWI could evaluate HCC necrosis of tumor after chemoembolization, and the ADC importance might be its ability to detect viable necrotic tumor tissues. Furthermore, DWI-MRI determines improved liver lesion location. So, DWI can be used as an option for HCC patients short term follow up after chemoembolization and may direct patient control for decreasing radiation CT examination exposure and the danger of contrast material-induced nephropathy.

Neurofibromin Deficiency and Extracellular Matrix Cooperate to Increase Transforming Potential through FAK-Dependent Signaling.

Plexiform neurofibromas (Pnfs) are benign peripheral nerve sheath tumors that are major features of the human genetic syndrome, neurofibromatosis type 1 (NF1). Pnfs are derived from Schwann cells (SCs) undergoing loss of heterozygosity (LOH) at the NF1 locus in an NF1+/- milieu and thus are variably lacking in the key Ras-controlling protein, neurofibromin (Nfn). As these SCs are embedded in a dense desmoplastic milieu of stromal cells and abnormal extracellular matrix (ECM), cell-cell cooperativity (CCC) and the molecular microenvironment play essential roles in Pnf progression towards a malignant peripheral nerve sheath tumor (MPNST). The complexity of Pnf biology makes treatment challenging. The only approved drug, the MEK inhibitor Selumetinib, displays a variable and partial therapeutic response. Here, we explored ECM contributions to the growth of cells lacking Nfn. In a 3D in vitro culture, NF1 loss sensitizes cells to signals from a Pnf-mimicking ECM through focal adhesion kinase (FAK) hyperactivation. This hyperactivation correlated with phosphorylation of the downstream effectors, Src, ERK, and AKT, and with colony formation. Expression of the GAP-related domain of Nfn only partially decreased activation of this signaling pathway and only slowed down 3D colony growth of cells lacking Nfn. However, combinatorial treatment with both the FAK inhibitor Defactinib (VS-6063) and Selumetinib (AZD6244) fully suppressed colony growth. These observations pave the way for a new combined therapeutic strategy simultaneously interfering with both intracellular signals and the interplay between the various tumor cells and the ECM.

Naturalistic follow-up in bipolar patients after successful electroconvulsive therapy

BackgroundElectroconvulsive therapy (ECT) is an effective treatment for acute depression, mania and mixed states. We evaluated the long-term outcome of patients with bipolar depression or mixed state, responsive to ECT. Methodsthis observational follow-up study was conducted in 70 patients with Bipolar Disorder: 36 patients met DSM-IV-TR criteria for a major depressive episode (MDE) and 34 for a mixed episode (MXE). During the follow-up after ECT, the relapse rates and the duration of response and remission periods were recorded. Resultsthe mean duration of the follow-up was 57 weeks. 93% of the patients maintained at least a partial therapeutic response for more than 90% of the follow-up period. 73% of patients fulfilled the criteria for a full remission, 33% showed a depressive relapse and 10% a mixed relapse. No manic relapses occurred but almost 1/3 of the sample presented hypomanic episodes. MDE patients presented higher rates of remission compared to MXE ones. Patients with anxiety disorders reported earlier relapses than those without this comorbidity. Relapsed-patients showed higher functional impairment at baseline evaluation, compared to non-relapsed ones. Limitationsnonrandom allocation, limited sample size, possible influence of psychopharmacological treatment. ConclusionsGiven several methodological limitations, this study cannot draw definite conclusions but could suggest that in treatment-resistant bipolar patients with severe depression or mixed state, ECT may represent a useful treatment option. Patients with mixed features, comorbid anxiety disorders and higher functional impairment present less favorable outcome. Future research on long-term efficacy of ECT and on clinical predictors of relapse is needed.

1073P - Prognostic factors influencing outcome after therapy with brentuximab vedotin in patients with relapsed or refractory Hodgkin’s lymphoma

BackgroundBrentuximab Vedotin (BV) treatment has improved the prognosis and survival of patients with Hodgkin’s lymphoma, relapsed after stem cell transplantation or having refractory disease. Aim: To analyze the prognostic factors, influencing the outcome after therapy with BV in relapsed or refractory patients with Hodgkin’s lymphoma. MethodsWe studied sixty-four (64) Hodgkin’s lymphoma patients treated with BV in six Hematology clinics in Bulgaria. The male / female ratio was 1 / 1, the mean age at the time of BV therapy was 40.66+/-13.1 years. The most common histological variant was nodular sclerosis 46 (71.9%). In the II clinical stage there were 26 patients (40.6%), in IIIrd - 17 (26.6%), in IVth - 21 (32.8%). All patients before treatment with BV received median of 4 (2-12) treatment lines, 30 ( 46.9%) received =/>3 lines. Autologous stem cell transplantation (autoSCT) was performed in 45 (70.3%) patients, two of which were second autologous SCTs, and in one auto/ allo SCT. ResultsORR was 60.9% (N=39). Complete response was achieved in 39.1% (25) and partial response in 21.9% (14) patients. Stable disease was registered in 10.9% (7) and progression in 28.1% (18). PFS for the entire group was 14 months. The median survival (MS) was not reached by the end of the analysis. At least partial therapeutic response was significantly higher in patients with chemosensitive disease before autoSCT ( P=0.006, R=+0.340), these who have undergone autoSCT ( P=0.021, R= -0.335) and when BV was started as consolidation therapy by month 3 after autoSCT ( P=0.02, R=+0.287). The only significant prognostic factor that determines a remarkably longer EFS is the type of therapeutic response itself: in the CR + PR group, the median PFS is not reached by the time of the analysis, while in patients with stable disease and progression EFS is 7 months (P<0.001). ConclusionsBV is most effective in patients with chemosensitive disease, and when used as consolidation therapy early, by 3-rd month after autoSCT. Our results confirm the international experience. BV improves the therapeutic response and prolongs progression-free survival in the patients with Hodgkin’s lymphoma who previously had really bad prognosis. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Pregabalin augmentation in the treatment of borderline personality disorder with partial therapeutic response – case report

IntroductionEmotional dysregulation is one of the core problems of borderline personality disorder (BPD). Forty-one year-old married female diagnosed with BPD at the age of 21, was admitted to the partial hospitalization unit due to a depressive symptoms and emotional dysregulation and poor overall functioning.ObjectivePatient was previously treated with numerous psychotropic agents: antipsychotics (AP) – fluphenazine, levomepromazine, risperidone, clozapine; antidepressants (AD) sertraline, mirtazapine, maprotiline, amitriptyline; psychostabilizers – carbamazepine/valproate) without achieving the full therapeutic response. After switching to combination of clomipramine and aripiprazole, we have reached partial clinical response.AimThe aim of this treatment was to improve clinical response and achieve emotional stability by augmentation with neuromodulator pregabalin.MethodAugmentation strategy was realized by gradual titration and tapering of pregabalin (300 mg/d) over a two-week period. We started with pregabalin dose of 75 mg/d, followed by gradual increase to the dose of 300 mg/d. The Beck Depression Scale (BDS) and the Emotional Dysregulation Scale-short form (EDS) have been used for efficacy monitoring.ResultsMental state before augmentation therapy: the BDS (score 30-moderate depression) and the EDS-short form (score 127). Parameter status after augmentation with pregabalin: BDS score 16-mild mood disturbance, EDS score 87.ConclusionsAugmentation strategy with pregabalin have improved emotional control, maintained affective and behavioral stability, with significant reduction of feelings of emptiness, as well as the achievement and maintaining of emotional attachment.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Correlation between the suppressor of cytokine signaling-1 and 3 and hepatitis B virus: possible roles in the resistance to interferon treatment

BackgroundThe suppressor of cytokine signaling family (SOCS) is an important negative regulator in the JAK-STAT signaling pathway. This study was designed to explore the correlation between SOCS-1, 2 and 3, Hepatitis B Virus (HBV) and interferon (IFN), and the relationship between SOCS and IFN therapeutic efficacy.MethodsFour types of mouse models were established. Mice were administered with HBV replicative plasmid pHBV4.1 and IFN inducer Poly IC (Group A), pHBV4.1 (Group B), Poly IC (Group C) and saline (Group D), respectively. Liver tissues were harvested from the mice and SOCS expression was determined. Meanwhile, patients with chronic hepatitis B (CHB) were treated with pegylated interferon α-2b for 24-48 weeks. Liver biopsy was collected and the baseline SOCS expression was determined. Serum assay was performed for efficacy evaluation and correlation analysis.ResultsIn animal studies, the expression level of SOCS-1 and 3 was found in the descending order of B, A, C and D. The difference between Group B and D suggested that HBV could induce SOCS. The difference between Group A and C suggested that HBV could still induce SOCS with up-regulated endogenous IFN. The difference between Group C and D suggested that ploy IC could induce SOCS, while the difference between Group B and A suggested that Poly IC might have a stronger inhibition effect for SOCS. There was no difference in SOCS-2 expression. In clinical studies, eight of twenty-four enrolled patients achieved either complete or partial therapeutic response. The expression of both SOCS-1 and 3 was higher in CHB patients than in normal controls. The baseline HBV-DNA level was positively correlated with SOCS-1 and 3. The age, viral genotype, HBVDNA, SOCS-1 and SOCS-3 were found to be related to IFN efficacy.ConclusionHBV could induce both SOCS-1 and 3 expression regardless of endogenous IFN level. Elevated IFN could directly up-regulate SOCS-1 and 3 expression, but it could also indirectly down-regulate SOCS-1 and 3 expression by inhibiting HBV replication. HBV might play a more important role in the SOCS up-regulation than IFN, a possible reason why patients with high HBV viral load encounter poor efficacy of IFN treatment.

Comparison of therapeutic effect between thalidomide with and without alkylating agents on patients with new-onset multiple myeloma

Objective To compare the efficacy and toxicity of thalidomide-COMP (T-COMP) and thalidomide-VAD (T-VAD) regimens in previously untreated multiple myeloma (MM) patients.Methods Forty-nine newly diagnosed MM patients were randomly allocated to either A group (thalidomide-MP/-COMP,19 cases) or B group (thalidomide-VAD,30 cases).All patients received thalidomide 200 mg p.o.daily.Patients in group A received additionally vincristine 0.4 mg i.v.on day 1-4,cyclophosphamide 200 mg i.v.on day 1-4,melphalan 4 mg tid p.o.on days 1-5,prednisone 60 mg p.o.daily on days 1-5.Patients in group B received additionally vincristine 0.4 mg i.v.on day 1-4 and epirubicin 10 mg/m2 i.v.,on day 1-4 and dexamethasone 40 mg p.o.daily on days 1-4,9-12 and 17-20 for the first cycle and on days 1-4 for the next three cycles.Treatment was administered every 28 days.The therapeutic response was evaluated based on the International Myeloma Working Group Criteria (IMWG 2006) after the treatment.The toxicity was graded according to NCI common terminology criteria for adverse events v 3.0.Results On an intention-to-treat basis,at least partial therapeutic response was observed.The rates were 73.7 ％ and 53.3 ％ in group A and B respectively (x2 =2.029,P =0.154).Overall survival (OS) rate at 2 years were 52.6 ％ (10/19) in group A and 53.3 ％ (16/30) in group B,respectively (x2 =2.468,P =0.116).Considering overall toxicity,constipation,peripheral neuropathy,dizziness/somnolence,skin rash and edema were significantly higher in group B compared with group A,but the incidence of toxicities grade 3-4 was low and similar in both arms.Conclusion The overall response rate of T-MP/T-COMP regimen is similar with that of T-VAD regimen,suggesting this regimen cannot be chosen as the first treatment for patients with non-implantation therapy. Key words: Multiple myeloma ; Thalidomide ; Alkylating agent

Partial therapeutic response to Rituximab for the treatment of chronic alloantibody mediated rejection of kidney allografts

Background and ObjectivesChronic rejection leads to kidney allograft failure and develops in many kidney transplant recipients. One cause of chronic rejection, chronic antibody mediated rejection (CAMR), is attributed to alloantibodies. Maintenance immunosuppression including prednisone, mycophenolate mofetil (MMF) and calcineurin inhibitors may limit alloantibody production in some patients, but many maintain or develop alloantibody production, leading to CAMR. Therefore, no efficacious therapy to treat CAMR is presently available to prevent the progression of CAMR to kidney allograft failure. Design, Setting, Participants, and MeasurementsWe performed a retrospective review of 31 subjects with CAMR, of which 14 received Rituximab and 17 subjects did not. Response to Rituximab was defined as decline or stabilization of serum creatinine for at least one year. Data reviewed included demographic, clinical, allograft, post-transplant, and pathological variables. Pathological variables in the diagnostic allograft biopsy were scored according to Banff criteria. ResultsThe median survival time (MST) for allografts in the control group was 439days, and for the Rituximab treated group was 685days. The Rituximab group was dichotomous with 8 subjects showing a medial survival time of 1180days, and 6 subjects having a median survival time of 431days. The MST for the responders was statistically significant from the non-responders and controls. No pathological parameter distinguished any subset of subjects. ConclusionsThese data show that Rituximab followed by standard maintenance immunosuppression shows a therapeutic effect in the treatment of CAMR, which is confined to a subset of treated subjects, not identifiable a priori.

Rituximab Therapy in Refractory Neuropsychiatric Lupus: Current Clinical Evidence

To review and summarize published information on the effectiveness and safety of rituximab (RTX) in adult patients with refractory neuropsychiatric systemic lupus erythematosus (NPSLE). We describe a patient with persistently active NPSLE, despite conventional therapy, who responded dramatically to RTX. Current evidence on the therapeutic use of RTX in this complex situation is also analyzed through a systematic review of the English-language literature, based on a PubMed search. Available data on the use of RTX in refractory NPSLE come from a large number of case reports and some open-label studies. Including our case, 35 patients have been well documented. A complete or partial therapeutic response was achieved in 85% of patients after 1 cycle of treatment. A positive correlation between serological markers of disease activity and clinical outcome has also been demonstrated in some of these patients. Clinical improvement was accompanied by a significant reduction in the daily dose of oral corticosteroids. Relapse after RTX treatment was noted in 45% of cases (median 9.5 months; range, 4-33 months). Infections were observed in 29% of patients. Evidence for the effectiveness of RTX as induction therapy in NPSLE is based solely on several case reports and noncontrolled trials. Although it is not yet possible to make definite recommendations, the global analysis of these cases supports the off-label use of RTX in cases of severe refractory NPSLE.

Clinical screening assay for EGFR exon 19 mutations using PNA-clamp smart amplification process version 2 in lung adenocarcinoma

The presence of EGFR mutations is correlated with a positive therapeutic response to tyrosine kinase inhibitors; therefore, the accurate detection of EGFR mutations is crucial when deciding appropriate therapeutic strategies. Recently, the rapid and sensitive assay smart amplification process version 2 (SmartAmp2) was developed. However, this method can only detect one type of mutation in EGFR exon 19; therefore, we applied the PNA technology to the SmartAmp2 assay to develop PNA-clamp SmartAmp2 for the detection of many types of deletions in EGFR exon 19, in a single reaction. This new assay was evaluated using 172 clinical samples. Thirty-nine (22.7%) samples were found to have deletions by PNA-clamp SmartAmp2; whereas 30 (17.4%) and 38 (22.1%) tumors were found to have deletions by direct sequencing and PNA-enriched sequencing, respectively. Three cases, in which we detected mutations with PNA-clamp SmartAmp2, but not with direct sequencing, were treated with gefitinib, and all cases showed a partial therapeutic response. Using clinical samples, we demonstrated that PNA-clamp SmartAmp2 can detect various types of mutations in EGFR exon 19 in a relatively short time and with high sensitivity. This method detected small amounts of mutant DNA and identified patients for whom clinical information was previously unavailable from other tests. This test may contribute to the administration of efficient therapeutic strategies.

P03-118 - Treatment of patient with depressive disorder - therapy with duloxetine

AimTo present a case of a patient with depression who recovered during treatment with duloxetine.Case reportPatient, 68 years old, was treated for the past 20 years because of depression. The patients described that worsening in mental condition usually started with depressed mood, followed by prostration and loss of motivation. So far, she was treated with different antidepressants, with partial therapeutic response. On the control examination, depressed mood, anxiety, fatigue, prostration, insomnia and loss in motivation were noticed. The patient reported spending most of the time in bed, with lack of interest for daily activities. Also, she reported indistinct pain in the back. She was afraid that there was no adequate cure for her condition. Treatment with duloxetine was initiated, in daily dosage of 60 mg. The patient was advised to take the medication along with the richest meal, so she started taking duloxetine after lunch. Also, the patient started taking zolpidem 10 mg in the evening because of insomnia. On the next control examination, ten days later, improvement in her mental condition was observed, and she said that she felt better. Her mood improved, as well as motivation, and anxiety was reduced. The patient continued taking duloxetine in daily dosage of 60 mg and on the following control examinations her condition remained stable, pain in the back was reduced, and she reported that she was able to function socially and was satisfied with her condition.

Rituximab Therapy in Lupus Nephritis: Current Clinical Evidence

The complexity of the therapeutic approach in lupus nephritis (LN) is increased by the large number of patients who do not respond to first-line therapies and by relapses after initial clinical remission. The emergence of biological agents has increased the therapeutic armamentarium available in these complex situations, but their use is limited by the lack of licensing. We analysed current evidence on the therapeutic use of rituximab in adult LN patients by systematic analysis of seven observational studies published since 2005 (four in 2009), which included 106 LN patients treated with rituximab. A complete or partial therapeutic response was achieved in 73 (69%) patients. The response according to the type of LN was stated in 79 cases: 8 (80%) patients with type III LN had a favourable, 26 (67%) of those with type IV, 4 (57%) of those with type V and 18 (78%) of those with mixed membranous-proliferative LN. The main factors associated with no response were younger age, black race and lack of CD19(+) cell depletion. The lowest rates of complete response were observed in patients with type V LN, especially those with associated proliferative lesions. Although it is not yet possible to make definite recommendations, the global analysis of these cases supports the off-label use of rituximab in severe, refractory LN cases.

Abstract 3568: Treatment of Organ-Specific Chloroleukemia by Cytotech Labs API 31510 and Chemotherapy

Abstract The development of chloroleukemia in the rat after transplantation leads to 100% mortality. Recently, two novel clones have been developed. Following intraperitoneal injection, one clone preferentially migrates and forms tumors in the lungs (CHL-L), while another clone forms tumors in the liver (CHL-Li). In vitro, proliferation of both clones were inhibited in a dose-dependent manner by a novel IV solution of API 31510. Accordingly, in the present study we examined the hypothesis that Cytotech Labs API 31510 alone or in combination with cyclophosphamide (CTX) could be effective in the treatment of both clones in vivo. In the first experiments, 24 rats were randomized into 4 groups of six rats each and injected intraperitoneally with CHL-L. In the control group, 100% developed CHL-L. In the group receiving CTX, 5 out of 6 developed CHL-L, while 1 animal remained disease-free. In the group receiving API 31510, 3 out of 6 rats remained disease-free and 3 out of 6 had a partial therapeutic response. In the group which received API 31510 and CTX, 100% of the animals remained disease-free. In a separate experiment, the same protocol was followed using CHL-Li. As observed with the other clone, animals injected with all control animals developed CHL-Li tumors. Similarly, in the group receiving CTX alone, 5 out of 6 developed CHL-Li and 1 remained disease-free. In the group receiving API 31510, 3 out of 6 animals remained disease-free and 3 out of 6 had a partial response. When combining 31510 and CTX, 5 out of 6 animals remained disease-free and 1 had a partial response. No side effects were observed in the animals receiving API 31510 as evidenced by weight gain and behavior. Taken together, these results indicate that API 31510 as a single agent was effective against both chloroma clones used and as an adjuvant to chemotherapy, API 31510 exhibited treatment efficacy in over 90% of animals treated. These data provide a strong foundation for further development of Cytotech Labs API 31510 intravenous formulation as a viable agent for cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3568.

Effect of Anti-CD25 Antibody Daclizumab in the Inhibition of Inflammation and Stabilization of Disease Progression in Multiple Sclerosis

Several questions arise concerning the use of the anti-CD25 antibody daclizumab to treat multiple sclerosis (MS). To answer the following 3 questions related to the efficacy of daclizumab therapy in patients with MS: Is the therapeutic effect of daclizumab dependent on combination with interferon beta? Is a higher dosage of daclizumab more efficacious in patients with persistent disease activity? Can biomarkers predict full vs partial therapeutic response to daclizumab? An open-label baseline vs treatment phase II clinical trial of daclizumab in patients having MS with inadequate response to interferon beta. Three months of interferon beta treatment at baseline were followed by 5.5 months of interferon beta-daclizumab combination therapy. If patients experienced more than 75% reduction of contrast-enhancing lesions (CELs) on brain magnetic resonance imaging at month 5.5 compared with baseline, daclizumab was continued as monotherapy for 10 months. Otherwise, the dosage of daclizumab was doubled. Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland. Fifteen patients with MS receiving standard preparations of interferon beta who experienced more than 1 MS exacerbation or whose clinical disability increased in the preceding 12 months and who had at least 2 CELs on baseline brain magnetic resonance images. Daclizumab (1 mg/kg) as an intravenous infusion every 4 weeks in combination with interferon beta (months 0-5.5) and as monotherapy (months 6.5-15.5). The primary outcome was the reduction of CELs among interferon beta monotherapy, interferon beta-daclizumab combination therapy, and daclizumab monotherapy. The secondary outcomes included immunologic biomarkers and changes in clinical disability. Overall, 5 of 15 patients (33%) experienced adverse effects of therapy. Two patients developed systemic adverse effects, and daclizumab therapy was discontinued. Although daclizumab monotherapy was efficacious in 9 of 13 patients with MS, interferon beta-daclizumab combination therapy was necessary to stabilize disease activity in the other 4 patients. Daclizumab therapy led to 72% inhibition of new CELs and significant improvement in clinical disability. Pilot biomarkers (increase in CD56bright natural killer cells and decrease in CD8+ T cells) were identified that can differentiate between full and partial daclizumab responders. Daclizumab monotherapy is effective in most patients who experienced persistent MS disease activity with interferon beta therapy. Interferon beta-daclizumab combination therapy or higher dosages of daclizumab may be necessary to achieve optimal therapeutic response in all patients. Biomarkers may identify patients with suboptimal response to daclizumab monotherapy. Administration among a large patient sample during a longer period is needed to fully define the safety and long-term efficacy of daclizumab as treatment for high-inflammatory MS. clinicaltrials.gov Identifier: NCT00001934.