scholarly journals Investigational Immunotherapeutics for B-Cell Malignancies

2010 ◽  
Vol 28 (5) ◽  
pp. 884-892 ◽  
Author(s):  
Alfonso Quintás-Cardama ◽  
William Wierda ◽  
Susan O'Brien

The use of rituximab-based chemoimmunotherapy regimens has remarkably improved the response rates, long-term outcomes, and quality of life of patients with B-cell malignancies. However, a substantial number of patients exhibit either primary or acquired resistance to rituximab, which suggests that novel immunotherapeutics with distinct mechanisms of action are necessary. A series of monoclonal antibodies with specificity against different surface antigens expressed on malignant B cells (eg, CD22, CD23, CD40, CD70) and novel immunotherapeutics (eg, bispecific monoclonal antibodies, small-modular immunopharmaceuticals, T-cell engagers) are currently in clinical or final preclinical stages of development. Although these agents offer reason for optimism, considerable challenges lie ahead in establishing their real clinical value, as well as in integrating them into current therapeutic algorithms for patients with B-cell malignancies. This review describes some of the most promising investigational immunotherapeutics for the treatment of B-cell malignancies.

2015 ◽  
Vol 21 (2) ◽  
pp. 281-287 ◽  
Author(s):  
Ryan D. Cassaday ◽  
Barry E. Storer ◽  
Mohamed L. Sorror ◽  
Brenda M. Sandmaier ◽  
Katherine A. Guthrie ◽  
...  

Author(s):  
Teresa Zetzl ◽  
Andre Pittig ◽  
Agnes Renner ◽  
Birgitt van Oorschot ◽  
Elisabeth Jentschke

Abstract Objective To examine the efficacy of reminder e-mails to continue yoga therapy on practice frequency and fatigue in cancer patients and long-term effects of yoga on fatigue, depression, and quality of life. Methodology One hundred two cancer patients who completed an 8-week yoga therapy were randomly allocated to two groups: reminder (N = 51) vs. no-reminder group (N = 51). After completing yoga therapy, the reminder group received weekly e-mails for 24 weeks, which reminded them of practicing yoga, whereas the no-reminder group did not. Primary outcomes were fatigue and practice frequency, and long-term outcomes were fatigue, depression, and quality of life. Data were assessed using questionnaires after yoga therapy (T1) and 6 months after completing yoga therapy (T2). Result A significantly stronger reduction of general (p = 0.038, d = 0.42) and emotional fatigue (p = 0.004, d = 0.59) and a higher increase of practice frequency (p = 0.015, d = 0.52) between T1 and T2 were found for the reminder group compared to the no-reminder group. In the mediation model, practice frequency as a mediator partially explained the changes in emotional fatigue (indirect effect B =  − 0.10). Long-term effects of yoga therapy regarding fatigue, depression, and quality of life were found (F > 7.46, p < 0.001, d > 0.54). Conclusion Weekly reminder e-mails after yoga therapy can positively affect general and emotional fatigue and help cancer patients with fatigue establish a regular yoga practice at home. However, higher practice frequency did not lead to higher physical or cognitive fatigue improvement, suggesting other factors that mediate efficacy on physical or cognitive fatigue, such as mindfulness or side effects of therapy.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2942
Author(s):  
Tamara Mc Erlain ◽  
Aileen Burke ◽  
Cristina M. Branco

To prevent cancer cells replacing and outnumbering their functional somatic counterparts, the most effective solution is their removal. Classical treatments rely on surgical excision, chemical or physical damage to the cancer cells by conventional interventions such as chemo- and radiotherapy, to eliminate or reduce tumour burden. Cancer treatment has in the last two decades seen the advent of increasingly sophisticated therapeutic regimens aimed at selectively targeting cancer cells whilst sparing the remaining cells from severe loss of viability or function. These include small molecule inhibitors, monoclonal antibodies and a myriad of compounds that affect metabolism, angiogenesis or immunotherapy. Our increased knowledge of specific cancer types, stratified diagnoses, genetic and molecular profiling, and more refined treatment practices have improved overall survival in a significant number of patients. Increased survival, however, has also increased the incidence of associated challenges of chemotherapy-induced morbidity, with some pathologies developing several years after termination of treatment. Long-term care of cancer survivors must therefore become a focus in itself, such that along with prolonging life expectancy, treatments allow for improved quality of life.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Danling Gu ◽  
Hanning Tang ◽  
Jiazhu Wu ◽  
Jianyong Li ◽  
Yi Miao

AbstractB cell receptor (BCR) signaling is involved in the pathogenesis of B cell malignancies. Activation of BCR signaling promotes the survival and proliferation of malignant B cells. Bruton tyrosine kinase (BTK) is a key component of BCR signaling, establishing BTK as an important therapeutic target. Several covalent BTK inhibitors have shown remarkable efficacy in the treatment of B cell malignancies, especially chronic lymphocytic leukemia. However, acquired resistance to covalent BTK inhibitors is not rare in B cell malignancies. A major mechanism for the acquired resistance is the emergence of BTK cysteine 481 (C481)  mutations, which disrupt the binding of covalent BTK inhibitors. Additionally, adverse events due to the off-target inhibition of kinases other than BTK by covalent inhibitors are common. Alternative therapeutic options are needed if acquired resistance or intolerable adverse events occur. Non-covalent BTK inhibitors do not bind to C481, therefore providing a potentially effective option to patients with B cell malignancies, including those who have developed resistance to covalent BTK inhibitors. Preliminary clinical studies have suggested that non-covalent BTK inhibitors are effective and well-tolerated. In this review, we discussed the rationale for the use of non-covalent BTK inhibitors and the preclinical and clinical studies of non-covalent BTK inhibitors in B cell malignancies.


2017 ◽  
Vol 28 (05) ◽  
pp. 445-454 ◽  
Author(s):  
Tania Mahler ◽  
Martine Dassonville ◽  
Dinh Truong ◽  
Annie Robert ◽  
Philippe Goyens ◽  
...  

Introduction Patients after pull-through operation for Hirschsprung's disease (HD) are at high risk of defecation disorders. This study aimed at investigating their long-term outcomes and quality of life (QoL) in comparison with controls. Patients and Methods Patients older than 5 years operated on for HD were interviewed to complete detailed questionnaires on bowel function. Patients without neurologic impairment were enrolled in a QoL survey to compare with controls matched for sex and age and selected randomly from the general population using sampling set in a ratio of four controls to one case of HD. Results In total, 53 operated patients were enrolled. Mean age of the patients was 16 ± 8 years, with 68% boys. Rectosigmoid aganglionosis was the most seen form of HD in 38 (72%) cases. Open Soave was performed in 40 (75.5%) cases, and minimally invasive surgery Soave (MIS Soave) in 13 (24.5%) cases. At investigation, prevalence of fecal incontinence and constipation were 22.6 and 13.2%, respectively. Regarding QoL survey, 45 patients and 180 controls were enrolled, excluding 8 patients with neurologic impairment. Thirty-seven (82.2%) patients were classified as having a good QoL (score ≥ 9 points); whereas six had a fair QoL (5–8 points) and two had a poor QoL (< 5 points). QoL score in the cases and the controls were 10.2 ± 2.5 and 11.9 ± 0.4 points, respectively. Long aganglionosis form of HD was significantly associated with a low QoL (score < 8 points), adjusted odds ratio = 9, 95% confidence interval [1.3; 64.1] (p < 0.05). In subscales analyses, the prevalence of each dimension including fecal continence, school absenteeism, unhappiness or anxiety, food restriction, and peer rejection was significantly higher in operated patients than in controls (p <0.001). Conclusion Although the QoL of patients operated on for HD in general was with good outcomes, fecal incontinence and constipation still are problematic issues and challenges in a high percentage of patients. Therefore, a long-term and multidisciplinary follow-up is essentially required for these patients.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Farhaan Vahidy ◽  
Liang Zhu ◽  
Nancy J Edwards

Introduction: The American Heart Association’s updated guidelines for management of patients with primary intracerebral hemorrhage (ICH) recommend monitoring and early care at centers with advanced nursing and neuro-critical care expertise. This entails frequent transfer of ICH patients to certified Comprehensive Stroke Centers (CSC) for higher level of care. We hypothesized that transferred patients (TP) to a CSC will differ from directly admitted patients (DAP) in terms of patient characteristics, treatment factors, and functional and quality of life (QOL) outcomes. Methods: We analyzed data from a prospectively collected ICH registry at our CSC. Patients with traumatic or secondary causes of ICH were excluded. We collected data on demographics, comorbidities, presentation lab values, clinical characteristics, radiological parameters, in-hospital treatment variables, and discharge and long term outcomes. Functional outcomes were captured as modified Rankin Scale (mRS) and EuroQol 5D (EQ-5D) was used to assess QOL indices. Results: Out of a total 192 primary ICH patients, 114 (59.4%) were transferred-in. TP were significantly older, had lower diastolic blood pressure, lower arrival National Institutes of Health Stroke Scale (NIHSS) score, and smaller hematoma volumes as compared to DAP. A higher proportion of TP had a good discharge functional outcome (mRS score 0 - 3) as compared to DAP (29.8% vs. 15.4%, p = 0.02), this trend was also observed for Day-90 mRS (34.2% vs. 24.4%, p = 0.09). TP also reported significantly better QOL indices at Day-90; EQ-5D total median (Q1, Q3) score [10 (6,16) vs. 15 (9.5,18), p = 0.02] and self-reported median (Q1,Q3) score [75 (50,88) vs. 62.5(40,70)], p < 0.01]. Day-90 data are complete for approximately 50% patients. After adjusting for initial stroke severity, the discharge mRS was however not significantly different between TP and DAP. Conclusions: A larger proportion of ICH patients were transferred-in. Our data suggest that TP have lower disease severity, and better discharge and long term outcomes. However, they had similar treatment intensity as DAP at the CSC. We continue to capture day-90, 6 and 12-month functional and QOL data, which will be presented.


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