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Current Treatment Options in Oncology Sep 2021Choice of therapy in mycosis fungoides is based on both patient- and lymphoma-specific factors, such as disease characteristics, comorbidities, symptoms and effect on... (Review)
Review
Choice of therapy in mycosis fungoides is based on both patient- and lymphoma-specific factors, such as disease characteristics, comorbidities, symptoms and effect on quality of life, potential associated toxicities of therapy, response and tolerance to prior lines of therapy, and convenience and practicality. Generally, we sequence therapies from least toxic, targeted, nonimmunosuppressive to more toxic, immunosuppressive and from single agent to multiple agents, as necessary. If more toxic, immunosuppressive agents are required to alleviate disease burden or symptoms, we generally use them just long enough to control the disease, then transition to a maintenance regimen with less toxic, less immunosuppressive agents.
Topics: Biomarkers, Tumor; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Mycosis Fungoides; Neoplasm Grading; Neoplasm Staging; Skin Neoplasms; Treatment Outcome
PubMed: 34570278
DOI: 10.1007/s11864-021-00899-0 -
The Journal of Allergy and Clinical... Jan 2021In 2020, the first food allergy treatment, an oral immunotherapy (OIT) product for peanut allergy, was approved by the Food and Drug Administration, and a peanut... (Review)
Review
In 2020, the first food allergy treatment, an oral immunotherapy (OIT) product for peanut allergy, was approved by the Food and Drug Administration, and a peanut epicutaneous immunotherapy patch was under review. As food allergy therapies become available and widespread, allergy offices will need to adjust practices to be able to offer their patients these new treatments. OIT is an intensive therapy that requires commitment from patients and their families, and open communication with the practice is paramount. OIT may not be the right therapy for every patient, and although identifying good candidates is still an area rich for research opportunity, experience from cohorts and clinical trials provides some insight. It is important to understand the scope of practice for each member of the OIT team based on state regulations for a particular location. Staffing and space will likely dictate how many patients at an individual office could be on active OIT at one time. Emergency medications, supplies, and protocols must be in place. Screening, scheduling, visit procedures, monitoring, home dosing, dose modifications, safety precautions, adverse reactions, and maintenance will be addressed in this article. Finally, adjunct therapies under investigation will be reviewed.
Topics: Arachis; Desensitization, Immunologic; Humans; Peanut Hypersensitivity
PubMed: 33436161
DOI: 10.1016/j.jaci.2020.11.011 -
Transplantation and Cellular Therapy May 2021Mantle cell lymphoma (MCL) is a subtype of B cell non-Hodgkin lymphoma characterized by a heterogeneous clinical presentation. Patients who demonstrate an objective... (Review)
Review
Mantle cell lymphoma (MCL) is a subtype of B cell non-Hodgkin lymphoma characterized by a heterogeneous clinical presentation. Patients who demonstrate an objective response to induction therapy(ies) and are eligible for intensive therapies are offered an autologous hematopoietic cell transplant (HCT) as front-line consolidation followed by rituximab maintenance. Allogeneic HCT is an option for younger and fit patients with high-risk disease or in patients who have relapsed after autologous HCT. Recent advances in T cell engineering brought chimeric antigen receptor T cell (CAR T) therapy from the bench to the bedside, with brexucabtagene autoleucel being the first CAR T product approved by the US Food and Drug Administration for use in relapsed/refractory MCL. In this comprehensive review, we summarize the literature on available cellular therapies for MCL and present a treatment algorithm that incorporates HCT, autologous or allogeneic, and CAR T therapies.
Topics: Adult; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Lymphoma, Mantle-Cell; Neoplasm Recurrence, Local; Transplantation, Autologous; United States
PubMed: 33965173
DOI: 10.1016/j.jtct.2021.01.026 -
Clinical Medicine (London, England) Nov 2023Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to...
Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to achieve endoscopic healing, symptom resolution and improvement in quality of life. Therapeutic approaches in CD vary depending on disease phenotype. Thiopurines are important in steroid-sparing maintenance therapy, while anti-tumour necrosis factor agents play a fundamental role, especially in fistulising CD. Suboptimal response to these medications may require escalation to other immunosuppressive and biologic therapies, and surgical intervention is still required in a proportion of patients. Tailoring treatment to target specific patient phenotypes, disease severity and patient wishes is becoming more feasible with the growing array of therapeutic options in CD.
Topics: Humans; Crohn Disease; Quality of Life; Immunosuppressive Agents; Remission Induction
PubMed: 38065612
DOI: 10.7861/clinmed.2023-0493 -
Current Pain and Headache Reports Jun 2023The purpose of this review is to provide a summary of the utilization of sleep as a therapeutic target for chronic pain and to evaluate the recent literature on current... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide a summary of the utilization of sleep as a therapeutic target for chronic pain and to evaluate the recent literature on current and proposed pharmacologic and non-pharmacologic sleep interventions used in the management of pain disorders.
RECENT FINDINGS
Sleep is a promising therapeutic target in the treatment of pain disorders with both non-pharmacologic and pharmacologic therapies. Non-pharmacologic therapies include cognitive behavioral therapy and sensory-based therapies such as pink noise, audio-visual stimulation, and morning bright light therapy. Pharmacologic therapies include melatonin, z-drugs, gabapentinoids, and the novel orexin antagonists. However, more research is needed to clarify if these therapies can improve pain specifically by improving sleep. There is a vast array of investigational opportunities in sleep-targeted therapies for pathologic pain, and larger controlled, prospective trials are needed to fully elucidate their efficacy.
Topics: Humans; Pain Management; Hypnotics and Sedatives; Sleep Initiation and Maintenance Disorders; Prospective Studies; Sleep; Chronic Pain
PubMed: 37162641
DOI: 10.1007/s11916-023-01115-4 -
Handbook of Experimental Pharmacology 2022Prevention of allograft rejection is one of the crucial goals in solid organ transplantation to ensure durability of the graft and is chiefly mediated by cellular and...
Prevention of allograft rejection is one of the crucial goals in solid organ transplantation to ensure durability of the graft and is chiefly mediated by cellular and humoral pathways targeting cell surface alloantigens. The risk of rejection is highest in the first post-transplant year and wanes with time albeit the risk always exists and varies with the type of organ transplanted. Induction therapies refer to the use of high-intensity immunosuppression in the immediate post-operative period to mitigate the highest risk of rejection. This term encompasses chiefly the use of antibody therapies directed against one of the key pathways in T-cell activation or abrogating effects of circulating alloantibodies. These antibodies carry more potent immunomodulatory effect than maintenance immunosuppressive therapy alone and many of them lead to durable immune cell depletion. A variety of monoclonal and polyclonal antibodies have been utilized for use not only for induction therapy, but also for treatment of allograft rejection when it occurs and as components of desensitization therapy before and after transplantation to modulate circulating alloantibodies.
Topics: Antibodies, Monoclonal; Graft Rejection; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Induction Chemotherapy; Isoantibodies
PubMed: 35474024
DOI: 10.1007/164_2021_570 -
The American Journal of Gastroenterology May 2024Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients with UC through 4 years.
METHODS
Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks [q8w or q12w] or placebo). Starting at week 56, randomized patients could receive dose adjustment to 90 mg q8w. Symptoms and adverse events were assessed through the study; endoscopic assessment was conducted at week 200.
RESULTS
Of the 348 patients randomized to subcutaneous ustekinumab at maintenance baseline (q8w and q12w combined), 55.2% were in symptomatic remission at week 200. A greater proportion of biologic-naive patients (67.2% [117/174]) were in symptomatic remission than those with a history of biologic failure (41.6% [67/161]). Among patients in symptomatic remission at week 200, 96.4% were corticosteroid-free. Of the 171 patients with endoscopic evaluation at week 200, 81.6% (71/87) in the q12w group and 79.8% (67/84) in the q8w group had endoscopic improvement. From weeks 156 to the final safety visit (up to week 220), no deaths, major adverse cardiovascular events, or tuberculosis occurred in patients receiving ustekinumab. Nasopharyngitis, UC worsening, and upper respiratory tract infections were the most frequently reported adverse events.
DISCUSSION
The long-term efficacy of ustekinumab maintenance in patients with UC was confirmed through 4 years. No new safety signals were observed. ClinicalTrials.gov number NCT02407236.
Topics: Ustekinumab; Humans; Colitis, Ulcerative; Male; Female; Adult; Middle Aged; Maintenance Chemotherapy; Treatment Outcome; Double-Blind Method; Remission Induction; Injections, Subcutaneous
PubMed: 38095692
DOI: 10.14309/ajg.0000000000002621 -
Pharmacotherapy Aug 2020Hematopoietic cell transplantation (HCT) is an essential component of potentially curative therapy for patients with hematologic malignancies. High-dose chemotherapy... (Review)
Review
Hematopoietic cell transplantation (HCT) is an essential component of potentially curative therapy for patients with hematologic malignancies. High-dose chemotherapy with autologous (auto) stem cell rescue is used to overcome chemoresistance in multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Alternatively, poor-risk acute leukemias rely on the graft versus leukemia effect of allogeneic (allo) products. Long-term remissions are feasible with both auto- and allo-HCT; however, disease relapse is the leading cause of death after HCT for many patients. In recognition of this, novel therapies are being investigated in the upfront, relapsed/refractory, and post-HCT maintenance settings to deepen response and maintain disease control. To date, the most robust data to support this approach are in multiple myeloma, where post-transplant maintenance therapy has improved clinical outcomes. In Hodgkin lymphoma, patients with high-risk features may benefit from post-auto-HCT vedotin (BV) regardless of pre-HCT BV exposure. Apart from mantle cell lymphoma, where rituximab maintenance is generally accepted, post-auto-HCT maintenance in other forms of NHL is less established. In patients who undergo allo-HCT, the utilization of maintenance therapy is an important component of improving post-HCT outcomes, however, an individualized approach that considers patient factors such as residual toxicity from HCT, an immature graft with poor graft function, infection, and graft-versus-host disease create a complex environment for aggressive interventions. Initiation of directed agents in patients with identified mutations prior to allo-HCT, including FLT3 in acute myeloid leukemia and Philadelphia chromosome in acute lymphoid leukemia have generally improved post-HCT outcomes. Ongoing studies are exploring the safety and efficacy of additional maintenance strategies post-allo-HCT in an effort to further improve post-HCT outcomes.
Topics: Antineoplastic Agents; Combined Modality Therapy; Drug Resistance, Neoplasm; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Transplantation, Autologous
PubMed: 32343426
DOI: 10.1002/phar.2407 -
Blood Aug 2023Autologous stem cell transplantation (ASCT) is often used as consolidation for several subtypes of peripheral T-cell lymphoma (PTCL) in first remission. However, many...
Autologous stem cell transplantation (ASCT) is often used as consolidation for several subtypes of peripheral T-cell lymphoma (PTCL) in first remission. However, many patients relapse after ASCT and have a very poor prognosis. There are no approved treatment options for posttransplantation maintenance or consolidation in PTCL. PD-1 blockade has demonstrated some efficacy for patients with PTCL. We, therefore, conducted a phase 2 multicenter study of the anti-PD-1 monoclonal antibody pembrolizumab after ASCT in patients with PTCL in first remission. Pembrolizumab was administered at 200 mg IV every 3 weeks for up to 8 cycles within 21 days from post-ASCT discharge (and within 60 days of stem cell infusion). The primary end point was progression-free survival (PFS) at 18 months after ASCT. Twenty-one patients were treated in this study and 67% (n = 14) completed 8 cycles of treatment. Among all patients who were evaluable, 13 of 21 were alive and achieved PFS at 18 months after ASCT, meeting the study's primary end point. The estimated 18-month PFS was 83.6% (95% confidence interval [CI], 68-100), and overall survival 94.4% (95% CI, 84-100). The toxicity profile was consistent with the known toxicity profile of pembrolizumab, with no grade 5 toxicities. In conclusion, PD-1 blockade after ASCT with pembrolizumab is feasible with a favorable safety profile and promising activity, supporting further confirmatory studies. This trial was registered at www.clinicaltrials.gov as #NCT02362997.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Disease-Free Survival; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Transplantation, Autologous; Lymphoma, T-Cell, Peripheral; T-Lymphocytes; Stem Cell Transplantation
PubMed: 37319432
DOI: 10.1182/blood.2023020244 -
Current Oncology Reports Jun 2021Advanced epithelial ovarian cancer remains the most lethal gynaecological cancer. Most patients with advanced disease will relapse within 3 years after primary treatment... (Review)
Review
PURPOSE OF REVIEW
Advanced epithelial ovarian cancer remains the most lethal gynaecological cancer. Most patients with advanced disease will relapse within 3 years after primary treatment with surgery and chemotherapy. Recurrences become increasing difficult to treat due to the emergence of drug resistance and 5-year survival has changed little over the last decade. Maintenance treatment, here defined as treatment given beyond primary chemotherapy, can both consolidate the response and prolong the control of disease which is an approach to improve survival.
RECENT FINDINGS
Here we review maintenance strategies such as targeting angiogenesis, interference of DNA repair through inhibition of PARP, combinations of targeting agents, and immunotherapy and hormonal therapy. Much has been learnt from the success and challenges of these treatments that have in the last few years which led to significant reduction in disease recurrence, changed the guidelines for treatment, and established a new paradigm for the treatment of ovarian cancer.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Ovarian Epithelial; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Salvage Therapy
PubMed: 34125335
DOI: 10.1007/s11912-021-01088-w