scholarly journals Optimizing First-Line Therapy for Follicular Lymphoma: Is It Time for Chemotherapy-Free Approaches?

2019 ◽  
Vol 17 (11.5) ◽  
pp. 1414-1416
Author(s):  
Richard I. Fisher

Over the past several decades, tremendous progress has been made in the treatment of follicular lymphoma. The addition of rituximab to chemotherapy led to significant improvements in survival in the 1990s. Current standard of care in advanced-stage, previously untreated follicular lymphoma is rituximab plus chemotherapy, sometimes followed by rituximab maintenance. Now, as more research is conducted in the field of chemotherapy-free treatment, Dr. Richard I. Fisher discussed the importance of carefully constructed phase II or III trials at the NCCN 2019 Annual Congress: Hematologic Malignancies. He maintained that a nonchemotherapy treatment regimen comprising rituximab + lenalidomide can be considered in carefully selected patients, and that it is currently the only chemotherapy-free treatment that should be recommended.

2019 ◽  
Vol 17 (11.5) ◽  
pp. 1408-1410 ◽  
Author(s):  
Jennifer R. Brown ◽  
William G. Wierda

With the enormous progress made in treatment and management, many oncologists have called this the golden age of chronic lymphocytic leukemia (CLL). The past few years alone have seen the approval of multiple agents, including small molecule inhibitors that have led to longer, more durable periods of disease control. However, the introduction of these new drugs into the armamentarium has raised an important question regarding standard of care: is there still a role for chemoimmunotherapy in the first-line setting? At the NCCN 2019 Annual Congress: Hematologic Malignancies, Drs. William G. Wierda and Jennifer R. Brown presented opposing sides of the debate.


2014 ◽  
Vol 3 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Sunil Kapur ◽  
Moussa Mansour

Cardioembolic stroke is a major cause of morbidity and mortality in patients with atrial fibrillation (AF). The left atrial appendage (LAA) is the prominent source of clot formation. While systemic anticoagulation is the current standard of care, anticoagulants carry many contraindications and possible complications. Techniques for elimination of the LAA are in various stages of development and early clinical use. In the coming years, accumulating data will help guide the management of AF patients at risk of bleeding as well as potentially become first-line therapy to reduce the risk of thromboembolic stroke. The purpose of this article is to review current endovascular and epicardial catheter-based LAA occlusion devices and the clinical data supporting their use.


2010 ◽  
Vol 4 (5) ◽  
pp. 673-677
Author(s):  
Julian H. Elliott

Abstract Limited access to virological monitoring has led to a high prevalence of resistance to nucleoside reverse transcriptase inhibitors (NRTIs) at the time of first line failure in most studies from low- and middle-income countries (LMIC). Nevertheless, the current standard of care is to include NRTIs in second line regimens. The activity of tenofovir/emtricitabine following failure of stavudine/lamivudine or zidovudine/lamivudine is dependent on the sensitivity of the monitoring strategy used during first line therapy and the threshold for switching, whereas these factors are less important if the opposite sequencing strategy is used. Boosted protease inhibitors (PIs) are the foundation of effective second-line therapy with demonstrated efficacy in early salvage regimens and high barrier to resistance. Lopinavir/ritonavir and ritonavir-boosted atazanavir have recently been described by the World Health Organization as preferred boosted PIs for use in LMIC. Alternative approaches currently under investigation include boosted PI monotherapy, dual boosted PIs, and the combination of raltegravir (an HIV integrase inhibitor) and a boosted PI.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1053
Author(s):  
Jasmine L. King ◽  
Soumya Rahima Benhabbour

Gliomas are the most common type of brain tumor that occur in adults and children. Glioblastoma multiforme (GBM) is the most common, aggressive form of brain cancer in adults and is universally fatal. The current standard-of-care options for GBM include surgical resection, radiotherapy, and concomitant and/or adjuvant chemotherapy. One of the major challenges that impedes success of chemotherapy is the presence of the blood–brain barrier (BBB). Because of the tightly regulated BBB, immune surveillance in the central nervous system (CNS) is poor, contributing to unregulated glioma cell growth. This review gives a comprehensive overview of the latest advances in treatment of GBM with emphasis on the significant advances in immunotherapy and novel therapeutic delivery strategies to enhance treatment for GBM.


2018 ◽  
Vol 29 ◽  
pp. ix150 ◽  
Author(s):  
D. Planchard ◽  
M. Boyer ◽  
J.-S. Lee ◽  
A. Dechaphunkul ◽  
P. Cheema ◽  
...  

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Ali McBride ◽  
Daniel O. Persky

Introduction: The choice of initial therapy in follicular lymphoma can be a key determinant in future therapy, as irreversible toxicities with first line regimens can impact the patient's ability to tolerate future treatment. Minimizing drug exposure will result in less frequent occurrence of significant adverse events and associated treatment costs. In the era of COVID-19 pandemic, there is additional benefit to minimizing the number of patient visits and hospital admissions. Limited information exists related to the outcomes and associated costs of existing treatment sequences. Additionally, treatment administration at different types of clinical sites results in varied reimbursement models, making informed evaluation of clinical and financial evidence challenging. Methods: The current study applies a budget impact model methodology in order to describe the associated impact of treatment selection and sequencing on outcomes and costs in the treatment of relapsed or refractory low-grade follicular lymphoma in first line therapy followed by Consolidation and also in first line therapy to second line therapy. Key model inputs included: Number of treatment cycles, number of days a treatment was received, duration of response (DOR), rate of side effects and associated costs, and total treatment costs, including drugs, medical treatment, laboratory testing and adverse event costs. Treatment outcomes were based on the published literature that summarized the overall response rate, median DOR, and toxicity. Treatment regimen costs were evaluated based on payer pricing, Wholesale Acquisition Cost (WAC), Average Selling Price (ASP) and Average Wholesale Price (AWP) and modified to adjust for weight-based dosing and negotiate payer reimbursement rates. Associated medical costs for medical treatment and supportive care were estimated using current Medicare fee schedule rates. Included were seven options for first line therapy of follicular lymphoma from 2020 NCCN Guidelines - (Bendamustine + rituximab (BR); Bendamustine + Obinutuzumab (OB); CHOP rituximab (RCHOP); CHOP + Obinutuzumab (OCHOP); CVP+ rituximab (RCVP); CVP + Obinutuzumab (OCVP); Lenalidomide + rituximab (R2)), followed by three for Consolidation (Rituximab maintenance (RM); Obinutuzumab maintenance (O); Radioimmunotherapy (RIT with 90 Y-ibritumomab tiuxetan (Y90-IT, Zevalin)) and three Second Line therapy options (RIT; Lenalidomide only; Lenalidomide + Obinutuzumab (LO)). Results: The treatment sequence of first line BR followed by Consolidation with RIT Y90 (Zevalin) had the longest predicted DOR (2586 days). The associated treatment sequence costs were $212,485 for BR followed by Y90-IT, compared with $233, 388 for BR followed by rituximab maintenance, which had a predicted DOR of 2478 days. The predicted DOR for treatment sequences starting with OCHOP, OCVP and RCHOP and followed by RIT with Y90-IT was approximately 1000 days less than BR followed by Y90-IT for a cost difference of $4,421, $12,914 and $25,826, respectively. The treatment sequence of first line BR followed by Second Line RIT Y90-IT had the second longest predicted DOR of 2586 days at costs of $212,485, compared to 2778 days for BR followed by LO, at a total sequence costs of $796,695. Conclusion: The use of Y90-IT in Consolidation or Second Line treatment demonstrated desired patient outcomes at one of the lowest cost profiles. Additionally, Y90-IT administration can be completed in only two clinic visits, reducing patient travel and contact, improving safety in an era of COVID-19 precautionary measures and reducing cost. Figure 1. Duration of Response and Total Sequence Costs for Twelve First Line to Consolidation and First Line to Second Line Treatment Regimens. Disclosures McBride: Merck: Speakers Bureau; Coherus BioSciences: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; MorphoSys: Consultancy; Sandoz: Consultancy.


2019 ◽  
Vol 3 (12) ◽  
pp. 2295-2304 ◽  
Author(s):  
Lia Head ◽  
Katja Kiseljak-Vassiliades ◽  
Toshimasa J Clark ◽  
Hilary Somerset ◽  
Jonathan King ◽  
...  

Abstract Adrenocortical carcinoma (ACC) is a rare orphan disease with a dismal prognosis. Surgery remains the first-line treatment, but most patients eventually develop metastatic disease. Mitotane is often used with chemotherapy with modest success. Little information is available concerning the efficacy of immunotherapy in combination with mitotane. We conducted a retrospective review of our initial six patients with metastatic ACC, for whom mitotane alone or with chemotherapy failed, and who were subsequently treated with a combination of pembrolizumab and mitotane, between July 2016 and March 2019. Imaging was analyzed per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Two patients had a partial response and four patients had stable disease (8 to 19 months). One patient had grade 3 hepatitis and pembrolizumab was discontinued after 8 months. She died with disease progression 16 months after initiating pembrolizumab. One patient developed brain metastasis after 19 months of treatment and was transitioned to hospice. One patient had focal pneumonitis after 18 months of treatment, and pembrolizumab was discontinued. Three remaining patients continue pembrolizumab plus mitotane at the time of this writing. The current standard of care for ACC is a combination of etoposide, doxorubicin, cisplatin, and mitotane with an overall survival of 14.8 months. All six patients lived for at least 16 months after starting pembrolizumab added to mitotane therapy. The therapy appeared to be effective in both microsatellite instability-high and microsatellite stable tumors, suggesting some synergistic effect with mitotane. Combined immunotherapy and mitotane should be considered in future clinical trials in patients with ACC.


2018 ◽  
Vol 38 (01) ◽  
pp. 050-061 ◽  
Author(s):  
Zachary Reitman ◽  
Frank Winkler ◽  
Andrew Elia

Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis. Here, we review these molecular features and discuss major clinical trials that have recently defined the field. We describe genetic alterations in isocitrate dehydrogenase, ATRX, the telomerase promoter, and histone H3 variants that promote GBM tumorigenesis and have altered GBM categorization. We also discuss intratumoral genetic heterogeneity as one explanation for therapeutic failures and explain how ultra-long extensions of glioma cells, called tumor microtubes, mediate therapeutic resistance. These findings provide new insights into GBM biology and offer hope for the development of next-generation therapies.


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