High-dose interleukin-2 (HD IL-2) for metastatic renal Cell carcinoma (mRCC): Contemporary utilization trends in the United States.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 449-449
Author(s):  
Christopher B. Allard ◽  
Francisco Gelpi-Hammerschmidt ◽  
Lauren Christine Harshman ◽  
Izak Faiena ◽  
Parth K Modi ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Lung Metastases ◽  
Interleukin 2 ◽  
Standard Of Care ◽  
Good Health ◽  
The United States ◽  
High Dose ◽  
Study Cohort ◽  
Severe Hypotension ◽  
Nationally Representative

449 Background: Targeted therapies (TT) have revolutionized treatment of mRCC with broad based efficacy and tolerability but ultimately all patients progress. While HD IL-2, the prior standard of care treatment, is associated with significant toxicities, it remains the only agent proven to elicit durable complete responses albeit rarely. This study evaluated trends in HD IL-2 use for patients with mRCC during the TT era. Methods: Our study cohort was comprised of a weighted sample of 2,351 patients with mRCC undergoing HDIL-2 treatment from 2004-2012, from the Premier Hospital Database (Premier Inc., Charlotte, NC), a nationally representative hospital discharge database. We employed descriptive statistics and fitted multivariable regression models, accounting for clustering and weighting, to identify predictors of treatment toxicity and tolerability. Results: We found a progressive decrease in the use of HD IL-2 from 2004 to 2008 with a general upward trend thereafter. HD IL-2 was increasingly concentrated at academic centers representing the site of treatment for 24% of patients in 2004 versus 90% of patients in 2012. Most patients were men (75.3%), Caucasian (70.7%) and aged <60 (59.6%) with lung metastases (60.9%) and otherwise healthy (64.72%, Charlson comorbidity index=0). Our adjusted analysis showed that severe hypotension was associated with patients <50 years (odds ratio [OR]: 1.35, p=0.045), while the likelihood of receiving ≥2 cycles of HDIL-2 was associated with good health (CCI=0, OR: 1.72, p=0.004) and having >1 metastatic site (OR: 4.32, p<0.001). Conclusions: Over the past decade, the use of HD IL-2 initially diminished coinciding with the widespread availability of TT but has remerged potentially due to renewed enthusiasm for immunotherapies showing promising efficacy with novel immune checkpoint inhibitors in mRCC. HD IL-2 has increasingly been limited to academic centers and our analysis suggests a strong selection bias for younger, healthier patients who can better tolerate the toxicities and those with a greater burden of metastatic disease. Future studies are warranted to determine the optimal role of HDIL-2 in the contemporary treatment of mRCC.

scholarly journals Racial Differences in Mechanical Thrombectomy Utilization for Ischemic Stroke in the United States

2020 ◽  
Vol 30 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Charles Esenwa ◽  
Alain Lekoubou ◽  
Kinfe G. Bishu ◽  
Kemar Small ◽  
Ava Liberman ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Racial Differences ◽  
Population Sample ◽  
Standard Of Care ◽  
Stroke Care ◽  
The United States ◽  
Vessel Occlusion ◽  
Stroke Treatment ◽  
Nationally Representative ◽  
Adjusted Model

Background: Compared with non-Hispanic Whites (NHW), racial-ethnic minorities bear a disproportionate burden of stroke and receive fewer evidence-based stroke care processes and treatments. Since 2015, me­chanical thrombectomy (MT) has become standard of care for acute ischemic stroke (AIS) patients with proximal anterior circula­tion large vessel occlusion (LVO).Objectives: Our objectives were to: assess recent trends in nationwide MT utilization among patients with AIS; determine if there were racial differences; and identify what factors were associated with such differ­ences.Methods: We performed a retrospective cohort study using nationally representative data of a non-institutionalized population sample from 2006 to 2014 obtained from the Nationwide Inpatient Sample (NIS). We identified a total of 889,309 observations of AIS, of which there were 5,256 MT observa­tions.Results: In the fully adjusted model, rate of thrombectomy utilization was significantly lower in African Americans (AA) (OR .67, CI .58-.76, P<.001) compared with NHW and Hispanics (OR .94, CI .78-1.13, P=.5).Conclusion: We found a significant dispar­ity in MT utilization for AA compared with NHW and Hispanics. More work is needed to understand the drivers of this racial disparity in stroke treatment. Ethn Dis. 2020;30(1):91-96; doi:10.18865/ed.30.1.91

scholarly journals Evolving Treatment of Advanced Urothelial Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 309-315 ◽  
Author(s):  
Srikala S. Sridhar
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Metastatic Disease ◽  
Urothelial Cancer ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Standard Of Care ◽  
The United States ◽  
Poor Performance Status ◽  
Cancer Of The Bladder

Urothelial cancer of the bladder is a smoking-related cancer and the fifth most common cancer in the United States. At presentation, up to 25% of patients will have muscle-invasive disease and, despite cystectomy or bladder-sparing trimodality approaches, will develop metastatic disease. Cisplatin-based combination chemotherapy regimens remain the standard of care in first-line metastatic disease. Although response rates to these regimens are high, they are rarely durable, and median overall survival is only 12 to 15 months. Treatment options following progression on cisplatin-based regimens or for patients unfit for cisplatin due to poor performance status, impaired renal function, or comorbidities have been quite limited. However, there is now a new class of drugs known as immune checkpoint inhibitors, which target the programmed cell death 1/programmed cell death-ligand 1 axis and promote antitumor immunity, that are showing both efficacy and tolerability. These drugs have now been approved for use in both cisplatin-treated and most recently cisplatin-unfit patients. Clinical trials are currently ongoing to determine how best to use these drugs and whether they should be used alone or in combination with other treatments. This review will discuss the current standard of care in the management of urothelial cancer and highlight recent trials of immunotherapy in this disease.

Paradigm towards Tailored Therapies and Complete Responses in the Treatment of Metastatic Renal Cell Carcinoma

2012 ◽  
Vol 08 (01) ◽  
pp. 30
Author(s):  
Mayer Fishman ◽  
Thomas Hutson ◽  
Neeraj Agarwal ◽  
Eric Jonasch ◽  
◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
Standard Of Care ◽  
Complete Response ◽  
High Dose

In recent years, the management of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of targeted therapies. Multitargeted kinase inhibitors (such as sunitinib, sorafenib, pazopanib, and axitinib), the vascular endothelial growth factor inhibitor bevacizumab, and mammalian target of rapamycin inhibitors (such as everolimus and temsirolimus) have become the standard of care for the palliation of metastatic disease. Unfortunately, cumulative toxicities and the lack of marked benefits have prevented the combined use of most molecularly targeted agents. Selected patients with mRCC benefit from immunotherapy, as subsets of patients can experience long-term disease remission or complete response with high-dose interleukin-2. In order to optimize the value of immunotherapy, improvements in the selection of drugs and combinations with novel immunomodulatory agents must be pursued.

Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells.

1990 ◽  
Vol 8 (7) ◽  
pp. 1138-1147 ◽  
Author(s):  
M H Bar ◽  
M Sznol ◽  
M B Atkins ◽  
N Ciobanu ◽  
K C Micetich ◽  
...  
Keyword(s):  
Lymph Node ◽  
Continuous Infusion ◽  
Lung Metastases ◽  
Interleukin 2 ◽  
Advanced Melanoma ◽  
Lak Cells ◽  
High Dose ◽  
Severe Toxicity ◽  
Lymphokine Activated Killer Cells

Fifty patients with advanced melanoma received high-dose bolus and continuous infusion interleukin-2 (IL-2) with lymphokine-activated killer (LAK) cells in an attempt to improve the therapeutic index of this active but toxic therapy. Treatment began with up to nine bolus doses of IL-2 administered over 3 days. After 1 day of rest, patients underwent daily leukapheresis for 4 days, and the leukocytes were cultured with IL-2 in vitro to prepare LAK cells. Continuous infusion IL-2 was begun 1 day after the last leukapheresis and continued for up to 148 hours; LAK cells were administered on days 1, 2, and 4 of the infusion. Responding patients were eligible to receive up to two additional cycles of therapy at 3-month intervals. Most patients completed each cycle without dose reduction. One patient had a complete response and six patients had partial responses (14% response rate). The complete responder and three of the partial responders (8%) remain free from disease progression with follow-up of 21 to 24 months. Of these four patients with durable remissions, one had extensive liver and lymph node metastases, one had lymph node, pleural, and parenchymal lung metastases, and two had disease limited to lymph nodes or subcutaneous tissues. Seventeen patients (34%) required pressors for hypotension, three patients (6%) developed hemodynamically significant arrhythmias, and six patients (12%) developed dyspnea at rest, but none required intubation and there were no treatment-related deaths. Unacceptable toxicity developed in two patients during bolus IL-2 administration and therapy was aborted; both returned to baseline status within 4 days of discontinuing IL-2. Fever, oliguria, and elevated creatinine or transaminase levels occurred frequently but were also transient. Despite less frequent severe toxicity with this modified regimen, these results confirm the ability of IL-2 and LAK cell therapy to induce durable remissions in some patients with advanced melanoma.

Management Of Immunotherapy Adverse Events In Oncological Patients: Anti-Ctla-4, Anti-Pd-1/Pd-L1

2020 ◽  
Vol 15 ◽  
Author(s):  
Mattia Brigida ◽  
Alessia Perricelli ◽  
Fausto Sposato ◽  
Maria Giovanna Spadafora ◽  
Angelo Pomillo ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Corticosteroid Treatment ◽  
High Dose ◽  
Emergency Setting ◽  
Serious Adverse Events ◽  
Oncological Patients ◽  
Grade Ii ◽  
Dose Corticosteroid

Background: The widespread use of immunotherapy drugs in the oncological field has led to the spread of new toxicities compared to the more common chemotherapy treatments. This is because immunotherapy with anti-CTLA-4 (Cytotoxic T Lymphocytes-Associated Antigen 4), anti-PD-1 and anti-PD-L1 monoclonal antibodies has become the standard-of-care in a growing number of indications. Any organ or tissue can be involved, but more commonly side effects are reported regarding skin, colon, endocrine glands, liver, lung and kidney. Other less frequent, but more serious, adverse events are neurological and myocarditis. Methods: We performed an electronic search on PUBMED of the literature concerning immunotherapy-related toxicities and their management in oncological patients from 2007 to 2020, with particular attention to the most recent publications. Aim: To summarize the different types of immunotherapy-related toxicities, together with their incidence and diagnosis, and to simplify their management, especially in the emergency setting. Conclusion: Usually, for grade I toxicities it is not recommended to stop immunotherapy; for most of grade II toxicities, immunotherapy should be postponed to when toxicity will have regressed to grade I, considering the possibility of a corticosteroid treatment for most of toxicities. The majority of grade III and IV require administration of high-dose corticosteroid intravenous therapy and suspension of immunotherapy. Mortality related to immune checkpoint inhibitors’ toxicity, occurring at a rate of 0.3-1.3%, is well below fatality rates due to other oncologic interventions and should not discourage the promising results so far reached by immunotherapy.

Clinical benefit (CB) of high-dose interleukin-2 (HD IL-2) in clear cell (cc) metastatic renal cell carcinoma (mRCC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 461-461
Author(s):  
Neeraj Agarwal ◽  
Kinjal Parikh ◽  
Srinivas Kiran Tantravahi ◽  
Hilda Crispin ◽  
Joan Van Atta ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Clear Cell ◽  
Objective Response ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
High Dose ◽  
Select Group ◽  
Best Response

461 Background: HD IL-2, an immunotherapy, is a standard of care for a select group of patients (pts) with mRCC. Generally objective response (OR) rates, i.e. complete response (CR) + partial response (PR), of 16-20% are discussed with pts, but not disease stabilization (SD). Recent data suggest that cancer immunotherapy may improve survival without inducing OR. Thus, treatment with HD IL-2 may provide survival benefit to an additional group of pts not experiencing OR, but only SD as the best response. Here we report CB ( OR+SD), and specifically report outcomes of cc mRCC pts experiencing SD as the best response, on treatment with HD IL-2. Methods: All sequential cc mRCC pts treated with HD IL-2 at the University of Utah Huntsman Cancer Institute from 2000-2012 were included. Pts were evaluated for best response, progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS). Two practitioners independently reviewed HD IL-2 response with discrepancies adjudicated by a third reviewer. Results: 85 pts, 79% male, were identified with a median age of 56 (range 32-76) years. Pts belonged to the following MSKCC risk categories: 11 (13%) good, 70 (82%) intermediate, and 4 (5%) poor risk. A CR was identified in 9 (11%), PR in 5 (6%), SD in 26 (31%), progressive disease (PD) in 38 (45%), and unknown/not evaluable (NE) in 7 (8%) pts; yielding a clinical benefit in 40 (47%) pts. The median PFS, TNT, and OS in these individual groups of pts are compared in the table. Conclusions: A clinical benefit of HD IL-2 was achieved in nearly half of all clear cell mRCC pts. OS was not significantly different in OR and SD groups. Even though OR favorably determine outcomes, SD is also an important response criterion, and may be discussed during counseling pts for treatment with HD IL-2. [Table: see text]

A review of checkpoint inhibitors in the management of renal cell carcinoma

2019 ◽  
Vol 26 (2) ◽  
pp. 445-458 ◽  
Author(s):  
Kirollos S Hanna
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Mammalian Target Of Rapamycin ◽  
The United States ◽  
High Dose ◽  
Cancer Type

Renal cell carcinoma is a common malignancy of the genitourinary system and is the eight most common cancer type in the United States. The overall incidence of renal cell carcinoma appears to be increasing but death rates have been declining. Patients with poor risk, advanced disease have a two-year survival rate of approximately 7%. Prior to the advent of tyrosine kinase inhibitors, anti-vascular endothelial growth factor antibodies, mammalian target of rapamycin inhibitors, and checkpoint inhibitors, IFN-α and high-dose IL-2, were standard of care treatment options but, conversely, their use is now limited to select patients. Immunotherapies have played a significant role in the treatment of various cancers and have continued to expand. It is of utmost importance that practitioners include checkpoint inhibitors as treatment options for renal cell carcinoma as they mark a new era in the treatment of advanced or relapsed setting. Nivolumab, pembrolizumab, avelumab, ipilimumab, and atezolizumab all play a role in management of disease as either monotherapy or in combination with other agents. Ongoing clinical trials are ongoing to further assess the benefits of inducing cellular immunity in the treatment of renal cell carcinoma. In this article, the available data on immune checkpoint inhibitors for the treatment of advanced or relapsed renal cell carcinoma and their place in therapy are reviewed.

scholarly journals Contemporary trends in high-dose interleukin-2 use for metastatic renal cell carcinoma in the United States

2015 ◽  
Vol 33 (11) ◽  
pp. 496.e11-496.e16 ◽  
Author(s):  
Christopher B. Allard ◽  
Francisco Gelpi-Hammerschmidt ◽  
Lauren C. Harshman ◽  
Toni K. Choueiri ◽  
Izak Faiena ◽  
...  
Keyword(s):  
United States ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Interleukin 2 ◽  
The United States ◽  
High Dose

scholarly journals A Wolf in Sheep's Clothing: Systemic Immune Activation Post Immunotherapy

2021 ◽  
Author(s):  
Crescens Tiu ◽  
Rajiv Shinde ◽  
Abhijit Pal ◽  
Andrea Biondo ◽  
Alex Lee ◽  
...  
Keyword(s):  
Immune Activation ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Standard Of Care ◽  
High Dose ◽  
Systemic Immune Activation ◽  
Development Unit ◽  
Royal Marsden Hospital ◽  
Time To Onset ◽  
Timely Treatment

ABSTRACT Introduction Immune checkpoint inhibitors (ICIs) are increasingly a standard of care for many cancers; these agents can result in immune-related adverse events (irAEs) including fever, which is common but can rarely be associated with systemic immune activation (SIA or acquired HLH). Methods All consecutive patients receiving ICIs in the Drug Development Unit of the Royal Marsden Hospital between May 2014 and November 2019 were retrospectively reviewed. Patients with fever ≥ 38°C or chills/rigors (without fever) ≤ 6 weeks of commencing ICIs were identified for clinical data collection. Results Three patients met diagnostic criteria for SIA/HLH with median time to onset of symptoms of 10 days. We describe the clinical evolution, treatment used, and outcomes for these patients. High-dose steroids are used first-line with other treatments, such as tocilizumab, immunoglobulin and therapeutic plasmapheresis can be considered for steroid-refractory SIA/HLH. Conclusion SIA/HLH post ICI is a rare but a potentially fatal irAE that presents with fever and a constellation of nonspecific symptoms. Early recognition and timely treatment are key to improving outcomes.

P08.01 Immune-Related Acute Motor Axonal Neuropathy: A Small Case Series and Review of the Literature

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii26-ii26
Author(s):  
Y Pina ◽  
N Tran ◽  
P Forsyth ◽  
S Mokhtari ◽  
E Peguero
Keyword(s):  
Checkpoint Inhibitors ◽  
Axonal Neuropathy ◽  
Case Series ◽  
Standard Of Care ◽  
Cancer Center ◽  
High Dose ◽  
Acute Motor Axonal Neuropathy ◽  
First Case ◽  
Oncological Patients ◽  
Solid Malignancies

Abstract BACKGROUND Immunotherapy have revolutionized cancer treatment in the past decade, with a significant increased survival in patients with solid tumors. However, the use of immune checkpoint inhibitors (ICIs) has been associated with a growing number of neurotoxicities, some of which can be fatal if not recognized and treated promptly. Some of these neurotoxicities include very uncommon syndromes like Acute Motor Axonal Neuropathy (AMAN). Herein we present four oncological cases of patients who underwent immunotherapy and developed AMAN. METHODS Four patients were diagnosed with immune-related AMAN between 2017 and 2000 at H. Lee Moffitt Cancer Center. The patients were treated with standard of care and currently follow up in clinic. RESULTS We describe four oncological patients who developed a motor axonal neuropathy (i.e., AMAN) confirmed on nerve conduction studies following 2 cycles of immunotherapy, including a 28 year old woman with melanoma brain metastasis and a 50 year old woman with renal cell carcinoma both treated with ipilimumab and nivolumab, a 32 year old man with Hodgkin lymphoma who was treated with nivolumab and brentuximab, and a 77 year old woman with renal urothelial cancer who was treated with pembrolizumab and cabozantinib. All four patients were promptly recognized as having immune-related neurotoxicity (irNs), were promptly treated (i.e., high dose steroids +/- IVIG +/- other immunomodulators), and significantly improved and have remained stable. CONCLUSION This is the first case series of patients with AMAN following two cycles of immunotherapy, who were successfully treated. It is crucial to develop a better understanding of the irNs associated with ICIs, including those rare conditions that are difficult to diagnose and treat, as the utilization of these immunomodulating therapies continues to increase and expand to include other solid malignancies. Neurologists should be involved early on in any case of suspected irN to assist in the management of these complicated patients and a swift work up should be initiated for timely diagnosis and treatment.

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