The need for mental health services on campuses across the country has intensified during the pandemic. With it has come an increased awareness among college counselors and administrators about the importance of meeting the needs of every student especially those who hold marginalized identities and may have experienced extraordinary hardship over the past two years.

While grappling with pandemic-related challenges and typical college student woes, Black students may be dealing with increased public attention on police brutality and distress in their communities, for example. Latino students may be grappling with heated debates on immigration policy that affect their loved ones, or the challenges of straddling two different cultures. LGBTQ+ students may face questions about gender, sexuality, identity and acceptance.

Kelsey Moran is a counselor and coordinator of LGBTQIA+ counseling services and programming at the College of the Holy Cross in Massachusetts. When were working with them, were not just working with them and their anxiety, she said of the LGBTQIA+ students she serves. Were working with them and their full background and identity as an understanding of self.

Related: Students to administrators: Lets talk about mental health on campus

Research shows mental health treatment is more effective when its in line with the clients culture and when clients perceive their therapist to be culturally competent. But many colleges are still figuring out how exactly to care for students from underserved groups.

Others, like College of the Holy Cross, have been able to rely on systems they built before the pandemic to help students through a particularly difficult time.

Moran started as Holy Crosss first LGBTQIA+ coordinator in 2018. Alongside a multicultural services coordinator and a coordinator who works specifically with student athletes, Moran works across campus to make sure that queer and transgender students are able to get the mental health care they need. She provides individual therapy and also runs three support groups for queer and trans students on campus.

The resources have become even more relevant as queer and trans students suffered particular challenges during the pandemic.

Two years ago, when the coronavirus first caused the college to shut down, some students were excited to spend time at home and be reunited with family. But for many queer and trans students, particularly those whose families werent accepting of their gender or sexuality, it was a terrifying shift, Moran said.

Related: Nations skeletal school mental health network will be severely tested

Politics have also presented a challenge for LGBTQ+ students, they said. The wave of bills to limit the mention of LGBTQ+ topics, ban certain books and categorize gender affirming care for trans children as abuse is targeting peoples existence and their ability to feel safe and supported, Moran said.

Keygan Miller, advocacy manager at The Trevor Project, a nonprofit focused on suicide prevention for LGBTQ+ youth, said that a therapist doesnt have to identify as queer or trans to help a student who does. Instead, therapists need to be well versed on what Miller called 101-level issues in the LGBTQ community and affirm the students identity.

Queer and trans students may come to therapy with extra layers of concern and distrust, they said. Students may have fears that the therapist will disclose information about their identity to their family, or that they will be asked to change who they are.Trans students also often need therapists to help them access gender affirming care, like surgery and hormone replacement therapy, with letters and other documentation, Miller said.

In addition to recognizing and affirming the identities of LGBTQ+ students, counselors also need to be sensitive to students race, ethnicity, socioeconomic status, immigration status, religion and disability status, among other identities, therapists and administrators said. That hasnt always been easy for college campus center staff, some 70 percent of whom are white.

Reyna Smith, a doctoral candidate at the University of the Cumberlands in Kentucky, was working in a college counseling center in 2020 when George Floyd was murdered by a former Minneapolis police officer. When she felt the center didnt handle it appropriately for students or staff, she left her position.

Especially as enrollment increases, and diversity increases on campus, you need to be able to support the needs of all students.

There are students here on campus that are affected by this, are you going to do something about it? Smith said she remembers thinking.

Now, she is studying the experiences of Black students seeking mental health care on predominantly white college campuses.

Related: Anxiety, depression hit students in underrepresented groups

She said that when someone is part of a minority group and feels isolated or misunderstood, it can contribute to anxiety and depression and produce other social and academic harms. And when students dont see themselves reflected in counseling staff, they can be discouraged from seeking treatment or end treatment early if they dont feel their therapist understands them.

She said campus counseling centers should aim to hire more Black staff and people from other underrepresented groups. But like Miller, she believes they can improve services by training the staff they already have on the best ways to counsel people of different identity groups.

I think theres a need to adjust to the population, Smith said. Especially as enrollment increases, and diversity increases on campus, you need to be able to support the needs of all students.

This story about LGBTQ+ student counseling was produced by The Hechinger Report, a nonprofit, independent news organization focused on inequality and innovation in education . Sign up for the higher education newsletter.

The Hechinger Report provides in-depth, fact-based, unbiased reporting on education that is free to all readers. But that doesn't mean it's free to produce. Our work keeps educators and the public informed about pressing issues at schools and on campuses throughout the country. We tell the whole story, even when the details are inconvenient. Help us keep doing that.

Join us today.

More here:
Rethinking campus mental health to better serve LGBTQ+ students and others - The Hechinger Report

CONTRIBUTED CONTENT Have you felt worse after CBD or cannabis use? If so, what were your reactions?

CBD (cannabidiol) and cannabis have been shown to help with conditions such as epilepsy, seizures, muscle stiffness, arthritis, autoimmunity, Parkinsons, ALS, anxiety, OCD, PTSD, depression, inflammation, bacterial infection, pain, depression, GI ulcers, and mood.

However, either CBD or cannabis makes some of our patients feel worse. This led us down a rabbit hole of research and we found two main reasons CBD or cannabis can have a negative effect.

Of the more than 1,000 strains of cannabis and CBD, some stimulate this immune response and can worsen autoimmunity.

Although the identification of the immune properties of various strains of cannabis is improving, at this time theres no way to know which ones are immune stimulating. Just be aware of this prior to use in case you have a negative reaction.

Boosting the immune response isnt inherently bad. For those who do not have autoimmunity it can actually be beneficial to improve immune resilience.

But for the autoimmune patient, it can be like pouring gasoline onto a fire.

When you have an autoimmune disease such as Hashimotos low thyroid, you want to balance the immune system, not boost it. Some people with autoimmunity already have over-zealous immune systems that hyper react to things, including foods, chemicals, and their own bodies.

In these people, using herbs or compounds that stimulate immunity will make their symptoms and condition worse.

Typically, the best strains for pain and inflammation are those that have higher amounts of CBD to THC. CBD is the compound best known for fighting pain and inflammation.

Im not saying *not* to use CBD. In fact, I have become a regular user of and advocate for CBD for back pain after fracturing my back and becoming paralyzed for a few days.

Im simply sharing this information so you arent caught off guard if you have a reaction.

To learn more about our services and to schedule a free consultation, please visitredriverhealthandwellness.com. We work with your prescribing physician for optimal results. Do not discontinue medication or hormone replacement therapy without consulting your prescribing physician.

S P O N S O R E D C O N T E N T

Sponsored content may be submitted to or developed by Cache Valley Daily for publication on behalf of the sponsor and in the sponsors interest. It may include promotional pieces, features, announcements, news releases and advertisements. Opinions expressed in sponsored content are those of the sponsor and not representative of Cache Valley Daily. Sponsors have no influence over Cache Valley Daily reporting and product apart from their own sponsored content.

Read the rest here:
CBD and cannabis have many proven health benefits, but if you have an autoimmune disease or Hashimoto's low thyroid, proceed cautiously - Cache Valley...

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol Myers Squibb (NYSE: BMY) today announced that OpdualagTM (nivolumab and relatlimab-rmbw), a new, first-in-class, fixed-dose combination of nivolumab and relatlimab, administered as a single intravenous infusion, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma.1 The approval is based on the Phase 2/3 RELATIVITY-047 trial, which compared Opdualag (n=355) to nivolumab alone (n=359).1,2

The trial met its primary endpoint, progression-free survival (PFS), and Opdualag more than doubled the median PFS when compared to nivolumab monotherapy, 10.1 months (95% Confidence Interval [CI]: 6.4 to 15.7) versus 4.6 months (95% CI: 3.4 to 5.6); (Hazard Ratio [HR] 0.75; 95% CI: 0.62 to 0.92, P=0.0055).1 The Opdualag safety profile was similar to that previously reported for nivolumab.1,2 No new safety events were identified with the combination when compared to nivolumab monotherapy.1,2 Grade 3/4 drug-related adverse events were 18.9% in the Opdualag arm compared to 9.7% in the nivolumab arm.2 Drug-related adverse events leading to discontinuation were 14.6% in the Opdualag arm compared to 6.7% in the nivolumab arm.2

Since the approval of the first immune checkpoint inhibitor more than 10 years ago, weve seen immunotherapy, alone and in combination, revolutionize the treatment of patients with advanced melanoma, said F. Stephen Hodi, M.D., director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber Cancer Institute.3 Todays approval is particularly significant, as it introduces an entirely new combination of two immunotherapies that may act together to help improve anti-tumor response by targeting two different immune checkpoints LAG-3 and PD-1.1,2

Opdualag is associated with the following Warnings & Precautions: severe and fatal immune-mediated adverse reactions (IMARs) including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, myocarditis and other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); and embryo-fetal toxicity.1 Please see Important Safety Information below.

While we have made great progress in the treatment of advanced melanoma over the past decade, we are committed to expanding dual immunotherapy treatment options for these patients, said Samit Hirawat, chief medical officer, global drug development, Bristol Myers Squibb.3 Inhibiting LAG-3 with relatlimab, in a fixed-dose combination with nivolumab, represents a new treatment approach that builds on our legacy of bringing innovative immunotherapy options to patients. The approval of a new medicine that includes our third distinct checkpoint inhibitor marks an important step forward in giving patients more options beyond monotherapy treatment.

Lymphocyte activation gene-3 (LAG-3) and programmed death-1 (PD-1) are two distinct inhibitory immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes, thus contributing to tumor-mediated T-cell exhaustion.2 The combination of nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) results in increased T-cell activation compared to the activity of either antibody alone.1 Relatlimab (in combination with nivolumab) is the first LAG-3-blocking antibody to demonstrate a benefit in a Phase 3 study.1 It is the third checkpoint inhibitor (along with anti-PD-1 and anti-CTLA-4) for Bristol Myers Squibb.

Todays approval is exciting news and offers new hope to the melanoma community. The availability of this treatment combination may enable patients to potentially benefit from a new, first-in-class dual immunotherapy, said Michael Kaplan, president and CEO, Melanoma Research Alliance.

The FDA-approved dosing for adult patients and pediatric patients 12 years of age or older who weigh at least 40 kg is 480 mg nivolumab and 160 mg relatlimab administered intravenously every four weeks.1 The recommended dosage for pediatric patients 12 years of age or older who weigh less than 40 kg, and pediatric patients younger than 12 years of age, has not been established.1

This application was approved under the FDAs Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.4 The review was also conducted under the FDAs Project Orbis initiative, which enabled concurrent review by the health authorities in Australia, Brazil and Switzerland, where the application remains under review.

About RELATIVITY-047

RELATIVITY-047 is a global, randomized, double-blind Phase 2/3 study evaluating the fixed-dose combination of nivolumab and relatlimab versus nivolumab alone in patients with previously untreated metastatic or unresectable melanoma.1,2 The trial excluded patients with active autoimmune disease, medical conditions requiring systemic treatment with moderate or high dose corticosteroids or immunosuppressive medications, uveal melanoma, and active or untreated brain or leptomeningeal metastases.1 The primary endpoint of the trial is progression-free survival (PFS) determined by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST v1.1).1 The secondary endpoints are overall survival (OS) and objective response rate (ORR).1 A total of 714 patients were randomized 1:1 to receive a fixed-dose combination of nivolumab (480 mg) and relatlimab (160 mg) or nivolumab (480 mg) by intravenous infusion every four weeks until disease progression or unacceptable toxicity.1

Select Safety Profile From RELATIVITY-047

Adverse reactions leading to permanent discontinuation of Opdualag occurred in 18% of patients.1 Opdualag was interrupted due to an adverse reaction in 43% of patients.1 Serious adverse reactions occurred in 36% of patients treated with Opdualag.1 The most frequent (1%) serious adverse reactions were adrenal insufficiency (1.4%), anemia (1.4%), colitis (1.4%), pneumonia (1.4%), acute myocardial infarction (1.1%), back pain (1.1%), diarrhea (1.1%), myocarditis (1.1%), and pneumonitis (1.1%).1 Fatal adverse reactions occurred in three (0.8%) patients treated with Opdualag and included hemophagocytic lymphohistiocytosis, acute edema of the lung, and pneumonitis.1 The most common (20%) adverse reactions were musculoskeletal pain (45%), fatigue (39%), rash (28%), pruritus (25%), and diarrhea (24%).1 The Opdualag safety profile was similar to that previously reported for nivolumab.1,2 No new safety events were identified with the combination when compared to nivolumab monotherapy.1,2 Grade 3/4 drug-related adverse events were 18.9% in the Opdualag arm compared to 9.7% in the nivolumab arm.2 Drug-related adverse events leading to discontinuation were 14.6% in the Opdualag arm compared to 6.7% in the nivolumab arm.2

About Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin.5 Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs.5,6 The incidence of melanoma has been increasing steadily for the last 30 years.5,6 In the United States, approximately 99,780 new diagnoses of melanoma and about 7,650 related deaths are estimated for 2022.5 Melanoma can be mostly treatable when caught in its very early stages; however, survival rates can decrease as the disease progresses.6

OPDUALAG INDICATION

OpdualagTM (nivolumab and relatlimab-rmbw) is indicated for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma.

OPDUALAG IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions (IMARs) listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

IMARs which may be severe or fatal, can occur in any organ system or tissue. IMARs can occur at any time after starting treatment with a LAG-3 and PD-1/PD-L1 blocking antibodies. While IMARs usually manifest during treatment, they can also occur after discontinuation of Opdualag. Early identification and management of IMARs are essential to ensure safe use. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying IMARs. Evaluate clinical chemistries including liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected IMARs, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue Opdualag depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if Opdualag requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose IMARs are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

Opdualag can cause immune-mediated pneumonitis, which may be fatal. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.7% (13/355) of patients receiving Opdualag, including Grade 3 (0.6%), and Grade 2 (2.3%) adverse reactions. Pneumonitis led to permanent discontinuation of Opdualag in 0.8% and withholding of Opdualag in 1.4% of patients.

Immune-Mediated Colitis

Opdualag can cause immune-mediated colitis, defined as requiring use of corticosteroids and no clear alternate etiology. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

Immune-mediated diarrhea or colitis occurred in 7% (24/355) of patients receiving Opdualag, including Grade 3 (1.1%) and Grade 2 (4.5%) adverse reactions. Colitis led to permanent discontinuation of Opdualag in 2% and withholding of Opdualag in 2.8% of patients.

Immune-Mediated Hepatitis

Opdualag can cause immune-mediated hepatitis, defined as requiring the use of corticosteroids and no clear alternate etiology.

Immune-mediated hepatitis occurred in 6% (20/355) of patients receiving Opdualag, including Grade 4 (0.6%), Grade 3 (3.4%), and Grade 2 (1.4%) adverse reactions. Hepatitis led to permanent discontinuation of Opdualag in 1.7% and withholding of Opdualag in 2.3% of patients.

Immune-Mediated Endocrinopathies

Opdualag can cause primary or secondary adrenal insufficiency, hypophysitis, thyroid disorders, and Type 1 diabetes mellitus, which can be present with diabetic ketoacidosis. Withhold or permanently discontinue Opdualag depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. In patients receiving Opdualag, adrenal insufficiency occurred in 4.2% (15/355) of patients receiving Opdualag, including Grade 3 (1.4%) and Grade 2 (2.5%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of Opdualag in 1.1% and withholding of Opdualag in 0.8% of patients.

Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Hypophysitis occurred in 2.5% (9/355) of patients receiving Opdualag, including Grade 3 (0.3%) and Grade 2 (1.4%) adverse reactions. Hypophysitis led to permanent discontinuation of Opdualag in 0.3% and withholding of Opdualag in 0.6% of patients.

Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Thyroiditis occurred in 2.8% (10/355) of patients receiving Opdualag, including Grade 2 (1.1%) adverse reactions. Thyroiditis did not lead to permanent discontinuation of Opdualag. Thyroiditis led to withholding of Opdualag in 0.3% of patients. Hyperthyroidism occurred in 6% (22/355) of patients receiving Opdualag, including Grade 2 (1.4%) adverse reactions. Hyperthyroidism did not lead to permanent discontinuation of Opdualag. Hyperthyroidism led to withholding of Opdualag in 0.3% of patients. Hypothyroidism occurred in 17% (59/355) of patients receiving Opdualag, including Grade 2 (11%) adverse reactions. Hypothyroidism led to the permanent discontinuation of Opdualag in 0.3% and withholding of Opdualag in 2.5% of patients.

Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated. Diabetes occurred in 0.3% (1/355) of patients receiving Opdualag, a Grade 3 (0.3%) adverse reaction, and no cases of diabetic ketoacidosis. Diabetes did not lead to the permanent discontinuation or withholding of Opdualag in any patient.

Immune-Mediated Nephritis with Renal Dysfunction

Opdualag can cause immune-mediated nephritis, which is defined as requiring use of steroids and no clear etiology. In patients receiving Opdualag, immune-mediated nephritis and renal dysfunction occurred in 2% (7/355) of patients, including Grade 3 (1.1%) and Grade 2 (0.8%) adverse reactions. Immune-mediated nephritis and renal dysfunction led to permanent discontinuation of Opdualag in 0.8% and withholding of Opdualag in 0.6% of patients.

Withhold or permanently discontinue Opdualag depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

Immune-Mediated Dermatologic Adverse Reactions

Opdualag can cause immune-mediated rash or dermatitis, defined as requiring use of steroids and no clear alternate etiology. Exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and Drug Rash with eosinophilia and systemic symptoms has occurred with PD-1/L-1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.

Withhold or permanently discontinue Opdualag depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

Immune-mediated rash occurred in 9% (33/355) of patients, including Grade 3 (0.6%) and Grade 2 (3.4%) adverse reactions. Immune-mediated rash did not lead to permanent discontinuation of Opdualag. Immune-mediated rash led to withholding of Opdualag in 1.4% of patients.

Immune-Mediated Myocarditis

Opdualag can cause immune-mediated myocarditis, which is defined as requiring use of steroids and no clear alternate etiology. The diagnosis of immune-mediated myocarditis requires a high index of suspicion. Patients with cardiac or cardio-pulmonary symptoms should be assessed for potential myocarditis. If myocarditis is suspected, withhold dose, promptly initiate high dose steroids (prednisone or methylprednisolone 1 to 2 mg/kg/day) and promptly arrange cardiology consultation with diagnostic workup. If clinically confirmed, permanently discontinue Opdualag for Grade 2-4 myocarditis.

Myocarditis occurred in 1.7% (6/355) of patients receiving Opdualag, including Grade 3 (0.6%), and Grade 2 (1.1%) adverse reactions. Myocarditis led to permanent discontinuation of Opdualag in 1.7% of patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant IMARs occurred at an incidence of <1% (unless otherwise noted) in patients who received Opdualag or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: Cardiac/Vascular: pericarditis, vasculitis; Nervous System: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other IMARs, consider a Vogt-Koyanagi-Haradalike syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: myositis/polymyositis, rhabdomyolysis (and associated sequelae including renal failure), arthritis, polymyalgia rheumatica; Endocrine: hypoparathyroidism; Other (Hematologic/Immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

Opdualag can cause severe infusion-related reactions. Discontinue Opdualag in patients with severe or life-threatening infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild to moderate infusion-related reactions. In patients who received Opdualag as a 60-minute intravenous infusion, infusion-related reactions occurred in 7% (23/355) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 receptor blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 receptor blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and data from animal studies, Opdualag can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Opdualag for at least 5 months after the last dose of Opdualag.

Lactation

There are no data on the presence of Opdualag in human milk, the effects on the breastfed child, or the effect on milk production. Because nivolumab and relatlimab may be excreted in human milk and because of the potential for serious adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with Opdualag and for at least 5 months after the last dose.

Serious Adverse Reactions

In Relativity-047, fatal adverse reaction occurred in 3 (0.8%) patients who were treated with Opdualag; these included hemophagocytic lymphohistiocytosis, acute edema of the lung, and pneumonitis. Serious adverse reactions occurred in 36% of patients treated with Opdualag. The most frequent serious adverse reactions reported in 1% of patients treated with Opdualag were adrenal insufficiency (1.4%), anemia (1.4%), colitis (1.4%), pneumonia (1.4%), acute myocardial infarction (1.1%), back pain (1.1%), diarrhea (1.1%), myocarditis (1.1%), and pneumonitis (1.1%).

Common Adverse Reactions and Laboratory Abnormalities

The most common adverse reactions reported in 20% of the patients treated with Opdualag were musculoskeletal pain (45%), fatigue (39%), rash (28%), pruritus (25%), and diarrhea (24%).

The most common laboratory abnormalities that occurred in 20% of patients treated with Opdualag were decreased hemoglobin (37%), decreased lymphocytes (32%), increased AST (30%), increased ALT (26%), and decreased sodium (24%).

Please see U.S. Full Prescribing Information for Opdualag.

OPDIVO + YERVOY INDICATIONS

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO + YERVOY IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%).

In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%).

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%).

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%).

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%).In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%).

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (<0.1%) and Grade 2 (1.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%).

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis.

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (<0.1%), Grade 3 (0.5%), and Grade 2 (0.6%).

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received OPDIVO monotherapy or OPDIVO in combination with YERVOY or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions: cardiac/vascular: myocarditis, pericarditis, vasculitis; nervous system: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; ocular: uveitis, iritis, and other ocular inflammatory toxicities can occur; gastrointestinal: pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis; musculoskeletal and connective tissue: myositis/polymyositis, rhabdomyolysis, and associated sequelae including renal failure, arthritis, polymyalgia rheumatica; endocrine: hypoparathyroidism; other (hematologic/immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis (HLH), systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1% of patients unless otherwise specified: nervous system: autoimmune neuropathy (2%), myasthenic syndrome/myasthenia gravis, motor dysfunction; cardiovascular: angiopathy, temporal arteritis; ocular: blepharitis, episcleritis, orbital myositis, scleritis; gastrointestinal: pancreatitis (1.3%); other (hematologic/immune): conjunctivitis, cytopenias (2.5%), eosinophilia (2.1%), erythema multiforme, hypersensitivity vasculitis, neurosensory hypoacusis, psoriasis.

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Haradalike syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions.

In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO.

See original here:
U.S. Food and Drug Administration Approves First LAG-3-Blocking Antibody Combination, Opdualag (nivolumab and relatlimab-rmbw), as Treatment for...