Opdivo and Cardio Myopathy

Hey Linda, 

So sorry you are dealing with that!!  However, your docs sound like they are on top of things.  While I have not dealt with any cardiac side effects personally, I have been following side effects caused by all melanoma therapies for years.  Here are some abstracts from posts as they relate to immunotherapy and cardiac toxicity.  I don't post these to frighten you but as a resource for you and your docs to contact the authors should they feel the need.

Myocarditis as an immune-related adverse event with ipilimumab/nivolumab combination therapy for metastatic melanoma.  Mehta, Gupta, Hannallah, et al.  Melanoma Res. 2016 Jun;26

Autoimmune Cardiotoxicity of Cancer Immunotherapy. Cheng, Loscalzo. Trends Immunol. 2016 Dec 2.

Contemporary immunotherapies (e.g., immune checkpoint inhibitors), which enhance the immune response to cancer cells, improve clinical outcomes in several malignancies. A recent study reported the cases of two patients with metastatic melanoma who developed fatal myocarditis during ipilimumab and nivolumab combination immunotherapy; these examples highlight the risk of unbridled activation of the immune system.

New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma.Behling, Kaes, Munzel, et al. Melanoma Res. 2017 Apr;27.

There has been considerable progress in treating malignant melanoma over the last few years. The immune-checkpoint-inhibitors nivolumab and pembrolizumab have been approved by the Food and Drug Administration in 2014 for the therapy of metastatic melanoma. Anti-programmed cell death-1-blocking antibodies are known to cause immune-related adverse events. Physicians should be aware of common and rare side effects and pay attention to new ones. We therefore report a severe and life-threatening side effect of anti-programmed cell death-1 immunotherapy with nivolumab that has not been previously reported: the development of a third-degree atrioventricular block. After a second infusion with nivolumab, our patient developed a troponin I-positive and autoantibody-positive myositis and a few days later a new-onset third-degree atrioventricular block. This is most likely because of an autoimmune-induced myositis with a cardiac impairment in terms of a myocarditis, which led to an impairment of the conduction of cardiac electrical stimuli.

Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy.  Heinzerling, Ott, Hodi, et al.  J Immunother Cancer. 2016 Aug 16. 

Immune-checkpoint blocking antibodies have demonstrated objective antitumor responses in multiple tumor types including melanoma, non-small cell lung cancer (NSCLC), and renal cell cancer (RCC). In melanoma, an increase in overall survival has been demonstrated with anti-CTLA-4 and PD-1 inhibition. However, a plethora of immune-mediated adverse events has been reported with these agents. Immune-mediated cardiotoxicity induced by checkpoint inhibitors has been reported in single cases with variable presentation, including myocarditis and pericarditis. Among six clinical cancer centers with substantial experience in the administration of immune-checkpoint blocking antibodies, eight cases of immune-related cardiotoxicity after ipilimumab and/or nivolumab/pembrolizumab were identified. Diagnostic findings, treatment and follow-up are reported. A large variety of cardiotoxic events with manifestations such as heart failure, cardiomyopathy, heart block, myocardial fibrosis and myocarditis was documented. This is the largest case series to date describing cardiotoxicity of immune-checkpoint blocking antibodies. Awareness, monitoring of patients with pre-existing cardiac disorders and prompt evaluation by the treatment team is essential. Treatment including application of steroids is critical for patient safety.

Fulminant Myocarditis with Combination Immune Checkpoint Blockade.  Johnson, Balko, Compton, Chalkias, … Sosman, Moslehi, et al.  N Engl J Med. 2016 Nov 3.  

Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates. Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle. Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction.

Here is a link to a full post on cardiac toxicity and immunotherapy:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2017/04/the-mice-told-us-socardiac-toxicity-and.html  

So…I am super glad that your docs found this early and started treatment!!!  

Also on the good side, there is this regarding folks who have to stop immunotherapy due to side effects (should that turn out to be the case for you): 

 http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2017/08/40-of-melanoma-patients-stop-ipinivo.html  

Hope this helps a bit.  Hang in there.  I wish you my best.  Celeste

Just finished my doctor visits today for the exact same issue regarding 10 Nivo treatments and Myocarditis for stage 3-C adjuvant therapy.  It started with an emergency room visit to MDA for colitis.  When I arrived I had a Ventricular Tachardia (racing of the heart for a few seconds) so they did a blood test for CRT that measured 44.20-Anything above 3.0 requires further investigation.

They immediately put me on iv steroids of 125mg and did a MRI Cardiac w/wo contrast which showed inflammation.  They then started 650ml Privigen once daily for 4 days to go along with the steroids.  During this time I also had a Heart Cath that took a biopsy of some inflamed heart tissue.  By this time the Privigen and steroids had done its job and my CRT was 14 with minor inflammation and no more tachycardias.

We got to see multiple melanoma specialists and other doctors while in the hospital for 10 days.  Here is the info we gathered.

Happens to about 1/1000 on Nivo alone.  So far complete recovery for treated patients with this problem.  I am pretty much back to normal in 3 weeks.  Cardiologist did state 1 person had died early on from this.

Treatment was stopped for me because of risk with no measurable disease.  If melanoma returns will start again-My doctor did not seem concerned at all.  I had grade 3 colitis, Myocarditis, and endocrine system problems.

Their treatment history of stage 4 patients showed "better response rates"  for someone with my adverse events if weined from steroids quickly.  The doc used those words and "glass half full" when discussing my prognosis.  I was able to stop steroids completely within 7 days of leaving hospital.