Melanoma patients teach us more about complications with Ipi

As more melanoma patients utilize Ipilimumab (Yervoy) for treatment, we are all learning more about potential side effects as well as ways to deal with them.

Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution.  Ryder, Wolchok, et al.  Edocr Relat Cancer.  2014 March 7.

"Novel immune checkpoint blockade with [ipi], an antibody blocking the cytotoxic T-lymphocyte antigen 4 is revolutionizing cancer therapy.  However, [ipi] induces symptomatic and sometimes severe, endocrine immune-related adverse events that are inconsistently recognized and reported."  In a retrospective study these folks looked at 256 records of patients receiving ipi in clinical trials between 2007 and 2013.  They looked at their hormone related labs, X-ray results, and clinical histories.  After ipi, they found that the patients demonstrated an 8% incidence of hypophysitis, 6% dealt with hypothyroidism/thyroiditis, and primary adrenal dysfunction was rare.  When Nivo and ipi
were given together, there was a 22% incidence of either thyroiditis or hypothyroidism, and a 9% incidence of hypophysitis.  "Symptomatic relief, in particular, for hypophysitis, was achieved in all patients with hormone replacement, although endogenous hormone secretion was rarely recovered."  "Prompt initiation with hormone replacement reverses symptoms."


Atypical neurological complications of ipilimumab therapy in patients with metastatic melanoma.  Liao, et al. Neuro Oncology. 2014 Jan 30. [Epup ahead of print]

"Ipi is a novel FDA approved recombinant human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 and has been used to treat patients with metastatic melanoma.  Immune-related side effects include inflammatory myopathy, aseptic meningitis, posterior reversible encephalopathy syndrome, Guillain-Barre' syndrome, myasthenia gravis-type syndrome, sensorimotor neuropathy, and inflammatory enteric neuropathy.  To date, there is no report for ipi-induced chronic inflammatory demyelinating polyneuropathy (CIDP), transverse myelitis, or concurrent myositis and myasthenia gravis-type syndrome."  So....these peeps wanted to get the word out about what they saw in their patients and what they did about it.  They had three patients to develop the last three syndromes after treatment with ipi at MD Anderson between July 2012 and June 2013.  Median time to onset of adverse effects after ipi was 1-2 weeks.  Ipi was discontinued.  Plasmapheresis (in which the antibodies in the plasma are skimmed off and the red blood cells returned to the patient) was initiated in the patient with CIDP and the concurrent myositis and myasthenia gravis-type syndromes.  High dose steroids were given to the other patient. The patients got better.  "Conclusion:  Ipi could induce a wide spectrum of neurological adverse effects.  Our findings support the standard treatment of withholding or discontinuing ipi.  Plasmapheresis or high-dose IV steroids may be considered as...initial treatment...  Improvement...may be seen within 2 weeks."

SO....Tricky business!!! Clearly Yervoy [ipi] can provide great help in treating melanoma but it is important to be aware of  potential side effects.  I'm glad they are putting this kind of information out there for doctors and patients since it seems that once such side effects are recognized for what they are...treatments and help are available.  Hang in there. - c