Very comprehensive guide of PD-1 and PD-L1 blocking drugs associated toxicity/side effects management.
Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group
https://www.ncbi.nlm.nih.gov/pmc/articl ... le_300.pdf
As many of our patients are taking these drugs in an out of town clinical trial setting or off label without the close supervision, it is important to educate ourselves re. numerous side immunotherapy effects that are very variable, non-specific and can be very acute/need to be managed in an emergency type of response. Do not expect local ER to know how to manage them, always have a note on yourself with the contact information of the drug prescribing physician/nurse or a clinical trial investigator. You can also print out the recommendations in advance so you can and give it to the ER crew.
Managing toxicities associated with immune checkpoint inhibitors (Updated recommendations)
Re: Managing toxicities associated with immune checkpoint inhibitors (Updated recommendations)
Severe cytokine release syndrome in a patient receiving PD-1-directed therapy
The catastrophic event of the severe adverse reaction happened 3 daays after the second dose of the Opdivo (nivolumab). High-dose corticosteroids
and the IL-6 inhibitor tocilizumab were used to manage this acute toxicity.
"Four days after the second infusion of nivolumab, the patient presented
with 3 days of severe fatigue, myalgias, fever, diffuse maculopapular
rash, and subsequent encephalopathy. On presentation, the
patient had a temperature of 41.0 °C, heart rate of 160–170 beats per
minute, blood pressure of 83/44 mm Hg, pulse oximetry of 88%, and
was disoriented. She received resuscitation with 4 l of normal saline and mentation improved.
Due to initially refractory hypotension and
tachycardia, she was started on stress-dose hydrocortisone. Blood cultures
were obtained and broad-spectrum antibiotics were administered.
Initial laboratory assessment was notable for thrombocytopenia,
lactic acidosis, evidence of acute kidney and liver injury, and abnormal
coagulation studies (Table 1). Lactic acid and kidney injury improved
within 12 hr with fluid resuscitation. A chest X-ray was unchanged and
urinalysis and ammonia were normal. C-reactive protein, which has
been shown to be a surrogate marker for IL-6 in CRS,5,6 was also elevated
to 4.97 mg/l (reference <0.30 mg/l) (Fig. 1). A cytokine profile
was obtained and results eventually demonstrated elevated levels of
IL-6, IL-8, IL-10, and interferon-gamma.
Given the patient had no central line, was not considered significantly
immunocompromised, had serial negative blood cultures, and
had no obvious source of infection, a diagnosis of immune hyperactivation
due to nivolumab was considered. In addition to continuing broadspectrum
antibiotics, the patient received high-dose corticosteroids
and the IL-6 inhibitor tocilizumab1,2 Over the initial 48 hr of targeted
CRS therapy, fevers improved and C-reactive protein (CRP) declined.
A second dose of tocilizumab was given 72 hr after the first, when the
patient again became febrile. The patient’s diffuse rash improved over
the following week and she was discharged from hospital on a corticosteroid
taper 11 days nivolumab postinfusion.
At follow-up visit 14 days postinfusion, coagulation studies, complete
blood count, and liver function were all normal and patient was
asymptomatic. However, 25 days postinfusion patient reported new
headaches, double vision, and nausea. An magnetic resonance imaging
(MRI) was undertaken and demonstrated no additional lesions,
but increased edema surrounding multiple brain metastasis. Additionally
at this time, repeat laboratory evaluation demonstrated a platelet
count of 98,000/mcl and fibrinogen of 106 mg/dl. Patient was started
on dexamethasone and symptoms resolved over 48 hr and laboratory
values again normalized. The patient was restarted on and remains on
pazopanib monotherapy at this time and is doing well 2 months post-
CRS.
and the IL-6 inhibitor tocilizumab were used to manage this acute toxicity.
"Four days after the second infusion of nivolumab, the patient presented
with 3 days of severe fatigue, myalgias, fever, diffuse maculopapular
rash, and subsequent encephalopathy. On presentation, the
patient had a temperature of 41.0 °C, heart rate of 160–170 beats per
minute, blood pressure of 83/44 mm Hg, pulse oximetry of 88%, and
was disoriented. She received resuscitation with 4 l of normal saline and mentation improved.
Due to initially refractory hypotension and
tachycardia, she was started on stress-dose hydrocortisone. Blood cultures
were obtained and broad-spectrum antibiotics were administered.
Initial laboratory assessment was notable for thrombocytopenia,
lactic acidosis, evidence of acute kidney and liver injury, and abnormal
coagulation studies (Table 1). Lactic acid and kidney injury improved
within 12 hr with fluid resuscitation. A chest X-ray was unchanged and
urinalysis and ammonia were normal. C-reactive protein, which has
been shown to be a surrogate marker for IL-6 in CRS,5,6 was also elevated
to 4.97 mg/l (reference <0.30 mg/l) (Fig. 1). A cytokine profile
was obtained and results eventually demonstrated elevated levels of
IL-6, IL-8, IL-10, and interferon-gamma.
Given the patient had no central line, was not considered significantly
immunocompromised, had serial negative blood cultures, and
had no obvious source of infection, a diagnosis of immune hyperactivation
due to nivolumab was considered. In addition to continuing broadspectrum
antibiotics, the patient received high-dose corticosteroids
and the IL-6 inhibitor tocilizumab1,2 Over the initial 48 hr of targeted
CRS therapy, fevers improved and C-reactive protein (CRP) declined.
A second dose of tocilizumab was given 72 hr after the first, when the
patient again became febrile. The patient’s diffuse rash improved over
the following week and she was discharged from hospital on a corticosteroid
taper 11 days nivolumab postinfusion.
At follow-up visit 14 days postinfusion, coagulation studies, complete
blood count, and liver function were all normal and patient was
asymptomatic. However, 25 days postinfusion patient reported new
headaches, double vision, and nausea. An magnetic resonance imaging
(MRI) was undertaken and demonstrated no additional lesions,
but increased edema surrounding multiple brain metastasis. Additionally
at this time, repeat laboratory evaluation demonstrated a platelet
count of 98,000/mcl and fibrinogen of 106 mg/dl. Patient was started
on dexamethasone and symptoms resolved over 48 hr and laboratory
values again normalized. The patient was restarted on and remains on
pazopanib monotherapy at this time and is doing well 2 months post-
CRS.
Olga
Re: Managing toxicities associated with immune checkpoint inhibitors (Updated recommendations)
Olga
Thanks for the resource and link.
It’s alwsys helpful to know of the what if’s ...
In reading of the young lady’s tumor load, she is certainly a canidate for the potiential of cytokine overload , don’t you agree ? Lungs ,brain leg etc ?
However for the doctors to of managed her vitals somewhat crashing , is amazing .
The possibility of a person with any significant tumor load, having a reaction to some degree , is a likely hood with these immune inhibitors/ targeted antibody therapies .
I hope the patient in the study ,continues to find success with the immune therapy.
I found a study of several studies of the various immune therapies , that list the statistical info thus far on various cancer and users of immune therapies adverse reaction from typical to grade 3/4 ,reactions.
I’ll post it in “other medical reports “
Thanks for the resource and link.
It’s alwsys helpful to know of the what if’s ...
In reading of the young lady’s tumor load, she is certainly a canidate for the potiential of cytokine overload , don’t you agree ? Lungs ,brain leg etc ?
However for the doctors to of managed her vitals somewhat crashing , is amazing .
The possibility of a person with any significant tumor load, having a reaction to some degree , is a likely hood with these immune inhibitors/ targeted antibody therapies .
I hope the patient in the study ,continues to find success with the immune therapy.
I found a study of several studies of the various immune therapies , that list the statistical info thus far on various cancer and users of immune therapies adverse reaction from typical to grade 3/4 ,reactions.
I’ll post it in “other medical reports “
Debbie