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SC ICIs for Solid Tumors
Subcutaneous Administration of Immune Checkpoint Inhibitors for Solid Tumors

Released: June 09, 2026

Patrick Forde
Patrick Forde, MD, PhD
Zev A. Wainberg
Zev A. Wainberg, MD
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Key Takeaways
  • Approved subcutaneous immune checkpoint inhibitor formulations may help reduce treatment burden by limiting the need for routine IV access and shortening administration time.
  • Timing of adverse events can be a useful clue to identify the cause in patients treated with combination regimens of immune checkpoint inhibitors and chemotherapy.
  • Counsel patients and caregivers that stopping immune checkpoint inhibitor therapy for adverse events when medically necessary does not appear to compromise response or survival outcomes.

Approval of Immune Checkpoint Inhibitor (ICI) Products in Subcutaneous Formulation
Zev A. Wainberg, MD:
Subcutaneous (SC) formulations for atezolizumab with hyaluronidase, nivolumab with hyaluronidase, and pembrolizumab with berahyaluronidase alfa are approved. After approximately 10-15 years of exclusively using intravenous (IV) immunotherapy options across various solid tumors, this is a remarkable advancement for the care of patients with solid tumors, with potential for saving time and resources, while improving patient quality of life.

Compared with IV administration, SC dosing could reduce treatment burden and improve outcomes by eliminating the need for routine IV access and shortening administration time, thereby opening up chair time to increase the number of patients who can be treated. SC administration can be delivered in outpatient clinic or infusion center settings, which could also broaden access to treatment. SC administration also typically requires no more than 1 “poke” for administration. By contrast, IV administration generally requires separate infusion appointments, IV access, and, in some cases, more than 1 “poke.”

Spectrum of Immune-Related Toxicity
Patrick Forde, MD, PhD:
Adverse events (AEs) related to immunotherapies span multiple organ systems and require early recognition to address effectively. Both caregivers and patients should be instructed to alert the clinic promptly if patients develop any new, unusual symptoms. This is not a situation where “watching and waiting” is an acceptable course of action, as ICI-related AEs can become very serious very quickly.

In general, the grade of toxicity should guide management of immune-related AEs, with treatment intensity increasing with increasing severity. Mild grade 1 AEs are often managed with symptomatic and supportive care in the outpatient setting. For grade 2 AEs, treatment is commonly held, and oral steroids may be started. For grade 3/4 AEs, patients often require hospital-based care, IV steroids, referral to the appropriate specialist, and, in some cases, stronger immunosuppressive therapy. For rash or pruritus, therapy may be restarted after resolution, depending on severity and clinical context.

When patients are receiving ICIs combined with chemotherapy, it can be challenging to determine whether an AE is more consistent with chemotherapy or ICI therapy, but timing can be a useful clue. Chemotherapy-related AEs usually have a rapid onset after treatment and tend to follow a cyclical pattern of onset and recovery. By contrast, ICI-related AEs may not appear until after several treatment cycles and can persist or worsen over time. This distinction matters for management. Holding treatment can be appropriate in either setting, but chemotherapy-related AEs may also be managed by dose reduction or switching to a different agent, whereas those strategies do not apply to immune-related AEs. Steroids are rarely useful for chemotherapy-related AEs but are a standard tool for immune-related AEs. In severe cases, either chemotherapy or immunotherapy may be permanently discontinued to prevent persistent or worsening AEs.

Colitis Management
Zev A. Wainberg, MD:
ICI-induced colitis is a common AE. For grade 1/2 colitis, management depends on symptom severity, whether symptoms are improving, and the overall clinical context. For grade 1 diarrhea, ICI therapy may be continued with close monitoring and supportive care, such as antidiarrheals and hydration, with a stool workup when appropriate. However, if grade 1 symptoms persist beyond 2 weeks or if there is concern for progression, low-dose prednisone may be started. For grade 2 diarrhea, ICI therapy is generally held, supportive measures are continued, and prednisone is recommended. In these instances, colonoscopy can also be considered after stool studies. If symptoms improve to grade 1 or resolve, steroids can be tapered off, and treatment may be resumed at the healthcare professional’s discretion.

Management of grade 3 colitis builds and intensifies on the grade 2 approach, with a higher dose of prednisone or the equivalent recommended until symptoms improve to grade 1, followed by a 4- to 6-week taper. In patients with high-risk endoscopic features or an inadequate response to steroids after 3 days, infliximab or vedolizumab should be considered. Hospitalization may also be needed, particularly when dehydration or electrolyte abnormalities are present, and repeat colonoscopy can be considered in immunosuppression-refractory cases. Permanent discontinuation of ICI therapy may be appropriate.

Grade 4 colitis is life-threatening and requires urgent intervention. In these cases, treatment should be permanently discontinued, and the patient should be managed with inpatient care. Methylprednisolone or an equivalent regimen is recommended until symptoms improve to grade 1, followed by a 4- to 6-week taper. If there is still an inadequate response after 3 days of steroids, infliximab or vedolizumab should be considered, and lower gastrointestinal endoscopy may help evaluate refractory symptoms or exclude new infection. Additional refractory options include fecal transplant, tofacitinib, or an IL-12–blocking antibody.

Concomitant hepatitis and colitis are uncommon but may require permanent ICI discontinuation and systemic immunosuppression.

Management of Immune-Related Hepatobiliary Toxicities
Zev A. Wainberg, MD:
Immune-related hepatobiliary toxicity should be managed by grade after other causes have been ruled out, such as viral hepatitis, disease-related liver dysfunction, other drug-induced injury, or muscle-related sources. For grade 1 elevations, treatment may continue with more frequent monitoring. For grade 2 elevations, the ICI should be withheld, and prednisone can be considered. Liver tests should be repeated every 3-5 days. For grade 3 elevations, the ICI should be withheld, and prednisone or methylprednisolone should be started, with additional immunosuppression or hepatology referral considered if there is no improvement. For grade 4 elevations, the ICI should be discontinued and inpatient care considered.

Counseling Patients and Caregivers
Patrick Forde, MD, PhD:
Counseling for patients and caregivers should set evidence-based expectations for immunotherapy, including that benefits may take longer to emerge than with chemotherapy or targeted therapy. Patients and caregivers should be told to monitor closely for new symptoms and to contact the oncology team promptly if any arise. They should also be instructed to report any emergency department visits or care from other healthcare professionals, carry an immunotherapy wallet card at all times, and receive clear education on immune-related AE management. Counseling can also address that, when clinically necessary, stopping ICIs because of AEs and treating immune-related AEs with steroids does not appear to compromise response or survival.

Frequently Asked Questions

Are you concerned about potential resistance to immunotherapy?
Patrick Forde, MD, PhD:
Unfortunately, in many tumor types, there are limited options once a patient’s tumor becomes resistant to immunotherapy. However, this varies across tumor types. I would select a few common tumor types, such as lung, kidney, and melanoma, and review resistance mechanisms in those settings, including upregulation of other immune checkpoints, such as LAG3 or TIM-3. Unusual mechanisms, such as neoantigen loss, may also occur.

Are there any clinical factors that push you away from standard pembrolizumab plus chemotherapy for advanced NSCLC despite guidelines?
Patrick Forde, MD, PhD:
For NSCLC, I favor pembrolizumab if PD-L1 is high. Within this group, patients who have a lower burden of disease tend to do well on pembrolizumab. I am also more likely to use pembrolizumab monotherapy vs pembrolizumab plus chemotherapy for these patients. Moreover, we also see a role for atezolizumab monotherapy in those with a lower PD-L1 score, including frail and elderly patients.

What are some of the most common challenges and barriers to optimal use of SC ICIs?
Patrick Forde, MD, PhD:
I would not recommend SC ICIs for very thin patients, due to a lack of SC tissue, but that is not a common occurrence. Practice challenges include reimbursement and explaining to the patient that SC administration is equivalent to IV administration.

Are there differences in side effects between IV and SC administration?
I have switched most patients to SC ICI administration and have not observed differences in AEs. There have not been any differences in antidrug antibodies or ICI-related AEs with SC ICI vs IV ICI administration in my practice.

Your Thoughts
What challenges or questions do you have regarding implementation of SC ICI formulations for your patients with solid tumors? Answer the polling question and leave a comment to join the discussion.
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