Immunotherapy has reshaped oncology in the last decade, with more than 20 FDA approvals for immune-based cancer drugs since 2011—but the treatments come with serious trade-offs.
Beginning with immune checkpoint inhibitors and more recently expanding into engineered cell therapies, immune-based approaches have produced durable remissions in cancers that were once almost uniformly fatal.
The disadvantages of immunotherapy are real for patients, clinicians, and health systems: powerful benefits for some come alongside unique toxicities, logistical hurdles, and steep costs that deserve clear-eyed discussion.
Clinical and safety limitations
Altering the immune system brings a distinctive spectrum of harms and an uneven benefit profile across tumor types. The next three items explain the main clinical and safety disadvantages: severe immune-related adverse events, some permanent organ damage, and widely variable response rates.
1. Severe immune-related adverse events
Immune-related adverse events (irAEs) can be severe and affect multiple organs, from lungs and gut to heart and nervous system.
Grade 3–4 irAEs occur in a meaningful minority of patients—roughly 10–30% depending on drug and regimen—and are more frequent with combination checkpoint blockade. Organs commonly involved include the lungs (pneumonitis), colon (colitis), liver (hepatitis), and heart (myocarditis).
Severe events often lead to hospitalization, intensive-care support, high‑dose corticosteroids or other immunosuppressants (for example, infliximab or mycophenolate), and discontinuation of cancer therapy. For guidance see ASCO recommendations (ASCO) and FDA safety communications (FDA).
2. Chronic autoimmune conditions and irreversible organ damage
Some toxicities are long-lasting or permanent, rather than transient treatment side effects.
Endocrine injuries are a clear example: hypophysitis and thyroiditis can lead to lifelong hormone replacement in a measurable fraction of patients. Checkpoint inhibitors have been linked to new insulin-dependent diabetes and permanent adrenal insufficiency after hypophysitis in case series and registry reports.
That reality changes survivorship: patients may live longer but then require chronic endocrine follow-up, replacement medications, and altered quality-of-life plans. Endocrinology society statements and peer-reviewed series document these patterns and recommend long-term monitoring.
3. Limited and unpredictable effectiveness for many patients
While some cancers respond spectacularly, many patients derive little or no benefit from immunotherapy.
Objective response rates in many solid tumors commonly fall in the 20–40% range; other tumors—pancreatic and many ovarian cancers, for example—show much lower rates. Certain biomarkers help enrich for responders but are imperfect.
PD‑L1 expression and tumor mutational burden (TMB) increase the probability of response in some settings, but neither is definitive. Mismatch repair–deficient tumors show high response rates, whereas so-called “cold” tumors generally do not. The practical consequence: some patients undergo toxic, expensive treatment without clinical benefit.
Practical, manufacturing, and monitoring challenges
Delivering modern immunotherapies often requires complex infrastructure, long lead times, and tight coordination between clinics, manufacturers, and couriers. The following items highlight cost, manufacturing fragility, and post‑treatment monitoring burdens.
4. Very high cost and limited affordability
Some immunotherapies carry six‑figure price tags that limit who can access them.
For example, list prices for autologous CAR‑T products have been in the hundreds of thousands: Yescarta (Gilead/Kite) around $373,000 and Kymriah (Novartis) around $475,000 at launch—figures that exclude hospitalization, supportive care, and management of complications.
Those additional costs—ICU stays, tocilizumab doses, rehabilitation, travel and lodging for patients—push total episode-of-care costs higher. Insurance approvals, prior authorizations, and appeals are common, and patients without robust coverage face catastrophic financial strain.
5. Complex manufacturing, supply-chain failures, and delays
Autologous cell therapies require specialized collection, manufacturing, and quality‑control steps that can fail or be delayed.
Typical vein‑to‑vein timelines for CAR‑T products run roughly 2–6 weeks. During that interval a fraction of patients experience manufacturing failures, product-release holds, or logistic hiccups that prevent infusion.
Those delays may force bridging systemic therapy, allow disease progression, or eliminate a patient’s chance for a potentially curative infusion. Centralized manufacturing models (used by some Novartis and Gilead/Kite products) create transport dependencies; decentralized models reduce shipping but demand local capacity.
6. Intensive monitoring and potential for hospitalization
Many immune-based treatments require close observation after infusion because complications can emerge rapidly.
Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are common post‑CAR‑T complications; severe CRS or ICANS occur in roughly 10–20% of recipients depending on product and population.
Management may include tocilizumab, high‑dose corticosteroids, and ICU-level care. That need for experienced teams and sometimes inpatient monitoring limits safe delivery to specialized centers and increases both cost and travel burden for patients.
Financial, ethical, and long-term unknowns
Money, ethics, and incomplete long‑term data create systemic challenges beyond immediate safety and logistics. The final two items cover patient-level financial toxicity and gaps in long‑term evidence.
7. Financial toxicity and insurance barriers
Even when a therapy itself is technically covered, patients often face substantial out‑of‑pocket and indirect costs.
Surveys show nearly one‑third of cancer survivors report significant financial distress, and immunotherapies add new drivers: large co‑payments, travel to specialized centers, lodging, and lost wages during prolonged evaluation or monitoring.
Prior‑authorization denials and lengthy appeals are common with novel agents, delaying care. Some systems are experimenting with outcomes‑based contracts between manufacturers and payers, but these arrangements are complex and not yet widespread, leaving many patients with difficult choices about whether to proceed.
8. Unknown long-term effects and data gaps
Many immunotherapies are still relatively new, so data beyond five to ten years remain limited for a number of agents and indications.
Open questions include the frequency of late autoimmune sequelae, risk of secondary malignancies after immune modulation, fertility effects, and whether some durable remissions will ultimately relapse. Special populations—pregnant people, children, and patients with preexisting autoimmune disease—are underrepresented in trials.
Addressing these gaps requires robust post‑marketing surveillance, long‑term registries, and routine enrollment of treated patients into follow‑up studies. Clinicians should emphasize informed consent and encourage participation in registries when possible.
Summary
- Severe immune-related toxicities can be life‑threatening and sometimes permanent, affecting organs such as the heart, lungs, gut, and endocrine system.
- Delivering modern immune therapies often means six‑figure drug costs, weeks‑long manufacturing timelines, and centralized care that limits access for many patients.
- Response rates vary widely by tumor biology; biomarkers like PD‑L1 and TMB help but do not guarantee benefit, so some patients endure harms without clear advantage.
- Long‑term safety, late effects, and equity issues remain under-studied—supporting registries, trials, and policy reforms will be crucial to manage these gaps.
