Immunotherapy for Mesothelioma: How Keytruda and Opdivo Are Changing Treatment in 2026

Immunotherapy has fundamentally changed mesothelioma treatment, offering patients new hope through drugs that harness the body's own immune system to fight cancer [1]. In October 2020, the FDA approved the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) as the first new first-line treatment for mesothelioma in over 15 years [2]. These checkpoint inhibitors are extending survival and producing durable responses that were rarely seen with chemotherapy alone.

Executive Summary

Immunotherapy represents a breakthrough in mesothelioma treatment, with FDA-approved checkpoint inhibitors now available as first-line therapy. The CheckMate 743 trial demonstrated that Opdivo plus Yervoy extends median overall survival to 18.1 months compared to 14.1 months with chemotherapy—a 26% reduction in death risk [1]. Keytruda (pembrolizumab) shows promising results in clinical trials and off-label use [3]. New approaches combining immunotherapy with surgery and chemotherapy are producing even better outcomes, with some perioperative trials showing 80% surgical success rates and median survival exceeding 28 months [4]. Understanding these treatments helps patients make informed decisions about their care.

9 Key Facts About Mesothelioma Immunotherapy in 2026

FDA Approval: Opdivo + Yervoy approved October 2020 for first-line treatment [2]
Median Survival: 18.1 months with immunotherapy vs. 14.1 months with chemotherapy [1]
3-Year Survival: 23% alive at 3 years with immunotherapy vs. 15% with chemotherapy [1]
How It Works: Checkpoint inhibitors release the immune system's brakes on cancer cells
Key Drugs: Opdivo (nivolumab), Yervoy (ipilimumab), Keytruda (pembrolizumab)
Treatment Schedule: IV infusion every 2-4 weeks depending on regimen
Side Effects: Different from chemotherapy—immune-related, often manageable
Combination Trials: Immunotherapy + surgery showing 80% surgical success [4]
Clinical Trials: 56+ active trials testing new immunotherapy approaches

How Does Immunotherapy Work for Mesothelioma?

Immunotherapy drugs work differently than chemotherapy. Instead of directly killing cancer cells, they help your immune system recognize and destroy cancer [5].

Understanding Checkpoint Inhibitors

Your immune system has built-in "checkpoints"—proteins that prevent immune cells from attacking healthy tissue. Cancer cells exploit these checkpoints to hide from the immune system:

PD-1/PD-L1 pathway: Cancer cells display PD-L1 protein, which binds to PD-1 on immune cells, telling them not to attack
CTLA-4 pathway: This checkpoint normally prevents T-cells from activating too strongly

Checkpoint inhibitors block these proteins, releasing the immune system's "brakes" and allowing it to attack cancer cells:

Opdivo (nivolumab): Blocks PD-1 on immune cells
Keytruda (pembrolizumab): Blocks PD-1 on immune cells
Yervoy (ipilimumab): Blocks CTLA-4, enhancing T-cell activation

18.1 Months

Median overall survival with Opdivo + Yervoy in the CheckMate 743 trial

Why Combination Therapy Works Better

The FDA-approved regimen combines two checkpoint inhibitors that work through different mechanisms [2]:

Opdivo blocks PD-1, preventing cancer cells from hiding
Yervoy blocks CTLA-4, boosting T-cell activation and proliferation
Together, they attack cancer through two complementary pathways

"The approval of Opdivo plus Yervoy marked a turning point in mesothelioma treatment. For the first time in 15 years, patients had a new first-line option. In my years working in pharmaceuticals and patient advocacy, I've seen how immunotherapy has given hope to families who had few options before."
— David Foster, Executive Director of Client Services, Danziger & De Llano

What Are the Results of Immunotherapy for Mesothelioma?

Clinical trial data shows immunotherapy produces meaningful improvements in survival for mesothelioma patients.

CheckMate 743 Trial Results

This Phase 3 trial compared Opdivo + Yervoy to standard chemotherapy in 605 patients with unresectable pleural mesothelioma [1]:

Outcome	Opdivo + Yervoy	Chemotherapy
Median Overall Survival	18.1 months	14.1 months
2-Year Survival Rate	41%	27%
3-Year Survival Rate	23%	15%
Response Rate	40%	43%
Duration of Response	11.0 months	6.7 months

Key findings:

26% reduction in death risk compared to chemotherapy
Responses lasted nearly twice as long with immunotherapy
Benefit seen across most patient subgroups
Particularly strong benefit for non-epithelioid subtypes

Keytruda Trial Results

Pembrolizumab (Keytruda) has shown activity in mesothelioma through several trials [3]:

KEYNOTE-028: 20% response rate in pretreated patients
KEYNOTE-158: 8-10% response rate, with some long-term survivors
DREAM Trial: Combined with chemotherapy, showed improved outcomes

While not FDA-approved specifically for mesothelioma, Keytruda is used off-label and in clinical trials.

Long-Term Survivors

One of the most encouraging aspects of immunotherapy is the potential for durable responses:

Some patients remain in remission for years
"Long-tail" survivors continue responding long after treatment ends
Immune memory may provide ongoing protection against recurrence

"What excites me most about immunotherapy is the tail of the survival curve—there are patients who were treated years ago who are still doing well. That durability was rarely seen with chemotherapy alone. It doesn't happen for everyone, but it shows what's possible."
— David Foster, Executive Director of Client Services, Danziger & De Llano

Who Qualifies for Mesothelioma Immunotherapy?

Most patients with unresectable pleural mesothelioma are candidates for immunotherapy, but several factors determine eligibility.

FDA-Approved Indication

Opdivo + Yervoy is approved for [2]:

Adults with unresectable malignant pleural mesothelioma
First-line treatment (no prior systemic therapy)
No specific biomarker requirement (unlike some other cancers)

General Eligibility Factors

Your oncologist will evaluate:

Performance status: Ability to carry out daily activities
Organ function: Adequate liver, kidney, and thyroid function
Autoimmune conditions: Active autoimmune diseases may increase side effect risk
Current medications: Steroids may interfere with immunotherapy effectiveness

Biomarker Testing

While not required for FDA approval, some biomarkers may predict response:

PD-L1 expression: Higher levels may indicate better response
Tumor mutation burden: More mutations may mean better response
Histological subtype: Non-epithelioid may respond particularly well

The treatment options guide provides additional information about available therapies.

What Are the Side Effects of Immunotherapy?

Immunotherapy side effects differ from chemotherapy because they result from an activated immune system [5].

Common Side Effects

Fatigue: Feeling tired or weak (very common)
Skin reactions: Rash, itching, vitiligo
Gastrointestinal: Diarrhea, nausea, decreased appetite
Fever and chills: During or after infusions

Immune-Related Adverse Events

Because immunotherapy activates the immune system, it may also attack healthy tissue:

Pneumonitis: Lung inflammation (important to monitor in mesothelioma patients)
Colitis: Intestinal inflammation causing diarrhea
Hepatitis: Liver inflammation
Thyroiditis: Thyroid inflammation affecting hormone levels
Nephritis: Kidney inflammation

Managing Side Effects

Most immune-related side effects are manageable:

Regular monitoring with blood tests and imaging
Steroids can often control inflammation
Treatment may be paused and resumed when side effects resolve
Some patients develop hypothyroidism requiring thyroid medication

80%

Surgical success rate with perioperative immunotherapy at Johns Hopkins

Combining Immunotherapy with Other Treatments

Researchers are exploring combinations that may enhance immunotherapy effectiveness. The clinical trials database lists ongoing studies.

Immunotherapy Plus Surgery

Perioperative immunotherapy—given before and/or after surgery—is showing promising results [4]:

Johns Hopkins trial: 80% surgical success rate
Median survival: 28.6 months
Immunotherapy may shrink tumors before surgery
Post-surgical immunotherapy may prevent recurrence

Immunotherapy Plus Chemotherapy

Adding immunotherapy to chemotherapy may improve outcomes:

DREAM trial: Pembrolizumab + chemotherapy showed activity
IND.227 trial: Testing cisplatin/pemetrexed + pembrolizumab
Chemotherapy may enhance immune response

Emerging Approaches

New immunotherapy combinations under investigation:

CAR T-cell therapy: Genetically modified immune cells targeting mesothelin
Triple combination: Two checkpoint inhibitors plus chemotherapy
Immunotherapy + radiation: Radiation may sensitize tumors to immune attack

"What we're learning about combining immunotherapy with surgery and chemotherapy is encouraging. The perioperative approach—giving immunotherapy before and after surgery—is producing some of the best outcomes we've seen. Patients should ask their oncologists about combination approaches and clinical trials."
— David Foster, Executive Director of Client Services, Danziger & De Llano

Accessing Immunotherapy Treatment

Patients have several pathways to access immunotherapy for mesothelioma.

FDA-Approved Treatment

Opdivo + Yervoy is covered by most insurance for eligible patients:

Prescribed by oncologist at most cancer centers
Administered as IV infusion every 2-3 weeks
Treatment continues until disease progression or unacceptable toxicity

Clinical Trials

Trials offer access to newer immunotherapy approaches:

56+ active mesothelioma trials
Testing new drugs and combinations
Often available at major cancer centers
Treatment costs typically covered by trial sponsors

Treatment Centers

Specialized centers offer expertise in mesothelioma immunotherapy:

The mesothelioma treatment centers guide lists specialized facilities nationwide.

Frequently Asked Questions

What immunotherapy drugs are FDA-approved for mesothelioma?

The FDA has approved the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) for first-line treatment of unresectable pleural mesothelioma. While Keytruda (pembrolizumab) is not specifically FDA-approved for mesothelioma, it is used off-label and in clinical trials based on promising results from studies showing improved survival.

How does immunotherapy work for mesothelioma?

Immunotherapy drugs called checkpoint inhibitors work by blocking proteins that prevent your immune system from attacking cancer cells. Mesothelioma cells use these checkpoints (PD-1, PD-L1, CTLA-4) to hide from the immune system. By blocking these checkpoints, immunotherapy allows your immune cells to recognize and destroy cancer cells.

What are the survival rates with immunotherapy for mesothelioma?

The CheckMate 743 trial showed patients receiving Opdivo plus Yervoy had a median overall survival of 18.1 months compared to 14.1 months with chemotherapy. At three years, 23% of patients on immunotherapy were still alive compared to 15% on chemotherapy. Some patients achieve long-term responses lasting years.

Who qualifies for mesothelioma immunotherapy?

Most patients with unresectable pleural mesothelioma qualify for first-line immunotherapy with Opdivo/Yervoy. Factors affecting eligibility include overall health status, organ function, and absence of certain autoimmune conditions. Your oncologist will evaluate whether immunotherapy is appropriate for your specific situation.

What are the side effects of immunotherapy for mesothelioma?

Immunotherapy side effects differ from chemotherapy and may include fatigue, skin rash, diarrhea, and inflammation of organs (pneumonitis, colitis, hepatitis, thyroiditis). These immune-related side effects occur because the activated immune system may also attack healthy tissue. Most are manageable with steroids and medication adjustments.

Can immunotherapy be combined with surgery or chemotherapy?

Yes. Clinical trials are testing immunotherapy combined with surgery (perioperative immunotherapy) and chemotherapy. The DREAM study showed promising results combining chemotherapy with Keytruda. Perioperative immunotherapy trials at Johns Hopkins have achieved 80% surgical success rates with extended survival times.

Next Steps: Exploring Immunotherapy Options

If you have been diagnosed with mesothelioma, immunotherapy may offer new treatment options that can extend survival. Talk to your oncologist about whether immunotherapy is appropriate for your situation.

While pursuing treatment, don't forget that compensation may be available to help cover medical expenses and provide financial security for your family. Many patients recover significant amounts through trust fund claims and lawsuits.

Related Resources

Mesothelioma Clinical Trials 2026 — Find clinical trials near you
Top 6 Mesothelioma Treatment Centers — Specialized care facilities
Find Mesothelioma Lawyers — Explore compensation options
Free Case Assessment — Get a personalized evaluation

Learn More About Treatment

Treatment Options — Complete treatment guide
Clinical Trials — Active research studies
Treatment Centers — Specialized facilities

Sources:

CheckMate 743 Trial: Opdivo Plus Yervoy for Pleural Mesothelioma. The Lancet. (2021).
FDA Approval of Nivolumab Plus Ipilimumab for Mesothelioma. U.S. Food and Drug Administration. (2020).
KEYNOTE-028 and KEYNOTE-158 Trials: Pembrolizumab in Mesothelioma. Journal of Clinical Oncology. (2024).
Perioperative Immunotherapy for Mesothelioma: Trial Results. Johns Hopkins Sidney Kimmel Cancer Center. (2025).
Immune Checkpoint Inhibitors in Mesothelioma: A Comprehensive Review. Journal of Thoracic Oncology. (2025).

Last updated: January 31, 2026