Cancer Immunotherapy: What the non-oncology physicians need to know?

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Dr. Muhammad N. Siddique is one of the most highly qualified cancer doctors in Lahore.

T-Cell attacking a malignant cell

Until about 10 years ago, chemotherapy was the only meaningful option to treat most advanced malignancies. In the past two decades, rigorous research work has expanded treatment options by bringing forth immunotherapy and targeted therapy. Nivolumab was the first approved check point inhibitor (a form of immunotherapy), by US FDA in 2011. Its approval was granted for use in metastatic melanoma, for which really no meaningful therapy existed prior to that. Soon afterwards new drugs were developed. Cooperative research groups worked globally and with the help of collaborative trials very soon immunotherapy was confirmed to be useful in multiple other malignancies. Now, it is in widespread use for lung cancers, skin cancers, GI cancers, head and neck cancers, brain tumors, GU cancers, breast cancers, lymphoma, GYN malignancies etc.

Unlike chemotherapy – which destroys rapidly dividing cells and thus besides causing cancer cell death can also result in alopecia, myelosuppression and GI toxicity – cancer immunotherapy works by countering the inhibitory effect of malignant cells on the host immune cells. Hence, these drugs helps in unlocking the ability of immune system to detect altered proteins on malignant cells in order to attack and kill these cells. These drugs include programmed death (PD-1)-inhibitors and PD-L1-inhibitors (such as pembrolizumab, atezolizumab, nivolumab), and cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors (ipilimumab).

The speed of global approvals for these drugs has outstripped the general understanding of their efficacy, and side effects even for many physicians in the West. If you’re working in Pakistan, especially bigger cities such as Karachi, Lahore or Islamabad, you might have noticed a recent rise in the use of immune checkpoint inhibitors as availability of these drugs is catching up in Pakistan. If you are a non-oncology specialist and see patients who are undergoing oncology treatments, here are some immunotherapy facts you should know:


Does immunotherapy benefit all patients?

Immunotherapy benefits some, but not all, cancer patients. It is more efficacious in cancers with higher levels of PD-L1 protein and/or high tumor mutational burden due to DNA repair defects. However, there are many exceptions, and we do not fully understand how best to select patients who will benefit.

How long does the tumor control by immunotherapy last?

When a tumor responds to immunotherapy, the remission tends to last a long time (typically a year or more for single agent immunotherapy regimen, and 2-3 years for immunotherapy combinations), unlike a response to chemotherapy (weeks or months).

What is pseudo-progression of cancers on immunotherapy?

With immunotherapy, tumors initially may swell as immune cells engage with the cancer cells and mount a strong inflammatory response. Responding tumors later shrink as cancer cells die. The early progression noted on radiographs is called pseudo-progression. This could be a tricky situation and can potentially lead to medical errors, especially if the physician is unaware of this phenomenon and/or is not keeping a high index of suspicion.

What about side effects?

Immunotherapy with PD1/PD-L1 inhibitors is generally well tolerated, but serious adverse effects may occur. This happens in about 20% of people given PD1/PD-L1-inhibitors. It occurs in 40% to 60% of people given a combination of PD1-inhibitor and CTLA4-inhibitor immunotherapies.

Most side effects appear around two to three months after therapy starts. Early recognition is the key to successful management and damage control. Therefore, treating physicians need to be aware of potential IRAE’s (immune related adverse events). Because immunotherapy drugs unleash immune cells, patients can develop autoimmune issues such as colitis, pneumonitis, thyroiditis, hepatitis, nephritis and virtually immune mediated disease involving any organ. Proper understanding of immunotherapy on the part of physicians involved in care, early recognition, and prompt therapy can help limit the resultant morbidity and mortality.

How are side effects of immunotherapy managed?

Severe side effects are controlled by stopping the immunotherapy and starting corticosteroids (such as prednisone), which are tapered slowly over a period of weeks. For life or organ threatening immune process, IV steroids and even more potent immunosuppressants such as infliximab are employed. It is imperative that any new symptoms while being on immunotherapy should prompt a follow up visit with treating oncologist, as timely recognition and intervention is the key. We have seen patients where self-treatment led to dire consequences. For example, if patient has diarrhea, taking loperamide (Imodium) may arrest the symptom, but it won’t address the underlying pathophysiology, which is inflammation of the colon. Uncontrolled colitis may lead to perforation, which can be life-threatening. Similarly, if patient develops a cough, anti-tussive may suppress the symptomatology but allows the pneumonitis to progress and become potentially life-threatening.

Do antibiotics affect how well immunotherapy works?

There is emerging observational data which suggests that concurrent use of antibiotics may reduce the efficacy of immunotherapy. Underlying mechanisms is poorly understood, but immunotherapy experts believe antibiotics may reduce the population of gut microbiota which in turn suppresses their positive effect on shaping a proper immune response against cancer cells. Hence, it appears important to avoid unnecessary antibiotics for minor infections, which may be prescribed for patients visiting the ER for fever, cough, or other symptoms suggestive of infections. Check with your cancer team about this.


Key Points

Cancer Immunotherapy was first approved by US FDA in 2011 for use in advanced melanoma and since then its uses are rapidly expanding across various different types of malignant diseases.

Not all patients respond but if patients are properly selected based upon various biomarkers response rates are better than conventional chemotherapy.

Typically, patients who respond to cancer immunotherapy show more prolonged disease control than those patients who show response to traditional chemotherapy.

Assessing response to immunotherapy radiographically may be very tricky. Care team needs to be very careful in identifying pseudo-progression which if missed could lead to a very detrimental medical error. Key is to always keep the oncologist in loop. What the radiologist might label as progression may not be so in the eyes of the treating oncologist.

While the typical side effects of cancer therapies such as alopecia, nausea and vomiting are uncommon with cancer immunotherapy, they can lead to autoimmune damage. Care team needs to be mindful of such potential issues, as early recognition is key for management. Indeed successfully managed complications may allow re-challenge of immunotherapy.

Antibiotics use during cancer immunotherapy may impair the efficacy of later. Therefore, use of antibiotics in patients who are on cancer immunotherapy should be limited to serious infections and benefits and risks should be carefully weighed ideally with mutual consultation of oncology and infectious disease teams.


About the author: Dr. Muhammad N. Siddique is CEO at ilaj.org. He is one of the few American Board certified Hematologists and Oncologists who are providing cancer care in Pakistan. He is considered one of the top cancer doctors in Lahore as well as in USA.

Author Disclosure:  Dr Muhammad Nauman Siddique prescribes cancer immunotherapy on daily basis but does not receive any financial compensation on any account from any immunotherapy pharmaceuticals.

This Post Has 6 Comments

  1. The best oncologist in Lahore. Nauman Siddique is the well, knowledge, and professionalism person in the cancer field.

    1. Muhammad N. Siddique

      Thank you for kind words Muhammad Bilal.

  2. Adnan

    An excellent article indeed. I’m sure it’s very valuable for the non-oncology physicians, or those who are just at the start of their oncology training. Thanks a lot 🙂

  3. Muhammad N. Siddique

    Thank you Adnan. We are glad you found it helpful 🙂

  4. Saad Ali Chughtai

    Muhammad Nauman Siddique is one of the top oncologist in the world, due to his best Experience in United States .

    1. Muhammad N. Siddique

      Dear Saad thank you for your positive feedback

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