In the JournalsPerspective

Cancer immunotherapy safe for patients with rheumatic diseases

Uma Thanarajasingam

Fewer than 40% of patients with rheumatic diseases who received modern cancer immunotherapies experienced a flare up or any other immune related adverse effect related to their rheumatologic condition, according to findings published in Arthritis and Rheumatology.

The study included the largest single-center cohort of patients with rheumatic diseases who received a prescription for immune checkpoint inhibitors for cancer, the researchers said.

“New cancer immunotherapies, called ‘immune checkpoint inhibitors,’ have revolutionized the landscape of cancer treatment in the past few years,” Uma Thanarajasingam, MD, PhD, of the Mayo Clinic College of Medicine, in Rochester, Minnesota, told Healio Rheumatology. “Patients with advanced cancers are demonstrating response to these drugs and in some cases, they have been life-saving.”

However, patients with autoimmune rheumatic disease were largely excluded from the trials leading up to the drug approvals, due to concerns over flare or worsening autoimmune disease as a consequence of exposure to these treatments, she said.

Among patients with rheumatologic diseases who were prescribed modern cancer immunotherapy, less than 40% experienced a flare up or any other immune related adverse effect related to their rheumatologic condition.
Source: Shutterstock

“As a result, patients with autoimmune disease who then went on to develop cancer might not have been able to access these potentially life-saving treatments,” Thanarajasingam said.

To evaluate the risk for rheumatic flares and other adverse effects among those with pre-existing rheumatologic conditions treated with checkpoint inhibitor therapy, the researches conducted a retrospective medical record review of all the approximately 5,200 patients who received ipilimumab (Yervoy, Bristol-Myers Squibb), nivolumab (Opdivo, Bristol-Myers Squibb), pembrolizumab (Keytruda, Merck) or any combination thereof at the Mayo Clinic between 2011 and 2016. Of those, researchers found 33 patients with pre-existing rheumatic autoimmune diseases and included 16 in the study based on a confirmed diagnosis using the American College of Rheumatology criteria.

The researchers reviewed each participant’s entire inpatient and outpatient medical record from all providers at the Mayo Clinic, collecting baseline characteristics and all other relevant data.

According to the researchers, five of the 16 included patients received a diagnosis of rheumatoid arthritis, while another five had polymyalgia rheumatica, two had Sjogren's syndrome and 2 received a diagnosis of systemic lupus erythematosus. Additionally, seven patients received treatment with immunosuppressive therapy or glucocorticoids when they first received a checkpoint inhibitor. The most common cancer was melanoma, which researchers found in 10 patients: four patients had pulmonary and two had hematologic malignancies.

Six of the 16 patients in the studyexperienced immune-related adverse effects, and all were successfully treated with corticosteroids. Age, sex, duration of immunotherapy and differences in the time from cancer diagnosis to immunotherapy produced no differences between patients who experienced adverse effects and those who did not.

“Our study, while small, is the largest single center cohort of patients with pre-existing autoimmune disease who developed cancer and were treated with ICIs,” Thanarajasingam said. “Our findings are significant in that only one of the 16 patients identified had a flare of their underlying autoimmune disease, suggesting that, in the appropriate patient with pre-existing autoimmune disease and with close monitoring, ICI therapy can be used. This opens up a new realm of treatment possibilities for patients with cancer and autoimmune disease, that might not have been available to them prior.” – by Jason Laday

Disclosure: Uma Thanarajasingam reports advisory board membership at Bristol-Myers Squibb. The researchers report no other financial disclosures.

Uma Thanarajasingam

Fewer than 40% of patients with rheumatic diseases who received modern cancer immunotherapies experienced a flare up or any other immune related adverse effect related to their rheumatologic condition, according to findings published in Arthritis and Rheumatology.

The study included the largest single-center cohort of patients with rheumatic diseases who received a prescription for immune checkpoint inhibitors for cancer, the researchers said.

“New cancer immunotherapies, called ‘immune checkpoint inhibitors,’ have revolutionized the landscape of cancer treatment in the past few years,” Uma Thanarajasingam, MD, PhD, of the Mayo Clinic College of Medicine, in Rochester, Minnesota, told Healio Rheumatology. “Patients with advanced cancers are demonstrating response to these drugs and in some cases, they have been life-saving.”

However, patients with autoimmune rheumatic disease were largely excluded from the trials leading up to the drug approvals, due to concerns over flare or worsening autoimmune disease as a consequence of exposure to these treatments, she said.

Among patients with rheumatologic diseases who were prescribed modern cancer immunotherapy, less than 40% experienced a flare up or any other immune related adverse effect related to their rheumatologic condition.
Source: Shutterstock

“As a result, patients with autoimmune disease who then went on to develop cancer might not have been able to access these potentially life-saving treatments,” Thanarajasingam said.

To evaluate the risk for rheumatic flares and other adverse effects among those with pre-existing rheumatologic conditions treated with checkpoint inhibitor therapy, the researches conducted a retrospective medical record review of all the approximately 5,200 patients who received ipilimumab (Yervoy, Bristol-Myers Squibb), nivolumab (Opdivo, Bristol-Myers Squibb), pembrolizumab (Keytruda, Merck) or any combination thereof at the Mayo Clinic between 2011 and 2016. Of those, researchers found 33 patients with pre-existing rheumatic autoimmune diseases and included 16 in the study based on a confirmed diagnosis using the American College of Rheumatology criteria.

The researchers reviewed each participant’s entire inpatient and outpatient medical record from all providers at the Mayo Clinic, collecting baseline characteristics and all other relevant data.

According to the researchers, five of the 16 included patients received a diagnosis of rheumatoid arthritis, while another five had polymyalgia rheumatica, two had Sjogren's syndrome and 2 received a diagnosis of systemic lupus erythematosus. Additionally, seven patients received treatment with immunosuppressive therapy or glucocorticoids when they first received a checkpoint inhibitor. The most common cancer was melanoma, which researchers found in 10 patients: four patients had pulmonary and two had hematologic malignancies.

Six of the 16 patients in the studyexperienced immune-related adverse effects, and all were successfully treated with corticosteroids. Age, sex, duration of immunotherapy and differences in the time from cancer diagnosis to immunotherapy produced no differences between patients who experienced adverse effects and those who did not.

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“Our study, while small, is the largest single center cohort of patients with pre-existing autoimmune disease who developed cancer and were treated with ICIs,” Thanarajasingam said. “Our findings are significant in that only one of the 16 patients identified had a flare of their underlying autoimmune disease, suggesting that, in the appropriate patient with pre-existing autoimmune disease and with close monitoring, ICI therapy can be used. This opens up a new realm of treatment possibilities for patients with cancer and autoimmune disease, that might not have been available to them prior.” – by Jason Laday

Disclosure: Uma Thanarajasingam reports advisory board membership at Bristol-Myers Squibb. The researchers report no other financial disclosures.

    Perspective

    Elizabeth Kirchner

    The paper by Richter and colleagues discussing immune-related adverse events in patients with prior immune-mediated inflammatory disease illustrates just how much work still needs to be done in this area. Their cohort is unusual: Of 16 patients with confirmed IMIDs, only two had received DMARDs and none received treatment with biologics. There are still many unanswered questions when it comes to immune-related adverse events, both for patients with and without pre-existing IMIDs.

    Richter and colleagues are to be commended for at least trying to look at the issue, but unfortunately the rheumatology community is left with few answers. While the fact that patients whose rheumatic diseases weren’t active enough to require treatment did not flare is — on some level — reassuring, what about patients with active disease? Are there rheumatology medications that don’t ‘play well’ with checkpoint inhibitors? Or, since other groups have seen success in treating immune-related adverse events with biologics, will patients already on these agents fare better than expected once they start their immunotherapies? The rheumatology/checkpoint story is in its infancy — stay tuned for much more to come.

    • Elizabeth Kirchner, CNP, RN-BC
    • Chair of Education and Curriculum
      Rheumatology Nurses Society
      Department of Immunology
      Cleveland Clinic

    Disclosures: Kirchner reports no relevant financial disclosures.

    Perspective

    Cassandra M. Calabrese

    The use of immunotherapy in patients with pre-existing autoimmune diseases (AID) remains and area of uncertainly, as these patients were largely excluded from all clinical trials that led to the approval of currently used checkpoint inhibitors.

    The findings from this small retrospective chart review are somewhat conflicting with the existing literature as they noted a significantly lower incidence of flare — 1 patient, compared to 75% of 123 patients in recent review by Abdel-Wahab and colleagues in the Annals of Internal Medicine. The reason for this discrepancy is likely related to the limitations that come with any retrospective review including lack of details about the underlying AID.

    It is also interesting that about half of the patients had ever received a DMARD in the past, and only 2 were taking a DMARD at the time of checkpoint inhibitor initiation, raising the question of whether these patients had true AID vs. “burned out” disease. While this study leaves us wondering if it may be safer than we think to use checkpoint inhibitors in this patient population, this needs to be validated in larger, prospective studies.

    • Cassandra M. Calabrese, DO
    • Fellow
      Department of Rheumatic and Immunologic Diseases
      Department of Infectious Diseases
      Cleveland Clinic

    Disclosures: Dr. Calabrese reports no relevant financial disclosures.