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LAKE BUENA VISTA, FLA. – “Crude and uninformed.”
That’s how Leonard H. Calabrese, DO, described the general approach to managing immune-related adverse events (irAEs) in cancer patients treated with checkpoint inhibitor therapy.
Rheumatologists have the expertise to change that, he said during a presentation at the annual meeting of the Florida Society of Rheumatology.
“The therapy is where it’s at – this is where rheumatologists come into play,” said Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic.
According to relevant guidelines, such as those recently developed by the American Society of Clinical Oncology/National Comprehensive Cancer Network and the Society for the Immunotherapy of Cancer, irAEs are graded on a severity-based scale. Grade 1 events are mild and generally require observation; grade 2 events may include arthralgias and myalgias that are typically treated with symptomatic therapy; grade 3 events involve more serious conditions and may require hospitalization; and grade 4 events are life-threatening and may require targeted therapies.
“Grade 3 – these would be people with profound polyarthritis, vasculitis, myositis – rely heavily on glucocorticoids, and if patients don’t tolerate glucocorticoids or don’t respond to tapering doses, consider the use of [disease-modifying antirheumatic drugs],” he said, noting that the guidelines are vaguely written and refer to both conventional and biologic DMARDs.
“This is all anecdotal at the present time; this is a story to be discovered as we move along,” he explained.
A recommendation for the use of targeted therapies, such as tumor necrosis factor inhibitors, anti-interleukin (IL)-6, and antimetabolites, in patients with the most advanced disease is similarly vague and just represents “the beginning of the beginning,” he said.
The “crude and uninformed” nature of the current approach to irAEs, as he described it, is related to a failure to consider the immunopathogenesis of specific conditions.
“The oncologists, who have done such an incredible job with this – learning about derm[atitis] and colitis that respond to steroids and infliximab, immediately extrapolated that steroids and infliximab are for everything,” he said. “They give it for pneumonitis, they give it for [central nervous system] disease, they give it for everything.”
However, there’s no pathophysiologic basis for doing so, and not surprisingly, some patients don’t respond.
“Here we are sitting on this amazing armamentarium of targeted therapies and only now just starting to ask the questions: ‘Do they offer benefit for these irAEs? Do they offer risk? Will they blunt the antitumoral response of this?’ ” he said.
A “Personal View” published in Lancet Oncology in January 2019 was among the first from the oncology arena to pose these questions (20[1]:PE54-64. doi: 10.1016/S1470-2045[18]30828-3).
“It said, ‘well maybe we should look at the immunopathogenesis of each of these diseases and then pick the therapy – if it’s IL-17 mediated, we’ve got drugs for that; if it’s IL-1 mediated, we’ve got drugs for that; if it’s interferon-mediated, we can deal with that,’ ” he said. “The problem is we don’t yet have detailed immunopathogenic knowledge of these diseases, but it’s coming.”
Data needed to define best treatments
Data also are emerging to define the roles of various targeted therapies for treating irAEs, but most of the evidence remains anecdotal, he said.
For example, anecdotal reports suggest that rituximab has some efficacy in cytopenias, arthritis, and myositis, and a case report suggests that secukinumab and other IL-17 inhibitors may have benefit in psoriasis and inflammatory bowel disease with tumoral progression, he said.
A reasonable question has been whether attacking T cells might be worthwhile given that “these things are all T-cell mediated,” but until very recently, “no one has had the temerity to actually do this,” he said.
However, two cases reported in the June 13 issue of the New England Journal of Medicine described “very successful” treatment of checkpoint inhibitor-associated myocarditis. One case described the use of alemtuzumab in a 71-year-old woman being treated with first-line pembrolizumab for stage IV melanoma, and another case involved the use of abatacept for severe, glucocorticoid-refractory myocarditis in a 66-year-old woman who had been treated with nivolumab for metastatic lung cancer (2019;380:2375-6 and 2377-79).Dr. Calabrese urged rheumatologists who are interested in addressing the treatment of irAEs to “get involved.”
“People need good rheumatologists, and I will tell you that whoever your oncologists are who you refer patients to for cancer – they’re seeing this and they need help,” he said. “Particularly outside of these big major centers, just having someone to lean on is very important.”
Keep in mind, however, that triage is very important, he said, stressing that patients with irAEs “actually need to be seen.”
Between three and five new irAE patients are being seen each week at the Cleveland Clinic, he noted.
Need for multidisciplinary collaboration
Collaboration was the focus of an article in the June 2019 issue of the Journal of the National Comprehensive Cancer Network, which looked at the value of a virtual “multidisciplinary toxicity team” for managing cancer irAEs. The investigators found that such an approach was feasible, used by oncology providers, and effective for facilitating toxicity identification and management.
A number of other recent studies have attempted to assess confidence and knowledge of rheumatologists and others with respect to the treatment of irAEs in cancer patients, and the findings highlight the need for education at the oncologist, specialist, generalist, and advanced practitioner level, Dr. Calabrese said, adding that the findings also highlight a need for assistance from “big pharma, which makes these drugs,” in supporting this type of education.
The need for “novel venues for such educational interchange” also was the topic of a study on a new Cleveland Clinic irAE tumor board that he and his colleagues presented at the 2018 annual meeting of the American College of Rheumatology.
The study showed that the tumor board, which is now “one of the most popular conferences at the clinic,” has educational value for participants, and “may increase skill and confidence in patient management.”
“We just present case after case of new things. Last week was autoimmune lipodystrophy from checkpoint inhibitors,” he said, noting that the rheumatologists and oncologists at the clinic co-chair the events.
In another 2018 article, he and coauthor Xavier Mariette, MD, further highlighted the “evolving role of the rheumatologist” in managing cancer treatment–related irAEs.
“We think that rheumatologists have a lot to offer here,” he said. “We understand these drugs better than all of these guys, and as we gain more knowledge in this field, we have guidance, and counsel, and experience to add to this.”
He encouraged rheumatologists to “stay tuned on this, follow this along,” adding that their help is needed.
“It’s really simple – talk to your oncologists and say, ‘Hey, what are you doing with these patients?’ – and I think you’ll have something new, exciting, and invigorating.”
Dr. Calabrese reported serving as a consultant and/or speaker for Bristol-Myers Squibb, Genentech, AbbVie, Pfizer, Crescendo Bioscience, UCB, Janssen, Gilead, Sanofi-Regeneron, Novartis, AstraZeneca, and Amgen.
LAKE BUENA VISTA, FLA. – “Crude and uninformed.”
That’s how Leonard H. Calabrese, DO, described the general approach to managing immune-related adverse events (irAEs) in cancer patients treated with checkpoint inhibitor therapy.
Rheumatologists have the expertise to change that, he said during a presentation at the annual meeting of the Florida Society of Rheumatology.
“The therapy is where it’s at – this is where rheumatologists come into play,” said Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic.
According to relevant guidelines, such as those recently developed by the American Society of Clinical Oncology/National Comprehensive Cancer Network and the Society for the Immunotherapy of Cancer, irAEs are graded on a severity-based scale. Grade 1 events are mild and generally require observation; grade 2 events may include arthralgias and myalgias that are typically treated with symptomatic therapy; grade 3 events involve more serious conditions and may require hospitalization; and grade 4 events are life-threatening and may require targeted therapies.
“Grade 3 – these would be people with profound polyarthritis, vasculitis, myositis – rely heavily on glucocorticoids, and if patients don’t tolerate glucocorticoids or don’t respond to tapering doses, consider the use of [disease-modifying antirheumatic drugs],” he said, noting that the guidelines are vaguely written and refer to both conventional and biologic DMARDs.
“This is all anecdotal at the present time; this is a story to be discovered as we move along,” he explained.
A recommendation for the use of targeted therapies, such as tumor necrosis factor inhibitors, anti-interleukin (IL)-6, and antimetabolites, in patients with the most advanced disease is similarly vague and just represents “the beginning of the beginning,” he said.
The “crude and uninformed” nature of the current approach to irAEs, as he described it, is related to a failure to consider the immunopathogenesis of specific conditions.
“The oncologists, who have done such an incredible job with this – learning about derm[atitis] and colitis that respond to steroids and infliximab, immediately extrapolated that steroids and infliximab are for everything,” he said. “They give it for pneumonitis, they give it for [central nervous system] disease, they give it for everything.”
However, there’s no pathophysiologic basis for doing so, and not surprisingly, some patients don’t respond.
“Here we are sitting on this amazing armamentarium of targeted therapies and only now just starting to ask the questions: ‘Do they offer benefit for these irAEs? Do they offer risk? Will they blunt the antitumoral response of this?’ ” he said.
A “Personal View” published in Lancet Oncology in January 2019 was among the first from the oncology arena to pose these questions (20[1]:PE54-64. doi: 10.1016/S1470-2045[18]30828-3).
“It said, ‘well maybe we should look at the immunopathogenesis of each of these diseases and then pick the therapy – if it’s IL-17 mediated, we’ve got drugs for that; if it’s IL-1 mediated, we’ve got drugs for that; if it’s interferon-mediated, we can deal with that,’ ” he said. “The problem is we don’t yet have detailed immunopathogenic knowledge of these diseases, but it’s coming.”
Data needed to define best treatments
Data also are emerging to define the roles of various targeted therapies for treating irAEs, but most of the evidence remains anecdotal, he said.
For example, anecdotal reports suggest that rituximab has some efficacy in cytopenias, arthritis, and myositis, and a case report suggests that secukinumab and other IL-17 inhibitors may have benefit in psoriasis and inflammatory bowel disease with tumoral progression, he said.
A reasonable question has been whether attacking T cells might be worthwhile given that “these things are all T-cell mediated,” but until very recently, “no one has had the temerity to actually do this,” he said.
However, two cases reported in the June 13 issue of the New England Journal of Medicine described “very successful” treatment of checkpoint inhibitor-associated myocarditis. One case described the use of alemtuzumab in a 71-year-old woman being treated with first-line pembrolizumab for stage IV melanoma, and another case involved the use of abatacept for severe, glucocorticoid-refractory myocarditis in a 66-year-old woman who had been treated with nivolumab for metastatic lung cancer (2019;380:2375-6 and 2377-79).Dr. Calabrese urged rheumatologists who are interested in addressing the treatment of irAEs to “get involved.”
“People need good rheumatologists, and I will tell you that whoever your oncologists are who you refer patients to for cancer – they’re seeing this and they need help,” he said. “Particularly outside of these big major centers, just having someone to lean on is very important.”
Keep in mind, however, that triage is very important, he said, stressing that patients with irAEs “actually need to be seen.”
Between three and five new irAE patients are being seen each week at the Cleveland Clinic, he noted.
Need for multidisciplinary collaboration
Collaboration was the focus of an article in the June 2019 issue of the Journal of the National Comprehensive Cancer Network, which looked at the value of a virtual “multidisciplinary toxicity team” for managing cancer irAEs. The investigators found that such an approach was feasible, used by oncology providers, and effective for facilitating toxicity identification and management.
A number of other recent studies have attempted to assess confidence and knowledge of rheumatologists and others with respect to the treatment of irAEs in cancer patients, and the findings highlight the need for education at the oncologist, specialist, generalist, and advanced practitioner level, Dr. Calabrese said, adding that the findings also highlight a need for assistance from “big pharma, which makes these drugs,” in supporting this type of education.
The need for “novel venues for such educational interchange” also was the topic of a study on a new Cleveland Clinic irAE tumor board that he and his colleagues presented at the 2018 annual meeting of the American College of Rheumatology.
The study showed that the tumor board, which is now “one of the most popular conferences at the clinic,” has educational value for participants, and “may increase skill and confidence in patient management.”
“We just present case after case of new things. Last week was autoimmune lipodystrophy from checkpoint inhibitors,” he said, noting that the rheumatologists and oncologists at the clinic co-chair the events.
In another 2018 article, he and coauthor Xavier Mariette, MD, further highlighted the “evolving role of the rheumatologist” in managing cancer treatment–related irAEs.
“We think that rheumatologists have a lot to offer here,” he said. “We understand these drugs better than all of these guys, and as we gain more knowledge in this field, we have guidance, and counsel, and experience to add to this.”
He encouraged rheumatologists to “stay tuned on this, follow this along,” adding that their help is needed.
“It’s really simple – talk to your oncologists and say, ‘Hey, what are you doing with these patients?’ – and I think you’ll have something new, exciting, and invigorating.”
Dr. Calabrese reported serving as a consultant and/or speaker for Bristol-Myers Squibb, Genentech, AbbVie, Pfizer, Crescendo Bioscience, UCB, Janssen, Gilead, Sanofi-Regeneron, Novartis, AstraZeneca, and Amgen.
LAKE BUENA VISTA, FLA. – “Crude and uninformed.”
That’s how Leonard H. Calabrese, DO, described the general approach to managing immune-related adverse events (irAEs) in cancer patients treated with checkpoint inhibitor therapy.
Rheumatologists have the expertise to change that, he said during a presentation at the annual meeting of the Florida Society of Rheumatology.
“The therapy is where it’s at – this is where rheumatologists come into play,” said Dr. Calabrese, professor of medicine and chair of clinical immunology at the Cleveland Clinic.
According to relevant guidelines, such as those recently developed by the American Society of Clinical Oncology/National Comprehensive Cancer Network and the Society for the Immunotherapy of Cancer, irAEs are graded on a severity-based scale. Grade 1 events are mild and generally require observation; grade 2 events may include arthralgias and myalgias that are typically treated with symptomatic therapy; grade 3 events involve more serious conditions and may require hospitalization; and grade 4 events are life-threatening and may require targeted therapies.
“Grade 3 – these would be people with profound polyarthritis, vasculitis, myositis – rely heavily on glucocorticoids, and if patients don’t tolerate glucocorticoids or don’t respond to tapering doses, consider the use of [disease-modifying antirheumatic drugs],” he said, noting that the guidelines are vaguely written and refer to both conventional and biologic DMARDs.
“This is all anecdotal at the present time; this is a story to be discovered as we move along,” he explained.
A recommendation for the use of targeted therapies, such as tumor necrosis factor inhibitors, anti-interleukin (IL)-6, and antimetabolites, in patients with the most advanced disease is similarly vague and just represents “the beginning of the beginning,” he said.
The “crude and uninformed” nature of the current approach to irAEs, as he described it, is related to a failure to consider the immunopathogenesis of specific conditions.
“The oncologists, who have done such an incredible job with this – learning about derm[atitis] and colitis that respond to steroids and infliximab, immediately extrapolated that steroids and infliximab are for everything,” he said. “They give it for pneumonitis, they give it for [central nervous system] disease, they give it for everything.”
However, there’s no pathophysiologic basis for doing so, and not surprisingly, some patients don’t respond.
“Here we are sitting on this amazing armamentarium of targeted therapies and only now just starting to ask the questions: ‘Do they offer benefit for these irAEs? Do they offer risk? Will they blunt the antitumoral response of this?’ ” he said.
A “Personal View” published in Lancet Oncology in January 2019 was among the first from the oncology arena to pose these questions (20[1]:PE54-64. doi: 10.1016/S1470-2045[18]30828-3).
“It said, ‘well maybe we should look at the immunopathogenesis of each of these diseases and then pick the therapy – if it’s IL-17 mediated, we’ve got drugs for that; if it’s IL-1 mediated, we’ve got drugs for that; if it’s interferon-mediated, we can deal with that,’ ” he said. “The problem is we don’t yet have detailed immunopathogenic knowledge of these diseases, but it’s coming.”
Data needed to define best treatments
Data also are emerging to define the roles of various targeted therapies for treating irAEs, but most of the evidence remains anecdotal, he said.
For example, anecdotal reports suggest that rituximab has some efficacy in cytopenias, arthritis, and myositis, and a case report suggests that secukinumab and other IL-17 inhibitors may have benefit in psoriasis and inflammatory bowel disease with tumoral progression, he said.
A reasonable question has been whether attacking T cells might be worthwhile given that “these things are all T-cell mediated,” but until very recently, “no one has had the temerity to actually do this,” he said.
However, two cases reported in the June 13 issue of the New England Journal of Medicine described “very successful” treatment of checkpoint inhibitor-associated myocarditis. One case described the use of alemtuzumab in a 71-year-old woman being treated with first-line pembrolizumab for stage IV melanoma, and another case involved the use of abatacept for severe, glucocorticoid-refractory myocarditis in a 66-year-old woman who had been treated with nivolumab for metastatic lung cancer (2019;380:2375-6 and 2377-79).Dr. Calabrese urged rheumatologists who are interested in addressing the treatment of irAEs to “get involved.”
“People need good rheumatologists, and I will tell you that whoever your oncologists are who you refer patients to for cancer – they’re seeing this and they need help,” he said. “Particularly outside of these big major centers, just having someone to lean on is very important.”
Keep in mind, however, that triage is very important, he said, stressing that patients with irAEs “actually need to be seen.”
Between three and five new irAE patients are being seen each week at the Cleveland Clinic, he noted.
Need for multidisciplinary collaboration
Collaboration was the focus of an article in the June 2019 issue of the Journal of the National Comprehensive Cancer Network, which looked at the value of a virtual “multidisciplinary toxicity team” for managing cancer irAEs. The investigators found that such an approach was feasible, used by oncology providers, and effective for facilitating toxicity identification and management.
A number of other recent studies have attempted to assess confidence and knowledge of rheumatologists and others with respect to the treatment of irAEs in cancer patients, and the findings highlight the need for education at the oncologist, specialist, generalist, and advanced practitioner level, Dr. Calabrese said, adding that the findings also highlight a need for assistance from “big pharma, which makes these drugs,” in supporting this type of education.
The need for “novel venues for such educational interchange” also was the topic of a study on a new Cleveland Clinic irAE tumor board that he and his colleagues presented at the 2018 annual meeting of the American College of Rheumatology.
The study showed that the tumor board, which is now “one of the most popular conferences at the clinic,” has educational value for participants, and “may increase skill and confidence in patient management.”
“We just present case after case of new things. Last week was autoimmune lipodystrophy from checkpoint inhibitors,” he said, noting that the rheumatologists and oncologists at the clinic co-chair the events.
In another 2018 article, he and coauthor Xavier Mariette, MD, further highlighted the “evolving role of the rheumatologist” in managing cancer treatment–related irAEs.
“We think that rheumatologists have a lot to offer here,” he said. “We understand these drugs better than all of these guys, and as we gain more knowledge in this field, we have guidance, and counsel, and experience to add to this.”
He encouraged rheumatologists to “stay tuned on this, follow this along,” adding that their help is needed.
“It’s really simple – talk to your oncologists and say, ‘Hey, what are you doing with these patients?’ – and I think you’ll have something new, exciting, and invigorating.”
Dr. Calabrese reported serving as a consultant and/or speaker for Bristol-Myers Squibb, Genentech, AbbVie, Pfizer, Crescendo Bioscience, UCB, Janssen, Gilead, Sanofi-Regeneron, Novartis, AstraZeneca, and Amgen.
REPORTING FROM FSR 2019