In the Journals

Combined immunotherapy associated with pneumonitis

Pneumonitis in patients who receive anti–PD-1 or anti–PD-L1 monoclonal antibodies is characterized by variable onset, as well as clinical, radiologic and pathologic appearance, according to study results.

The condition is more common among patients who receive anti–PD-1 or anti–PD-L1 monoclonal antibodies in combination with anti-cytotoxic T-cell lymphocyte-4 monoclonal antibodies, results showed.

“One of the remarkable characteristics of anti–PD-1/PD-L1 monoclonal antibodies is their relatively mild toxicity profile. However, immune-related adverse events can occur and may be severe,” Jarushka Naidoo, MBBCh, of Sidney Kimmel Cancer Center at Johns Hopkins University, and colleagues wrote. “With the recent approval of anti–PD-1/PD-L1 monoclonal antibodies, and several other anticipated indications, use is expected to expand rapidly. A critical need exists to gain familiarity with the clinical features of pneumonitis and to optimize management.”

Researchers identified 915 patients at Memorial Sloan Kettering Cancer Center and Melanoma Institute of Australia treated with anti–PD-1/PD-L1 monoclonal antibodies alone or in combination with anti-cytotoxic T-cell lymphocyte-4 monoclonal antibodies. Patients in Australia (n = 337) were treated for melanoma from 2013 to 2015, whereas those in the United States (n = 578) were treated for advanced solid cancers from 2009 to 2014.

Pneumonitis occurred among 43 patients (5%), including 27 of those treated at Memorial Sloan Kettering Cancer Center and 16 of those treated at Melanoma Institute of Australia.

The onset of pneumonitis ranged from 9 days to 19.2 months.

Pneumonitis was more common in patients who received combined immunotherapy than those who received monotherapy (19 of 199 [10%] vs. 24 of 716 [3%]; P < .001). The incidence was similar in patients with melanoma and non–small cell lung cancer.

Most pneumonitis cases (72%) were grade 1 to grade 2, and 86% improved or resolved with drug holding or immunosuppression. Five patients died during the study period, one of whom died of pneumonitis.

“Most [pneumonitis] cases are mild and managed successfully with favorable outcomes,” Naidoo and colleagues wrote. “However, worsening pneumonitis may develop in a subset of patients despite additional immunosuppression, and they may suffer from the immunosuppressive consequences of pneumonitis treatment. Improvements in the treatment and understanding of the biology of pneumonitis are needed to optimize management.” – by Andy Polhamus

Disclosure: Naidoo reports a consultant or advisory role with, honoraria from, and compensation for travel, accommodations and expenses from AstraZeneca and Bristol-Myers Squibb. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Pneumonitis in patients who receive anti–PD-1 or anti–PD-L1 monoclonal antibodies is characterized by variable onset, as well as clinical, radiologic and pathologic appearance, according to study results.

The condition is more common among patients who receive anti–PD-1 or anti–PD-L1 monoclonal antibodies in combination with anti-cytotoxic T-cell lymphocyte-4 monoclonal antibodies, results showed.

“One of the remarkable characteristics of anti–PD-1/PD-L1 monoclonal antibodies is their relatively mild toxicity profile. However, immune-related adverse events can occur and may be severe,” Jarushka Naidoo, MBBCh, of Sidney Kimmel Cancer Center at Johns Hopkins University, and colleagues wrote. “With the recent approval of anti–PD-1/PD-L1 monoclonal antibodies, and several other anticipated indications, use is expected to expand rapidly. A critical need exists to gain familiarity with the clinical features of pneumonitis and to optimize management.”

Researchers identified 915 patients at Memorial Sloan Kettering Cancer Center and Melanoma Institute of Australia treated with anti–PD-1/PD-L1 monoclonal antibodies alone or in combination with anti-cytotoxic T-cell lymphocyte-4 monoclonal antibodies. Patients in Australia (n = 337) were treated for melanoma from 2013 to 2015, whereas those in the United States (n = 578) were treated for advanced solid cancers from 2009 to 2014.

Pneumonitis occurred among 43 patients (5%), including 27 of those treated at Memorial Sloan Kettering Cancer Center and 16 of those treated at Melanoma Institute of Australia.

The onset of pneumonitis ranged from 9 days to 19.2 months.

Pneumonitis was more common in patients who received combined immunotherapy than those who received monotherapy (19 of 199 [10%] vs. 24 of 716 [3%]; P < .001). The incidence was similar in patients with melanoma and non–small cell lung cancer.

Most pneumonitis cases (72%) were grade 1 to grade 2, and 86% improved or resolved with drug holding or immunosuppression. Five patients died during the study period, one of whom died of pneumonitis.

“Most [pneumonitis] cases are mild and managed successfully with favorable outcomes,” Naidoo and colleagues wrote. “However, worsening pneumonitis may develop in a subset of patients despite additional immunosuppression, and they may suffer from the immunosuppressive consequences of pneumonitis treatment. Improvements in the treatment and understanding of the biology of pneumonitis are needed to optimize management.” – by Andy Polhamus

Disclosure: Naidoo reports a consultant or advisory role with, honoraria from, and compensation for travel, accommodations and expenses from AstraZeneca and Bristol-Myers Squibb. Please see the full study for a list of all other researchers’ relevant financial disclosures.

    See more from Immuno-Oncology Resource Center