The treatment practice of CIP was shared after treatment of Navuliu monoto-hypertherapy in a case of lung adenocarcinoma.

Lung cancer is the first cancer in China.patients with lung adenocarcinoma have poor overall prognosis due to their strong tumor invasion, high metastasis rate, rapid disease progression and low efficiency of chemotherapy.in 2018, the Chinese non-small cell lung cancer (NSCLC) entered the era of immunotherapy.the addition of these PD-1 inhibitors opens a door for the treatment of lung adenocarcinoma patients.of course, we should also pay attention to the prevention and treatment of immune related adverse reactions (iraes) in the process of rational use of immune drugs.yimaitong has the honor to invite Professor Lin Lin Lin of Cancer Hospital of Chinese Academy of Medical Sciences to share with you a classic case of immune associated pneumonia (CIP) in lung adenocarcinoma patients treated with navulizumab and PFS up to 21 months after hormone treatment, and invited Professor Duan Jianchun of Cancer Hospital of Chinese Academy of Medical Sciences to give a wonderful comment on this case, which is shared as follows.case introduction basic medical history of expert: male patient, 55 years old.in November 2015, he was hospitalized because of "double pulmonary nodules found in physical examination".they were healthy in the past, denied the history of chronic diseases, infectious diseases and other diseases, and denied the history of allergy.smoking for 30 years denied family genetic history.auxiliary examination: puncture biopsy: ① right lung puncture (external hospital, November 2015) pathology: poorly differentiated adenocarcinoma; gene detection: EGFR mutation gene, ALK fusion gene, ros-1, c-Met were all wild-type.② pathological consultation (our hospital, November 2015): adenocarcinoma.immunohistochemistry: TTF-1 (+), CK7 (+), napsina focal (+), CD56, syn, CK5, p63 were all (-), Ki-67 25%, ALK (weak +) and alk neg (-).the expression of PD-L1 was not detected.imaging examination: ① head enhanced MRI (2015-12): right parietal lobe enhanced small nodule, about 0.5cm in diameter, considering intracranial metastasis.② PET-CT (2015-12): the metabolism of the 10th thoracic vertebrae was active, except for bone metastasis.Others: Color Doppler ultrasound of cervical lymph nodes (2015-12): multiple enlarged lymph nodes on the left clavicle, be aware of lymph node metastasis. diagnosis: peripheral adenocarcinoma of right lung middle lobe (t4n3m1 stage IV), left supraclavicular lymph node metastasis, mediastinal lymph node metastasis, brain metastasis, thoracic vertebral metastasis. treatment history: first line chemotherapy: from December 2015, bevacizumab combined with pemetrexed and carboplatin was given for 4 cycles, and the specific drugs were bevacizumab 600 mg D1, pemetrexed 900 mg D1, carboplatin 550 mg D2 q3w. after 2 cycles and 4 cycles, the curative effect evaluation was SD. bevacizumab was discontinued due to epistaxis. the patients were treated with pemetrexed + carboplatin for 2 cycles. after 6 cycles, the curative effect was evaluated as SD. in July 2016, chest CT showed that "multiple nodules and masses in both lungs, some of which were larger than before, and some of the solid components were increased compared with the former, the larger was 7.6x2.7cm". The curative effect was evaluated as PD. Figure 1 chest CT image of the patient after six cycles of chemotherapy on April 19, 2016 2 Chest CT second line treatment reviewed by the patient on July 5, 2016: in July 2016, the patient participated in ca209-078 "open, randomized, Multi Country phase III trial of navulizumab versus docetaxel in the treatment of previously treated advanced or metastatic non-small cell lung cancer"; since July 19, 2016, the patient was given 3 mg / kg of navulizumab for immunotherapy, and the specific drug was navulil The titer was 252 mg IVGTT D1 Q2 W. after 3-4 days of medication, the patient developed chest tightness, shortness of breath, cough and expectoration. The immune related side effects should not be excluded, and the patient's condition was observed. on August 2, 2016, chest CT Reexamination showed that "multiple nodules and masses in both lungs were larger than before, some were fused, and some were not clearly demarcated with surrounding lung consolidation shadow; bilateral emphysema". Figure 3: chest CT anti infective treatment of the patient reviewed on August 2, 2016: interstitial pneumonia caused by immune cell infiltration was not excluded. Therefore, from August 2, 2016, the patient was given methylprednisolone 82mg (1mg / kg) IVGTT D1-3 for symptomatic treatment. the chest CT examination on August 5 showed that "the interstitial lung lesions decreased compared with before". Therefore, the dosage of methylprednisolone was reduced by half until August 7. since August 8, the oral administration of prednisone 80 mg QD was used, and the reduction plan was to reduce 10 mg every 3 days. At the end of steroid therapy on August 31, CT Reexamination showed that pulmonary interstitial lesions were significantly improved. Figure 4: chest CT reexamined after 3 days of methylprednisolone treatment on August 5, 2016; chest CT reexamined after steroid therapy on August 31, 2016 continued immunotherapy: after hormone treatment, the lung condition of the patient was significantly improved, and he continued to participate in ca209-078 "clinical study of navulizumab", and the specific medication was the same as before. from July 2016 to March 2018, a total of 42 cycles of treatment were used. in the follow-up treatment, the patient did not appear immune-related interstitial pneumonia, no obvious adverse reactions, and was well tolerated. Figure 6 The chest CT reexamined after immunotherapy on June 27, 2017, December 04, and February 26, 2018 showed that the patient's symptoms worsened in April 2018. The CT Reexamination indicated that the disease was likely to progress. In order to clarify the nature of the tumor, PET-CT examination was carried out. The results showed that "the right lower lung cancer, with increased metabolism, should be considered; the right axillary lymph node, with increased metabolism, should be considered for metastasis; the slightly low-density nodule in the right lobe of the liver should be considered for conversion The curative effect was evaluated as PD, considering the progress of the disease. third line treatment: in May 2018, bevacizumab combined with gemcitabine was used for treatment, but the specific medication was unknown. After three cycles of treatment (July 2018), CT Reexamination showed that "the tumor in the right lower lobe (2.8 * 2.5cm) was smaller than the previous one," and the lung lesion was considered to be a reduced SD, and the liver lesion could not be evaluated. later, due to the poor general condition of the patient, he was transferred to the local hospital for nutritional support treatment and died on November 21, 2018. case summary: in November 2015, the patient was diagnosed as "peripheral adenocarcinoma of right lung middle lobe (t4n3m1 stage IV), left supraclavicular lymph node metastasis, mediastinal lymph node metastasis, brain metastasis and thoracic vertebral metastasis" by imaging and pathological examination. The first-line treatment was bevacizumab combined with pemetrexed + carboplatin for 6 cycles, PFS for 6 months, and the best judgment effect was SD. the second-line treatment was changed to navulizumab for 42 cycles, PFS was 21 months, and the best judgment effect was pr. the third line treatment was changed to bevacizumab combined with gemcitabine, PFS was 6 months, the best judgment effect was SD, and then died due to deterioration of the disease, OS reached 36 months. case review key points of expert review 1. The patient obtained long-term survival after treatment with navulizumab, and it was well tolerated. In the process of immunotherapy, the doctor-patient education about Irae is very important. Early detection, early diagnosis and early intervention are the key to effective treatment of Irae. After effective treatment of iraes, it is suggested to restart immunotherapy. summarize the second-line treatment of the patient. at present, PD-1 inhibitors are playing an increasingly important role in advanced lung cancer. the patient's condition progressed after targeted combined chemotherapy, and the second-line use of navulizumab for immunotherapy, during which CIP appeared. After hormone symptomatic treatment, the patient was improved, and the immunotherapy was restarted; after the disease progressed again, the chemotherapy scheme was used, and the OS lasted for 36 months, and the patient benefited significantly in the immunotherapy. the patient did not detect PD-L1 during the second-line treatment with navulizumab, but still achieved long-term survival benefits, suggesting that regardless of the PD-L1 expression status, patients can benefit from the treatment of navulizumab. CIP appeared in the course of treatment. After timely and effective treatment, the patients were given immunotherapy again and benefited continuously from it. It is suggested that early detection, early diagnosis and early intervention are the key to the effective treatment of Irae; and after effective treatment of iraes, we can consider restarting immunotherapy. at the same time, in the process of immunotherapy, the doctor-patient education about Irae is very important. OPD-OO-0699-200709-220709