Abstract
15092 Background: CET and PAN are chimeric and fully human monoclonal antibodies respectively against epidermal growth factor receptor (EGFR) used in treatment of mCRC. Incidence of documented HSR is more common with CET (all grades [g]: 15 - 21%; g 3/4: 2 - 5%) than PAN (all g: 4%; g 3/4: 1%). Anecdotal reports suggest successful challenge with PAN following HSR with CET. However, safety of CET after HSR with PAN is not known. We report two pts successfully desensitized with CET after HSR with PAN and CET respectively. Methods: A 42-yr-old female with mCRC received PAN as a third-line agent. She developed severe chest tightness, pain and SOB, 5 mins after 1st PAN infusion. She responded to O2, fluid replacement, dexamethasone, and diphenhydramine. A 70-yr-old male with mCRC received PAN plus irinotecan as a second-line therapy. 1st administration was uneventful. He developed severe facial flushing, back pain, SOB, tachycardia and hypotension, 5 mins after 2nd dose of PAN. He responded to O2, fluid replacement, and dexamethasone. Both pts were premedicated with prednisone 50 mg PO 24 hrs, 12 hrs and 3 hrs from receiving CET, diphenhydramine 50 mg iv and famotidine 20 mg iv prior to CET. Then they received desensitization protocol for CET after a test dose of 20mg iv over 10 mins followed by a slow infusion 10% of original rate in 0–2 hrs, 25% of original rate in 2–2.5 hrs, 50% reduced rate in 2.5–3 hrs and then 100% infusion rate after 3 hrs. Pts were observed 4 hrs after completion of infusion. Results: First pt is currently on 10th cycle of CET with stable disease, no recurrence of HSR and grade 1 acneiform rash that developed after 3rd cycle. Second pt is currently on 7th cycle of CET with no recurrence of HSR. Conclusions: Thanks to hybridoma technology that HSR are less frequent with fully human and humanized antibodies. Though anecdotal reports suggest safety of PAN in pts following HSR with CET but PAN can also cause severe HSR. Our experience suggests that in case of limited options, such pts can be successfully challenged with CET in a hospital after appropriate desensitization and premedication. Further studies focusing on desensitization and identifying hypersensitivity profile of different anti-EGFR antibodies are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb ImClone
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