Management of infusion-related reactions (IRRs) in patients receiving amivantamab in the CHRYSALIS study

Keunchil Park, Joshua K. Sabari, Eric B. Haura, Catherine A. Shu, Alexander Spira, Ravi Salgia, Karen L. Reckamp, Rachel E. Sanborn, Ramaswamy Govindan, Joshua M. Bauml, Joshua C. Curtin, John Xie, Amy Roshak, Patricia Lorenzini, Dawn Millington, Meena Thayu, Roland E. Knoblauch, Byoung Chul Cho

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. Infusion-related reaction(s) (IRR[s]) are reported commonly with amivantamab. We review IRR and subsequent management in amivantamab-treated patients. Methods: Patients treated with the approved dose of intravenous amivantamab (1050 mg, <80 kg; 1400 mg, ≥80 kg) in CHRYSALIS—an ongoing, phase 1 study in advanced EGFR-mutated NSCLC—were included in this analysis. IRR mitigations included split first dose (350 mg, day 1 [D1]; remainder, D2), reduced initial infusion rates with proactive infusion interruption, and steroid premedication before initial dose. For all doses, pre-infusion antihistamines and antipyretics were required. Steroids were optional after the initial dose. Results: As of 3/30/2021, 380 patients received amivantamab. IRRs were reported in 256 (67%) patients. Signs/symptoms of IRR included chills, dyspnea, flushing, nausea, chest discomfort, and vomiting. Most of the 279 IRRs were grade 1 or 2; grade 3 and 4 IRR occurred in 7 and 1 patients, respectively. Most (90%) IRRs occurred on cycle 1, D1 (C1D1); median time-to-first-IRR onset during C1D1 was 60 min; and first-infusion IRRs did not compromise subsequent infusions. Per protocol, IRR was mitigated on C1D1 with holding of infusion (56% [214/380]), reinitiating at reduced rate (53% [202/380]), and aborting infusion (14% [53/380]). C1D2 infusions were completed in 85% (45/53) of patients who had C1D1 infusions aborted. Four patients (1% [4/380]) discontinued treatment due to IRR. In studies aimed at elucidating the underlying mechanism(s) of IRR, no pattern was observed between patients with versus without IRR. Conclusion: IRRs with amivantamab were predominantly low grade and limited to first infusion, and rarely occurred with subsequent dosing. Close monitoring for IRR with the initial amivantamab dose and early intervention at first IRR signs/symptoms should be part of routine amivantamab administration.

Original languageEnglish
Pages (from-to)166-171
Number of pages6
JournalLung Cancer
StatePublished - Apr 2023


  • Amivantamab
  • Epidermal growth factor receptor
  • Exon 20 insertion
  • Non-small cell lung cancer


Dive into the research topics of 'Management of infusion-related reactions (IRRs) in patients receiving amivantamab in the CHRYSALIS study'. Together they form a unique fingerprint.

Cite this