Lung Cancer Therapy Side Effects: CRS, ICANS & Skin Reactions
Experts at ASCO 2025 highlighted BiTE agents like tarlatamab and bispecific antibodies such as amivantamab, offering new hope in lung cancer treatment.
Novel BiTE agents and Bispecific Antibodies Advance Lung Cancer Treatment
updated June 2,2025
At the 2025 ASCO Annual Meeting,experts discussed the potential of BiTE agents and bispecific antibodies in
treating lung cancer. Focus was given to managing toxicities associated with these novel immunotherapies,
specifically cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
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Tarlatamab-dlle for SCLC
Tarlatamab-dlle, a first-in-class BiTE agent, targets DLL3, a ligand overexpressed in 70% to 80% of SCLC tumors.
The FDA granted accelerated approval to tarlatamab in 2024 for extensive-stage SCLC that progressed after
platinum-based chemotherapy. The DELLphi-301 trial supported this decision,demonstrating a 40% objective
response rate with tarlatamab treatment.
Dr. abdul Rafeh Naqash, from the Stephenson Cancer Center, noted the durability of the response, stating that
the median duration of response was around 9.7 months, with approximately 26% of patients experiencing disease
control for over 52 weeks, and a median overall survival of about 15.2 months.
Tarlatamab is associated with toxicities, including CRS and ICANS, resulting from T-cell overactivation. CRS
is more prevalent, occurring at a rate of 53% compared to 15% for ICANS, and tends to occur early in treatment.
Naqash explained that CRS typically occurs within the first two doses, with a median onset time of around 14
hours. ICANS, on the other hand, usually occurs within the first three months, with a median onset time of
around 30 days.
Management of CRS includes monitoring patients for approximately 20 hours after the first two doses.Grade 1
CRS, characterized by a fever of 100.4°F or higher, usually requires close monitoring. Grade 2 CRS may require
treatment with dexamethasone, and tocilizumab may be considered if cardiac or respiratory symptoms are present.
ICU transfer is generally reserved for grade 3 or higher CRS. No grade 4 or 5 CRS events were reported in
phase 1 and 2 trials.
for ICANS, intravenous steroids are recommended for grade 2 symptoms. Supportive treatment with anti-epileptic
medications may also be used. ICU transfer is typically reserved for patients who reach grade 3 or higher.
Dr. Melinda laine Hsu, from the University Hospitals Seidman Cancer Center, noted the difficulty in
differentiating between CRS-induced encephalopathy and ICANS, especially early in treatment. She also suggested
that there is little harm in adding levetiracetam as a supportive measure.
Prophylactic tocilizumab, commonly used in hematologic malignancies, was discussed as an innovative approach.A
small study of five patients with high-risk SCLC showed no cases of CRS and only one case of ICANS with
prophylactic tocilizumab.Though, the cost of tocilizumab is a concern, and more research is needed to confirm
its effectiveness in preventing CRS for BiTEs in solid tumors.
Hsu emphasized the importance of managing and understanding these toxicities, stating that T-cell engagers are
likely to change the treatment landscape. Learning from hematological colleagues who have more experience with
these toxicities will be crucial.
Amivantamab for NSCLC
Amivantamab, a bispecific antibody, targets MET and EGFR to block ligand-induced activation and induce receptor
internalization. It was initially approved in 2024 in combination with carboplatin and pemetrexed for
first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. The
PAPILLON trial reported a 73% overall response rate with amivantamab, compared to 47% for chemotherapy alone.
The FDA granted additional approvals for amivantamab as a first-line treatment of classical EGFR NSCLC and in
combination with lazertinib for EGFR exon 19 deletion and L85