Rapid disease progression and hydrocephalus following tarlatamab therapy initiation: A case report

Abstract

Tarlatamab is a novel bispecific T-cell engager immunotherapy that has demonstrated efficacy against small-cell lung cancer (SCLC) in terms of noteworthy anticancer activity and survival outcomes. However, no studies have detailed the patterns of disease progression during tarlatamab treatment. Herein, we present a case of acute disease progression after tarlatamab initiation in a 71-year-old male patient with extensive-stage SCLC. Following tarlatamab administration, he developed symptoms of cognitive impairment, which raised suspicion of immune effector cell-associated neurotoxicity syndrome (ICANS), an adverse event associated with the drug. Diagnostic evaluation revealed that the symptoms were caused by obstructive hydrocephalus due to worsening brain metastases. Following tarlatamab administration, we observed rapid progression of the previously indolent SCLC, leading to deterioration in the patient's overall condition. This case highlights the need to consider the possibility of rapid disease progression following tarlatamab administration and underscores the importance of adequate assessment to exclude ICANS. Since rapid tumor progression may lead to a decline in the patient's general condition, careful follow-up is advised.

Keywords: Extensive-stage small-cell lung cancer; Hydrocephalus; Hyperprogressive disease; Pineal gland metastasis; Tarlatamab.

Fig. 1

Brain MRI and CT findings during AMR treatment. a) Axial images obtained after 12 cycles of AMR therapy showing newly detected lung, liver, and brain metastases (red arrows), including a pineal gland metastasis, indicating progressive disease; b) Same-level axial images obtained after 18 cycles of AMR therapy (before tarlatamab initiation) showing enlargement of the liver metastasis in hepatic segment S8. The lung, mediastinal lymph node, and other liver metastases were also enlarged (red arrows), but their progression was slow. MRI, magnetic resonance imaging; CT, computed tomography; AMR, amrubicin.

Fig. 2

Brain MRI and CT findings during tarlatamab treatment. Images obtained a) before and b) 1 month after tarlatamab treatment initiation showing enlargement of the pineal gland metastasis and hydrocephalus (coronal view, top left panels, red circles), as well as enlargement of the cerebellar metastasis (axial view, bottom left panels, red arrows), mediastinal lymph node metastasis (axial view, top right panels), and left lung tumor (axial view, bottom right panels, red arrows). MRI, magnetic resonance imaging; CT, computed tomography.

Fig. 3

Clinical course of this case. A timeline figure depicting the clinical course following amrubicin initiation, showing months elapsed, corresponding imaging findings at each timepoint, and Pro-GRP values, the Hasegawa dementia scale-revised scores. From 7 to 14 months after initiation of amrubicin, it seems the tumor's rate of progression was slow. Nevertheless, tumor enlargement notably accelerated after starting tarlatamab. Despite whole-brain radiotherapy, hydrocephalus persisted and worsening of the trunk lesions was also observed.