Patterns of Gastrointestinal Injury Associated With CAR-T Therapy for Patients With Multiple Myeloma

Area of Science:

• Gastroenterology
• Oncology
• Immunology

Background:

• B-cell maturation antigen (BCMA)-targeted CAR-T therapy is a novel treatment for multiple myeloma (MM).
• Gastrointestinal (GI) side effects are common but specific histopathological changes are not well-characterized.

Purpose of the Study:

• To investigate the spectrum of gastrointestinal histopathological changes in patients with multiple myeloma undergoing BCMA-targeted CAR-T therapy.

Main Methods:

• Retrospective analysis of 26 gastrointestinal biopsy specimens from 10 patients with MM treated with BCMA-targeted CAR-T therapy.
• Histopathological examination focusing on plasma cell counts, lymphocytic infiltration, villous architecture, and apoptosis.

Main Results:

• Markedly reduced or absent plasma cells were observed in most specimens.
• The small intestine, particularly the duodenum, showed the most significant changes: lamina propria lymphocytic infiltration, villous atrophy, foveolar metaplasia, and increased apoptotic bodies (7/10 hpf).
• Terminal ileum also showed increased apoptosis (9.5/10 hpf), villous atrophy, and lymphocytic infiltration. Stomach biopsies showed mild inflammation; colonic biopsies varied, with some showing active colitis and others minimal changes.

Conclusions:

• BCMA-targeted CAR-T therapy induces a distinct pattern of intestinal injury, predominantly affecting the small intestine.
• Histologic findings include plasma cell depletion, lymphocytic infiltration, villous atrophy, and increased apoptosis.
• Upper endoscopy is crucial for symptomatic patients post-CAR-T therapy due to disproportionately greater duodenal injury.