Here, the authors provide an interesting roadmap for the care of patients in long-term remission after chimeric antigen receptor (CAR) T-cell therapies.

Key points:

●      Infections are a major complication of CAR T-cell therapy, occurring in 20%-60% of CAR T-cell recipients.

●      17% of patients with lymphoma required hospitalization or intravenous antibiotics between 6 and 12 months after CAR T-cell therapy, and 10% between 1 and 2 years after infusion.

●      Among patients with lymphoma, recovery of normal B cells typically occurs in 50%-70% by 1 year after therapy, with a greater proportion recovering by 3 years. By contrast,  B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy depletes plasma cells, which are critical for maintaining existing humoral immunity. This may account for increased late infections in this patient population; however, responses to new vaccination can still occur.

o   Revaccination with nonlive vaccines is reasonable to consider beginning 3-6 months postinfusion and is more likely to be effective in patients demonstrating B-and T-cell reconstitution.

●      There are no data supporting cytomegalovirus prophylaxis (ie, letermovir), but this warrants further evaluation.

●      Recommendations for antimicrobial prophylaxis mainly rely on retrospective experiences and extrapolations from the transplant literature. The authors recommended prophylactic fluoroquinolones for patients with prolonged, severe neutropenia.

●      For herpes simplex virus and varicella zoster virus prevention, they use acyclovir or valacyclovir for at least 6 months and often longer in patients with prolonged B-cell aplasia who do not generate humoral responses to the zoster vaccine.

●      Trimethoprim/sulfamethoxazole or atovaquone for at least 6 months, and continue until the CD4 count is >200 cells/mm, to prevent Pneumocystis jirovecii infection.

●      Antimold azoles are recommended for those with risk factors such as prolonged cytopenias, prolonged steroid use, or a history of invasive fungal infections, which, although rare, can be life-threatening.

●      For patients receiving plasma cell–directed therapies, prophylactic immunoglobulin replacement is recommended until IgG levels recover above 400 mg/dL. For CD19 CAR T-cell therapy survivors, replacement for IgG levels ≤400 mg/dL is recommended for those with recurrent infections.

●      See Figure 2 in original paper, which illustrates the recommended workup and management of post–CAR T-cell cytopenia.

●      Long-term data indicate a 4%-16% incidence of secondary malignancies after CAR T-cell therapy. While these rates are comparable with those seen with conventional treatments for hematologic cancers, the underlying mechanisms remain incompletely understood. Contributing factors may include previous genotoxic therapies, CAR T–induced inflammation, prolonged B-cell aplasia, immunosuppression, and pre-existing clonal hematopoiesis of indeterminate potential (CHIP).

●      Adherence to age-appropriate cancer screening, including dermatologic screening, per national guidelines, should be a core component of long-term care. For individuals with prolonged cytopenias, poor immune reconstitution, or known CHIP, more frequent and individualized monitoring may be warranted. As we gain deeper insights into the interplay between CAR-T-cell therapy, CHIP, and long-term immune dysfunction, personalized surveillance frameworks will be essential for mitigating late toxicities and optimizing outcomes for CAR T-cell recipients.

●      See Table 2 in original paper for key questions and proposed approaches for survivorship post–CAR T-cell therapies.