TOPLINE

Nearly half of the patients who received chimeric antigen receptor (CAR) T-cell therapy for lymphoma or myeloma developed laboratory-documented respiratory viral infections (RVIs), with most episodes occurring beyond day 100 post-infusion. Patients with absolute lymphocyte counts (ALCs) below 0.5 × 109/L had an increased risk for both recurrent and severe RVIs, and lower CD19+ B-cell counts were independently associated with severe disease.

METHODOLOGY

• Researchers conducted a retrospective cohort study to describe the long-term incidence, recurrence, severity, and risk factors for RVIs among individuals who received CAR T-cell therapy.
• The study included 563 patients (median age, 65 years); those with B-cell lymphoma had received CD19-directed CAR T-cell therapy, and those with multiple myeloma had received B-cell maturation antigen-directed CAR T-cell therapy.
• An RVI was counted only when a nasopharyngeal swab or bronchoalveolar lavage sample tested positive by reverse transcription polymerase chain reaction for SARS-CoV-2, rhinovirus, influenza virus, respiratory syncytial virus, parainfluenza virus, human metapneumovirus, seasonal coronavirus, or adenovirus.
• RVI episodes were categorized as upper respiratory tract infections or lower respiratory tract infections (LRTIs) and graded for severity, with severe RVIs being graded 3 or higher.
• Researchers collected data on immune reconstitution markers, including ALCs, absolute neutrophil counts, CD4+ T cells, CD19+ B cells, and serum immunoglobulin levels. They also measured the cumulative burden of recurrent infections using mean cumulative function (MCF) estimates, which show the expected RVI episodes each patient had accumulated by a given timepoint.

TAKEAWAY

• Among 563 CAR T-cell therapy recipients, 259 patients (46%) had a total of 446 laboratory-documented RVI episodes. At 2 years, the MCF was 1.15 for any RVI and 0.25 for severe RVI.
• SARS-CoV-2 (41%) and rhinovirus (27%) were the pathogens detected most often. LRTIs occurred in 18% of all episodes. Ten infection-related deaths were recorded, with SARS-CoV-2 accounting for nine and influenza A accounting for one.
• In multivariable analyses that considered recurrent infections, compared with patients with ALCs < 0.5 × 109/L, those with ALCs ≥ 0.5 × 109/L had a significantly reduced risk for any RVI (hazard ratio [HR], 0.70; P = .007) and a reduced risk for severe RVI (HR, 0.59; P = .043).
• Patients with higher CD19+ B-cell counts had a lower risk for severe RVIs (HR per log increase, 0.67; P < .001). Patients with mantle cell lymphoma carried a markedly higher risk for severe RVIs than those with large B-cell lymphoma (HR, 2.64; P = .002).

IN PRACTICE

"Despite recovery from early treatment-related toxicity, a substantial proportion of laboratory-documented RVI occurring beyond day 100 progress to severe disease. Impaired immune reconstitution, particularly lymphopenia, was associated with both RVI incidence and severity, with an ALC < 0.5 × 109/L identifying patients at increased risk," the authors of the study wrote.

SOURCE

The study was led by Sigrun Einarsdottir, Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center in New York City. It was published online on September 26, 2026, in the International Journal of Infectious Diseases.

LIMITATIONS

The study was retrospective in nature and restricted to one institution. Because testing depended on routine clinical care, the study captured only episodes that came to medical attention and hospitalized or more immunosuppressed patients were tested more frequently. Severity grading was imperfect, and those with frequent encounters contributed more laboratory data, which may have skewed the models. Immune marker data density reduced after 12 months. Confounding by indication could not be ruled out for vaccination or immunoglobulin replacement therapy.

DISCLOSURES

The study was supported wholly or partly by grants from the National Institutes of Health through the National Cancer Institute Cancer Center Support and other NIH awards. Multiple authors reported receiving fees or research support, having consulting relationships, or having other ties with pharmaceutical companies, including Kite/Gilead, Bristol Myers Squibb, Janssen, Novartis, and others. Full author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.