INfections in Patients Treated With CAR-T

This is a single-center observational study involving adult patients with relapsed/refractory multiple myeloma or B-cell non-Hodgkin lymphoma who received/will receive CAR-T cell therapy at the IRCCS Azienda Ospedaliero-Universitaria di Bologna. The study aims to evaluate how often infections occur during the first 12 months after CAR-T infusion and to describe their main characteristics and risk factors. Both patients treated since 2019 (retrospective cohort) and newly enrolled patients during the year following study approval (prospective cohort) will be included, with one year of follow-up after infusion.

The study will investigate factors associated with infection risk, the impact of preventive and therapeutic anti-infective strategies, the distinction between infection-related fever and cytokine release syndrome (CRS), post-discharge infections, and immune recovery after CAR-T therapy. In the prospective cohort, patients who develop their first fever episode after CAR-T infusion will also undergo a validated rapid molecular blood test (PilotGene ddPCR Blood System), alongside standard blood cultures, to improve the speed of bloodstream infection diagnosis. The test is already used in clinical practice and will serve as a complementary diagnostic tool without changing standard patient management. Approximately 290 patients are expected to be included, most of whom with lymphoma.

Primary outcomes

• Cumulative Incidence of Participants With at Least One Infectious Complication After CAR-T Infusion. [Within 12 months after CAR-T infusion]: Percentage of participants experiencing at least one infectious complication of any type within 12 months after CAR-T infusion.

Secondary outcomes

• Adjusted Odds Ratios for Predefined Pre- and Post-Infusion Factors Associated With Infectious Complications. [Within 12 months after CAR-T infusion]: Adjusted odds ratios with 95% confidence intervals for the association between predefined pre-infusion and post-infusion variables and the occurrence of at least one infectious complication after CAR-T infusion.
• Classification of the first febrile episode within 30 days after CAR-T infusion. [Within the first 30 days after CAR-T infusion]: Classification of each participant's first febrile episode as no fever, infection-related fever, indeterminate fever, or cytokine release syndrome (CRS)-related fever.
• Participants with microbiologically documented infection at the first febrile episode. [Within the first 30 days after CAR-T infusion.]: Number (or percentage) of participants with a microbiologically documented infection identified at the time of the first febrile episode.
• Post-Discharge Infectious Complications. [From hospital discharge up to 12 months after CAR-T infusion.]: Percentage of participants with at least one infectious complication occurring after hospital discharge.
• Diagnostic Yield of the Pilot Gene ddPCR Blood Test. [Up to 12 months after enrollment (at the first febrile episode)]: Percentage of first febrile episodes with at least one pathogen and/or antimicrobial resistance marker detected by the Pilot Gene droplet digital polymerase chain reaction blood test.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Diagnosis of relapsed/refractory multiple myeloma or B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), high-grade B-cell lymphoma (HGBCL), primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL)
* Receipt of CAR-T infusion at IRCCS AOUBo
* Age ≥18 years at the time of CAR-T infusion
* Signed informed consent

Exclusion Criteria:

* None

• Zeno Adrien Igor Pasquini, Principal investigator, IRCCS Azienda Ospedaliero-Universitaria di Bologna