Clinical Scorecard: Immune Responses to Vaccination After CAR T-Cell Therapy in Patients with Blood Cancers
At a Glance
Category
Detail
Condition
Immune deficiency and infection risk following CAR T-cell therapy in blood cancers
Key Mechanisms
Multifactorial immune deficiency due to underlying disease, prior therapies, lymphodepleting chemotherapy, and CAR T-cell mediated depletion of B cells or plasma cells
Target Population
Patients with lymphoma and myeloma treated with CD19- or BCMA-targeted CAR T-cell therapy
Care Setting
Post-CAR T-cell therapy outpatient and clinical follow-up settings
Key Highlights
Infections are the leading cause of non-relapse mortality after CAR T-cell therapy due to profound immune deficiencies.
CD19 CAR T-cell therapy causes near-universal and prolonged B cell aplasia; BCMA CAR T-cell therapy depletes plasma cells, resulting in distinct humoral immune defects.
Vaccine response rates post-CAR T-cell therapy are low (27-35%) for COVID-19 mRNA and influenza vaccines, with variable responses between CD19 and BCMA CAR T recipients.
Guideline-Based Recommendations
Diagnosis
Assess baseline seroprotection and humoral immunity prior to vaccination post-CAR T-cell therapy using commercially available serological assays.
Exclude patients who received IVIG within 8 weeks prior to serological testing to avoid confounding antibody levels.
Management
Implement vaccination schedules including pneumococcal conjugate vaccines, tetanus/diphtheria/pertussis, Hib, IPV, hepatitis B, and recombinant zoster vaccines post-CAR T-cell therapy.
Administer booster doses 6-12 months after primary pneumococcal vaccination series to enhance immune response.
Consider timing of vaccination post-CAR T-cell therapy carefully, though optimal timing remains to be established.
Monitoring & Follow-up
Perform post-vaccination serological titers to evaluate vaccine response and immunity retention.
Use composite measures of vaccine response to categorize patients as global responders, non-responders, or no call to guide clinical decisions.
Risks
Recognize that 31% of infections post-BCMA CAR T-cell therapy are vaccine-preventable, underscoring the importance of vaccination despite suboptimal responses.
Be aware of persistent immune deficiencies that may limit vaccine efficacy and increase infection risk.
Patient & Prescribing Data
Patients with lymphoma and myeloma receiving commercial CD19- or BCMA-targeted CAR T-cell therapies
Vaccination post-CAR T-cell therapy yields limited humoral responses; BCMA CAR T recipients may have better COVID-19 vaccine responses than CD19 recipients, but overall immunity remains impaired.
Clinical Best Practices
Exclude recent IVIG recipients when assessing vaccine-induced antibody responses to avoid false elevations.
Use standardized institutional definitions for protective antibody levels and vaccine response thresholds.
Employ a comprehensive vaccination schedule covering multiple vaccine-preventable infections tailored to CAR T-cell therapy recipients.
Monitor serological responses longitudinally to identify patients who may benefit from additional vaccine doses or alternative preventive strategies.
by Sigrun Einarsdottir, Stephanie Lobaugh, Danny Luan, Marina Gomez-Llobell, Padmapriya Subramanian, Sean Devlin, David Chung, Parastoo B. Dahi, Lorenzo Falchi, Sergio Giralt, Heather Landau, Alexander M. Lesokhin, Richard Lin, Jennifer Lue, Sham Mailankody, M. Lia Palomba, Jae H. Park, Gilles Salles, Michael Scordo, Silvia Escribano-Serrat, Jaime Sanz, Kai Rejeski, Roni Shouval, Saad Usmani, Miguel-Angel Perales, Gunjan Shah, Zainab Shahid
Dr. Nikhil Munshi and colleagues reported a study demonstrating that COVID-19 vaccination offers less protection for multiple myeloma patients, reinforcing the need for these patients to use additional precautions.
