Clinical Scorecard: Evaluation of Infectious Complications Associated with BCMA-Targeted Treatments in Multiple Myeloma
At a Glance
Category
Detail
Condition
Relapsed/refractory multiple myeloma
Key Mechanisms
BCMA-targeted therapies including antibody drug conjugates (ADC), CAR-T, and bispecific antibodies (BsAb) targeting B-cell maturation antigen on plasma cells
Target Population
Adult patients (≥18 years) with relapsed/refractory multiple myeloma
Care Setting
Single-center tertiary cancer center (Memorial Sloan Kettering Cancer Center), clinical trials and commercial treatment settings
Key Highlights
BCMA-targeted CAR-T and BsAb therapies show unprecedented response rates but are associated with a spectrum of infectious complications.
Infections were analyzed retrospectively comparing BCMA-targeted CAR-T, BsAb, and ADC therapies in heavily pretreated multiple myeloma patients.
Primary endpoint was incidence of severe (grade ≥3) infections; secondary endpoints included infection rates, organisms, sites, risk factors, and impact of hypogammaglobulinemia and neutropenia.
Guideline-Based Recommendations
Diagnosis
Monitor for infectious events from day of treatment initiation until next therapy or last follow-up.
Grade infections using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Management
Administer prophylactic antimicrobials per institutional and protocol guidelines.
Use granulocyte colony-stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) at physician discretion based on neutropenia and hypogammaglobulinemia.
Monitoring & Follow-up
Regularly assess IgG levels to identify hypogammaglobulinemia (IgG <400 mg/dL) and neutrophil counts (<1000/mcL) as risk factors for infection.
Baseline labs should be obtained prior to lymphodepleting chemotherapy (CAR-T) or treatment initiation (BsAb, ADC).
Risks
Patients with relapsed/refractory multiple myeloma receiving BCMA-targeted T-cell redirecting therapies are at increased risk of severe infections.
Hypogammaglobulinemia and neutropenia are modifiable risk factors associated with infectious complications.
Patient & Prescribing Data
256 patients: 92 CAR-T, 55 BsAb, and 109 ADC recipients with relapsed/refractory multiple myeloma
CAR-T patients had median 7 prior therapies, median age 62; BsAb patients median 6 prior therapies, median age 65; majority treated on clinical trials for CAR-T and BsAb.
Clinical Best Practices
Exclude cytokine release syndrome without concurrent infection from infectious event classification.
Include only first CAR-T or first BsAb treatment infectious events in analysis to avoid confounding.
Use multivariable statistical models adjusting for age, refractory status, prior BCMA therapy, neutropenia, lymphopenia, and hypogammaglobulinemia to assess infection risk.
by Karthik Nath, Tala Shekarkhand, David Nemirovsky, Andriy Derkach, Bruno Almeida Costa, Noriko Nishimura, Tasmin Farzana, Colin Rueda, David J. Chung, Heather J. Landau, Oscar B. Lahoud, Michael Scordo, Gunjan L. Shah, Hani Hassoun, Kylee Maclachlan, Neha Korde, Urvi A. Shah, Carlyn Rose Tan, Malin Hultcrantz, Sergio A. Giralt, Saad Z. Usmani, Zainab Shahid, Sham Mailankody, Alexander M. Lesokhin
