MM Infection Risk and Bridging Therapy: Mateo Mejia Saldarriaga, MD

As patients with multiple myeloma live longer on highly effective immunotherapies, managing infection risk and toxicity has become nearly as important as controlling the disease, according to Mateo Mejia Saldarriaga, MD, hematologist and oncologist at Weill Cornell Medicine and NewYork-Presbyterian. In an interview for The American Journal of Managed Care^®, Mejia Saldarriaga discussed infection prophylaxis with bispecific antibodies and the evolving role of bridging therapy before chimeric antigen receptor (CAR) T-cell therapy.

Why IVIG Is Essential With Teclistamab-Daratumumab

The largest second-line data sets in myeloma come from CARTITUDE-4 (NCT04181827), which compared B-cell maturation antigen (BCMA)–directed CAR T-cell therapy with a standard triplet, and MajesTEC-3 (NCT05083169), which compared teclistamab plus daratumumab with the standard of care, Mejia Saldarriaga explained. Teclistamab is a bispecific antibody targeting BCMA and CD3, and daratumumab targets CD38.

Each drug carries an increased risk of infection on its own, especially viral infections and pneumonia. In combination, MajesTEC-3 showed a clear signal for increased infection and even mortality in the first 6 months, which led the study to mandate routine intravenous immunoglobulin (IVIG) from the start of treatment.

"If you're going to do teclistamab-daratumumab, you need to do IVIG, and it's almost as important as the anti-myeloma component," Mejia Saldarriaga said.

IVIG has no activity against myeloma, but it mitigates infection risk. Because patients are now living so long, Mejia Saldarriaga said, these "nonmyeloma factors" demand more attention.

"I don't care if my patient gets admitted to the hospital because of a relapse or because of pneumonia," Mejia Saldarriaga said. "They both can be quite devastating."

When to Use PCP Prophylaxis With Bispecifics

Infection risk varies by regimen. With teclistamab-daratumumab, the main signal has involved respiratory infections and pneumonia. In internal analyses and some published data, Mejia Saldarriaga's team has not seen an increase in Pneumocystis pneumonia (PCP) among patients receiving bispecifics, so routine trimethoprim-sulfamethoxazole prophylaxis is not used.

Mejia Saldarriaga acknowledged that many centers do use PCP prophylaxis and called that reasonable, framing it as a risk-benefit assessment that weighs the number needed to treat against added medications and complexity for patients. Mejia Saldarriaga routinely checks CD4 counts, because T-cell engagers can cause significant drops, and may use prophylaxis in those specific cases.

Why Bridging Response Matters Before CAR T-Cell Therapy

Bridging therapy was once viewed as a way to hold the disease until CAR T cells were ready. That view has changed with ciltacabtagene autoleucel (cilta-cel), the most widely used CAR T product, because of its risk of delayed neurotoxicity and parkinsonism. Tumor burden before infusion, or poor response to bridging, may be associated with that risk.

"These patients have amazing myeloma responses, but they have significant morbidity related to the neurotoxicity that might not be fully reversible, so it's critical," Mejia Saldarriaga said.

Talquetamab is a strong bridging option because it has one of the highest single-agent response rates, responses come quickly, and it targets GPRC5D rather than BCMA, avoiding overlap with the CAR T target. Its skin, nail, and oral mucosal toxicities remain a concern. Because many patients receive only 1 to 3 doses after step-up dosing before stopping, those effects tend to be less severe than with long-term use, Mejia Saldarriaga said, though some patients still describe them as the worst part of treatment.