Megan M. Herr

Bispecific antibodies (BsAbs) are effective treatments in aggressive B‑cell lymphomas but carry immune-mediated risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), particularly during the first cycle. We analyzed 255 patients receiving BsAbs across 14 institutions to identify predictors of CRS/ICANS. CRS occurred in 31% (Grade 3+: 5%) and ICANS in 8% (Grade 3+: 2%) of patients, with no significant differences across glofitamab, mosunetuzumab, or epcoritamab. CRS rates with glofitamab and epcoritamab as monotherapy were lower than reported in trials. In multivariable analysis, concurrent systemic chemotherapy was associated with Grade 2+ CRS, and the development of any-grade CRS and elevated ferritin independently was associated with ICANS. All patients with Grade 3+ CRS had very high serum C-Reactive Protein (sCRP, ≥15 mg/L) and elevated ferritin (>336 ng/mL) when available. These findings identify candidate laboratory thresholds and treatment related factors that warrant prospection validation for risk stratification and outpatient BsAb administration.

Patients with plasma cell leukemia (PCL) are generally excluded from pivotal T-cell redirecting bispecific antibody (BsAb) trials. We evaluated real-world outcomes in a multicenter retrospective study of 122 patients with primary or secondary PCL across 15 academic centers, categorized as 'active' (≥5% circulating plasma cells within 30 days of BsAb initiation) or 'historical'. In a heavily pretreated population, patients received teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (Tal LOT, 42%), or talquetamab as bridging therapy to CAR-T (Tal Bridge, 11%). Cytokine release syndrome (CRS) was grade 1-2 in 56% and grade 3-4 in 4%, whereas neurotoxicity was grade 1-2 in 16% and grade 3-4 in 5%. Among 110 evaluable patients, the overall response rate (ORR) was 55%, including 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. With a median follow-up of 8.3 months, talquetamab demonstrated superior survival. Tal LOT showed a median progression-free survival (mPFS) of 5.5 months and a median overall survival (mOS) of 11.5 months, and both were unreached in the Tal Bridge cohort. In contrast, teclistamab and elranatamab showed a mPFS of 1.2 and 1.6 months and mOS of 8.1 and 3.6 months, respectively (P=0.007, P=0.023). In active PCL, Tal LOT achieved mPFS/mOS of 6.9/12.2 months versus 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab, respectively (P<0.001, P=0.002). Multivariable analysis associated active PCL with worse survival and Tal LOT with improved outcomes. BsAbs were safe in PCL, with talquetamab showing superior outcomes compared with BCMA-directed BsAbs.

CD86 expression on patient MM cells prior to CAR T therapy.

Characterization of CAR T cell mitochondrial metabolism.

Key Resources Table 1 from Endogenous CD28 Drives the Persistent Activity of CAR T Cells in Myeloma and Lymphoma Models

Effect of transient abatacept exposure on MM.1S growth.

Characterization of human and mouse CD28 knockout CAR T cells, and mouse myeloma target cells.