While CELMoDs frequently cause neutropenia, this effect is most pronounced in early cycles and manageable with growth factors. This contrasts sharply with the persistent, quality-of-life-impairing non-hematologic side effects of lenalidomide, such as rash and severe fatigue. This trade-off results in a significantly better long-term tolerability profile for patients.

The phase 3 EPCOR FL-1 trial showed that adding epcoritamab to the lenalidomide/rituximab (R-squared) backbone profoundly improved progression-free survival in relapsed follicular lymphoma. Presented as the most important FL abstract at ASH, this result is expected to establish a new standard of care in this setting.

Corvus Pharmaceuticals is already planning frontline combination trials for its T-cell lymphoma drug. The drug's favorable safety profile is the critical enabler, allowing it to be paired with chemotherapy and used as a long-term maintenance therapy to prolong remissions—a strategy unavailable to more toxic drugs.

The FLAG-IDA plus venetoclax regimen achieves very high MRD-negative remission rates. However, its similar efficacy in both frontline and first salvage settings suggests it might be more strategically deployed as a salvage therapy, avoiding its high toxicity in all patients upfront.

An expert argues the path to curing metastatic cancer may mirror pediatric ALL's history: combining all highly active drugs upfront. Instead of sequencing treatments after failure, the focus should be on powerful initial regimens that eradicate cancer, even if it means higher initial toxicity.

In follicular lymphoma, the treatment goal is durable remission with manageable toxicity, not necessarily a cure. Therefore, clinicians frequently prefer using a bispecific antibody first, reserving the more complex and toxic CAR-T cell therapy for transformed disease or after a bispecific fails.

Three-year data for odronextumab, given until progression in follicular lymphoma, reveals a high rate of severe (Grade 3+) infections (45%), including fatal events. This highlights a critical safety concern with continuous dosing and strengthens the clinical argument for using fixed-duration bispecific regimens to mitigate long-term toxicity.

Actuate employed a master protocol that tested their drug alongside eight different standard-of-care chemotherapies in patients who had already failed them. This design efficiently demonstrated the drug's ability to reverse chemo-resistance across multiple histologies, informing their Phase 2 strategy.

Despite new therapies for follicular lymphoma (FL), bendamustine-rituximab (BR) will likely remain the community standard due to its simplicity. This may create a growing gap in treatment approaches between academic centers using novel agents and community practices favoring the familiar BR regimen.