Dose Modifications with Bispecifics

Dose Modifications with Bispecifics

Response-guided dosing strategies involve weekly light chain monitoring during initial therapy to detect early responses, which typically occur within 1-2 months. Dosing adjustments focus on interval extension rather than dose reduction, with more aggressive de-escalation than many colleagues practice. After step-up dosing, weekly administration continues until response is documented, then transitions to every-two-week dosing once partial response or better is achieved, followed by monthly dosing.

The long half-life of bispecific antibodies suggests current dosing schedules may exceed necessary exposure, and interval extension reduces infection risk substantially. Real-world data collection from institutional experience supports these dosing modifications. Some practitioners explore rapid de-escalation with step-up dosing followed by one weekly dose, assessing response, then moving responders to every-two-week intervals before transitioning to monthly maintenance.

Monthly dosing after achieving very good partial response or better represents a common practice modification supported by pharmacologic data showing sustained T-cell binding even with monthly administration. This approach balances maintaining efficacy while minimizing toxicity, particularly infection risk. The concept of fixed-duration therapy followed by drug holidays with retreatment at progression is emerging as a potential strategy to further reduce cumulative toxicity while maintaining long-term disease control.