Why Step-Up Dose With Bispecific Antibodies?

Step-up dosing with bispecific antibodies plays a critical role in managing toxicity for patients with multiple myeloma, explained Karolina Faysman, NP, a nurse practitioner at UCLA in Los Angeles, California.

In an interview with Oncology Nursing News following a Case-Based Roundtable with peer nurse practitioners, Faysman emphasized that the primary purpose of step-up dosing is to minimize immediate toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which are class effects of T-cell-engaging therapies.

“These toxicities can be life threatening if patients are not properly monitored and treated,” she noted. By gradually introducing the drug and increasing the dose every few days, clinicians can significantly lower the frequency and severity of CRS events.

According to Faysman, clinical trials have demonstrated that more conservative step-up approaches may further reduce CRS risk, particularly when tailored to a patient’s disease burden. While most patients are initially admitted for inpatient step-up dosing, she highlighted a shift toward outpatient management in centers with strong support systems, improving patient satisfaction and reducing hospital stays. Understanding and implementing this strategy is vital for ensuring patient safety and treatment success.

Transcript

The goal of step-up dosing is to decrease the immediate toxicity, which is cytokine release syndrome and ICANS. These are drug class effects. They are not specific to each drug. It’s an effect of T-cell engagement and the release of the cytokines in the cancer cells.

That toxicity can be life threatening if patients are not properly monitored and treated. Having step-up dosing, where the patient is introduced to the drug with the dosing broken up, and where the patient is getting a higher dose every couple of days, it decreases the rate and degree of CRS. Even if there’s a large patient population, but they experience only grade 1 CRS, where it’s very benign, that’s very different vs patients experiencing a higher grade. That is very important to understand.

There are trials that demonstrate that step-up dosing that is a bit more conservative may lead to better results regarding the decrease rate of CRS. Understanding what patient disease burden is and how that would affect the step-up dosing also decreases the rate of the severity of CRS in this patient population, and, therefore, [increases] patient experience.

As of today, the majority of patients are being admitted for step-up dosing. Initially, a lot of institutions, particularly large academic centers and tertiary cancer centers, that have significant outpatient support, are pulling these patients out and doing that in the outpatient setting, because of the safety and predictability of this phenomenon. Not being in the hospital for days will definitely improve patient satisfaction.

The whole goal of the step-up dosing is to decrease those immediate toxicities such as CRS and ICANs, so understanding that as an important part of the practice is vital to provide safe and successful outcome.

This transcript has been edited for clarity and conciseness.