The Impact of Cytoreduction on Blinatumomab Outcomes for Relapsed or Refractory B‐ <scp>ALL</scp> With High Disease Burden

Blinatumomab is approved for the treatment of relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Studies have correlated pre-blinatumomab high disease burden (HDB) [> 50% bone marrow blasts (BMB)] with lower response rates and increased risk for toxicities, including cytokine release syndrome (CRS) and neurotoxicity (NT). While the administration of pre-blinatumomab cytoreductive therapy is an appealing approach, larger studies validating the beneficial effect of this strategy in patients with HDB are lacking. We retrospectively analyzed 148 adult patients with R/R B-ALL treated with blinatumomab. Patients were grouped as low disease burden (LDB, n = 55), HDB without cytoreduction (n = 41), and HDB with cytoreduction (n = 52). The median age for the cohort was 40 years; the majority were males (63%) and Hispanic (73%), and the most common ALL subtype was Ph-like (40%). Patients with HDB with cytoreduction had a significantly higher rate of prior alloHCT (p = 0.041) and more lines of prior therapy (p = 0.006) compared to the other cohorts. Compared to patients with HDB, those with LDB had significantly higher response rates to blinatumomab (p < 0.0001), while rates of CRS and NT were not significantly different. Among patients with HDB, cytoreductive therapy was associated with a significantly lower rate of CRS compared to those who did not receive cytoreduction (p = 0.038). However, cytoreduction had no significant impact on treatment response, MRD negativity, or NT. Patients with B-ALL and HDB remain a challenging population for blinatumomab therapy; while cytoreduction may improve safety by reducing CRS, novel strategies are needed to enhance treatment efficacy.