Outcome after first relapse post-immunochemotherapy in older adults with Philadelphia-negative B-cell acute...

Inotuzumab (InO)-based frontline regimens have significantly improved the survival of older patients with Philadelphia-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL). Yet, outcome after relapse is not reported for this population.

The retrospective RELAPSINO study describes post-relapse outcome of 48 older patients treated front-line with a combination of InO and low-dose chemotherapy in the EWALL-INO trial (NCT03249870). At relapse (91% medullary), median age was 70 years and median duration of first complete remission (CR1) 15.2 months. CD19 or CD22 expression loss was observed in respectively 13% and 23% of evaluable cases. Most patients (85%) received salvage therapy (blinatumomab, low dose or intensive chemotherapy, in combination or not). There was no InO re-treatment.

Overall, CR2 was reached by 51% of the patients. Median event-free survivals (EFS, 3.2 months) and overall survivals (OS, 4.5 months) were dismal. For patients achieving CR2, 2-year OS was 46% and leukemia-free survival (LFS) was 36%. By multivariable analysis, not receiving intensive chemotherapy was associated with significantly lower EFS (hazard ratio [HR], 3.28; 95% confidence interval [CI], 1.43-7.53, p = .005), LFS (HR, 13.2; 95% CI, 2.46-70.88, p = .003), and OS (HR, 3.25; 95% CI, 1.39-7.59, p = .006). CR1 duration ≥12 months was significantly associated with better EFS (HR, 0.31; 95% CI, 0.14-0.67, p = .003), LFS (HR, 0.16; 95% CI, 0.04-0.72, p = .01), and OS (HR, 0.42; 95% CI, 0.20-0.89, p = .023). Not achieving CR2 was associated with lower OS (HR, 8.0; 95% CI, 3.25-20.1, p < .001). Receiving blinatumomab had no impact.

These results indicate that salvage regimen should be proposed in this context, allowing 50% of patients to achieve CR2 and have better survival.