Blinatumomab and Inotuzumab Ozogamicin Sequential Use for the Treatment of Relapsed/Refractory Acute Lymphoblastic...

Blinatumomab (Blina) and inotuzumab ozogamicin (InO) has improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, little is known about the outcome after recurrence and re-treatment with immunotherapy.

We describe 71 R/R B-ALL patients treated for different relapses with Blina and InO. Blina was the first treatment in 57 patients and InO in 14. Twenty-seven patients had a previous allogeneic hematopoietic stem cell transplantation (allo-HSCT).

In the Blina/InO group, after Blina, 36 patients (63%) achieved a complete remission (CR), with 42% of negative minimal residual disease (MRD-); after InO, a CR was achieved in 47 patients (82%, 34 MRD-). In the InO/Blina group, after InO, 13 cases (93%) reached a CR (6 MRD-); after Blina, a CR was re-achieved in 6 cases (43%, 3 MRD-). Twenty-six patients proceeded to allo-HSCT. In the Blina/InO group, the median overall survival (OS) was 19 months; the disease-free survival (DFS) after Blina was 7.4 months (11.6 vs. 2.7 months in MRD- vs. MRD+, p = 0.03) and after InO, 5.4 months. In the InO/Blina group, the median OS was 9.4 months; the median DFS after InO was 5.1 months and 1.5 months after Blina (8.7 vs. 2.5 months in MRD- vs. MRD+, p = 0.02). With a median follow-up of 16.5 months from the start of immunotherapy, 24 patients (34%) are alive and 16 (22%) are alive in CR.

In our series of R/R B-ALL, Blina and InO treatment demonstrate efficacy for subsequent relapses in terms of MRD response, OS and DFS, and as a bridge to allo-HSCT.