Treatment Outcomes of Adult B-Cell Acute Lymphoblastic Leukemia with Post-Transplant Relapse in the Era of Immunotherapeutic Agents

Abstract

Post-transplant relapse remains a major cause of treatment failure in adult B-cell acute lymphoblastic leukemia (ALL). The introduction of inotuzumab ozogamicin (InO) and blinatumomab (Blina) has expanded salvage options; however, their impact on outcomes and safety in patients relapsing after allogeneic stem cell transplantation has not been fully defined. To evaluate the impact of the availability of InO and Blina on clinical outcomes in adult B-cell ALL patients with post-transplant relapse, and to assess the safety of these agents in the post-transplant setting. We retrospectively analyzed 150 adult patients with B-cell ALL who relapsed after the first allogeneic stem cell transplantation. Patients were divided according to the time of their post-transplant relapse based on the approvals of InO and Blina in Japan: the pre-InO/Blina group (n = 95) and the post-InO/Blina group (n = 55). Outcomes were analyzed separately for Philadelphia chromosome (Ph)-negative and Ph-positive ALL. Overall survival (OS) after post-transplant relapse, complete remission (CR) rates as the best response before a second transplantation or last follow-up, and outcomes after a second transplantation were compared between groups. Adverse events associated with post-transplant use of InO and Blina were also evaluated. Among 95 patients with Ph-negative ALL, outcomes were significantly better in the post-InO/Blina group than in the pre-InO/Blina group, with the 2-year OS after post-transplant relapse improving from 19% to 51% (P = .003) and, among 88 treated patients, the CR rate increasing from 36% to 77% (P < .001). Multivariable analyses identified the time of post-transplant relapse and disease status at the first transplantation as independent prognostic factors for OS. Among 43 patients who underwent a second transplantation, the 2-year OS after second transplantation improved from 27% in the pre-InO/Blina group to 55% in the post-InO/Blina group (P = .029). In contrast, among 55 patients with Ph-positive ALL, OS after post-transplant relapse did not differ between groups. Among 32 patients treated with InO after post-transplant relapse, no patient developed veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) during InO therapy; however, 5 of 17 patients (29%) who subsequently underwent the second transplantation developed VOD/SOS. An interval of <2.5 months between InO and the second transplantation was associated with a higher VOD/SOS risk (56% versus 0%, P = .029). Among 30 patients treated with Blina, cytokine release syndrome occurred in 53% (grade 3 to 4, 7%) and immune effector cell-associated neurotoxicity syndrome in 13% (grade 3, 3%), with no fatal events. The prognosis of adult Ph-negative B-cell ALL after post-transplant relapse improved substantially in the post-InO/Blina era, including improved survival after a second transplantation. Overall, the safety profiles of InO and Blina in the post-transplant setting were acceptable, although VOD/SOS remains an important concern in patients proceeding to a second transplantation after InO.