Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study

Abstract

Background Blinatumomab, a bispecific T‐cell‐engaging (BiTE®) immuno‐oncology therapy, demonstrated superior overall survival versus standard‐of‐care chemotherapy (SOC) in adults with relapsed/refractory B‐cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab. Methods In the TOWER study, adults with R/R ALL were randomized 2:1 to receive blinatumomab or SOC. Study treatment consisted of 2 cycles of induction with blinatumomab or SOC followed by consolidation and maintenance therapy. At any time after the first cycle, patients who were eligible for HSCT could proceed to HSCT. Results Of the 97 patients who underwent HSCT during the study, baseline characteristics generally were comparable and donor types were similar between the patients treated with blinatumomab (65 patients) and those receiving SOC (32 patients). There was no evidence to suggest that the survival benefit of HSCT differed between the patients treated with blinatumomab and those receiving SOC (P = .68). On the basis of descriptive statistics, a survival benefit of HSCT versus no HSCT was not observed in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95% CI, 0.54‐2.53). The best outcomes were achieved in patients with no prior salvage therapy and with minimal residual disease response to blinatumomab regardless of on‐study HSCT status. Conclusions Survival was found to be driven by response to study treatment and by salvage status regardless of on‐study HSCT status. These data should be interpreted with caution because the current study was not designed to prospectively assess survival outcomes associated with HSCT after blinatumomab. Lay Summary Evidence before this study: Blinatumomab is associated with superior morphologic and molecular response rates and superior overall outcome when compared with standard of care chemotherapy in adults with relapsed/refractory B‐cell precursor acute lymphoblastic leukemia. Added value of this study: The best outcomes with blinatumomab were observed in patients who achieved minimal residual disease remission in first salvage treatment regardless of subsequent allogeneic stem cell transplantation (HSCT). Implications of all the available evidence: Patients achieving CR/CRh/CRi following blinatumomab can have a durable response with or without HSCT.

Hematopoietic stem cell transplantation in children and adolescents with nonremission acute lymphoblastic leukemia

“…[23][24][25] This to bridge to HSCT or to reduce relapse after HSCT. 26,27 Therefore, currently, for patients who have failed to achieve CR with chemotherapy, we would administer some immunotherapy to reduce the leukemic burden as much as possible to the minimal residual disease-negative level so that we could expect to improve the outcome. However, immunotherapy may make the patient's condition more difficult to manage once they become resistant to this form of therapy.…”

Concepts in immuno-oncology: tackling B cell malignancies with CD19-directed bispecific T cell engager therapies

“…Blinatumomab, beneficial for OS in first or later salvage, was particularly effective in first salvage, where it more than doubled median survival relative to chemotherapy [51]. Salvage status drove survival in responders regardless of subsequent allogeneic stem cell transplantation [52]. Blinatumomab also provided clinically meaningful benefits in health-related quality of life [53].…”

“…However, it also shows significant relapse rates. In a study in patients with R/R ALL who underwent allogenic HSCT after treatment with blinatumomab, it was found that transplantation reduced the risk of death by 55% and 46% in blinatumomab and SOC groups, respectively [52]. The best outcomes were in patients with no prior salvage therapy and MRD responses to blinatumomab regardless of on-study HSCT status [52].…”

“…In a study in patients with R/R ALL who underwent allogenic HSCT after treatment with blinatumomab, it was found that transplantation reduced the risk of death by 55% and 46% in blinatumomab and SOC groups, respectively [52]. The best outcomes were in patients with no prior salvage therapy and MRD responses to blinatumomab regardless of on-study HSCT status [52]. Effectiveness in terms of durable remission following post CAR T allogenic HSCT seems positive in several studies investigating treatment for R/R ALL [91,98,99].…”

Role of CAR-T cell therapy in B-cell acute lymphoblastic leukemia

“…Blinatumomab prolonged OS with a median OS of 7.7 months versus 4.0 months for SOC, respectively. Patients achieving CR, CRh, or CRi after therapy with blinatumomab reportedly achieved durable responses and promising OS rates with or without subsequent HSCT [4]. Due to study limitations it is currently unclear whether patients responding to blinatumomab and obtaining MRD-negativity should undergo HSCT.…”