Outcomes of Allogeneic Hematopoietic Cell Transplantation after Salvage Therapy with Blinatumomab in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia.

Historically, outcomes of adult patients with relapsed acute lymphoblastic leukemia (ALL) who fail to enter remission with conventional chemotherapy are very poor. Blinatumomab, a bispecific CD3/CD19 antibody, has shown remarkable activity in relapsed/refractory (r/r) ALL. Although allogeneic hematopoietic cell transplant (HCT) is the recommended consolidation therapy for patients with r/r ALL who respond to salvage therapy, HCT and toxicity outcomes for those who received blinatumomab salvage and HCT remain largely unknown. We treated 89 patients with r/r ALL with blinatumomab, of whom 43 patients (48%) achieved remission. Here we describe our single-center experience in the subset of patients who responded to blinatumomab salvage therapy for eradication of either gross (n = 24) or minimal residual disease (n = 11) before HCT. Overall survival at 1 and 2 years after allogeneic HCT was 77% and 52%, respectively. Leukemia-free survival at 1 and 2 years were 65% and 40%, respectively. Additionally, with blinatumomab administration pre-HCT, no unusual toxicities such as delayed neutrophil/platelet engraftment or graft failure were observed. Acute grades II to IV graft-versus-host disease (GVHD) at day +100 post-HCT was at 43% and 2-year chronic GVHD was 36%, both comparable with historic control subjects. Finally, results of our subset analysis based on pre-HCT minimal residual disease (MRD) status indicated no significant difference in survival outcomes among patients undergoing transplant in MRD-negative status and the entire cohort. In conclusion, based on results of this study, blinatumomab may be considered as a safe and effective agent for r/r ALL patients before HCT.

Salhotra A ，Yang D ，Mokhtari S ，Malki MMA ，Ali H ，Sandhu KS ，Aribi A ，Khaled S ，Mei M ，Budde E ，Snyder D ，Cao T ，Spielberger R ，Marcucci G ，Pullarkat V ，Forman SJ ，Nakamura R ，Stein A ，Aldoss I ... -  《-》

Blinatumomab Therapy Is Associated with Favorable Outcomes after Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients with B Cell Acute Lymphoblastic Leukemia.

Llaurador G ，Shaver K ，Wu M ，Wang T ，Gillispie A ，Doherty E ，Craddock J ，Read J ，Yassine K ，Morales E ，George A ，Steffin D ，Krance R ，Martinez C ，Heslop H ，Salem B ... -  《-》

Feasible outcome of blinatumomab followed by allogeneic hematopoietic cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first salvage.

In adult patients with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-negative) B-cell presursor acute lymphoblastic leukemia (BCP-ALL), complete remission (CR) and overall survival (OS) rates are poor. We analyzed treatment outcomes and prognostic factors for 32 adult patients with R/R Ph-negative BCP-ALL who received blinatumomab at first salvage. Patients who achieved CR proceeded to allogeneic hematopoietic cell transplantation (allo-HCT). At the time of blinatumomab treatment, 11 patients (34.3%) were primary refractory, 10 (31.4%) had relapsed with first CR duration (CRD1) ≥12 months, and 11 (34.3%) had relapsed with CRD1 <12 months. After the first blinatumomab cycle, 22 (68.8%) achieved CR. At the end of the second cycle, 20 of the 22 patients remained in persistent CR, and 1 patient achieved new CR. The overall minimal residual disease negativity rate was 75% among evaluable patients with persistent CR. Patients with CRD1 <12 months were associated with poorer response to blinatumomab. Twenty (62.5%) of 32 patients underwent allo-HCT in blinatumomab-induced CR. After a median follow-up of 15.2 months, the 1-year OS rates for all patients and patients receiving allo-HCT in CR were 55.5% (median OS, 18.2 months) and 70.7%, respectively. Patients with CRD1 <12 months, extramedullary disease (EMD), and high peripheral blood blasts were associated with poorer OS. Blinatumomab is effective for achieving good quality CR and bridging to allo-HCT for adult patients with R/R Ph-negative BCP-ALL in first salvage. The role of blinatumomab in patients with CRD1 <12 months, EMD, or high tumor burden should be evaluated in future trials.

Yoon JH ，Min GJ ，Park SS ，Park S ，Lee SE ，Cho BS ，Eom KS ，Kim YJ ，Kim HJ ，Min CK ，Cho SG ，Kim DW ，Lee JW ，Lee S ... -  《Cancer Medicine》

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

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. 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. 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. 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. 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.

Jabbour EJ ，Gökbuget N ，Kantarjian HM ，Thomas X ，Larson RA ，Yoon SS ，Ghobadi A ，Topp MS ，Tran Q ，Franklin JL ，Forman SJ ，Stein AS ... -  《-》

Pretransplant Blinatumomab Improves Outcomes in B Cell Acute Lymphoblastic Leukemia Patients Who Undergo Allogeneic Hematopoietic Cell Transplantation.

Blinatumomab, a bispecific monoclonal antibody, effectively controls refractory B cell acute lymphoblastic leukemia (ALL) and promotes measurable residual disease (MRD) negativity. This study investigated the impact of pretransplant blinatumomab on allogeneic hematopoietic cell transplantation (HCT) outcomes in B cell ALL patients. We analyzed the effect of pretransplant blinatumomab on transplant outcomes of 117 adults undergoing allogeneic HCT for B cell ALL at Princess Margaret Hospital, Toronto, between 2010 and 2021. Outcomes assessed included overall survival (OS), graft-versus-host disease and relapse-free survival (GRFS), cumulative incidences of relapse (CIR), and nonrelapse mortality (NRM). The median follow-up was 36 months. Thirty-one participants (26.5%) received blinatumomab. Blinatumomab group had higher proportions of individuals with high disease risk index, primary induction failure and was more likely to receive dual T cell depletion with antithymocyte globulin and post-transplant cyclophosphamide. Two-year OS, GRFS, NRM, and CIR in the blinatumomab and nonblinatumomab groups were, respectively: 65.4% versus 45.6% (P = .05), 42.2% versus 17.3% (P = .01), 3.2% versus 43.0% (P = .007) and 34.4% versus 14.4% (P = .02). Blinatumomab was associated with a lower incidence of day-100 grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD): 27.5% versus 56.7% (P = .009), and 10.9% versus 34.7% (P = .04), respectively. Multivariate analysis confirmed the association between pretransplant blinatumomab and improved OS and NRM. Pretransplant blinatumomab is associated with improved OS and lower risk of NRM in B cell ALL patients undergoing allogeneic HCT, likely reflecting lower burden of treatment-related toxicity in this population. Larger prospective trials are warranted to validate our findings.

Sayyed A ，Chen C ，Gerbitz A ，Kim DDH ，Kumar R ，Lam W ，Law AD ，Lipton JH ，Michelis FV ，Novitzky-Basso I ，Viswabandya A ，Mattsson J ，Pasic I ... -  《-》