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Nicola Gökbuget - One of the best experts on this subject based on the ideXlab platform.

  • Blinatumomab as first salvage versus second or later salvage in adults with relapsed refractory b cell precursor acute lymphoblastic leukemia results of a pooled analysis
    Cancer Medicine, 2021
    Co-Authors: Max S. Topp, Nicola Gökbuget, Monika Brüggemann, Giovanni Martinelli, Hagop M. Kantarjian, Anthony S. Stein, Heinzaugust Horst, Nicolas Boissel, Yuqi Chen, Gerhard Zugmaier
    Abstract:

    BACKGROUND Blinatumomab is a BiTE® immuno-oncology therapy indicated for the treatment of patients with relapsed or refractory (r/r) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Aims To assess the efficacy and safety of Blinatumomab as first salvage versus second or later salvage in patients with r/r BCP ALL. Materials & Methods Patient-level pooled data were used for this analysis. In total, 532 adults with r/r BCP ALL treated with Blinatumomab were included (first salvage, n = 165; second or later salvage, n = 367). Results Compared with patients who received Blinatumomab as second or later salvage, those who received Blinatumomab as first salvage had a longer median overall survival (OS; 10.4 vs. 5.7 months; HR, 1.58; 95% CI, 1.26-1.97; P < .001) and relapse-free survival (10.1 vs. 7.3 months; HR, 1.38; 95% CI, 0.98-1.93; P = .061), and higher rates of remission (n = 89 [54%] vs. n = 150 [41%]; odds ratio, 0.59; 95% CI, 0.41-0.85; P = .005), minimal residual disease response (n = 68 [41%] vs. n = 118 [32%]), and allogeneic hematopoietic stem cell transplant (alloHSCT) realization (n = 60 [36%] vs. n = 88 [24%]), and alloHSCT in continuous remission (n = 33 [20%] vs. n = 52 (14%]). In a subgroup analysis, there was no apparent effect of prior alloHSCT on median OS in either salvage group. The safety profile of Blinatumomab was generally similar between the groups; however, cytokine release syndrome, febrile neutropenia, and infection were more frequent with second or later salvage than with first salvage. Discussion In this pooled analysis, the logistic regression analyses indicated greater benefit with Blinatumomab as first salvage than as second or later salvage, as evident by the longer median OS, longer median RFS, and higher rates of remission. Conclusion Overall, Blinatumomab was beneficial as first salvage and as second or later salvage, but the effects were favorable as first salvage.

  • long term survival of patients with relapsed refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2021
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2020
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Blinatumomab vs historic standard‐of‐care treatment for minimal residual disease in adults with B‐cell precursor acute lymphoblastic leukaemia
    European journal of haematology, 2020
    Co-Authors: Nicola Gökbuget, Hervé Dombret, Sebastian Giebel, Monika Brüggemann, Michael Doubek, Robin Foà, Dieter Hoelzer, Christopher Kim, Giovanni Martinelli, Elena N. Parovichnikova
    Abstract:

    Objectives Survival outcomes from a single-arm phase 2 Blinatumomab study in patients with minimal residual disease (MRD)-positive B-cell precursor (BCP)-acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set. Methods The primary analysis comprised adult Philadelphia chromosome (Ph)-negative patients in first complete haematologic remission (MRD ≥ 10-3 ). Relapse-free survival (RFS) and overall survival (OS) were compared between Blinatumomab- and SOC-treatment groups. Baseline differences between groups were adjusted by propensity scores. Results The primary analysis included 73 and 182 patients from the Blinatumomab and historic data sets, respectively. When weighted by age to the Blinatumomab-treatment group, median RFS was 7.8 months and median OS was 25.9 months in the SOC-treated group. In the Blinatumomab study, median RFS was 35.2 months; median OS was not evaluable. Propensity score weighting achieved balance with seven baseline prognostic factors. With adjustment for haematopoietic stem cell transplantation (HSCT) status, a 50% reduction in risk of relapse or death was observed with Blinatumomab vs SOC. Median RFS, unadjusted for HSCT status, was 35.2 months with Blinatumomab and 8.3 months with SOC. Conclusions These analyses suggest that Blinatumomab improves RFS, and possibly OS, in adults with MRD-positive Ph-negative BCP-ALL vs SOC.

  • transplantation in adults with relapsed refractory acute lymphoblastic leukemia who are treated with Blinatumomab from a phase 3 study
    Cancer, 2019
    Co-Authors: Elias Jabbour, Nicola Gökbuget, Hagop M. Kantarjian, Xavier Thomas, Richard A. Larson, Sung-soo Yoon, Armin Ghobadi, Max S. Topp, Qui Tran, Janet Franklin
    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.

Max S. Topp - One of the best experts on this subject based on the ideXlab platform.

  • Blinatumomab as first salvage versus second or later salvage in adults with relapsed refractory b cell precursor acute lymphoblastic leukemia results of a pooled analysis
    Cancer Medicine, 2021
    Co-Authors: Max S. Topp, Nicola Gökbuget, Monika Brüggemann, Giovanni Martinelli, Hagop M. Kantarjian, Anthony S. Stein, Heinzaugust Horst, Nicolas Boissel, Yuqi Chen, Gerhard Zugmaier
    Abstract:

    BACKGROUND Blinatumomab is a BiTE® immuno-oncology therapy indicated for the treatment of patients with relapsed or refractory (r/r) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Aims To assess the efficacy and safety of Blinatumomab as first salvage versus second or later salvage in patients with r/r BCP ALL. Materials & Methods Patient-level pooled data were used for this analysis. In total, 532 adults with r/r BCP ALL treated with Blinatumomab were included (first salvage, n = 165; second or later salvage, n = 367). Results Compared with patients who received Blinatumomab as second or later salvage, those who received Blinatumomab as first salvage had a longer median overall survival (OS; 10.4 vs. 5.7 months; HR, 1.58; 95% CI, 1.26-1.97; P < .001) and relapse-free survival (10.1 vs. 7.3 months; HR, 1.38; 95% CI, 0.98-1.93; P = .061), and higher rates of remission (n = 89 [54%] vs. n = 150 [41%]; odds ratio, 0.59; 95% CI, 0.41-0.85; P = .005), minimal residual disease response (n = 68 [41%] vs. n = 118 [32%]), and allogeneic hematopoietic stem cell transplant (alloHSCT) realization (n = 60 [36%] vs. n = 88 [24%]), and alloHSCT in continuous remission (n = 33 [20%] vs. n = 52 (14%]). In a subgroup analysis, there was no apparent effect of prior alloHSCT on median OS in either salvage group. The safety profile of Blinatumomab was generally similar between the groups; however, cytokine release syndrome, febrile neutropenia, and infection were more frequent with second or later salvage than with first salvage. Discussion In this pooled analysis, the logistic regression analyses indicated greater benefit with Blinatumomab as first salvage than as second or later salvage, as evident by the longer median OS, longer median RFS, and higher rates of remission. Conclusion Overall, Blinatumomab was beneficial as first salvage and as second or later salvage, but the effects were favorable as first salvage.

  • long term survival of patients with relapsed refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2021
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2020
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Blinatumomab consolidation and maintenance therapy in adults with relapsed/refractory B-precursor acute lymphoblastic leukemia
    Blood advances, 2020
    Co-Authors: Alessandro Rambaldi, Qui Tran, Janet Franklin, Francoise Huguet, Pavel Zak, Paul Cannell, Max S. Topp
    Abstract:

    In a phase 3 clinical study of heavily pretreated adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL), overall survival (OS) following Blinatumomab, a BiTE (bispecific T-cell engager) immunooncology therapy, was significantly improved vs chemotherapy following induction (cycles 1 to 2). Here we report the efficacy and safety of those who received additional cycles of Blinatumomab. Blinatumomab was administered as a continuous IV infusion for 4 weeks in a 6-week cycle. Patients who achieved a bone marrow response (≤5% blasts) or complete remission (full, partial, or incomplete hematological recovery) during induction could receive additional cycles of Blinatumomab. OS and relapse-free survival (RFS) for consolidation (cycles 3 to 5) vs no consolidation, and maintenance (cycles ≥6) vs no maintenance were analyzed using Simon-Makuch and Mantel-Byar odds ratios. Of 267 patients who received Blinatumomab induction, 86 (32%) entered consolidation and 36 (13%) entered maintenance. Evidence of longer OS was demonstrated among the maintenance group compared with no-maintenance (median OS [95% confidence interval, CI]: not reached for maintenance vs 15.5 months for no maintenance). Median RFS (months; 95% CI) was numerically longer among maintenance group (14.5; 7.1 to 21.9) compared with no-maintenance (9.8; 8.5 to 11.1). A lower incidence of adverse events was seen during maintenance (72.2%) compared with induction (97.2%) and consolidation (86.1%). Adults with R/R ALL who achieved remission following Blinatumomab induction had longer survival on continuation therapy than those who discontinued Blinatumomab early, supporting the use of Blinatumomab as long-term therapy. No new safety signals were reported. This trial was registered at www.clinicaltrials.gov as #NCT02013167.

  • transplantation in adults with relapsed refractory acute lymphoblastic leukemia who are treated with Blinatumomab from a phase 3 study
    Cancer, 2019
    Co-Authors: Elias Jabbour, Nicola Gökbuget, Hagop M. Kantarjian, Xavier Thomas, Richard A. Larson, Sung-soo Yoon, Armin Ghobadi, Max S. Topp, Qui Tran, Janet Franklin
    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.

Hagop M. Kantarjian - One of the best experts on this subject based on the ideXlab platform.

  • Blinatumomab as first salvage versus second or later salvage in adults with relapsed refractory b cell precursor acute lymphoblastic leukemia results of a pooled analysis
    Cancer Medicine, 2021
    Co-Authors: Max S. Topp, Nicola Gökbuget, Monika Brüggemann, Giovanni Martinelli, Hagop M. Kantarjian, Anthony S. Stein, Heinzaugust Horst, Nicolas Boissel, Yuqi Chen, Gerhard Zugmaier
    Abstract:

    BACKGROUND Blinatumomab is a BiTE® immuno-oncology therapy indicated for the treatment of patients with relapsed or refractory (r/r) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Aims To assess the efficacy and safety of Blinatumomab as first salvage versus second or later salvage in patients with r/r BCP ALL. Materials & Methods Patient-level pooled data were used for this analysis. In total, 532 adults with r/r BCP ALL treated with Blinatumomab were included (first salvage, n = 165; second or later salvage, n = 367). Results Compared with patients who received Blinatumomab as second or later salvage, those who received Blinatumomab as first salvage had a longer median overall survival (OS; 10.4 vs. 5.7 months; HR, 1.58; 95% CI, 1.26-1.97; P < .001) and relapse-free survival (10.1 vs. 7.3 months; HR, 1.38; 95% CI, 0.98-1.93; P = .061), and higher rates of remission (n = 89 [54%] vs. n = 150 [41%]; odds ratio, 0.59; 95% CI, 0.41-0.85; P = .005), minimal residual disease response (n = 68 [41%] vs. n = 118 [32%]), and allogeneic hematopoietic stem cell transplant (alloHSCT) realization (n = 60 [36%] vs. n = 88 [24%]), and alloHSCT in continuous remission (n = 33 [20%] vs. n = 52 (14%]). In a subgroup analysis, there was no apparent effect of prior alloHSCT on median OS in either salvage group. The safety profile of Blinatumomab was generally similar between the groups; however, cytokine release syndrome, febrile neutropenia, and infection were more frequent with second or later salvage than with first salvage. Discussion In this pooled analysis, the logistic regression analyses indicated greater benefit with Blinatumomab as first salvage than as second or later salvage, as evident by the longer median OS, longer median RFS, and higher rates of remission. Conclusion Overall, Blinatumomab was beneficial as first salvage and as second or later salvage, but the effects were favorable as first salvage.

  • long term survival of patients with relapsed refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2021
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2020
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Blinatumomab compared with standard of care for the treatment of adult patients with relapsed refractory philadelphia chromosome positive b precursor acute lymphoblastic leukemia
    Cancer, 2020
    Co-Authors: Alessandro Rambaldi, Hervé Dombret, Christopher Kim, Josep-maria Ribera, Hagop M. Kantarjian, Anthony S. Stein, Oliver G Ottmann, Catherine A Tuglus, Xiaoyue Zhao, Giovanni Martinelli
    Abstract:

    Background A single-arm, phase 2 trial demonstrated the efficacy and safety of Blinatumomab, a bispecific T-cell-engaging antibody construct, in patients with relapsed/refractory (r/r) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), a rare hematologic malignancy with limited treatment options. This study compared outcomes with Blinatumomab with those of a historical control treated with the standard of care (SOC). Methods The Blinatumomab trial enrolled adult patients with Ph+ ALL who were r/r to at least 1 second-generation tyrosine kinase inhibitor (n = 45). Propensity score analysis (PSA) was used to compare outcomes with Blinatumomab with those of an external cohort of similar patients receiving SOC chemotherapy (n = 55). The PSA mitigated confounding variables between studies by adjusting for imbalances in the age at diagnosis and start of treatment, sex, duration from diagnosis to most recent treatment, prior allogeneic hematopoietic stem cell transplantation, prior salvage therapy, and number of salvage therapies. Bayesian data augmentation was applied to improve power to 80% with data from a phase 3 Blinatumomab study in r/r Philadelphia chromosome-negative ALL. Results In the PSA, the rate of complete remission or complete remission with partial hematologic recovery was 36% for Blinatumomab and 25% for SOC, and this resulted in an odds ratio of 1.54 (95% confidence interval [CI], 0.61-3.89) or 1.70 (95% credible interval [CrI], 0.94-2.94) with Bayesian data augmentation. Overall survival favored Blinatumomab over SOC, with a hazard ratio of 0.81 (95% CI, 0.57-1.14) or 0.77 (95% CrI, 0.61-0.96) with Bayesian data augmentation. Conclusions These results further support Blinatumomab as a treatment option for patients with r/r Ph+ ALL.

  • transplantation in adults with relapsed refractory acute lymphoblastic leukemia who are treated with Blinatumomab from a phase 3 study
    Cancer, 2019
    Co-Authors: Elias Jabbour, Nicola Gökbuget, Hagop M. Kantarjian, Xavier Thomas, Richard A. Larson, Sung-soo Yoon, Armin Ghobadi, Max S. Topp, Qui Tran, Janet Franklin
    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.

Hervé Dombret - One of the best experts on this subject based on the ideXlab platform.

  • long term survival of patients with relapsed refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2021
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2020
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Blinatumomab vs historic standard‐of‐care treatment for minimal residual disease in adults with B‐cell precursor acute lymphoblastic leukaemia
    European journal of haematology, 2020
    Co-Authors: Nicola Gökbuget, Hervé Dombret, Sebastian Giebel, Monika Brüggemann, Michael Doubek, Robin Foà, Dieter Hoelzer, Christopher Kim, Giovanni Martinelli, Elena N. Parovichnikova
    Abstract:

    Objectives Survival outcomes from a single-arm phase 2 Blinatumomab study in patients with minimal residual disease (MRD)-positive B-cell precursor (BCP)-acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set. Methods The primary analysis comprised adult Philadelphia chromosome (Ph)-negative patients in first complete haematologic remission (MRD ≥ 10-3 ). Relapse-free survival (RFS) and overall survival (OS) were compared between Blinatumomab- and SOC-treatment groups. Baseline differences between groups were adjusted by propensity scores. Results The primary analysis included 73 and 182 patients from the Blinatumomab and historic data sets, respectively. When weighted by age to the Blinatumomab-treatment group, median RFS was 7.8 months and median OS was 25.9 months in the SOC-treated group. In the Blinatumomab study, median RFS was 35.2 months; median OS was not evaluable. Propensity score weighting achieved balance with seven baseline prognostic factors. With adjustment for haematopoietic stem cell transplantation (HSCT) status, a 50% reduction in risk of relapse or death was observed with Blinatumomab vs SOC. Median RFS, unadjusted for HSCT status, was 35.2 months with Blinatumomab and 8.3 months with SOC. Conclusions These analyses suggest that Blinatumomab improves RFS, and possibly OS, in adults with MRD-positive Ph-negative BCP-ALL vs SOC.

  • Blinatumomab compared with standard of care for the treatment of adult patients with relapsed refractory philadelphia chromosome positive b precursor acute lymphoblastic leukemia
    Cancer, 2020
    Co-Authors: Alessandro Rambaldi, Hervé Dombret, Christopher Kim, Josep-maria Ribera, Hagop M. Kantarjian, Anthony S. Stein, Oliver G Ottmann, Catherine A Tuglus, Xiaoyue Zhao, Giovanni Martinelli
    Abstract:

    Background A single-arm, phase 2 trial demonstrated the efficacy and safety of Blinatumomab, a bispecific T-cell-engaging antibody construct, in patients with relapsed/refractory (r/r) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), a rare hematologic malignancy with limited treatment options. This study compared outcomes with Blinatumomab with those of a historical control treated with the standard of care (SOC). Methods The Blinatumomab trial enrolled adult patients with Ph+ ALL who were r/r to at least 1 second-generation tyrosine kinase inhibitor (n = 45). Propensity score analysis (PSA) was used to compare outcomes with Blinatumomab with those of an external cohort of similar patients receiving SOC chemotherapy (n = 55). The PSA mitigated confounding variables between studies by adjusting for imbalances in the age at diagnosis and start of treatment, sex, duration from diagnosis to most recent treatment, prior allogeneic hematopoietic stem cell transplantation, prior salvage therapy, and number of salvage therapies. Bayesian data augmentation was applied to improve power to 80% with data from a phase 3 Blinatumomab study in r/r Philadelphia chromosome-negative ALL. Results In the PSA, the rate of complete remission or complete remission with partial hematologic recovery was 36% for Blinatumomab and 25% for SOC, and this resulted in an odds ratio of 1.54 (95% confidence interval [CI], 0.61-3.89) or 1.70 (95% credible interval [CrI], 0.94-2.94) with Bayesian data augmentation. Overall survival favored Blinatumomab over SOC, with a hazard ratio of 0.81 (95% CI, 0.57-1.14) or 0.77 (95% CrI, 0.61-0.96) with Bayesian data augmentation. Conclusions These results further support Blinatumomab as a treatment option for patients with r/r Ph+ ALL.

  • Blinatumomab versus chemotherapy in first salvage or in later salvage for B-cell precursor acute lymphoblastic leukemia
    Leukemia & lymphoma, 2019
    Co-Authors: Hervé Dombret, Max S. Topp, Qui Tran, A.c. Schuh, A. Wei, Zachary Zimmerman, Simon Durrant, Christopher Larry Bacon, Hagop M. Kantarjian
    Abstract:

    Outcomes for adults with relapsed/refractory acute lymphoblastic leukemia (ALL) are poor with chemotherapy, particularly in later salvage. The TOWER study examined survival, remission, bridge to allogeneic hematopoietic stem cell transplantation (HSCT), and safety with Blinatumomab versus chemotherapy. This report examined outcomes separately for study treatment as first or later salvage. Adults with Philadelphia chromosome-negative B-cell precursor ALL relapsed/refractory to chemotherapy were randomly assigned 2:1 to receive Blinatumomab by continuous infusion for 4 weeks in 6-week cycles, or standard salvage chemotherapy. Overall survival for Blinatumomab versus chemotherapy was higher both in first salvage and in later salvage. Safety was similar between patients in first salvage and those in later salvage. Blinatumomab as later salvage was associated with higher complete remission rates and served as a bridge to allogeneic HSCT, supporting the use of Blinatumomab in both settings. This study is registered at www.clinicaltrials.gov as #NCT02013167.

Anthony S. Stein - One of the best experts on this subject based on the ideXlab platform.

  • Blinatumomab as first salvage versus second or later salvage in adults with relapsed refractory b cell precursor acute lymphoblastic leukemia results of a pooled analysis
    Cancer Medicine, 2021
    Co-Authors: Max S. Topp, Nicola Gökbuget, Monika Brüggemann, Giovanni Martinelli, Hagop M. Kantarjian, Anthony S. Stein, Heinzaugust Horst, Nicolas Boissel, Yuqi Chen, Gerhard Zugmaier
    Abstract:

    BACKGROUND Blinatumomab is a BiTE® immuno-oncology therapy indicated for the treatment of patients with relapsed or refractory (r/r) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Aims To assess the efficacy and safety of Blinatumomab as first salvage versus second or later salvage in patients with r/r BCP ALL. Materials & Methods Patient-level pooled data were used for this analysis. In total, 532 adults with r/r BCP ALL treated with Blinatumomab were included (first salvage, n = 165; second or later salvage, n = 367). Results Compared with patients who received Blinatumomab as second or later salvage, those who received Blinatumomab as first salvage had a longer median overall survival (OS; 10.4 vs. 5.7 months; HR, 1.58; 95% CI, 1.26-1.97; P < .001) and relapse-free survival (10.1 vs. 7.3 months; HR, 1.38; 95% CI, 0.98-1.93; P = .061), and higher rates of remission (n = 89 [54%] vs. n = 150 [41%]; odds ratio, 0.59; 95% CI, 0.41-0.85; P = .005), minimal residual disease response (n = 68 [41%] vs. n = 118 [32%]), and allogeneic hematopoietic stem cell transplant (alloHSCT) realization (n = 60 [36%] vs. n = 88 [24%]), and alloHSCT in continuous remission (n = 33 [20%] vs. n = 52 (14%]). In a subgroup analysis, there was no apparent effect of prior alloHSCT on median OS in either salvage group. The safety profile of Blinatumomab was generally similar between the groups; however, cytokine release syndrome, febrile neutropenia, and infection were more frequent with second or later salvage than with first salvage. Discussion In this pooled analysis, the logistic regression analyses indicated greater benefit with Blinatumomab as first salvage than as second or later salvage, as evident by the longer median OS, longer median RFS, and higher rates of remission. Conclusion Overall, Blinatumomab was beneficial as first salvage and as second or later salvage, but the effects were favorable as first salvage.

  • long term survival of patients with relapsed refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2021
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Long-term survival of patients with relapsed/refractory acute lymphoblastic leukemia treated with Blinatumomab
    Cancer, 2020
    Co-Authors: Max S. Topp, Gerhard Zugmaier, Ralf C. Bargou, Nicola Gökbuget, Hervé Dombret, Josep-maria Ribera, Anthony S. Stein, Yuqi Chen, Heinz A. Horst, Hagop M. Kantarjian
    Abstract:

    Background Blinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19. Methods A pooled analysis of long-term follow-up data from 2 phase 2 studies that evaluated Blinatumomab in heavily pretreated adults with Philadelphia chromosome-negative, relapsed/refractory B-cell precursor acute lymphoblastic leukemia was conducted. Results A total of 259 patients were included in the analysis. The median overall survival (OS) among all patients, regardless of response, was 7.5 months (95% confidence interval [CI], 5.5-8.5 months); the median follow-up time for OS was 36.0 months (range, 0.3-60.8 months). The median relapse-free survival (RFS) among patients who achieved a complete remission (CR) or complete remission with partial hematologic recovery (CRh) in the first 2 cycles (n = 123) was 7.7 months (95% CI, 6.2-10.0 months); the median follow-up time for RFS was 35.0 months (range, 9.5-59.5 months). OS and RFS plateaued with 3-year rates of 17.7% and 23.4%, respectively. The cumulative incidence function of the time to relapse, with death not due to relapse considered a competing risk, for patients who achieved a CR/CRh within 2 cycles of treatment also plateaued with a 3-year relapse rate of 59.3%. For patients who achieved a CR/CRh with Blinatumomab followed by allogeneic hematopoietic stem cell transplantation while in continuous CR, the median OS was 18.1 months (95% CI, 10.3-30.0 months) with a 3-year survival rate of 37.2%. Conclusions These data suggest that long-term survival is possible after Blinatumomab therapy. Lay summary Immuno-oncology therapies such as Blinatumomab activate the patient's own immune system to kill cancer cells. This study combined follow-up data from 2 Blinatumomab-related clinical trials to evaluate long-term survival in patients with relapsed and/or refractory B-cell precursor acute lymphoblastic leukemia at high risk for unfavorable outcomes. Among patients who achieved a deep response with Blinatumomab, one-third lived 3 years or longer. These findings suggest that long-term survival is possible after treatment with Blinatumomab.

  • Blinatumomab compared with standard of care for the treatment of adult patients with relapsed refractory philadelphia chromosome positive b precursor acute lymphoblastic leukemia
    Cancer, 2020
    Co-Authors: Alessandro Rambaldi, Hervé Dombret, Christopher Kim, Josep-maria Ribera, Hagop M. Kantarjian, Anthony S. Stein, Oliver G Ottmann, Catherine A Tuglus, Xiaoyue Zhao, Giovanni Martinelli
    Abstract:

    Background A single-arm, phase 2 trial demonstrated the efficacy and safety of Blinatumomab, a bispecific T-cell-engaging antibody construct, in patients with relapsed/refractory (r/r) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), a rare hematologic malignancy with limited treatment options. This study compared outcomes with Blinatumomab with those of a historical control treated with the standard of care (SOC). Methods The Blinatumomab trial enrolled adult patients with Ph+ ALL who were r/r to at least 1 second-generation tyrosine kinase inhibitor (n = 45). Propensity score analysis (PSA) was used to compare outcomes with Blinatumomab with those of an external cohort of similar patients receiving SOC chemotherapy (n = 55). The PSA mitigated confounding variables between studies by adjusting for imbalances in the age at diagnosis and start of treatment, sex, duration from diagnosis to most recent treatment, prior allogeneic hematopoietic stem cell transplantation, prior salvage therapy, and number of salvage therapies. Bayesian data augmentation was applied to improve power to 80% with data from a phase 3 Blinatumomab study in r/r Philadelphia chromosome-negative ALL. Results In the PSA, the rate of complete remission or complete remission with partial hematologic recovery was 36% for Blinatumomab and 25% for SOC, and this resulted in an odds ratio of 1.54 (95% confidence interval [CI], 0.61-3.89) or 1.70 (95% credible interval [CrI], 0.94-2.94) with Bayesian data augmentation. Overall survival favored Blinatumomab over SOC, with a hazard ratio of 0.81 (95% CI, 0.57-1.14) or 0.77 (95% CrI, 0.61-0.96) with Bayesian data augmentation. Conclusions These results further support Blinatumomab as a treatment option for patients with r/r Ph+ ALL.

  • Benefit-Risk Assessment of Blinatumomab in the Treatment of Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia.
    Drug safety, 2018
    Co-Authors: Anthony S. Stein, Janet Franklin, William Kormany, Victoria M. Chia, Deborah Arrindell, Jacqueline Wright, Mandy Parson, Hamid R. Amouzadeh, Jessica Choudhry, Guiandre Joseph
    Abstract:

    Blinatumomab is the first-and-only Food and Drug Administration (FDA)-approved cluster of differentiation (CD) 19-directed CD3 bispecific T-cell engager (BiTE®) immunotherapy. It is currently FDA approved for the treatment of adults and children with Philadelphia chromosome-positive (Ph+) and Philadelphia chromosome-negative (Ph−) relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL) and B-cell precursor ALL with minimal residual disease. Similarly, initial marketing authorization for Blinatumomab in the European Union was granted for the treatment of adults with Ph− R/R B-cell precursor ALL. The benefits of treating R/R B-cell precursor ALL patients with Blinatumomab include increased overall survival, more favorable hematologic remission and molecular response rates, and a lower incidence rate of selected adverse events when compared with standard-of-care chemotherapy. The key risks associated with Blinatumomab treatment include cytokine release syndrome, neurotoxicity, and medication errors. Here, we review the benefits and risks of Blinatumomab treatment and describe how these risks can be mitigated.