Real-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab

Badar, Talha; Szabó, Anikó; Advani, Anjali S.; Wadleigh, Martha; Arslan, Shukaib; Khan, Muhammad Ali; Aldoss, Ibrahim; Siebenaller, Caitlin; Schultz, Elizabeth; Hefazi, Mehrdad; Shallis, Rory M.; Yurkiewicz, Ilana R.; Podoltsev, Nikolai A.; Patel, Anand; Curran, Emily; Balasubramanian, Suresh Kumar; Yang, Jay; Mattison, Ryan J.; Burkart, Madelyn; Dinner, Shira; Liedtke, Michaela; Litzow, Mark R.; Atallah, Ehab

doi:10.1182/bloodadvances.2019001381

Cited by 32 publications

(27 citation statements)

References 24 publications

(33 reference statements)

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“…Blinatumomab therapy has demonstrated encouraging activity in patients with relapsed/refractory (r/r) and minimal residual disease-positive (MRD+) B-cell acute lymphoblastic leukemia (B-ALL). [1][2][3][4][5] Among patients with r/r B-ALL, disease relapse is common in blinatumomab responders, 6 and blinatumomab is often used as a bridging therapy toward curative allogeneic hematopoietic cell transplantation (HCT). Recently published outcomes of a post hoc analysis of the phase II confirmatory study suggest blinatumomab as a potential curative treatment without allogenic HCT in a subset of patients who achieve a complete MRD response.…”

Section: Introductionmentioning

confidence: 99%

Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia

Aldoss

Otoukesh

Zhang

et al. 2021

Cancer

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BACKGROUND: Blinatumomab has demonstrated encouraging activity in relapsed/refractory (r/r) and minimal residual disease-positive (MRD+) acute lymphoblastic leukemia (ALL). Extramedullary disease (EMD) relapse or relapse with CD19-disease has been observed after blinatumomab therapy in patients with r/r or MRD+ ALL. However, the pathophysiology and risk factors of treatment failure are not fully understood. METHODS: This study retrospectively reviewed the outcomes of adult patients with B-cell ALL treated with blinatumomab (n = 132) for either r/r (n = 103) or MRD+ disease (n = 29) at the authors' center (2013-2021) and analyzed factors associated with treatment response and EMD failure. RESULTS: The overall response rate was 64%. A lower marrow blast burden before blinatumomab (P = .049) and no history of previous EMD (P = .019) were significantly associated with a higher response. Among the patients who responded to blinatumomab, 56% underwent consolidation with allogeneic transplantation. Blinatumomab failure was observed in 89 patients; 43% of these patients (n = 38) either progressed or relapsed at extramedullary sites. A history of extramedullary involvement (53% vs 24%; P = .005) and retention of CD19 expression at the time of relapse/progression (97% vs 74%; P = .012) were associated with a higher risk for extramedullary failure. Central nervous system (CNS) failure after blinatumomab was encountered in 39% of the patients with EMD. CONCLUSIONS: A history of EMD predicted an inferior response to blinatumomab therapy with a higher risk for relapse/ progression at extramedullary sites (particularly CNS). Consolidation with allogenic transplantation in patients who primarily responded to blinatumomab did not abrogate the risk of extramedullary relapse. The incorporation of extramedullary assessment and the intensification of CNS prophylaxis may help in addressing extramedullary failure.

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Section: Introductionmentioning

confidence: 99%

Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia

Aldoss

Otoukesh

Zhang

et al. 2021

Cancer

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“…Consequently, most R/R B-ALL patients are unlikely to respond very well to blinatumomab treatment. Besides, it was reported that a substantial portion of R/R B-ALL patients with a history of or concurrent extramedullary disease failed to respond to blinatumomab, indicating the poor ability of blinatumomab in treating extramedullary disease 18 , 19 . To improve the treatment efficacy of blinatumomab, we proposed to apply the adoptive transfer of ex vivo expanded γδ T cells to supplement functional T cells in patients.…”

Section: Introductionmentioning

confidence: 99%

The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy

Chen

Wang

Liao³

et al. 2021

Sci Rep

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Blinatumomab, a bispecific T cell engager (BiTE) antibody targeting CD19 and CD3ε, can redirect T cells toward CD19-positive tumor cells and has been approved to treat relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However, chemotherapeutic regimens can severely reduce T cells’ number and cytotoxic function, leading to an inadequate response to blinatumomab treatment in patients. In addition, it was reported that a substantial portion of R/R B-ALL patients failing blinatumomab treatment had the extramedullary disease, indicating the poor ability of blinatumomab in treating extramedullary disease. In this study, we investigated whether the adoptive transfer of ex vivo expanded γ9δ2 T cells could act as the effector of blinatumomab to enhance blinatumomab’s antitumor activity against B-cell malignancies in vivo. Repeated infusion of blinatumomab and human γ9δ2 T cells led to more prolonged survival than that of blinatumomab or human γ9δ2 T cells alone in the mice xenografted with Raji cells. Furthermore, adoptive transfer of γ9δ2 T cells reduced tumor mass outside the bone marrow, indicating the potential of γ9δ2 T cells to eradicate the extramedullary disease. Our results suggest that the addition of γ9δ2 T cells to the blinatumomab treatment regimens could be an effective approach to enhancing blinatumomab’s therapeutic efficacy. The concept of this strategy may also be applied to other antigen-specific BiTE therapies for other malignancies.

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“…Inotuzumab mAb2 was an effective salvage therapy for patients who relapsed after blinatumomab mAb1 irrespective of CD19 expression or receipt of other interim salvage therapy between mAb1 and mAb2. The CR rate following inotuzumab mAb2 treatment was 68%, comparable to CR rates observed with inotuzumab when used in salvage 1 and 2 and blinatumomab naïve setting (18)(19)(20). Inotuzumab also yielded comparable responses whether it was used immediately following blinatumomab or after interim salvage therapy following post-blinatumomab.…”

Section: Discussionmentioning

confidence: 54%

Outcomes of relapsed B-cell acute lymphoblastic leukemia after sequential treatment with blinatumomab and inotuzumab

et al. 2022

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Novel monoclonal antibody-based therapies (mAbs) targeting CD19 and CD22, i.e. blinatumomab and inotuzumab, have demonstrated high rates of complete remission (CR) and been used as a bridging treatment to potentially curative allogeneic hematopoietic stem cell transplantation (alloHCT) in adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, limited data exist on the outcome of patients resistant to both mAbs as well as responses to each agent when progressed after the alternate antigen-targeted mAb. Herein, we report outcomes of 29 patients with R/R B-ALL previously treated with both blinatumomab and inotuzumab. Twenty-five patients (86.2%) received blinatumomab as first mAb (mAb1), and CD19neg/dim relapses were observed in 44% of the patients. Inotuzumab induced CR in 68% of the patients for post-blinatumomab relapse regardless of CD19 expression status. The median time between mAb1 and mAb2 was 99 days. Twelve of 19 patients (63.2%) who achieved remission after mAb2 underwent alloHCT. The median time from mAb2 to alloHCT was 37.5 days. Acute graft-versus-host disease and non-relapse mortality were observed in 58.3% (grade ≥3; 25%) and 41.7%, respectively. With a median follow-up of 16 months after mAb2, 19 patients (65.5%) relapsed and 21 patients (72.4%) have died. Overall survival (OS) was not different between alloHCT and non-alloHCT patients. In conclusion, patients with B-ALL who relapsed after blinatumomab could be successfully rescued by inotuzumab as a bridge to alloHCT, but represent an ultra-high risk group with poor OS. Further studies including novel consolidation and treatment sequence may improve outcomes of these patients.

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Real-world outcomes of adult B-cell acute lymphocytic leukemia patients treated with blinatumomab

Cited by 32 publications

References 24 publications

Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia

Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia

The potential of adoptive transfer of γ9δ2 T cells to enhance blinatumomab’s antitumor activity against B-cell malignancy

Outcomes of relapsed B-cell acute lymphoblastic leukemia after sequential treatment with blinatumomab and inotuzumab

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