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Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab.

ABSTRACT: In the phase 3 TOWER study, blinatumomab significantly improved overall survival in adults with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) relative to standard-of-care chemotherapy. A secondary objective of this study was to assess the impact of blinatumomab on health-related quality of life (HRQL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). This analysis included the 342 of 405 randomized patients for whom baseline and ?1 postbaseline result were available in any EORTC multi-item scale or single-item measure. In general, patients receiving blinatumomab (n = 247) reported better posttreatment HRQL across all QLQ-C30 subscales, based on descriptive mean change from baseline, than did those receiving chemotherapy (n = 95). The hazard ratios for time to deterioration (TTD) of ?10 points from baseline in HRQL or death ranged from 0.42 to 0.81 in favor of blinatumomab, with the upper bounds of the 95% confidence interval <1.0 across all measures, except insomnia, social functioning, and financial difficulties; sensitivity analysis of TTD in HRQL without the event of death were consistent with these findings. When treatment effect over time was tested using a restricted maximum likelihood-based mixed model for repeated measures analysis, P < .05 was reached for blinatumomab vs chemotherapy for all subscale measures except financial difficulties. The clinically meaningful benefits in overall survival and HRQL support the clinical value of blinatumomab in patients with R/R Ph- BCP-ALL when compared with chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT02013167.

SUBMITTER: Topp MS

PROVIDER: S-EPMC6024638 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab.

Topp Max S MS Zimmerman Zachary Z Cannell Paul P Dombret Hervé H Maertens Johan J Stein Anthony A Franklin Janet J Tran Qui Q Cong Ze Z Schuh Andre C AC

Blood 20180508 26

In the phase 3 TOWER study, blinatumomab significantly improved overall survival in adults with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph<sup>-</sup>) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) relative to standard-of-care chemotherapy. A secondary objective of this study was to assess the impact of blinatumomab on health-related quality of life (HRQL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questi ...[more]

PMID: 29739753

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Project description:BackgroundBlinatumomab is a CD19 BiTE (bispecific T-cell engager) immuno-oncology therapy that mediates the lysis of cells expressing CD19.MethodsA 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.ResultsA 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%.ConclusionsThese data suggest that long-term survival is possible after blinatumomab therapy.Lay summaryImmuno-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.

Project description:Adults with relapsed/refractory B-acute lymphoblastic leukemia (ALL) have a complete remission (CR) rate of 20-45% and median overall survival of 3-9 months, depending on the duration of the first remission and number of lines of salvage therapy. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative option for adult patients with relapsed/refractory ALL, and achievement of CR is a crucial step before alloHSCT. Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct with dual specificity for CD19 and CD3, simultaneously binding CD3-positive cytotoxic T cells and CD19-positive B cells, resulting in T-cell-mediated serial lysis of normal and malignant B cells. It recently gained accelerated approval by the US Food and Drug Administration (FDA) for the treatment of relapsed/refractory Philadelphia chromosome-negative ALL, based on a large phase II trial of 189 adults with relapsed/refractory B-ALL, which showed a CR/CRh (CR with partial hematologic recovery) of 43% after two cycles of treatment. Toxicities include cytokine-release syndrome (CRS) and neurologic events (encephalopathy, aphasia, and seizure). CRS can be alleviated by step-up dosing and dexamethasone, without affecting the cytotoxic effect of blinatumomab. The cause of neurologic toxicity is unclear but is also observed with other T-cell therapies and may relate to variable expression of CD19 within the brain. This review encompasses the preclinical rationale of using the BITE® class of compounds (blinatumomab being the only one that is FDA approved), with clinical data using blinatumomab in the relapsed/refractory setting (pediatrics and adults), the minimal residual disease setting (adults), as well as Philadelphia chromosome-positive ALL. The review also examines the main adverse events: their prevention, recognition, and management; possible mechanisms of resistance; causes of relapse. It also summarizes future trials evaluating the drug earlier in the treatment course to improve activity.

Project description:INTRODUCTION:No head-to-head studies have compared inotuzumab ozogamicin (InO) and blinatumomab (Blina) for the treatment of adults with relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL). Indirect treatment comparisons (ITCs), namely network meta-analysis (NMA), anchored matching-adjusted indirect comparison (MAIC), and simulated treatment comparison (STC), were conducted to compare the relative efficacy of these therapies. METHODS:Patient-level data from a study that evaluated InO with standard of care (SoC) chemotherapy (INO-VATE-ALL) and published data from a study that evaluated Blina with SoC chemotherapy (TOWER) were used in the analyses. Endpoints evaluated included remission rate defined as complete remission or complete remission with incomplete hematologic recovery (CR/CRi), hematopoietic stem cell transplantation (HSCT), overall survival (OS), and event-free survival (EFS). For each outcome, treatment-effect modifiers were adjusted for in the anchored MAIC and STC analyses. RESULTS:Analyses showed statistically significant higher rates of remission and HSCT with InO compared to Blina irrespective of the ITC method used or measure of the effect (i.e., odds ratio [OR] or rate difference). The treatment effects derived from the MAIC and STC analyses were consistent and stronger than those estimated from the NMA. A trend favoring InO was detected for EFS. The ITC results for OS suggest no difference between InO and Blina. CONCLUSION:Results from these ITCs indicated a statistically significant advantage for InO over Blina for rates of remission and HSCT in adults with relapsed or refractory B cell precursor ALL. It was not possible to fully adjust for all treatment-effect modifiers, and the similarity in chemotherapy regimens used in the SoC comparator arms of the INO-VATE-ALL and TOWER studies is worthy of further exploration. Both studies, however, used chemotherapy regimens that have a low response rate; therefore, no significant differences in efficacy outcomes are expected between SoC arms. FUNDING:Pfizer Inc, New York, NY. Plain language summary available for this article.

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Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab.

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Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab.

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