Long-term follow-up of hematological relapse-free survival in a phase 2 study of blinatumomab in patients with minimal residual disease (MRD) of B-precursor acute lymphoblastic leukemia (ALL).
ABSTRACT Persistence or recurrence of minimal residual disease (MRD) after chemotherapy results in clinical relapse in patients with acute lymphoblastic leukemia (ALL). In a phase II trial in B-lineage ALL patients with persistent or relapsed MRD, a T-cell engaging bispecific antibody construct, induced an 80% MRD response rate. In this report, we show that after a median follow up of 33 months the hematological relapse free survival (RFS) of the whole evaluable study cohort of 20 patients is 61% (Kaplan-Meier estimate). The hematological RFS rate of a subgroup of 9 patients, who received allogeneic hematopoietic stem cell transplantation (HSCT) after blinatumomab treatment, was 65% (Kaplan-Meier estimate). In the subgroup of 6 Ph - negative MRD responders with no further therapy after blinatumomab, 4 are in ongoing hematologic and molecular remission. Blinatumomab can induce long-lasting CRs in B-lineage ALL patients with persistent or recurrent MRD. (ClinicalTrials.gov identifier: NCT00198991, NCT00198978).
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ABSTRACT: The majority of patients with chronic lymphocytic leukemia (CLL) respond to chemo-immunotherapy. However, long-term remission remains elusive and the majority of patients will die of complications related to CLL. In this review we discuss the recent developments in targeted therapy for CLL. Targeted therapy has evolved beyond the cell surface targeting of CD20 with rituximab. Our review focuses on the evolution of antibody therapy in CLL, strategies to target effector T cells to the tumor, inhibition of the B-cell receptor signaling pathway, and finally targeting the mediators of apoptosis. With our improved understanding of the biology of CLL, the evolution of targeted therapy has resulted in significant clinical responses in patients who are refractory to traditional treatment options and holds the potential for a future where we can manage this disease without chemotherapy.
Article: Blinatumomab: First Global Approval.[Show abstract] [Hide abstract]
ABSTRACT: Blinatumomab (BLINCYTO™) is a novel, bispecific T-cell engaging antibody that binds cluster of differentiation (CD) 19 antigens on blast cells while also binding and activating the CD3/T cell receptor complex, causing cell lysis. The antibody is being developed by Amgen as a treatment for haematological cancers that originate from B cell lines. Blinatumomab was approved by the US FDA in December 2014 for the treatment of adults with Philadelphia chromosome (Ph)-negative relapsed/refractory B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). It is awaiting approval for this indication in the EU and is in phase III development in various countries. This article summarizes the milestones in the development of blinatumomab leading to its first approval for the treatment of Ph-negative BCP-ALL.
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ABSTRACT: An expanding panel of monoclonal antibodies (mAbs) that specifically target malignant cells or intercept trophic factors delivered by the tumor stroma is now available for cancer therapy. These mAbs can exert direct antiproliferative/cytotoxic effects as they inhibit pro-survival signal transduction cascades or activate lethal receptors at the plasma membrane of cancer cells, they can opsonize neoplastic cells to initiate a tumor-targeting immune response, or they can be harnessed to specifically deliver toxins or radionuclides to transformed cells. As an indication of the success of this immunotherapeutic paradigm, international regulatory agencies approve new tumor-targeting mAbs for use in cancer patients every year. Moreover, the list of indications for previously licensed molecules is frequently expanded to other neoplastic disorders as the results of large, randomized clinical trials become available. Here, we discuss recent advances in the preclinical and clinical development of tumor-targeting mAbs for oncological indications.OncoImmunology 01/2015; 4(1):e985940. DOI:10.4161/2162402X.2014.985940 · 6.28 Impact Factor