A Phase IB/II Study of Lirilumab with Azacytidine in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
Blockade of inhibitory killer-cell immunoglobulin receptor (KIR) receptors induces augmented NK-cell mediated tumor cell lysis (Romagne F et al., Blood 2009). Hypomethylating agents (HMAs) possess anti-leukemia activity, and increase MHC II expression, cancer antigen exposure in solid and hematologic malignancies, and interferon-gamma signature. KIR-receptor blockade by lirilumab (KIR2DL1/2/3-antibody) may improve responses to HMAs.
Available for licensing and co-development are antibody-drug conjugates (ADC) that incorporate one of two novel human CD56 antibodies, known as m900 and m906, in combination with a known cytotoxic drug, pyrrolobenzodiazepine (PBD).IC: NCINIH Ref. No.: E-221-2015Advantages: - Fully human antibodies (m900 or m906) targeting CD56 may offer improved properties over the humanized antibody IMGN901 Applications: - Therapeutic for the treatment of neuroblastoma - Therapeutic for the treatment of other CD56-positive cancers including small cell lung cancer, multiple myeloma, pancreatic cancer...
Conclusion Bendamustine is an effective therapy with limited long-term sequelae in patients with lymphoid malignancies. Micro-Abstract Bendamustine is an effective treatment for lymphoid malignancies and its role continues to expand. To determine the long-term sequelae associated with bendamustine, 194 patients treated with bendamustine (most commonly with rituximab) were retrospectively reviewed. The rate of secondary malignancies was minimal and no therapy-related myelodysplastic syndrome or acute myelogenous leukemia were reported. No deaths from infection were attributable to bendamustine.
Publication date: Available online 12 September 2017 Source:Methods Author(s): Andreas K. Buck, Antje Stolzenburg, Heribert Hänscheid, Andreas Schirbel, Katharina Lückerath, Margret Schottelius, Hans-Jürgen Wester, Constantin Lapa The C-X-C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical use, i.e. for m...
In this study we investigated mechanisms of acquired resistance to venetoclax in preclinical AML models.
Conclusion CLAG plus IM was well tolerated, with encouraging signs of activity in patients with poor-risk AML.
Given the lack of standard salvage chemotherapy regimen for relapsed or refractory (RR) acute myeloid leukemia (AML), a phase 2 clinical study of cladribine, cytarabine, G-CSF (CLAG) regimen in combination with imatinib mesylate (IM) in patients with RR-AML was conducted at the Moffitt Cancer Center. Between August 2009 and April 2011, 38 patients were treated and the overall response rate was 37% with a median overall survival of 11.1 month. Among responders, 8/14 patients proceeded to allogeneic hematopoietic cell transplant. Overall, CLAG plus IM was well tolerated, with encouraging signs of activity in patients with poor-risk AML.
Publication date: Available online 12 September 2017 Source:Methods Author(s): Andreas K. Buck, Antje Stolzenburg, Heribert Hänscheid, Andreas Schirbel, Katharina Lückerath, Margret Schottelius, Hans-Jürgen Wester, Constantin Lapa The C – X – C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical...
Monoclonal antibody (mAb)-based therapies have become an important modality for cancer treatment but have had limited success to date in acute myeloid leukemia (AML). Identification of new antigenic targets and antibody engineering techniques may overcome the modest anti-leukemic effects seen with most native antibodies studied previously in AML. Advances in bispecific immune-engaging antibody technology may improve the pharmacology of these agents, and the safety and efficacy of antibody-drug conjugates (ADCs) may be enhanced by better cytotoxic payloads and chemical linkers.
Beriberi is a rare disease caused by thiamine (vitamin B1) deficiency. There are two types: dry beriberi affecting the neurologic system and wet beriberi leading to high cardiac output heart failure. In extreme cases, brain damage may occur: Wernicke-Korsakoff syndrome. The most common risk factors for thiamine deficiency are: alcohol abuse, overt malnutrition, gastric bypass surgery, total parenteral nutrition (TPN), chronic dialysis, and cancer related cachexia.
Cancer survivors may develop a second cancer as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and this has been an emerging problem for acute promyelocytic leukemia (APL) patients in complete remission (CR).