Read by QxMD icon Read


Magali Guffroy, Hadi Falahatpisheh, Kathleen Biddle, John Kreeger, Leslie Obert, Karen Walters, Richard Goldstein, Germaine Boucher, Tim Coskran, William Reagan, Danielle Sullivan, Chunli Huang, Sharon A Sokolowski, Richard Giovanelli, Hans-Peter Gerber, Martin B Finkelstein, Nasir K Khan
PURPOSE: Adverse reactions reported in patients treated with antibody-calicheamicin conjugates such as gemtuzumab ozogamicin (GO, Mylotarg®) and inotuzumab ozogamicin (IO) include thrombocytopenia and sinusoidal obstruction syndrome (SOS). The objective of this experimental work was to investigate the mechanism for thrombocytopenia, characterize the liver injury and identify potential safety biomarkers. EXPERIMENTAL DESIGN: Cynomolgus monkeys were dosed intravenously at 6 mg/m2/dose once every 3 weeks with a non-binding antibody-calicheamicin conjugate (PF-0259) containing the same linker-payload as GO and IO...
September 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Elias Jabbour, Nicholas J Short, Jeffrey L Jorgensen, Musa Yilmaz, Farhad Ravandi, Sa A Wang, Deborah A Thomas, Joseph Khoury, Richard E Champlin, Issa Khouri, Partow Kebriaei, Susan M O'Brien, Guillermo Garcia-Manero, Jorge E Cortes, Koji Sasaki, Courtney D Dinardo, Tapan M Kadia, Nitin Jain, Marina Konopleva, Rebecca Garris, Hagop Kantarjian
BACKGROUND: Minimal residual disease (MRD) assessment predicts survival for patients with newly diagnosed acute lymphoblastic leukemia (ALL). Its significance in relapsed/refractory ALL is less clear. METHODS: This study identified 78 patients with relapsed/refractory B-cell ALL who achieved a morphologic response with inotuzumab ozogamicin (n = 41), blinatumomab (n = 11), or mini-hyperfractionated cyclophosphamide, vincristine, and doxorubicin plus inotuzumab (n = 26) during either salvage 1 (S1; n = 46) or salvage 2 (S2; n = 32) and had undergone an MRD assessment by multiparameter flow cytometry at the time of remission...
September 7, 2016: Cancer
Nosha Farhadfar, Mark R Litzow
Monoclonal antibodies represent a major advance in treatment of acute lymphoblastic leukemia (ALL). Targeted delivery of these agents based on leukemic cell-surface receptor recognition, improves efficacy and minimizes off-target toxicity. The antigens CD19, CD20, CD22 and CD52, are the most common antigens to which monoclonal antibodies in B-cell ALL have been directed. Rituximab, an anti-CD20 antibody, in combination with conventional chemotherapy has been shown to improve survival in newly diagnosed CD20 positive B-cell ALL...
October 2016: Leukemia Research
Kenneth T Luu, Joseph Boni
PURPOSE: The aim of this investigation was to develop a quantitative method to optimize inotuzumab ozogamicin (InO) dosage regimen in patients with indolent non-Hodgkin lymphoma (NHL) by simultaneously balancing safety and efficacy. METHODS: Pharmacokinetics (PK), safety and efficacy data were obtained from a phase 2 trial of InO administered intravenously to patients (n = 81) with indolent NHL. The PK was described by a two-compartment model which was linked to: (1) an exponential tumor growth model to describe tumor size time course (efficacy determinant expressed as objective response rate) and (2) a precursor-dependent platelet inhibition model to describe platelet time course (safety determinant expressed as thrombocytopenia grade)...
October 2016: Cancer Chemotherapy and Pharmacology
(no author information available yet)
According to a phase III study, the antibody-drug conjugate inotuzumab ozogamicin is more likely to induce complete remissions, with full or incomplete hematologic recovery, in patients with relapsed or refractory acute lymphocytic leukemia. Data from a phase I study of another antibody-drug conjugate, vadastuximab talirine, demonstrates that it is safe and effective against acute myeloid leukemia.
September 2016: Cancer Discovery
Hagop M Kantarjian, Daniel J DeAngelo, Matthias Stelljes, Giovanni Martinelli, Michaela Liedtke, Wendy Stock, Nicola Gökbuget, Susan O'Brien, Kongming Wang, Tao Wang, M Luisa Paccagnella, Barbara Sleight, Erik Vandendries, Anjali S Advani
BACKGROUND: The prognosis for adults with relapsed acute lymphoblastic leukemia is poor. We sought to determine whether inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, results in better outcomes in patients with relapsed or refractory acute lymphoblastic leukemia than does standard therapy. METHODS: In this phase 3 trial, we randomly assigned adults with relapsed or refractory acute lymphoblastic leukemia to receive either inotuzumab ozogamicin (inotuzumab ozogamicin group) or standard intensive chemotherapy (standard-therapy group)...
August 25, 2016: New England Journal of Medicine
Alison M Betts, Nahor Haddish-Berhane, John Tolsma, Paul Jasper, Lindsay E King, Yongliang Sun, Subramanyam Chakrapani, Boris Shor, Joseph Boni, Theodore R Johnson
A mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model was used for preclinical to clinical translation of inotuzumab ozogamicin, a CD22-targeting antibody-drug conjugate (ADC) for B cell malignancies including non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL). Preclinical data was integrated in a PK/PD model which included (1) a plasma PK model characterizing disposition and clearance of inotuzumab ozogamicin and its released payload N-Ac-γ-calicheamicin DMH, (2) a tumor disposition model describing ADC diffusion into the tumor extracellular environment, (3) a cellular model describing inotuzumab ozogamicin binding to CD22, internalization, intracellular N-Ac-γ-calicheamicin DMH release, binding to DNA, or efflux from the tumor cell, and (4) tumor growth and inhibition in mouse xenograft models...
September 2016: AAPS Journal
Michinori Ogura, Kensei Tobinai, Kiyohiko Hatake, Andrew Davies, Michael Crump, Revathi Ananthakrishnan, Taro Ishibashi, M Luisa Paccagnella, Joseph Boni, Erik Vandendries, David MacDonald
PURPOSE: To evaluate the safety, preliminary efficacy, and pharmacokinetics of inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, in combination with the immunochemotherapeutic regimen, rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL). EXPERIMENTAL DESIGN: In part 1 (n = 16), patients received inotuzumab ozogamicin plus R-CVP on a 21-day cycle with escalating doses of cyclophosphamide first then inotuzumab ozogamicin...
October 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Andre Goy, Andres Forero, Nina Wagner-Johnston, W Christopher Ehmann, Michaela Tsai, Kiyohiko Hatake, Revathi Ananthakrishnan, Angela Volkert, Erik Vandendries, Michinori Ogura
This phase 2 study evaluated the efficacy and safety of inotuzumab ozogamicin (InO) in patients with indolent B-cell non-Hodgkin lymphoma (NHL) refractory to rituximab alone, rituximab plus chemotherapy or anti-CD20 radioimmunotherapy. Patients received InO 1·8 mg/m(2) intravenously on a 28-d cycle for a planned 4-8 cycles. The initial InO dose and schedule could be adjusted for tolerability and patients were allowed to receive 2 additional cycles (up to 8 total) after achieving a complete response (CR). The primary endpoint was overall response...
August 2016: British Journal of Haematology
Elena Maino, Massimiliano Bonifacio, Anna Maria Scattolin, Renato Bassan
Recent developments in immunotherapy are improving treatment results of B-precursor acute lymphoblastic leukemia. This advancement is promoted by new monoclonal antibodies such as inotuzumab ozogamicin, ofatumumab and blinatumomab, by rituximab, and by genetically engineered chimeric antigen receptor-modified T-cells. These treatments, variously targeting CD22, CD20 and CD19 antigens, yield unprecedented high rates of hematologic and molecular remissions even when used in monotherapy and in chemo-resistant or post-transplantation relapsed patients...
June 2016: Expert Review of Hematology
Swati Sikaria, Ibrahim Aldoss, Mojtaba Akhtari
Adult B-acute lymphoblastic leukemia (B-ALL) does not share the favorable prognosis seen in pediatric patients with the same disease. Less than 50% of patients experience long-term survival and for those adults over age 60, long-term survival is only 10%. At time of relapse, 5-year prognosis is a dismal 7%. Novel and less toxic agents are urgently needed. The last few years have seen a surge in immune therapies for B-ALL. These agents may target CD19, CD20, CD22, and less frequently CD52. Expression of these surface markers and the drugs which target them are discussed...
April 2016: Immunology Letters
Jenny Dahl, Kayleigh Marx, Elias Jabbour
Over 90% of leukemic blasts in patients with acute lymphoblastic leukemia express the marker CD22. Inotuzumab ozogamicin (INO) is a CD22-directed humanized monoclonal antibody conjugated to the potent cytotoxin, calicheamicin, via an acid labile linker. INO has shown high rates of response in the treatment of relapsed and refractory (R/R) ALL in single-agent studies, with fewer adverse effects than traditional cytotoxic chemotherapy. Given this experience, studies are now being done to evaluate INO in combination with low-intensity chemotherapy as frontline treatment for older adults with ALL and patients with R/R disease...
2016: Expert Review of Hematology
Binsah George, Hagop Kantarjian, Elias Jabbour, Nitin Jain
Inotuzumab ozogamicin is a humanized anti-CD22 monoclonal antibody bound to a toxic natural calicheamicin, which is under investigation for the treatment of relapsed/refractory acute lymphoblastic leukemia. CD22 is commonly expressed in 90-100% of malignant mature B-lymphocyte lineage. The first Phase II study with inotuzumab ozogamicin conducted by Kantarjian et al. gave the opportunity for heavily pretreated patients with acute lymphoblastic leukemia to go for allogeneic stem cell transplant. Inotuzumab is well-tolerated with the exception of veno-occlusive disease...
February 2016: Immunotherapy
N J Morley, D I Marks
Whilst most adult patients with acute lymphoblastic leukaemia will go into remission with standard induction chemotherapy, many will relapse. Response rates to standard salvage chemotherapy regimens are low and the outlook on relapse is very poor and associated with significant morbidity and mortality hence the need for newer targeted approaches. Inotuzumab ozogamicin (previously known as CMC-544) is an antibody-drug conjugate and consists of a monoclonal anti-CD22 antibody bound to calicheamicin. The target, CD22, is widely expressed on acute lymphoblastic leukaemia cells making it a potential therapeutic target...
2016: Expert Review of Anticancer Therapy
Janice M Reichert
The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016...
2016: MAbs
Anjali Advani
Using a case study of a 57-year-old man with relapsed/refractory precursor-B (pre-B) acute lymphoblastic leukemia (ALL), this review discusses treatment with immunoconjugates and autologous therapy in acute ALL. Three therapies--blinatumomab, inotuzumab, and CAR T cells--are considered here, each with advantages in specific clinical situations. These therapies represent some of the exciting advances that have been made in the treatment of ALL over the last several years.
June 2015: Best Practice & Research. Clinical Haematology
Musa Yilmaz, Samantha Richard, Elias Jabbour
Antibody-drug conjugates (ADCs) are likely to make a significant contribution in the treatment of acute lymphoblastic leukemia (ALL) by combining the cytotoxicity of chemotherapy with the specificity of monoclonal antibodies. CD22, an endocytic receptor expressed by the majority of B cells, is an excellent target for ADCs. Inotuzumab ozogamicin (INO) is an ADC that consists of a cytotoxic moiety (derivative of calicheamicin) attached to a humanized monoclonal anti-CD22 antibody. As a single agent, INO, was shown to be effective with an objective response rate of 50% in the treatment of relapsed and refractory CD22 positive ALL patients...
October 2015: Therapeutic Advances in Hematology
Amitkumar Mehta, Andres Forero-Torres
Rituximab, a monoclonal antibody (MAb) against CD20, was the first MAb approved by the US Food and Drug Administration (FDA) for treatment of B cell non-Hodgkin lymphoma (B-NHL). Conjugating toxins to MAb was a technical challenge; however, with improvements in linker technology, immunoconjugates were constructed and revolutionized cancer treatment. Gemtuzumab ozogamicin was the first antibody drug conjugate (ADC) approved by the FDA. Because of the success of brentuximab vedotin and ado-trastuzumab emtansine in treating Hodgkin lymphoma (HL) and HER2-positive breast cancer, respectively, newer ADCs are being investigated...
September 2015: Current Oncology Reports
Elias Jabbour, Susan O'Brien, Farhad Ravandi, Hagop Kantarjian
With modern intensive combination polychemotherapy, the complete response (CR) rate in adults with acute lymphoblastic leukemia (ALL) is 80% to 90%, and the cure rate is 40% to 50%. Hence, there is a need to develop effective salvage therapies and combine novel agents with standard effective chemotherapy. ALL leukemic cells express several surface antigens amenable to target therapies, including CD20, CD22, and CD19. Monoclonal antibodies target these leukemic surface antigens selectively and minimize off-target toxicity...
June 25, 2015: Blood
Britny Rogala, Craig W Freyer, Evelena P Ontiveros, Elizabeth A Griffiths, Eunice S Wang, Meir Wetzler
INTRODUCTION: The approval of blinatumomab signals the long awaited arrival of immunotherapy for acute lymphoblastic leukemia (ALL). Previous options for relapsed or refractory disease were restricted to cytotoxic chemotherapy with limited efficacy and significant toxicity. Through an innovative mechanism of action, blinatumomab stimulates a polyclonal antitumor T-cell response, yielding unprecedented single agent efficacy in the relapsed/refractory setting. Success comes at the cost of immunological toxicities rarely encountered with previous therapies and challenging administration logistics requiring clinical expertise...
June 2015: Expert Opinion on Biological Therapy
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"