0000000000162723
AUTHOR
Igor Wolfgang Blau
Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia : results from a randomized, placebo-controlled trial
Purpose The prognosis of elderly patients with acute myeloid leukemia (AML) is still dismal even with intensive chemotherapy. In this trial, we compared the antileukemic activity of standard induction and consolidation therapy with or without the addition of the kinase inhibitor sorafenib in elderly patients with AML. Patients and Methods All patients received standard cytarabine and daunorubicin induction (7+3 regimen) and up to two cycles of intermediate-dose cytarabine consolidation. Two hundred one patients were equally randomly assigned to receive either sorafenib or placebo between the chemotherapy cycles and subsequently for up to 1 year after the beginning of therapy. The primary ob…
Depth of response to isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: Interim analysis of the GMMG-CONCEPT trial.
8508 Background: High-risk (HR) multiple myeloma (MM) still has a significant impaired prognostic outcome. Addition of CD38 monoclonal antibodies to standard-of-care regimens significantly improved response rates and depth of response in newly diagnosed (ND) and relapsed/refractory MM patients (pts). Here, we report the prespecified end of induction interim analysis (IA) of the investigator-initiated GMMG-CONCEPT trial (NCT03104842), evaluating the quadruplet regimen isatuximab plus carfilzomib, lenalidomide and dexamethasone (Isa-KRd) in HR NDMM pts. Methods: 153 pts with HR NDMM are planned to be included into the trial. HR MM is defined by the presence of del17p or t(4;14) or t(14;16) o…
Evaluation of Stem Cell Mobilization in Patients with Multiple Myeloma after Lenalidomide-Based Induction Chemotherapy within the GMMG-HD6 Trial
Abstract Introduction: The German-Speaking Myeloma Multicenter Group (GMMG) has initiated a randomized multicenter phase III trial on the effect of elotuzumab in VRD (bortezomib, lenalidomide, dexamethasone) induction/consolidation and lenalidomide maintenance in patients with newly diagnosed multiple myeloma (GMMG-HD6 trial, NCT02495922). The study compares four cycles induction therapy with VRD vs. VRD + elotuzumab, followed by standard intensification (i.e. mobilization and stem cell transplantation), two cycles consolidation with VRD/VRD + elotuzumab and lenalidomide maintenance +/- elotuzumab. The primary endpoint is determination of the best of four treatment strategies regarding prog…
Kinetics of Renal Function during Induction in Newly Diagnosed Multiple Myeloma: Results of Two Prospective Studies by the German Myeloma Study Group DSMM
Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex
Prediction of Early Death and Severe Infections during Novel Agent-Based Induction Therapy in Newly-Diagnosed Multiple Myeloma: An Intergroup Analysis from the German Speaking Myeloma Multicenter Group, the Dutch-Belgian Cooperative Trial Group for Hematology Oncology Foundation and the European Myeloma Network
Abstract Background: During the past decade, prognostic tools and outcomes of patients with newly-diagnosed multiple myeloma (NDMM) markedly improved. Data from clinical trials evaluating early morbidity and mortality including patients with transplant-eligible NDMM treated with novel agents are scarce. Thus, we aimed to analyze early morbidity and mortality in this patient cohort, devise and validate a predictive score to identify patients at risk. Patients and methods: Between July 2005 and January 2018, 1333 patients with transplant-eligible NDMM from three subsequent phase III trials, HD4, MM5 and HD6 from the German-speaking Myeloma Multicenter Group (GMMG), received a novel agent-base…
Sorafenib In Combination with Standard Induction and Consolidation Therapy In Elderly AML Patients: Results From a Randomized, Placebo-Controlled Phase II Trial
Abstract Abstract 333 Background: Standard chemotherapy for elderly AML patients results in a median overall survival of only about one year. Case reports and early phase I/II data have shown that the kinase inhibitor Sorafenib might show clinical benefit for Flt3-ITD-positive AML patients (Metzelder S Blood 2009; 113:6567) and that its addition to standard chemotherapy is feasible (Ravandi F JCO 2010; 28:1856). Sorafenib is a potent Raf, c-Kit and FLT3 inhibitor that may also affect AML blasts and bone marrow (BM) stroma cells via VEGFR and PDGFR-β inhibition. Therefore, we performed a multicenter, randomized, placebo-controlled, double-blind phase II trial in elderly (>60 y) AML pa…
Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation
Purpose Clonal hematopoiesis of indeterminate potential (CHIP) occurs in the blood of approximately 20% of older persons. CHIP is linked to an increased risk of hematologic malignancies and of all-cause mortality; thus, the eligibility of stem-cell donors with CHIP is questionable. We comprehensively investigated how donor CHIP affects outcome of allogeneic hematopoietic stem-cell transplantation (HSCT). Methods We collected blood samples from 500 healthy, related HSCT donors (age ≥ 55 years) at the time of stem-cell donation for targeted sequencing with a 66-gene panel. The effect of donor CHIP was assessed on recipient outcomes, including graft-versus-host disease (GVHD), cumulative incid…
Elotuzumab in Combination with Lenalidomide, Bortezomib, Dexamethasone and Autologous Transplantation for Newly-Diagnosed Multiple Myeloma: Results from the Randomized Phase III GMMG-HD6 Trial
Abstract Background: Treatment regimens including a proteasome inhibitor, immunomodulating agent and a monoclonal antibody (moAb) play an emerging role in the treatment of newly-diagnosed multiple myeloma (NDMM). This multicenter phase III trial of the German-speaking Myeloma Multicenter Group (GMMG HD6) investigated the addition of the anti-SLAMF7 moAb elotuzumab to lenalidomide / bortezomib / dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible NDMM. Patients and Methods: Patients were equally randomized into four treatment arms, stratified by International Staging System (ISS). Treatment consisted of four 21-da…
A phase II study of elacytarabine in combination with idarubicin and of human equilibrative nucleoside transporter 1 expression in patients with acute myeloid leukemia and persistent blasts after the first induction course.
Unlike cytarabine, cellular entry of Elacytarabine, the elaidic acid ester derivative of cytarabine, is independent of the human equilibrative nucleoside transporter 1 (hENT1). This phase II study tested whether the hENT1 blast expression level can be used as a predictive marker for cytarabine response and if the efficacy of elacytarabine is independent of hENT1 expression. A total of 51 patients with acute myeloid leukemia (AML) induction failure were given elacytarabine-idarubicin as a second induction course. The hENT1 expression level was analyzed prior to first induction and/or prior to treatment with elacytarabine. The overall response rate (ORR) was 41% and the safety profile was man…
A Phase II Study of Elacytarabine/Idarubicin As Second Course Remission-Induction in Patients with Acute Myeloid Leukemia Who Failed Cytarabine/Anthracycline
Abstract Abstract 46 Background Elacytarabine, a fatty acid derivative (elaidic acid ester) of cytarabine, has pharmacokinetic and pharmacodynamic properties that may lead to improved clinical outcomes (Adema et al., 2011) compared to cytarabine. A phase I study had established 1000 mg/m2/d continuous infusion on d 1 – 5 as a safe and effective dose of elacytarabine given in combination with idarubicin at 12 mg/m2/d IV d 1 – 3 (Giles et al., 2012). Mechanism of Action The mechanism of action is similar to cytarabine, but unlike cytarabine, plasma elimination half-life is long, intracellular distribution is prolonged and activity is independent of membrane nucleoside transporters. Resistance…