Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma.

Contains fulltext : 70833.pdf (publisher's version ) (Open Access)In the prospective phase 3 HOVON-50/GMMG-HD3 trial, patients randomized to TAD (thalidomide, doxorubicin, dexamethasone) had a significantly higher response rate (at least PR) after induction compared with patients randomized to VAD (vincristine, adriamycin, dexamethasone, 72% vs. 54%, p<0.001). Complete remission (CR) and very good partial remission (VGPR) were also higher after TAD. After High Dose melphalan 200mg/m(2) response was comparable in both arms, 76% and 79% respectively. However, CR plus VGPR were significantly higher in the patients randomized to TAD (49% vs. 32%, p<0.001). CTC grade 3-4 adverse events were similar in both arms

Midostaurin plus intensive chemotherapy for younger and older patients with AML and FLT3 internal tandem duplications

We conducted a single-arm phase-II trial (AMLSG 16-10) to evaluate midostaurin with intensive chemotherapy followed by allogeneic hematopoietic-cell transplantation (HCT) and a one-year midostaurin maintenance therapy in adult patients with acute myeloid leukemia (AML) and FLT3 internal tandem duplication (ITD). Patients 18-70 years of age with newly diagnosed FLT3-ITD-positive AML were eligible. Primary and key secondary endpoints were event-free (EFS) and overall survival (OS). Results were compared to a historical cohort of 415 patients treated on 5 prior AMLSG trials; statistical analysis was performed using a double-robust adjustment with propensity score weighting and covariate adjustment. Results were also compared to patients (18-59yrs) treated on the placebo arm of the CALGB 10603/RATIFY trial. The trial accrued 440 patients (18-60yrs, n=312; 61-70yrs, n=128). In multivariate analysis, EFS was significantly in favor of patients treated within the AMLSG 16-10 trial compared to the AMLSG control (HR 0.55; P<0.001); both in younger (HR 0.59; P<0.001) and older patients (HR 0.42; P<0.001). Multivariate analysis also showed a significant beneficial effect on OS compared to the AMLSG control (HR 0.57; P<0.001) as well as to the CALGB 10603/RATIFY trial (HR 0.71; p=0.005). The treatment effect of midostaurin remained significant in sensitivity analysis including allogeneic HCT as a time-dependent covariate. Addition of midostaurin to chemotherapy was safe in younger and older patients. In comparison to historical controls, the addition of midostaurin to intensive therapy led to a significant improvement in outcome in younger and older patients with AML and FLT3-ITD. The AMLSG 16-10 trial is registered at clinicaltrialsregistry.eu (Eudra-CT number 2011-003168-63) and clinicaltrials.gov (NCT01477606)