Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain.

Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.

Early Prediction of Subsequent Molecular Response to Nilotinib in Patients with Chronic Myeloid Leukemia: Comparison of the Quantification of BCR-ABL1 Ratios Using ABL1 or GUSB Control Genes.

Molecular monitoring of BCR-ABL1 transcripts is a critical prognostic indicator of treatment response in chronic myeloid leukemia (CML). Quantification of BCR-ABL1 transcripts using ABL1 or GUSB as control genes on the early molecular response (MR) to frontline nilotinib was studied using data from 60 patients with chronic-phase CML from the Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) substudy. Effects of BCR-ABL1/ABL1 and BCR-ABL1/GUSB ratios at early time points as independent variables on subsequent MR were determined by logistic regression analyses and predictive cut-off values determined by receiver operating curve analyses. From day 45, concordance was found for both control genes' early transcript kinetics and ability to predict subsequent deep MR at 18 months. From baseline to 3 months, transcripts descended linearly with both control genes. Use of ABL1 allowed for an earlier prediction (2 months) of subsequent MR than with GUSB (3 months), with cut-off values of 1.5% and 0.19%, respectively. The dynamic determination of BCR-ABL1 transcripts using either internal control gene is valid and predictive of subsequent MR. The use of GUSB to predict an earlier and more accurate response than ABL1 is not supported in the results. Accurate early indicators of MR are essential to identify patients likely to have inferior outcomes who may benefit from treatment with an alternative tyrosine kinase inhibitor.

Correction to: An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

Correction to: J Cancer Res Clin Oncol (2017) 143:2059-2066 DOI 10.1007/s00432-017-2445-z.

An analysis of the kinetics of molecular response during the first trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia patients in chronic phase.

PURPOSE: This study was aimed to analyze the association of very early molecular response to nilotinib with the achievement of deep molecular response (MR4) at 18 months. We hypothesized that the BCR-ABL1 levels during the first 3 months of therapy, and the kinetics of their descent in this period, could be predictive of deep molecular response thereafter. METHODS: This substudy of the ENEST1st trial included 60 patients with chronic myeloid leukemia in chronic phase treated with front-line nilotinib, and BCR-ABL1IS levels were measured using GUS as the control gene. The analysis included seven time points during the first trimester of treatment (baseline and fortnightly thereafter). RESULTS: The rates of MMR at 12 months, and of MR4 at 18 months (primary variable of the study), were 70 and 41%, respectively, similar to those obtained in the core study. BCR-ABL1IS ≤10% was achieved at 1, 1.5, 2 and 3 months in 50, 70, 83 and 93% of the patients, respectively. The observed shape of the BCR-ABL1IS descent was biphasic, with a faster slope during the first trimester and a median halving time (HT) of 11 days, the shortest reported in the literature. An HT ≤13 days was predictive of MMR at 12 months and MR4 at 18 months. CONCLUSIONS: The association of a shorter HT with response provides a rationale for exploring very early kinetics patterns in all patients treated with potent TKIs such as nilotinib.

Recombinant factor VIIa is an effective therapy for abdominal surgery and severe thrombocytopenia: a case report.

A 50-year-old woman was admitted to the emergency room. An appendectomy was done. On the sixth day the patient's general state deteriorated and she became somnolent with jaundice due to distal obstructive choledocholithiasis. The results of laboratory tests were platelets 12 x 10(9)/L, prothrombin time 13 seconds, international normalized ratio 1.19, activated partial thromboplastin time 31.8 seconds, and fibrinogen 8.78 g/L. There was no evidence of disseminated intravascular coagulation. In view of the patient's clinical condition, surgery was considered to be indicated. Because it was a life-threatening situation and at the time there was no platelet concentrate available for immediate transfusion, she was treated with a single dose of recombinant factor VIIa (rFVIIa) (60 microg/kg). The dose of 60 microg/kg was selected on the basis of experience with rFVIIa in the treatment of hemophilic patients. In this case, use of rFVIIa was a valid alternative to control the bleeding in a patient with thrombocytopenia. However, despite the efficacy of the treatment, it should not be forgotten that it was used because of the unavailability of platelets and that we were dealing with a life-threatening situation. Clinical trials should be carried out to verify the safety, effectiveness, and efficiency of rFVIIa in these cases.

Meningitis neumocócica como presentación de una macroglobulinemia de Waldenström / Pneumococcal meningitis as onset Waldenstroöm macroglobulinemia

Management values in the clinical relationship: ideology on the practice (AU)