Treatment patterns and outcomes in real-world transplant-ineligible patients newly diagnosed with multiple myeloma.

Despite the significant proportion of older patients with newly diagnosed multiple myeloma (MM), most clinical trials driving therapeutic decisions in routine practice include younger and presumably healthier patients than those in the real world. Furthermore, longitudinal studies suggest that elderly, transplant-ineligible patients with MM are not benefitting enough from new anti-MM agents. We retrospectively analyzed the profile of and treatment patterns and outcomes in 675 transplant-ineligible patients with MM who started frontline therapy in routine practice. The mean (SD) age was 75.6 (6.7) years; 152 (47.4%) had Eastern Cooperative Oncology Group performance status (ECOG PS) 2-4, and 73 (25.1%) had high cytogenetic risk. The most frequent frontline therapy was non-VMP bortezomib-based regimens (n=207; 30.7%), which were more frequent among patients with ECOG PS 0/1 and higher risk (e.g., international staging system (ISS) stage III, severely impaired glomerular filtrate rate (GFR), high lactate dehydrogenase (LDH), and high-risk cytogenetics); 185 patients (27.4%) started an attenuated (lite) VMP regimen, and 159 (23.6%) a VMP (VISTA) regimen. Median progression-free survival and overall survival (OS) were 15.3 months (95%CI 14.0-16.9) and 33.5 months (95%CI 29.1-37.2), respectively; 405 patients (78.2%) achieved partial response or better. Age, ECOG PS, ISS stage, serum LDH, GFR, cytogenetic risk, and treatment regimen significantly influenced OS. In this study, a remarkable proportion of transplant-ineligible patients with MM were older, frontline regimens were highly heterogeneous, and patients at higher risk often received less efficacious combinations. These findings suggest that clinicians have limited objective criteria for therapeutic decisions for this patient group.

Recommendations on the clinical use of bendamustine in lymphoproliferative syndromes and multiple myeloma.

Bendamustine is an increasingly used hybrid alkylating agent that is active in lymphoid neoplasias via a novel mechanism of action. There are some pending questions about its use in clinical practice because of its developmental features. A consensus panel of several leading Spanish hematologists with broad experience in the clinical use of bendamustine has established recommendations for the management and treatment of hematological patients with bendamustine based on available clinical data and the experience of the participants. These recommendations address the dose and treatment regimen for different clinical indications, the management of toxicity, and support therapy. This article contains the conclusions of this consensus panel, which are intended to serve as guidelines for the use of bendamustine.

Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival.

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.

Blastoschizomyces capitatus infection in patients with leukemia: report of 26 cases.

Twenty-six cases of Blastoschizomyces capitatus infection were diagnosed in 25 patients at 7 tertiary care hematology units in Spain over a 10-year period. Most patients (92%) had acute leukemia and developed infection during a period of severe and prolonged neutropenia. Two patients had esophagitis, and the rest had invasive infection. Fungemia (20 cases) was a common finding, with frequent visceral dissemination. The 30-day mortality associated with this infection was 52%, compared with 57% among patients with systemic infection. In a univariate analysis, the following 3 variables had a positive impact on 30-day survival: removal of the central venous catheter within 5 days after the onset of infection (P=.02), a good performance status (P=.003), and receipt of systemic prophylactic or empirical antifungal therapy before infection onset (P=.006). Outcome for neutropenic patients with B. capitatus infection is still poor. Rapid removal of the central venous catheter and novel antifungal therapies are recommended for treatment of this rare infection.

Comparative study of cognitive-behavioral psychotherapy and nutritional support in patients with different types of eating disorders.

BACKGROUND AND OBJECTIVE: There are several psychological approaches to treat ED with efficacy being revealed by empirical research; however none of them are universally accepted. The objective was to compare response to Cognitive Behavioral Therapy in patients with different clinical forms of Eating Disorders. MATERIAL AND METHOD: Seventy-four patients diagnosed with eating disorders, 32 with Anorexia nervosa (AN), 19 with Bulimia nervosa (BN) and 23 with Eating disorders not otherwise specified (EDNOS) were included. This is a prospective and comparative study. Patients were treated by psychotherapy, nutritional treatment and pharmacotherapy. RESULTS: The recovery rates in the groups of patients with AN, BN and EDNOS were 14 (43.7%), 8 (42.1%), 10 (43.4%), respectively, p>0.05. The rates of improvement were 14 (43.7%), 10 (52.6%), 12 (52.1%) for AN, BN and EDNOS, respectively, p>0.05. Finally, the rate of patients who had poor outcome were 3 (9.3%), 1 (5.2%), and 1 (4.3%), p>0.05, for AN, BN, and EDNOS, respectively. Cox regression analysis showed that the age of disease onset and no use of psychotropic drugs predicted a good response in patients with ED. CONCLUSIONS: The treatment response to Cognitive Behavioral Therapy, nutritional support and psychotropic drugs in the majority of patients was favorable and similar in most patients with different types of Eating Disorders. Furthermore, a young age and no use of psychotropic drugs predict a favorable outcome in patients with ED.