A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide.

INTRODUCTION: Lenalidomide plus dexamethasone is effective and well tolerated in relapsed/refractory multiple myeloma (RRMM). In this observational, noninterventional European post-authorization safety study, the safety profile of lenalidomide plus dexamethasone was investigated and compared with that of other agents in the treatment of RRMM in a real-world setting. PATIENTS AND METHODS: Patients had received ≥ 1 prior antimyeloma therapy; prior lenalidomide was excluded. Treatment was per investigator's routine practice. Adverse events were analyzed by incidence rates per 100 person-years to account for differences in observation length and treatment duration. RESULTS: In total, 2150 patients initiated lenalidomide, and 1479 initiated any other antimyeloma therapy, predominately bortezomib (80.3%), which was primarily administered intravenously (74.3%). The incidence rate of neuropathy was lower with lenalidomide (10.5) than with bortezomib (78.9) or thalidomide (38.7). Lenalidomide also had a lower incidence rate of infections (68.7) versus bortezomib (95.9) and thalidomide (76.0). Conversely, the incidence rate of neutropenia was higher with lenalidomide (38.0) than with bortezomib (18.2) or thalidomide (25.7). The incidence rates of thrombocytopenia were 24.4, 40.4, and 14.4 with lenalidomide, bortezomib, and thalidomide, respectively. CONCLUSION: No new safety signals for lenalidomide were identified in this study, which is the largest prospective real-world European study of lenalidomide in patients with RRMM to date. These results confirm that the safety profile of lenalidomide plus dexamethasone in RRMM in a real-world setting is comparable to that reported in clinical trials.

Pomalidomide Plus Low-Dose Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment: Results From a Phase II Trial.

Purpose Renal impairment (RI) limits treatment options in patients with relapsed/refractory multiple myeloma (RRMM). Here, we prospectively studied pomalidomide plus low-dose dexamethasone (LoDEX) in patients with RRMM and moderate or severe RI, including those receiving hemodialysis. Patients and Methods MM-013, a noncomparative, European phase II trial, enrolled three patient cohorts: moderate RI (cohort A; estimated glomerular filtration rate, 30 to < 45 mL/min/1.73 m2); severe RI (cohort B; estimated glomerular filtration rate, < 30 mL/min/1.73 m2); and severe RI that requires hemodialysis (cohort C). Patients received pomalidomide 4 mg/d on days 1 to 21 and LoDEX 20 or 40 mg once per week in 28-day cycles. The primary end point was overall response rate. Results Of 81 enrolled patients (33, 34, and 14 patients in cohorts A, B, and C, respectively), 13 were still receiving treatment at data cutoff (January 28, 2017). Overall response rates were 39.4%, 32.4%, and 14.3%, with a median duration of response of 14.7 months, 4.6 months, and not estimable, respectively. Of importance, 100%, 79.4%, and 78.6% of patients, respectively, achieved disease control. With a median follow-up of 8.6 months, median overall survival was 16.4 months, 11.8 months, and 5.2 months, respectively. Complete renal responses were observed only in cohort A (18.2%), and no patients in cohort C became hemodialysis independent. Grade 3 and 4 hematologic treatment-emergent adverse events and pomalidomide discontinuations as a result of treatment-emergent adverse events occurred more frequently in cohort C. Pomalidomide pharmacokinetics were comparable among the three renal cohorts. Conclusion Pomalidomide 4 mg/d plus LoDEX is efficacious in patients with RRMM with moderate or severe RI, including those who had more advanced disease and required hemodialysis. The safety profile was acceptable among the three groups, and no new safety signals were observed.

Efficacy, safety and quality-of-life associated with lenalidomide plus dexamethasone for the treatment of relapsed or refractory multiple myeloma: the Spanish experience.

Here we report the efficacy, safety and health-related quality-of-life (HRQoL) associated with long-term lenalidomide and dexamethasone (Len + Dex) treatment in patients with relapsed or refractory multiple myeloma (RRMM) enrolled in the Spanish cohort of the MM-018 study. In this open-label, multicenter, single-arm expanded access study, 63 patients received Len + Dex until disease progression. The overall response rate was 78%, with 21% of the patients achieving a complete response. The quality of response improved with continuous treatment. The median duration of response was 18.4 months. Median time-to-progression and progression-free survival was 13.3 months for both; median overall survival was not reached. Len + Dex had a manageable safety profile consistent with previously reported phase III studies. HRQoL assessments (n = 42) at baseline and 6 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ MY-20 questionnaires revealed that patients with RRMM treated with long-term lenalidomide reported clinically relevant improvements in certain QoL and symptoms scores regardless of treatment response (ClinicalTrials.gov: NCT00420849).

Stress-related psycho-physiological disorders: randomized single blind placebo controlled naturalistic study of psychometric evaluation using a radio electric asymmetric treatment.

BACKGROUND: The aim of this study is to investigate the effects of a radio electric asymmetric treatment on psycho-physiological disorders (PPD). PPD are often stress related and are under the unconscious control of the patient and cannot be traced back to any serious physical disease. The brain stimulation treatment protocol used is called Neuro Psycho Physical Optimization (NPPO) with a Radio Electric Asymmetric Conveyer (REAC) device. METHODS: Psychological stress and PPD were measured for a group of 888 subjects using the Psychological Stress Measure (PSM) test, a self-administered questionnaire. Data were collected immediately before and after the 4-weeks of REAC treatment cycle. RESULTS: This study showed a significant reduction in scores measuring subjective perceptions of stress for subjects treated with a cycle of NPPO REAC treatment. At the end-point the number of subjects reporting symptoms of stress-related PPD on the PSM test was significantly reduced, whereas in the placebo group the difference was not significant. CONCLUSION: A cycle of NPPO treatment with REAC was shown to reduce subjective perceptions of stress measured by the PSM test and in particular on PPD. TRIAL REGISTRATION: This trial has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) with the number: ACTRN12607000463471.

A new approach on stress-related depression and anxiety: Neuro-Psycho- Physical-Optimization with Radio Electric Asymmetric-Conveyer.

BACKGROUND & OBJECTIVES: Chronic social stress is an important factor responsible for the worsening of depressive disorders in humans. In this study we present the relational Neuro-Psycho-Physical Optimization (NPPO) with Radio Electric Asymmetric Conveyer (REAC-CRM) as the treatment to tackle the unconscious dysfunction adjustments carried out by the central nervous system as a response to environmental stresses. METHODS: Psychological stress was measured in a group of 888 patients using the Psychological Stress Measure (PSM) test, a self-administered questionnaire. Data were collected immediately before and after the 4-wk therapy cycle. The detection of anxiety and depression clusters by PSM test has been based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR, APA, 2000) criteria. Six hundred and eighty eight patients (212 males, 476 females, average PSM test total scores 107.9 +/- 23.13) were treated with REAC-CRM therapy; 200 (64 males, 136 females, average PSM test total scores 107.86 +/- 25.80) were treated with "placebo REAC-CRM therapy"and used as control. RESULTS: This study showed a significant reduction in scores measuring subjective perceptions of stress in the patients treated with a cycle of REAC-CRM therapy. At the end-point the number of patients reporting symptoms of stress-related anxiety and depression on the PSM test was significantly reduced (P<0.001); in the placebo group no significant difference was highlighted. INTERPRETATION & CONCLUSIONS: NPPO therapy with a cycle of REAC-CRM was shown to reduce subjective perceptions of stress measured by the PSM test and in particular, symptoms of stress-related anxiety and depression.