The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities.

Multiple myeloma (MM) is a plasma cell malignancy of the bone marrow. Despite therapeutic advances, MM remains incurable, and better risk stratification as well as new therapies are therefore highly needed. The proteome of MM has not been systematically assessed before and holds the potential to uncover insight into disease biology and improved prognostication in addition to genetic and transcriptomic studies.

Full or intensity-reduced high-dose melphalan and single or double autologous stem cell transplant with or without bortezomib consolidation in patients with newly diagnosed multiple myeloma.

Objective: A post hoc subgroup analysis of two phase III trials (NCT00416273, NCT00416208) was carried out to investigate the influence of 100/140 and 200 mg/m² melphalan as well as single/double autologous stem cell transplantation (ASCT) on progression-free survival (PFS). Additionally, the effect of bortezomib consolidation on PFS was analyzed.

Methods: Following induction therapy and high-dose melphalan with subsequent ASCT, patients with newly diagnosed multiple myeloma (NDMM) were randomized 1:1 to either four 35-day cycles of bortezomib consolidation (1.

Carfilzomib, bendamustine, and dexamethasone in patients with advanced multiple myeloma: The EMN09 phase 1/2 study of the European Myeloma Network.

Background: Combined therapy with carfilzomib, bendamustine, and dexamethasone was evaluated in this multicenter phase 1/2 trial conducted within the European Myeloma Network (EMN09 trial).

Methods: Sixty-three patients with relapsed/refractory multiple myeloma who had received ≥2 lines of prior therapy were included. The phase 1 portion of the study determined the maximum tolerated dose of carfilzomib with bendamustine set at 70 mg/m on days 1 and 8.

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; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD).

Cost-Effectiveness Analysis of Stereotactic Ablative Radiation Therapy in Patients With Oligometastatic Cancer.

Purpose: The Stereotactic Ablative Radiation therapy for Comprehensive Treatment of Oligometastatic Tumors phase 2 randomized clinical trial found that stereotactic ablative radiation therapy (SABR) improved outcomes among cancer patients with oligometastatic disease. Yet, the cost of SABR along with the large number of patients with oligometastatic disease raises the important question of value. This study sought to evaluate the cost-effectiveness of the addition of SABR compared with standard therapy alone among cancer patients with oligometastatic disease.

[Recurrent Therapy of Multiple Myeloma - Individualized Concepts from The Arsenal of Diverse Options].

The prognosis of patients with multiple myeloma has improved significantly over the past 20 years. However, the patient population in the relapse situation is very heterogeneous due to increasing age and the previous course of the disease and therapy. In particular, the approval of new targeted substances offers numerous treatment options that can be adapted to the individual situation.

Autologous stem cell transplantation in multiple myeloma patients: utilization patterns and hospital effects.

Evidence on volume outcome associations for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) is limited. We investigated ASCT utilization patterns and volume outcome associations in the German National Registry for Stem Cell Transplants (DRST). MM patients with an upfront ASCT between 1998 and 2014 registered in the DRST were included.

Clinical outcomes and prognostic factors in patients with multiple myeloma in South Tyrol: a retrospective single-center analysis.

High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) as well as the introduction of novel agents (NA) significantly improved survival for patients with multiple myeloma (MM). A total of 150 unselected newly diagnosed MM patients treated at our institution from 1998 to 2017 were retrospectively analyzed. Median age at diagnosis was 69 years (range 33-93 years) with a median follow-up of 48.

Combined Androgen Blockade in Localized Prostate Cancer Treated With Definitive Radiation Therapy.

Background: The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy.

Methods: This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer-specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively.

Insights on Multiple Myeloma Treatment Strategies.

The introduction of new agents and management strategies over the past decade has resulted in a major step change in treatment outcomes with deepening responses and increased survival for patients with multiple myeloma. In daily clinical practice, healthcare professionals are now faced with challenges including, optimal treatment sequencing and changing treatment goals. In light of this, a group of experts met to discuss diagnostic and treatment guidelines, examine current clinical practice, and consider how new clinical trial data may be integrated into the management of multiple myeloma in the future.

Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis.

This phase 3 trial compared tandem autologous stem cell transplantation (autoSCT) versus autoSCT followed by reduced-intensity conditioning allogeneic stem cell transplantation (auto/alloSCT) in patients with newly diagnosed multiple myeloma (MM) with deletion of (del) chromosome 13q (del13q). The availability/absence of a human leukocyte antigen-matched-related or matched-unrelated donor (MUD) determined the nature of the second SCT. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population (n = 199).

Bortezomib consolidation following autologous transplant in younger and older patients with newly diagnosed multiple myeloma in two phase III trials.

Objective: A post hoc analysis of two phase III trials was carried out to explore the influence of age and treatment factors on the effect of bortezomib consolidation on progression-free survival (PFS) post autologous stem cell transplantation (ASCT).

Methods: Patients with newly diagnosed multiple myeloma were assigned to one of two trials (ClinicalTrials.gov IDs: NCT00416273, NCT00416208), which were conducted in parallel, based on age (18-60 or 61-75 years, respectively).

European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias.

The introduction of novel agents in the management of multiple myeloma and related plasma cell dyscrasias has changed our treatment approaches and subsequently the outcome of patients. Due to current advances, the European Myeloma Network updated the diagnostic and therapeutic recommendations for patients with Waldenström's macroglobulinemia (WM), AL-amyloidosis, monoclonal immunoglobulin deposition disease (MIDD), POEMS syndrome, and primary plasma cell leukemia. For patients with WM, the combination of rituximab with chemotherapy remains the treatment cornerstone, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease.

Patient-centered practice in elderly myeloma patients: an overview and consensus from the European Myeloma Network (EMN).

Multiple myeloma is a disease typical of the elderly, and, because of the increase in life expectancy of the general population, its incidence is expected to grow in the future. Elderly patients represent a particular challenge due to their marked heterogeneity. Many new and highly effective drugs have been introduced in the last few years and results from clinical trials are promising.

From transplant to novel cellular therapies in multiple myeloma: European Myeloma Network guidelines and future perspectives.

Survival of myeloma patients has greatly improved with the use of autologous stem cell transplantation and novel agents, such as proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. Compared to bortezomib- and lenalidomide-based regimens alone, the addition of high-dose melphalan followed by autologous transplantation significantly improves progression-free survival, although an overall survival benefit was not observed in all trials. Moreover, follow up of recent trials is still too short to show any difference in survival.

Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial.

We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%).

IKZF1 expression is a prognostic marker in newly diagnosed standard-risk multiple myeloma treated with lenalidomide and intensive chemotherapy: a study of the German Myeloma Study Group (DSMM).

Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide.

Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial.

Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction.

Early and multiple PSA bounces can occur following high-dose prostate stereotactic body radiation therapy: Subset analysis of a phase 1/2 trial.

Purpose: We hypothesized that high-dose stereotactic body radiation therapy (SBRT) would lead to faster time to nadir and lower nadir values compared with conventional radiation therapy experiences. We now report prostate-specific antigen (PSA) kinetics following high-dose SBRT in patients treated with radiation alone.

Methods And Materials: Ninety-one patients were enrolled on the phase 1/2 dose escalation study of SBRT for localized prostate cancer.

Survival of elderly patients with multiple myeloma-Effect of upfront autologous stem cell transplantation.

Background: The aim of this study was to determine the value of upfront autologous transplantation (ASCT) in elderly patients (60-79 years) with myeloma.

Methods: We analysed relative survival (RS) of patients diagnosed in 1998-2011 and treated with ASCT within 12 months after diagnosis in Germany (n = 3591; German Registry of Stem Cell Transplantation) and compare RS with survival of myeloma patients diagnosed in the same years in Germany (n = 13,903; population-based German Cancer Registries).

Results: Utilisation of ASCT has increased rapidly between 2000-2002 and 2009-2011 (60-64years: 7.

Review of evolving etiologies, implications and treatment strategies for the superior vena cava syndrome.

Superior vena cava syndrome (SVCS) is a relatively common sequela of mediastinal malignancies and may cause significant patient distress. SVCS is a medical emergency if associated with laryngeal or cerebral edema. The etiologies and management of SVCS have evolved over time.

Long-term Outcome of Prostate Cancer Patients Who Exhibit Biochemical Failure Despite Salvage Radiation Therapy After Radical Prostatectomy.

Objectives: Salvage radiation therapy (SRT) is an effective treatment for recurrent prostate cancer (PCa) after radical prostatectomy. We report the long-term outcome of men who developed biochemical recurrence (BCR) after SRT and were treated >14 years ago.

Methods: In total, 61 patients treated with SRT from 1992 to 2000 at our institution were identified.

Stereotactic Body Radiation Therapy for Prostate Cancer: Review of Experience of a Multicenter Phase I/II Dose-Escalation Study.

Introduction: Stereotactic body radiation therapy (SBRT) is an area of active investigation for treatment of prostate cancer. In our phase I dose-escalation study, maximum-tolerated dose (MTD) was not reached, and subsequently phase II study has been completed. The purpose of this article is to review our experiences of dose-escalated SBRT for localized prostate cancer.

[State of the art treatment of progressive or refractory multiple myeloma].

Unlabelled: Multiple myeloma (MM) is with an incidence of 4-6/100 000 inhabitants a fairly frequent malignancy of B cells. The incidence increases markedly with age. In this review changes in the treatment of relapsed / refractory myeloma during the last decade have been analysed.