Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes.

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation's Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study ( NCT01454297 ) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n = 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.

Preferences and Priorities for Relapsed Multiple Myeloma Treatments Among Patients and Caregivers in the United States.

Introduction/Background: This study aimed to describe patient and caregiver preferences for treatments of relapsed or refractory multiple myeloma (MM). Materials and Methods: A survey including discrete-choice experiment (DCE) and best-worst scaling (BWS) exercises was conducted among US patients with relapsed or refractory MM and their caregivers. The DCE included six attributes with varying levels including progression-free survival (PFS), toxicity, and mode and frequency of administration. In addition, the impact of treatment cost was assessed using a fixed-choice question. The BWS exercise included 18 items (modes and frequency of administration, additional treatment convenience, and toxicity items). The survey was administered online to patients recruited from the Multiple Myeloma Research Foundation CoMMpass study (NCT01454297). Results: The final samples consisted of 94 patients and 32 caregivers. Avoiding severe nerve damage was most important to patients, followed by longer PFS. Caregivers considered PFS to be the most important attribute. We estimate that a third or more of patients were cost-sensitive, meaning their treatment preference was altered based on cost implications. Caregivers were not cost-sensitive. The three most bothersome treatment features in the BWS exercise were risk of kidney failure, lowering white blood cell counts, and weakening the immune system. Conclusion: Patients with relapsed or refractory MM and their caregivers consider many factors including efficacy, toxicity, mode/frequency of administration, and cost in their decisions regarding treatment options. The study provides a basis for future Research on patient and caregiver treatment preferences, which could be incorporated into shared decision-making with physicians.

Pegfilgrastim appears equivalent to daily dosing of filgrastim to treat neutropenia after autologous peripheral blood stem cell transplantation in patients with non-Hodgkin lymphoma.

BACKGROUND: Filgrastim decreases the time to neutrophil recovery after autologous peripheral blood stem cell transplantation (PBSCT). We hypothesized that single-dose pegfilgrastim would mimic multiple daily doses of filgrastim, resulting in an equivalent shortening of post-PBSCT neutropenia. PATIENTS AND METHODS: Patients who were eligible for PBSCT and aged >or= 18 years were identified before high-dose chemotherapy, after the harvesting and cryopreservation of peripheral blood progenitor cells (ie, > 2.5 x 10(6) CD34-positive cells/kg). Eligible patients received either standard carmustine/etoposide/cytarabine/melphalan (BEAM) or carmustine/etoposide/cytarabine/cyclophosphamide (BEAC) high-dose chemotherapy. Before high-dose chemotherapy, patients were randomly assigned to receive pegfilgrastim 6 mg on day 1 (arm A) or weight-based, dose-adjusted filgrastim beginning on day 1 (arm B) after transplantation until neutrophil engraftment. RESULTS: One-hundred and one patients were enrolled between April 2003 and April 2007. Three patients were not treated. Demographics were well-balanced in terms of stage at diagnosis, Eastern Cooperative Oncology Group performance status, histology, and lines of previous therapy. Results (arm A/arm B) pertained to mean doses received (1.0/12.6), mean absolute neutrophil count recovery days (9.3/9.8), red blood cell transfusions (1.7/1.9), red blood cell transfusion units (3.1/3.8), platelet transfusions (3.1/2.8), positive blood culture rate (18%/29.2%), febrile neutropenia (FN; 18%/16.7%), and duration of FN (days; 7.1/6.9). Transplantation-related mortality and grade 3 or 4 adverse events were comparable between arms. CONCLUSION: Pegfilgrastim after PBSCT appears equivalent to multiple daily doses of filgrastim. This approach might be considered in lieu of filgrastim, thus obviating the need for multiple daily injections.

Ovarian cancer care: a case study in determined living.

BACKGROUND: The balance between quality of life and aggressive treatment fuels strong debate in cancer care. Recently, more attention is focused on blending advanced care, palliative care and hospice treatments in a patient-specific, tailored manner. This case study explores quality of life, the role of psychosocial factors in treatment selection, and the role of medical bias in end-of-life decision-making. CASE REPORT: The patient was a 55-year-old woman with advanced recurrent epithelial ovarian cancer. The disease course was essentially unremitting with only 5 months of non-progression after initial treatment. Multiple courses of chemotherapy were provided, in addition to a wide range of advanced and aggressive therapies to treat the cancer, as well as prolong life. Hospice care was an active part of treatment over 2 separate time periods, with a 1-year hiatus between admissions into hospice care. CONCLUSION: This case study provides an example of blending aggressive treatment, palliative care and hospice care to allow a patient to achieve specific life milestones, while attempting to preserve quality of life.