Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma.

In this phase 2 multicenter study, we evaluated the incorporation of autologous stem cell transplantation (ASCT) into a carfilzomib-lenalidomide-dexamethasone (KRd) regimen for patients with newly diagnosed multiple myeloma (NDMM). Transplant-eligible patients with NDMM received 4 cycles of KRd induction, ASCT, 4 cycles of KRd consolidation, and 10 cycles of KRd maintenance. The primary end point was rate of stringent complete response (sCR) after 8 cycles of KRd with a predefined threshold of ≥50% to support further study. Seventy-six patients were enrolled with a median age of 59 years (range, 40-76 years), and 35.5% had high-risk cytogenetics. The primary end point was met, with an sCR rate of 60% after 8 cycles. Depth of response improved over time. On intent-to-treat (ITT), the sCR rate reached 76%. The rate of minimal residual disease (MRD) negativity using modified ITT was 70% according to next-generation sequencing (<10-5 sensitivity). After median follow-up of 56 months, 5-year progression-free survival (PFS) and overall survival (OS) rates were 72% and 84% for ITT, 85% and 91% for MRD-negative patients, and 57% and 72% for patients with high-risk cytogenetics. For high-risk patients who were MRD negative, 5-year rates were 77% and 81%. Grade 3 to 4 adverse events included neutropenia (34%), lymphopenia (32%), infection (22%), and cardiac events (3%). There was no grade 3 to 4 peripheral neuropathy. Patients with NDMM treated with KRd with ASCT achieved high rates of sCR and MRD-negative disease at the end of KRd consolidation. Extended KRd maintenance after consolidation contributed to deepening of responses and likely to prolonged PFS and OS. Safety and tolerability were manageable. This trial was registered at www.clinicaltrials.gov as #NCT01816971.

Mitotic instability in triploid and tetraploid one-year-old eastern oyster, Crassostrea virginica, assessed by cytogenetic and flow cytometry techniques.

For commercial oyster aquaculture, triploidy has significant advantages. To produce triploids, the principal technology uses diploid × tetraploid crosses. The development of tetraploid brood stock for this purpose has been successful, but as more is understood about tetraploids, it seems clear that chromosome instability is a principal feature in oysters. This paper is a continuation of work to investigate chromosome instability in polyploid Crassostrea virginica. We established families between tetraploids-apparently stable (non-mosaic) and unstable (mosaic)-and normal reference diploids, creating triploid groups, as well as tetraploids between mosaic and non-mosaic tetraploids. Chromosome loss was about the same for triploid juveniles produced from either mosaic or non-mosaic tetraploids or from either male or female tetraploids. However, there was a statistically significant difference in chromosome loss in tetraploid juveniles produced from mosaic versus non-mosaic parents, with mosaics producing more unstable progeny. These results confirm that chromosome instability, as manifested in mosaic tetraploids, is of little concern for producing triploids, but it is clearly problematic for tetraploid breeding. Concordance between the results from cytogenetics and flow cytometry was also tested for the first time in oysters, by assessing the ploidy of individuals using both techniques. Results between the two were non-concordant.

Impact of an Oncology Clinical Pharmacist Specialist in an Outpatient Multiple Myeloma Clinic.

INTRODUCTION: Improvements in cancer treatment and supportive care, as well as the approval of oral chemotherapy medications over the past decade, have resulted in an increasing number of cancer patients being treated in outpatient settings. Transitioning cancer treatments to the outpatient setting places greater emphasis on proper medication counseling and optimal management of adverse effects. We therefore evaluated the clinical and financial impact of an oncology clinical pharmacist specialist in an interdisciplinary multiple myeloma clinic by using a validated scoring tool. METHODS: The oncology clinical pharmacist specialist was available for consult by the multiple myeloma clinic staff. The pharmacist may be consulted for any medication-related inquiry. On the basis of the consult, the pharmacist categorized interventions into 12 predefined intervention categories. RESULTS: Implementation of a clinical pharmacy specialist into a multiple myeloma clinic over 39 clinic days resulted in 241 patient consults and 474 interventions made by the pharmacist. The most frequent interventions made by the pharmacist were medication teaching (n = 97), dose adjustments (n = 82), and medication reconciliation (n = 63). The value of interventions made by the pharmacist during the study period was $189,441, with a predicted annual value of $757,764. CONCLUSION: The addition of an oncology pharmacist to an outpatient multiple myeloma clinic can improve clinical and financial outcomes.