Stem Cell Mobilization for Multiple Myeloma Patients Receiving Daratumumab-Based Induction Therapy: A Real- World Experience.

For patients with newly diagnosed multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT), hematopoietic stem cell mobilization can be affected by induction chemotherapy. In clinical trials, the addition of daratumumab (dara) to a triplet backbone lowered hematopoietic stem cell yield, necessitating the administration of plerixafor to achieve the desired yield for ASCT. Here we describe our experience of stem cell mobilization and collection after dara-based and non-dara-based induction regimens. This single-center retrospective analysis included patients with newly diagnosed MM who had received induction chemotherapy and were candidates for upfront HDT-ASCT. Based on the induction regimen used, patients were divided into 2 groups, RVd (lenalidomide, bortezomib, and dexamethasone) and DRVd (RVd with the addition of dara). Based on our institutional practice, patients received pegylated growth colony-stimulating factor (G-CSF) on day -3 (at 0900 hours) in combination with plerixafor on day -1 (at 2300 hours) as a preemptive mobilization strategy. Patients continued apheresis for 1 to 3 days until the goal dose of hematopoietic stem cells was collected (2.5 × 106 cells/kg for one ASCT and 5.0 × 106 cells/kg for 2 ASCTs). Patients with a suboptimal stem cell yield on day 1 received additional doses of plerixafor with or without G-CSF. A total of 101 patients with newly diagnosed MM who underwent mobilization between July 2021 and June 2022 were analyzed. The median patient age was 61 years (range, 36 to 80 years), and 51.5% of the cohort was female. Patients received a median of 5 (range, 2 to 12) cycles of induction chemotherapy, with a median of 4 (range, 2 to 12) cycles of DRVd and 6 (range, 3 to 12) cycles of RVd. The median number of CD34+ cells collected in the DRVd and the RVd groups was 6.54 × 106/kg and 6.78 × 106/kg, respectively. Target CD34+ stem cells were collected in a median of 1 day (range, 1 to 4 day) in each group. On average, more patients in the DRVd group compared to the RVd group received additional doses of plerixafor (51% versus 43%) and additional doses of GCSF (19% versus 14%) to achieve the target stem cell yield. There were no mobilization failures or grade 3+ mobilization-related adverse events reported in either group. The addition of daratumumab to the RVd induction regimen did not lead to any clinically significant differences in stem cell yield or number of collection days, provided that the patient received preemptive G-CSF and plerixafor. Patients with suboptimal collection on day 1 were able to collect adequate stem cells with additional doses of plerixafor with or without G-CSF.

Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials.

Importance: Several meta-analyses of randomized clinical trials (RCTs) have demonstrated the many health benefits of intermittent fasting (IF). However, there has been little synthesis of the strength and quality of this evidence in aggregate to date. Objective: To grade the evidence from published meta-analyses of RCTs that assessed the associations of IF (zero-calorie alternate-day fasting, modified alternate-day fasting, the 5:2 diet, and time-restricted eating) with obesity-related health outcomes. Evidence Review: PubMed, Embase, and Cochrane database of systematic reviews were searched from database inception to January 12, 2021. Data analysis was conducted from April 2021 through July 2021. Meta-analyses of RCTs investigating effects of IF in adults were included. The effect sizes of IF were recalculated using a random-effects model. We assessed the quality of evidence per association by applying the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluations) as high, moderate, low, and very low. Findings: A total of 11 meta-analyses comprising 130 RCTs (median [IQR] sample size, 38 [24-69] participants; median [IQR] follow-up period, 3 [2-5] months) were included describing 104 unique associations of different types of IF with obesity-related health outcomes (median [IQR] studies per association, 4 [3-5]). There were 28 statistically significant associations (27%) that demonstrated the beneficial outcomes for body mass index, body weight, fat mass, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, and blood pressure. IF was found to be associated with reduced fat-free mass. One significant association (1%) supported by high-quality evidence was modified alternate-day fasting for 1 to 2 months, which was associated with moderate reduction in body mass index in healthy adults and adults with overweight, obesity, or nonalcoholic fatty liver disease compared with regular diet. Six associations (6%) were supported by moderate quality evidence. The remaining associations found to be significant were supported by very low (75 associations [72%]) to low (22 associations [21%]) quality evidence. Conclusions and Relevance: In this umbrella review, we found beneficial associations of IF with anthropometric and cardiometabolic outcomes supported by moderate to high quality of evidence, which supports the role of IF, especially modified alternate-day fasting, as a weight loss approach for adults with overweight or obesity. More clinical trials with long-term follow-up are needed to investigate the effects of IF on clinical outcomes such as cardiovascular events and mortality.

Erdafitinib: A novel therapy for FGFR-mutated urothelial cancer.

PURPOSE: To provide an overview of fibroblast growth factor receptor (FGFR) gene alterations and the pharmacology, clinical effectiveness, dosage and administration, cost, and place in therapy of erdafitinib in bladder cancer. SUMMARY: Erdafitinib (Balversa, Janssen Pharmaceuticals) is a novel pan-FGFR inhibitor recently approved for the treatment of patients with advanced urothelial cancer with specific FGFR genetic alterations who have received at least one prior platinum-containing regimen. Erdafitinib binding to the FGFR2 and FGFR3 receptors inhibits FGF activity, resulting in cell death. Erdafitinib is available in tablet form, and the current recommended daily dosing is 8 mg, with dose escalation to 9 mg after 14 to 21 days of therapy if tolerated. A phase 2 clinical trial demonstrated that patients who received erdafitinib experienced on average 5.5 months of progression-free survival (95% confidence interval [CI], 4.2-6.0 months). In addition, 40% (95% CI, 31-50%) of patients responded to erdafitinib therapy. Patients receiving erdafitinib therapy should be monitored specifically for elevations in serum phosphate levels and changes in vision. Other adverse effects include anemia, thrombocytopenia, and electrolyte abnormalities. CONCLUSION: Erdafitinib is the first small-molecule FGFR inhibitor approved for use in advanced bladder cancer.