Elotuzumab-based maintenance therapy following autologous stem cell transplant in multiple myeloma deepens post-transplant responses.

BACKGROUND: Post-transplant maintenance provides progression-free survival benefit in multiple myeloma (MM). Here we report our institution's experience with elotuzumab-based maintenance following autologous stem cell transplant. METHODS: We retrospectively evaluated the outcomes of MM patients who were started on elotuzumab-based maintenance (elotuzumab/lenalidomide/dexamethasone, elotuzumab/bortezomib/dexamethasone, or elotuzumab/bortezomib/methylprednisolone) following transplant (N = 7). Baseline characteristics, treatment response, survival, and adverse events were reviewed. RESULTS: Median age was 68 (56-81) years at the time of transplant, and median lines of induction therapy was 2 (1-6). Three patients (42.9%) had high-risk cytogenetics and five (71.4%) had stage II or greater disease at diagnosis. At a median follow-up of 24 months (12-50), five patients (71.4%) had improvement of quality of response, with a combined CR or VGPR rate increasing from 57.1% to 100% (CR = 3, VGPR = 4). All patients were alive without relapse or progression at the time of this analysis. Grade 3-4 adverse events were observed in three (42.9%) patients. None of the patients discontinued the treatment due to intolerance. CONCLUSIONS: Our study demonstrates that elotuzumab-based maintenance may deepen response post-transplant in MM and can be safely administered even in older patients. Given its unique action and rare side effects, further studies of elotuzumab in the post-transplant setting are warranted.

Elderly do benefit from induction chemotherapy: High dose mitoxantrone-based ("5 + 1") induction chemotherapy regimen in newly diagnosed acute myeloid leukemia.

An intensive "5 + 1" regimen, which included bolus high dose cytarabine (HiDAC) at 3 g/m2 once daily over 3 hours on days 1-5 and high dose mitoxantrone (HDM) 80 mg/m2 on day 2, was evaluated in 101 consecutively treated newly diagnosed acute myeloid leukemia (AML) patients at a single center since 2009. The median age was 65 (range 18-90) years. The 4 and 8-week mortality in our cohort was 3/101 (2.9%) and 7/99 (7%), respectively. The overall response (complete remission [CR] + CRi) was 76.2% (77/101). The median overall survival (OS) stratified by age group <60, 60-69 and ≥70 years were 56, 31 and 9 months respectively (log-rank, P = 0.02). 51.7% (45/84) of patients with intermediate/adverse risk category proceeded to allogeneic stem cell transplants. Among these 84 patients, the percentage of patients able to proceed to transplant in age groups <60, 60-69, and ≥ 70 years were 75% (18/24), 60.7% (17/28), and 31.2% (10/32), respectively. In conclusion, HDM-based chemotherapy regimen produces high CR rates, is well tolerated and more patients can undergo curative postremission therapy including stem cell transplant.

Utility of ampicillin-sulbactam for empiric treatment of ventilator-associated pneumonia in a trauma population.

BACKGROUND: Ampicillin-sulbactam is guideline-recommended treatment for early-onset ventilator-associated pneumonia (VAP). However, intensive care unit clinicians are encountering increasing resistance to ampicillin-sulbactam. We sought to analyze the time period for early-onset VAP in our trauma population by using daily evaluation of resistance to ampicillin-sulbactam. METHODS: A retrospective cohort study was completed on all mechanically ventilated trauma patients admitted to a rural level-1 trauma center from January 2003 to December 2008 who were diagnosed with VAP. Daily bacterial resistance to ampicillin-sulbactam > 15% was defined as the threshold for early empiric antibiotic failure for the first episode of VAP. A univariate analysis of risk factors for multi-drug resistant pathogens (MDRPs) and comorbidities was completed to assess for predisposing factors for ampicillin-sulbactam resistance. RESULTS: One hundred sixty-three pathogens were identified in 121 trauma patients diagnosed with VAP. Of these isolates, 71% were gram-negative, 28% were gram-positive, and 1% was fungal. Methicillin-susceptible Staphylococcus aureus (23.9%), H aemophilus influenzae (20.9%), and Pseudomonas aeruginosa (11.7%) were the most common infecting organisms. Daily ampicillin-sulbactam resistance was 40%, 26%, 32%, 43%, 50%, and 60% on days 3 to 7 and ≥ 8 days, respectively. Only the presence of MDRP risk factors (89% vs. 65%, p < 0.01) and hospital LOS (36.8 [22.8-49.0] vs. 25.7 days [19.0-32.5], p < 0.01) was different between ampicillin- sulbactam resistant and ampicillin-sulbactam susceptible VAP groups. On univariate analysis, hospital length of stay >4 days and antibiotic use within 90 days were associated with ampicillin-sulbactam resistant VAP (p < 0.01). CONCLUSIONS: Ampicillin-sulbactam is not an effective empiric therapy for early-onset VAP in our rural trauma population. The utility of ampicillin-sulbactam should be reviewed at other institutions to assess for appropriate empiricism.