Is the Success of Cefazolin plus Ertapenem in Methicillin-Susceptible Staphylococcus aureus Bacteremia Based on Release of Interleukin 1-beta?

Cefazolin and ertapenem has been shown to be an effective salvage regimen for refractory methicillin-susceptible Staphylococcus aureus bacteremia. Our findings suggest cefazolin plus ertapenem in vitro stimulates interleukin-1β release from peripheral blood monocytes both with and without S. aureus presence. This IL-1β augmentation was primarily driven by ertapenem. These findings support further exploration of cefazolin plus ertapenem in MSSA bacteremia and may partially explain its marked potency in vivo despite modest synergy in vitro .

Factors associated with an interruption in treatment of people living with HIV in USAID-supported states in Nigeria: a retrospective study from 2000–2020

Background Patient interruption of antiretroviral therapy (ART) continues to limit HIV programs’ progress toward epidemic control. Multiple factors have been associated with client interruption in treatment (IIT)— including age, gender, CD4 count, and education level. In this paper, we explore the factors associated with IIT in people living with HIV (PLHIV) in United States Agency for International Development (USAID)-supported facilities under the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria. Methods We conducted cross-sectional analyses on data obtained from Nigeria’s National Data Repository (NDR), representing a summarized record of 573 630 ART clients that received care at 484 PEPFAR/USAID-supported facilities in 16 states from 2000–2020. IIT was defined as no clinical contact for 28 days or more after the last expected clinical contact. Univariate and multivariate logistic regression models were computed to explore the factors associated with IIT. The variables included in the analysis were sex, age group, zone, facility level, regimen line, multi-month dispensing (MMD), and viral load category. Results Of the 573 630 clients analysed in this study, 32% have been recorded as having interrupted treatment. Of the clients investigated, 66% were female (32% had interrupted treatment), 39% were aged 25–34 at their last ART pick-up date (with 32% of them interrupted treatment), 59% received care at secondary level facilities (37% interrupted treatment) and 38% were last receiving between three- to five-month MMD (with 10% of these interrupted treatment). Those less likely to interrupt ART were males (aOR = 0.91), clients on six-month MMD (aOR = 0.01), adults on 2nd line regimen (aOR = 0.09), and paediatrics on salvage regimen (aOR = 0.02). Clients most likely to interrupt ART were located in the South West Zone (aOR = 1.99), received treatment at a tertiary level (aOR = 12.34) or secondary level facilities (aOR = 4.01), and had no viral load (VL) on record (aOR =10.02). Age group was not significantly associated with IIT. Conclusions Sex, zone, facility level, regimen line, MMD, and VL were significantly associated with IIT. MMD of three months and longer (especially six months) had better retention on ART than those on shorter MMD. Not having a VL on record was associated with a considerable risk of IIT.

Clinical Experience With Venetoclax in Patients With Newly Diagnosed, Relapsed, or Refractory Acute Myeloid Leukemia.

Background: Diagnosis of acute myeloid leukemia (AML) is associated with poor outcome in elderly and unfit patients. Recently, approval of the BCL-2 inhibitor Venetoclax (VEN) in combination with hypomethylating agents (HMA) led to a significant improvement of response rates and survival. Further, application in the relapsed or refractory (r/r) AML setting or in context of allogeneic stem cell transplantation (alloHSCT) seems feasible.Methods and Patients: Fifty-six consecutive adult AML patients on VEN from January 2019 to June 2021 were analyzed retrospectively. Patients received VEN either as first-line treatment, as subsequent therapy (r/r AML excluding prior alloHSCT), or at relapse after alloHSCT. VEN was administered orally in 28-day cycles either combined with HMA or low-dose cytarabine (LDAC).Results: After a median follow-up of 4.7 (range, 0.8 – 24.3) months median overall survival (OS) from start of VEN treatment was 13.3 (2.2 - 20.5) months, 5.0 (0.8 - 24.3) months and 4.0 (1.5 - 22.1) months for first-line, subsequent line treatment and at relapse post-alloHSCT, respectively. Median OS was 11.5 (10 - 22.3) months from start of VEN when subsequent alloHSCT was carried out. Overall response rate (composite complete remission + partial remission) was 51.8% for the total cohort (61.1% for VEN first-line treatment, 52.2% for subsequent line and 42.8% at relapse post-alloHSCT). Subgroup analysis revealed a significantly reduced median OS in FLT3-ITD mutated AML with 3.4 (1.9 - 8.0) months versus 10.4 (0.8 - 24.3) months for non-mutated cases, (HR 3.59, 95% CI 0.94 - 13.72, p = 0.001). Patients harboring NPM1 or IDH1/2 mutations lacking parallel FLT3-ITD mutations showed a survival advantage over patients without those mutations (11.2 (5 - 24.3) months versus 5.0 (0.8 - 22.1) months, respectively, (HR 0.53, 95% CI 0.23 – 1.21, p = 0.131). The most common adverse events were hematological, with grade 3 and 4 neutropenia and thrombocytopenia reported in 44.6% and 14.5% of patients, respectively. Conclusion: Detailed analyses on efficacy for common clinical scenarios such as first-line treatment, subsequent therapy (r/r AML), and application prior to and post-alloHSCT are presented. The findings suggest VEN treatment combinations efficacious not only in first-line setting but also in r/r AML. Furthermore, VEN might play a role in a subgroup of patients with failure to conventional chemotherapy as a salvage regimen aiming for potential curative alloHSCT.

Pomalidomide-Dexamethasone in the Management of Heavily Pretreated Multiple Myeloma

Pomalidomide is a new generation IMID, with a very good compliance, thanks to oral administration, which can be used also in heavily pretreated patients, in a domestic setting. In this retrospective observational trial, It has been evaluated efficacy and tolerance of pomalidomide plus dexamethasone (PD) as salvage regimen in heavily pretreated patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. 57 patients (31 M/26 F), with rrMM, median age at diagnosis 69 years (r. 52-86), and median age at start of treatment 76 years (r.56-90) treated with several lines of treatments (median 7, r. 2-11), every refractory to all the drugs previously received (also Bortezomib, Thalidomide and Lenalidomide), received Pomalidomide-Dexamethasone (Pomalidomide 4 mg for 21 days, Dexamethasone 40 mg days 1,8,15,22, pegfilgrastim day +8) every 28 days, until progression. ISS was equally distributed, and cytogenetic at relapse was evaluable in 14 patients. All the patients had previously been treated with schedule containing bortezomib and IMIDs. 63% (36/57) had undergone at least to a single ASCT. All patients were relapsed and refractory to last therapies received before PD. Pomalidomide was well tolerated, with grade 3-4 transfusion-dependent anemia in 58% (33/57) of patients, 44% (23/57) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no hospitalization was required, no septic shocks were observed), 40% (23/57) grade 3-4 thrombocytopenia without hemorrhagic events and transfusion-dependence. No severe extra-hematologic toxicity was observed. According to IMWG, ORR1 (≥PR) was 47.3% (27/57: 5 CR, 11 VGPR, 7 PR, 4 MR), but, considering that we are evaluating a cohort of heavily pretreated patients, with poor prognosis, another parameter should be considered, ORR2 (≥SD), considering stable disease as a successful result in progressive MM. ORR2 was 77.1% (17 SD). These can be considered as impressive result in this subset of patients. Oral treatment gives a really good compliance, in frail and unfit patients, and response, when present, is always really fast (median time to response: 2 months (r.1-6)), median OS from diagnosis was 94 months (range 21-234), median OS from start of pomalidomide was 9 months (range 1-25). Nine patients have surprisingly achieved a notable response (3 VGPR, 4 PR, 2 MR) after failure of novel agents (i.e. Carfilzomib, Daratumumab and Pomalidomide). Pomalidomide-dexamethasone has shown significant efficacy and a very good compliance, thanks to oral administration, in a particularly severe setting of heavily pretreated patients, relapsed and refractory to all available therapeutic resources, also after failure of novel agents. Disclosures Martinelli: Stemline Therapeutics: Consultancy; Incyte: Consultancy; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Daichii Sankyo: Consultancy; Jazz Pharmaceuticals: Consultancy; Abbvie: Consultancy; Astellas: Consultancy, Speakers Bureau.

Outcomes of Large B-Cell Lymphoma Patients By Post CAR-T Salvage Regimen at a Single Institution

Introduction: Outcomes of patients with large B-cell lymphoma that relapse after frontline anthracycline based chemotherapy are typically poor, with a 3-year event-free survival of approximately 30% (Gisselbrecht JCO 2010). Chimeric antigen receptor T-cell (CAR-T) therapy represents a breakthrough therapy for these patients, with an overall response rate (ORR) of 83% and a complete response (CR) rate of 58% for axicabtagene ciloleucel (axi-cel) seen in the ZUMA-1 trial, with similar rates for tisagenlecleucel in the JULIET trial (Locke Lancet Oncol 2018; Schuster NEJM 2018). Unfortunately, the majority of patients treated with CAR-T therapy experience disease progression. There is limited data evaluating the best salvage regimen for these patients. Thus, we sought to assess outcomes in large B-cell lymphoma patients with progressive disease post CAR-T cell therapy with the goal of identifying those therapies with optimal outcomes. Methods: A retrospective study was performed on all patients with large B-cell lymphoma undergoing leukapheresis for CAR-T therapy (tisagenlecleucel or axi-cel) at the Ohio State University from December 2017 to January 2021. Patients who died prior to CAR-T infusion were excluded from analysis. Demographics and disease characteristics as well as best response to CAR-T and date of relapse or progression following therapy were collected. First salvage therapy at relapse or progression and response to therapy were also collected, with choice of therapy driven by the treating physician. Patients were divided by salvage regimen into five groups for analysis: checkpoint inhibitor based, lenalidomide based, Bruton Tyrosine Kinase inhibitor (BTKi), chemoimmunotherapy, and other (including small molecular inhibitor, radiation, allogeneic stem cell transplant, antibody drug conjugates, and bispecific antibodies). The primary endpoint was overall survival (OS), which was calculated using Kaplan Meier Curves. Rates of CR and ORR were also assessed. Results: A total of 144 patients underwent leukapheresis for CAR-T cell therapy during the time period; of these patients, 13 died prior to undergoing CAR-T cell infusion and were excluded from analysis. The primary cohort included 131 patients. Median age at the time of T-cell collection was 62 years old (range 23-85) and 61% were male. The majority (50%) had germinal center (GCB) subtype, with 42% non-GCB and subtype unavailable for 8%. A small number (3%) had primary mediastinal B-cell lymphoma. The majority had high-risk disease, with 45% having primary refractory disease, 14.5% double or triple hit, and 81% Ann Arbor stage III or IV at diagnosis. Median prior lines of therapy was 3 (range 0-10). Sixty-six patients received axi-cel and 65 patients received tisagenlecleucel. Forty percent of patients attained a CR, 18% partial response (PR), 3% stable disease (SD), 33% progressive disease (PD), and 6% of patients died prior to disease assessment. For those 76 patients that received a CR or PR to therapy, 43% relapsed post CAR-T and 57% remained in CR at last follow-up. Of those patients who relapsed or progressed post CAR-T, 69% (54/78) patients received additional therapy. The most common therapies utilized were lenalidomide based (35%), BTKi (22%), chemoimmunotherapy (13%), and checkpoint inhibitor based (15%). Other therapies represented 15% of cases and included small molecular inhibitor, radiation, allogeneic stem cell transplant, antibody drug conjugates, and bispecific antibodies (Table 1). Overall response rates and median OS for the groups were 50% and 2.25 years for BTKi, 13% and 0.96 years for checkpoint inhibitor based, 71% and not reached (NR) for chemoimmunotherapy, 47% and 2.4 years for lenalidomide based, and 75% and NR for other (Table 1; Figure 1). Median OS for those patients who did not receive any salvage therapy was 0.19 years. Conclusion: Consistent with prior studies, median OS following relapse post CAR-T therapy was poor, with median OS 0.19 years for patients who did not receive therapy and ranging from 0.96 years to NR for those that did. Rates of CR were highest in patients treated with BTKis. In our series, ORR rate to checkpoint inhibitors was relatively low in contrast to other recently published retrospective reports. Future prospective studies are needed to further assess the optimal therapy for patients who relapse post CAR-T therapy. Figure 1 Figure 1. Disclosures Bond: Kite/Gilead: Honoraria. Brammer: Seattle Genetics: Speakers Bureau; Kymera Therapeutics: Consultancy; Celgene: Research Funding. de Lima: Miltenyi Biotec: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Jaglowski: Novartis: Consultancy, Research Funding; Takeda: Consultancy; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy. Kittai: Bristol-Meyers Squibb: Consultancy; Janssen: Consultancy; Abbvie: Consultancy.

Carfilzomib-Lenalidomide-Dexamethasone in the Management of Lenalidomide-Refractory Multiple Myeloma

Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, where lenalidomide-based regimens have no proven efficacy. 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43-82), median age at start of treatment 67 years (r. 48-84) previously treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2-18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. According to IMWG criteria, after a median follow-up of 9 months (r. 2-18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1-4), median OS from diagnosis was 62 months (r. 9-170), median OS from start of Carfilzomib was 11 months (r. 2-18). Carfilzomib was well tolerated, with grade 2 anemia in 39%(16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion-dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2-3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Carfilzomib-Lenalidomide-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT. Disclosures Martinelli: Jazz Pharmaceuticals: Consultancy; Stemline Therapeutics: Consultancy; Astellas: Consultancy, Speakers Bureau; Celgene /BMS: Consultancy, Speakers Bureau; Abbvie: Consultancy; Daichii Sankyo: Consultancy; Roche: Consultancy; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy.

Cepp in Previously Untreated Patients with Mature T Cell Lymphomas

Introduction There is currently no standard of care for the upfront management of patients with mature T cell non-Hodgkin lymphomas (T-NHL). The role of anthracyclines in the treatment of T-NHL remains unclear and is also associated with significant toxicity. CEPP (cyclophosphamide, etoposide, procarbazine, and prednisone), a non-anthracycline regimen, is an effective salvage regimen for relapsed/refractory NHL and has shown a favourable toxicity profile. Since 2005, CEPP has been used in Singapore in the upfront treatment of T-NHL patients either with a contraindication to anthracyclines or at physicians' discretion. Our study aimed to assess the efficacy of CEPP in the upfront treatment of T-NHL. Methods A retrospective study of all patients with newly diagnosed T-NHL treated with CEPP with curative intent from 2005-2021 was undertaken across 2 national cancer centers in Singapore. Outcomes of this population was also compared with a 1:1 control group treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) in the same time period, and matched for age, T-NHL subtype, clinical stage and international prognostic index (IPI). Patient demographics, disease characteristics and clinical outcomes (progression free survival, PFS and overall survival, OS) were evaluated. None of the patients had upfront autologous transplantation. Results We identified 34 patients treated with CEPP who met the inclusion criteria. Clinical characteristics were as follows: Median age was 71 (range 39-85), 24 (71%) were male, 26 (76%) had advanced disease (Stage III-IV) and 21 (62%) had a high intermediate or high risk IPI ( IPI 3, 14 (41%) and IPI 4-5, 21 (21%)). The most common T-NHL subtypes were peripheral T-NHL (PTCL-NOS) not otherwise specified, 11 (32%) as well as angioimmunoblastic T cell lymphoma (AITL), 16 (47%). At a median follow up of 20 months (range 2-197months), the median PFS and OS were 17.6mths and 37.2mths respectively for the CEPP group. 15/34 (44%) CEPP patients have died (8 with lymphoma, 2 from treatment toxicity and 5 from unrelated causes). In the matched control comparison, the 5yr PFS and OS were both similar for patients treated with CEPP compared to patients in the CHOP control group, PFS 30% vs 32%, p= 0.43 and OS 47% vs 52%, p = 0.32, respectively (Figure 1) Conclusion Our findings show that CEPP is a well-tolerated regimen which can cure a proportion of patients with T-NHL even without autologous transplantation consolidation. Outcome of these patients do not seem to be significantly different compared to a similar population treated with standard CHOP. This study supports CEPP as a tolerable treatment option for selected patients who cannot tolerate anthracyclines and as an alternative to CHOP regimen for older patients who are not planned for ASCT. Figure 1 Figure 1. Disclosures Jeyasekharan: Turbine Ltd: Consultancy; Janssen: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Perkin Elmer: Other: travel funding ; MSD: Consultancy.

Efficacy of Brentuximab Vedotin and Bendamustine Combination in Relapsed/Refractory Hodgkin Lymphoma: Experience from a Tertiary Care Hospital

Background: Hodgkin lymphoma (HL) is an uncommon B-cell malignant neoplasm, with high curable rate for patients with localized disease or advanced.However, up to 30% of patients with HL are either refractory or relapsed after primary treatment. Salvage chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the standard of care for eligible patients in relapsed setting. Brentuximab vedotin and Bendamustine (BvB) combination have been recommended by National Cancer Center Network (NCCN) as one of the salvage regimens for patients with relapsed or refractory HL prior to transplant or who relapsed after hematopoietic stem cell transplant (HSCT). Evidence from retrospective and prospective studies in regards of BvB have shown remarkable progression free survival (PFS) with 2-years PFS ranging from 62.2% up to 93.7%, and overall survival (OS) ranging from 88.1% up to 95%, and complete remission (CR) rates ranging from 43% to 90%. The objective of this study is to assess patient response to BvB in the treatment of relapsed/refractory HL especially for patients beyond first salvage therapy unlike many other studies. Methods: A retrospective study was conducted in patients with relapsed/refractory Hodgkin lymphoma treated with BvB chemotherapy at single tertiary hospital from January 2016 until July of 2021. Data collection was done including patient demographics data, comorbidities, disease stage, lines of chemotherapy regimens taken, and PET scan response with Deauville score. Brentuximab was given as 1.8mg/kg on day 1, and bendamustine was given as 90mg/m 2 on day 1 and day 2. Cycle was repeated every three weeks. Result: A total of 16 patients with relapsed/refractory HL whom treated with BvB chemotherapy were analyzed. Median age is 29 years (22-70 years), 5 patients were female, and median number of lines of therapy prior to starting BvB is 2 (0-5). The median number of cycles of BvB was 5.5 (3-8 cycles). 2 out of 16 patients had a prior autologous HSCT (12.5%). 15 patients were assessed for response and one patient died before disease assessment. The overall response rate was 80% with 50% of patients achieving complete metabolic response on PET scan. After median follow up of 14.5 months, the median PFS was 13.4 months (Figure 1), and the median OS was not reached (Figure 2). 4 patients underwent HSCT (3 autologous, and 1 allogeneic). Conclusion: BvB combination is an effective outpatient-based salvage regimen for heavily pretreated patients with multiple lines chemotherapy in relapsed/refractory HL, as majority of patients in our study were beyond first salvage. As there is no standard salvage regimen in this setting, randomized trials are needed to compare efficacy and safety BvB with other established regimens. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Trial in Progress: Pomalidomide Plus Rituximab, Ifosfamide, Carboplatin, and Etoposide for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (PRIDE)

Backgrounds: Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients have limited treatment options and are associated with poor prognosis. Patients generally receive salvage therapy as rituximab, ifosfamide, carboplatin and etoposide (R-ICE), followed by consolidation with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). However, only approximately 50% of patients can proceed to ASCT and only half of these achieve durable remission post-transplant. New therapeutic strategies are needed to improve response rates and to prevent recurrence following ASCT. The immunomodulatory agent lenalidomide has demonstrated direct anti-tumor effects in lymphoma. Some studies found that the addition of lenalidomide to the widely used R-ICE salvage regimen is feasible and results in promising response rates in R/R DLBCL patients. Pomalidomide is a third-generation immunomodulatory drug that has shown excellent therapeutic activity against relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL) with an acceptable toxicity profile. We aim to determine the safety, tolerability and efficacy of pomalidomide in combination with R-ICE in R/R DLBCL patients. Study Design and Methods: PRIDE (ChiCTR2100049327) is a phase I/II trial of pomalidomide plus R-ICE (PR-ICE) as a salvage regimen for first-relapse or primary refractory DLBCL. In phase I of the study, patients receive escalating doses of pomalidomide (2mg, 3mg or 4mg daily on d1-10) along with R-ICE therapy every 21 days by standard 3+3 design until the MTD has been determined. In stage II, all subjects receive three cycles of R-ICE plus pomalidomide, dosing as RP2D. Patients with CR or PR but not eligible for ASCT receive continuous pomalidomide as maintenance therapy for 12 months. Key eligibility criteria are as follows: histologically confirmed DLBCL; relapsed or refractory after one prior treatment for DLBCL; age 18-75 years; absolute neutrophil count >1500 /mm 3; platelet count > 75,000/mm 3; calculated creatinine clearance of over 60 mL/min by Cockroft-Gault formula; total bilirubin < 1.5×ULN; AST and ALT < 3×ULN. The primary endpoint of phase II is the CR rate after PR-ICE induction treatment. The CR rate for R-ICE in R/R DLBCL was estimated to be approximately 35%. We hypothesize that the addition of POM to R-ICE could increase the CR rate by approximately 20%. For phase II, it requires a sample size of 44 evaluable patients (one-sided alpha = 0.05, power 80%, dropout rate of 15%). Eligible patients who receive at least one dose of PRICE will be included in the efficacy and safety analyses. The 95% CI of CR was calculated using Clopper-Pearson method. The Kaplan-Meier method was used to estimate PFS and OS. All these analyses were conducted using SAS 9.4 software. Enrollment for phase I will begin in Q4 of 2021. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Pomalidomide is indicated for the treatment of adult patients: in combination with dexamethasone, for patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy in China. The abstract presents the rationale for the use of generic pomalidomide in combination with R-ICE, a combination that is not approved in China at present.

187. Vancomycin Plus Ceftaroline Salvage Therapy for Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia

Background The preferred antibiotic salvage regimen for persistent methicillin-resistant Staphylococcus aureus bacteremia (pMRSAB) is unclear. Vancomycin plus ceftaroline (V/C) has demonstrated potent in vitro synergistic activity against MRSA; however, clinical data is limited. Thus, we sought to evaluate V/C salvage therapy for pMRSAB. Methods This was a single-center, retrospective cohort study of patients with MRSAB who received V/C salvage therapy between 1/1/2016-3/10/2021. Adult patients were included if blood cultures (BC) were positive for MRSA for ≥ 72 hours, received anti-MRSA monotherapy initially, and subsequently received V/C ≥ 24 hours. Patients were excluded if they received other anti-MRSA antibiotics within 72 hours of V/C initiation. The primary outcome was time to BC clearance following V/C initiation. Secondary outcomes included 90-day all-cause mortality, microbiological cure, 90-day MRSAB recurrence, and length of stay (LOS). Microbiological cure was defined as BC clearance. Results Of 178 patients identified, 20 were evaluated after inclusion and exclusion criteria were applied. Mean (SD) age and Pitt Bacteremia score were 38.5 (14.5) years and 4.2 (3.1), respectively. Most patients were male (70%), intravenous drug users (65%), and admitted to the intensive care unit (65%). The most common source was intravenous drug use (55%) and the majority had infective endocarditis (70%). All patients received infectious disease consultation and median (IQR) vancomycin AUC:MIC was 527 (454, 611). Source control, if possible, was obtained in most patients (55%). Median (IQR) time to bloodstream clearance from first positive BC and from when ceftaroline was initiated was 9.7 (8.4, 10.2) and 2.4 (1.5, 3.1) days, respectively. 90-day all-cause mortality, microbiological cure, and 90-day MRSAB recurrence occurred in 35%, 95%, and 5% of patients, respectively. Median (IQR) LOS was 25 (14.5, 32.0) days. Conclusion To our knowledge, this is the largest cohort to evaluate V/C for pMRSAB. Patients were medically complex; however, median time to MRSAB clearance following ceftaroline initiation was < 2.5 days and microbiological cure was obtained in nearly all patients. V/C may represent a potential salvage regimen for pMRSAB. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) Jeffrey Steele, Pharm.D., Paratek Pharmaceuticals (Advisor or Review Panel member)