Hackensack University Medical Center Research Articles

Richard Hader Visionary Leader Award 2023 Visionary Leader Linda Casey.

The following manuscript is the winning 2023 Richard Hader Visionary Leader Award entry submitted to Nursing Management in recognition of Linda Casey, MHA, BSN, RN, OCN, NE-BC, director of nursing and operations and former director of nursing patient care for infusion at the John Theurer Cancer Center (JTCC) at Hackensack University Medical Center (HUMC) in Hackensack, N.J.

Comparison of Fludarabine/Cyclophosphamide Vs Bendamustine As Lymphodepleting Regimen for CAR-T: A Safety and Efficacy Analysis in Patients with Relapsed/ Refractory Multiple Myeloma

Background Two commercially available anti-BCMA chimeric antigen receptor T-cell therapies (CAR-T) are approved by FDA for use in patients with relapsed multiple myeloma (RRMM). Lymphodepletion (LD) with fludarabine in combination with cyclophosphamide (Flu/Cy) is used as a standard regimen sequentially prior to CAR-T. Due to a national shortage with regards to availability of fludarabine, bendamustine (B) has emerged as a possible alternative regimen for LD. We evaluated the impact of bendamustine as an alternative lymphodepleting regimen to Flu/Cy on safety and efficacy profile of CAR-T therapy in patients with relapsed multiple myeloma. Patients and methods We conducted a single center, retrospective, IRB-approved study for patients with RRMM who received LD with B and FC at Hackensack University Medical Center (HUMC). Efficacy outcomes included overall response rates (ORR), Progression free survival (PFS) and Overall survival (OS). Response to CAR-T was assessed by the treating physician per International Myeloma Working Group (IMWG) criteria. Safety outcomes included the incidence and severity of adverse events (AEs). AEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0). Cytokine release syndrome (CRS) and immune effector associated neurotoxicity syndrome (ICANS) were graded as per the American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Results We identified 53 patients with RRMM who received anti-BCMA CAR-T therapy between 6/2021 and 6/2023, who had a follow-up of at least 30 days following infusion. Due to shortage of fludarabine, the majority of pts (67.9%) received LD with B. Baseline characteristics are described in table 1. The median age of the entire cohort was 69.6 years, not significantly different between the B vs FC group. There were no statistically significant differences between the two groups with respect to the baseline characteristics except more pts were male in the B group (66.7% vs 32.1%, p=0.03) and the type of CAR-T product received. No significant differences were found with regards to the safety profile; however, the ORR were found to be higher in the FC group compared to the B group (88.2% vs 69.4%) although not statistically significant (p=0.1). Median PFS (mPFS) was shorted in the B group compared with the FC group (7.7 months vs 13.1 months) respectively (p=0.0047). Median OS (mOS) was not reached in the FC group, whereas it was 12.4 months in the B group, p=0.5. Conclusions LD with B was not found to have any significant impact on the CRS or ICANS, however a lower ORR (although not statistically significant) was found. mPFS was shorter for the B group compared to the FC group which was a statistically significant finding. Although the follow-up is short, our experience suggests that the use of B as LD may have a negative impact on outcomes of pts receiving CAR-T therapy for RRMM.

Fluoroquinolone-Resistant Enterobacteriaceae Prevalence for Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation (aHSCT) in the Treatment of Multiple Myeloma (MM)

Background: Fluoroquinolones (FQL) are commonly used in antimicrobial prophylaxis in immunocompromised cancer patients (pts) during prolonged neutropenia. A possibly high and increasing proportion of pts harboring FQL-resistant Enterobacteriaceae (FRE) challenges the assumption that prophylaxis with FQLs is still of benefit in preventing sepsis. Previous studies reported that colonization of FRE in allogeneic transplant patients may be an infection risk factor (cf. Satlin et al. Clin Infect Dis 202;73:1257-65). This prospective study aims to determine the prevalence of FRE in defined pt populations in two metropolitan areas treated with dose-intense melphalan with autologous peripheral blood stem cell (PBSC) transplantation, and to determine the possible clinical effects of FRE in the host microbiome on transplant outcomes. Methods: Pts eligible for this prospective, ongoing study have a diagnosis of MM and are undergoing autologous PBSC transplantation after conditioning with dose-intense melphalan 200 mg/m 2 at Hackensack University Medical Center (HUMC) and MedStar Georgetown University Hospital (MGUH). Peri-rectal swabs are scheduled before chemotherapy mobilization of PBSC given with FQL prophylaxis, before transplant admission with initiation of antimicrobial prophylaxis, at time of hospital discharge, and 3 months after aHSCT. Prophylaxis is discontinued with fever or hospital discharge. Blood cultures are obtained at time of fever (>38 °C) with adjustments in antibiotics per standard of care. A central catheter is placed for venous access in all patients throughout their transplant course. Pts are discharged after achieving neutrophil (ANC) engraftment and control of conditioning regimen toxicities. Bacterial cultures from perirectal swabs (fresh or frozen for shipping) were purified on CHROMagar™ Orientation Plates and grown in the presence of ≥5 ug/ml ciprofloxacin to select for quinolone-resistant organisms. Results: To date, 39 pts are evaluable (Table 1). PBSC were mobilized using filgrastim/plerixafor (G-Moz) or cyclophosphamide/etoposide/dexamethasone (CDE) followed by filgrastim with levofloxacin prophylaxis. The quantity of CD34+ cells infused is in Table 1. All pts achieved ANC engraftment at a median of 10.8 days (range 9-14) and were hospitalized for a median of 13 days (range 11-24). 37/39 pts collected swabs before transplant admission (and swabs were obtained at discharge for the other 2 pts). 13/37 (35%) admission swabs demonstrated FRE colonization (Table 2). 6/33 swabs at time of discharge were positive for FRE including for 4 pts negative for FRE on transplant admission with a total of 17/39 pts (44%) showing FRE colonization at some point during the transplant admission. Samples collected at 3 months after transplantation for 24 pts reaching that timepoint showed FRE colonization for 4 pts including 2 pts not previously testing positive at time of transplantation. 27/107 samples tested positive for FRE and 21/39 pts (54%) had at least one FRE positive culture. Seven pts (20%) developed neutropenic fever but no pt experienced a blood-stream infection (BSI). One pt developed Clostridium difficile colitis during the period of neutropenia. One pt tested positive for MRSA colonization at admission but did not develop fever or BSI. One pt was readmitted after initial hospital discharge for evaluation of fever without a source of infection determined. Ten pts (5 FRE colonized during transplant course) were given prednisone for persistent diarrhea attributed to engraftment syndrome (cf: Spitzer TR. Bone Marrow Transplant 2001;27:893-8) commencing at a median of 10 (range, 8-13) days after aHSCT and not associated with CDE mobilization or detection of FRE. Nineteen other patients, 8 of whom tested positive for FRE, did not receive corticosteroids for management of regimen-related toxicities (an additional 7 pts received preplanned corticosteroids starting at day +8). No center effect is yet evident. Conclusions: FRE are detected in a high proportion of pts undergoing aHSCT in the treatment of MM. However, FQL prophylaxis is not associated with FRE BSI in this ongoing study. FRE colonization is not predictive of delayed engraftment or prolonged hospitalization, and does not appear predictive of non-infectious diarrhea.

Single-Center Experience of Carfilzomib-Based Combinations for Patients with Lymphoplasmacytic Lymphoma

Single-Center Experience of Carfilzomib-based Combinations for patients with Lymphoplasmacytic Lymphomas Background Use of bortezomib in Waldenstrom macroglobulinemia (WM) produces a response rate of 60-70% in treatment naïve or relapsed WM(Dimopoulos et al., 2005)(Chen et al., 2006). However, it is associated with an increased risk of peripheral neuropathy (PN). This is important considering that WM can be associated frequently with PN. Carfilzomib(K) is a second-generation proteasome inhibitor that is associated with a lower PN risk and offers a PN-sparing approach for treatment for patients(pts) with WM. In the CARD trial, K-based combinations produced a high ORR with a tolerable safety profile(Treon et al., 2014). We report our single-center experience with the use of K-based combinations in pts with treatment naïve or relapsed lymphoplasmacytic lymphoma (LPL). Patients and Methods We conducted a single-center retrospective study on an IRB-approved protocol for all pts who were treated with K-based combinations at Hackensack University Medical Center between June 2015 and July 2022. Demographic characteristics, molecular studies, treatment and response information were recorded and included in the study. Efficacy outcomes included overall response rates (ORR), progression free survival (PFS), overall survival (OS). Survival analysis was performed using the Kaplan-Meier method including PFS and Overall survival (OS). PFS was defined as time from initiation of treatment to progression of disease or death whichever occurred first. OS was defined as time from initiation of treatment to death. The consensus criteria from the 6 th International Workshop on WM were utilized for response assessment. Results We identified 36 patients with a diagnosis of WM and 1 patient with IgA-kappa LPL who were treated with K-based combinations between June 2015 and July 2022. 4 patients (10.8%) had a concomitant diagnosis of systemic light chain amyloidosis (AL). 67.6% pts were male, the median age at treatment initiation was 67.5 yrs. Majority of the pts were treatment naïve (86.4%, N=32). Data for MYD88 mutation was available in 30 pts, 93.3% (n=28) were found to have MYD88 mutation on next generation sequencing (NGS) performed on bone marrow aspirate samples. As per the RPISSWM risk stratification, 30% (9) pts were found to have poor risk, 33.3% (10) had intermediate risk and 36.7% (11) had good risk. Median bone marrow involvement by WM was 30%. The majority of the pts (91.9%, n=34) received KCD-R (Carfilzomib, cyclophosphamide, dexamethasone and rituximab) as their treatment regimen, while the remaining patients received KD-R(carfilzomib, dexamethasone and rituximab). Pts received a median of 6 cycles of treatment. ORR was found to be 97.3% (n=36) with 48.6%(n=18) pts achieving a very good partial response or better (>=VGPR). Median PFS was found to be 51.08 months and median OS was not reached (NR). Two patients needed treatment discontinuation following 1 cycle or less, due to toxicity (dyspnea, one of which was non-cardiogenic) associated with carfilzomib and were changed to an alternative regimen (Bortezomib, cyclophosphamide, dexamethasone and rituximab). Further data for toxicities are being gathered and will be presented at the meeting. Baseline characteristics and outcomes data are summarized in Table 1. Conclusions K-based combinations produce a high ORR with durable responses in patients with symptomatic LPL. Treatment discontinuation rate due to toxicity was low with only two patients needing change of therapy in our cohort. Our data supports the use of K-based combinations in pts with treatment naïve or relapsed LPL.

Sequential Administration of Selinexor and CAR-T Therapy in Relapsed/ Refractory Multiple Myeloma

Introduction: Selinexor is a novel, oral selective inhibitor of nuclear export (SINE) that binds to exportin 1 and exhibits anti-tumor activity by impairing nuclear export of proteins including oncogenes and tumor suppressor proteins and is approved for use in patients with relapsed refractory multiple myeloma(RRMM). Anti-BCMA directed CAR-T therapy for patients with relapsed/refractory multiple myeloma (RRMM) is a promising new class of therapy, which has shown a high level of efficacy. Sequential administration of selinexor followed by CD19 CAR-T has shown enhanced efficacy in human phase II trials and animal models of human non-hodgkin lymphoma(Stadel et al., 2022). In this retrospective single institutional study, we report outcomes of patients with RRMM who were treated with Selinexor based regimen prior to apheresis for CAR-T therapy. Methods: We conducted a retrospective study on an IRB-approved protocol for all patients who were treated with Selinexor based regimen immediately prior to apheresis as a prior line of therapy at Hackensack University Medical Center between June 2015 and July 2022. Demographic characteristics, molecular studies, treatment and response information were recorded and included in the study. Response to CAR-T was assessed by the treating physician per International Myeloma Working Group (IMWG) criteria. Survival analysis was performed using the Kaplan-Meier method including PFS and Overall survival (OS). Results: Between September 9, 2021, and April 3, 2023, 7 patients received CAR-T who were treated with Selinexor immediately prior to apheresis. The median age was 65.7 years (range: 55.1-77.1 years). Patients had a median of 6 (range: 4-10) lines of therapy (LOT) prior to CAR-T. 5 out of the 7 patients had double hit myeloma (all 5 with 17p and one other high risk). Four patients were treated with selinexor, carfilzomib and dexamethasone; two patients were treated with selinexor, daratumumab and dexamethasone and one patient was treated with selinexor, pomalidomide and dexamethasone. Four patients received Idecabtagene vicleucel (ide-cel) and three patients received ciltacabtagene autoleucel (cilta-cel). ORR was 100% with all 7 pts achieving very good partial response or better (>=VGPR). 2 patients had bone marrow biopsies that confirmed MRD -ve sCR in both patients. None of the patients have progressed so far, although median follow-up is short at 5.6 months. All patients had hematologic toxicities, 4/7 with grade III anemia (57.1%), 3/7 (42.8%) with grade or higher thrombocytopenia and 4/7 (57.1%) had grade 3 neutropenia. 2 of 7 patients had prolonged cytopenia for >6 months because of pre-existing underlying diagnoses of CCUS and MDS. 5 out of 7 patients had grade 1 Cytokine release syndrome (CRS). The other two patients did not experience CRS. Time of CRS onset was variable 2-10 days. No ICANS or infectious complications were observed. Conclusions: These results suggest that sequential use of Selinexor and CART in high risk RRMM may be an effective treatment strategy to provide deep and durable responses. The findings of our study are promising although it is limited by a small sample size and short follow-up. Further investigation in a larger study and longer follow up would be important to confirm our findings.

A Real-World Comparison of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel CAR-T Therapy: A Single Center Experience for Relapsed/ Refractory Multiple Myeloma

Background Chimeric antigen receptor modified T-cell therapy is a promising new treatment for patients with heavily pre-treated multiple myeloma (MM). BCMA (B-cell maturation antigen) directed therapies including idecabtagene vicleucel (Ide-Cel) and ciltacabtagene autoleucel (Cilta-Cel) are currently approved for use in patients with four prior lines of therapy. Both therapies have shown efficacy producing a high overall response rates and durable responses. Both are second-generation designs with identical endodomain (CD3ζ - 4-1BB) to target BCMA on the target cells for patients with relapsed and refractory MM who have been triple-class exposed. The two distinct differences are ectodomain structure and recommended dose. In this single center retrospective study, we report our experience with the use of both CAR-T therapies in patients with heavily pre-treated MM. Methods Following institutional review board approval, we included all patients with MM who were treated with commercially approved BCMA directed CAR-T therapy. Demographic characteristics, molecular studies, treatment and response information were recorded and included in the study. Safety outcomes included the incidence and severity of adverse events (AEs). AEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE 5.0). Cytokine release syndrome (CRS) and immune effector associated neurotoxicity syndrome (ICANS) were graded as per the American Society for Transplantation and Cellular Therapy criteria. Efficacy outcomes included overall response rates (ORR), progression free survival (PFS), overall survival (OS), duration of response (DOR). Survival analysis was performed using the Kaplan-Meier method including PFS and Overall survival (OS). PFS was defined as time from initiation of treatment to progression of disease or death whichever occurred first. OS was defined as time from initiation of treatment to death. The IMW response criteria was utilized for response assessment. Results We identified 56 patients who were treated consecutively at Hackensack University Medical Center between 6/28/2021 and 7/3/2023. 53 patients had data available for evaluable responses and were included in our analysis. 35(66%) patients received Ide-cel, whereas 18(34%) patients received Cilta-Cel. For the entire cohort, 30(56.6%) were male, median age was 69.6 years median time from diagnosis to treatment was 8.1 years. Patients had received a median of 5 prior lines of therapy. 50(94.3%) patients were triple class refractory, all except one patient (98.1%) had a prior autologous stem cell transplant (ASCT). 27(60%) patients had high risk FISH defined as those with t(4;14), t(14;16), 17p(-) or 1q(+), 24(60%) patients were ISS-2 or 3 at diagnosis. Treatment was overall well tolerated, with only one therapy related mortality, 42(79.3%) patients experienced CRS, with only 1(1.9%) having grade 3 or higher CRS. 6(11.3%) patients experienced ICANS, with 2(3.8%) having grade 3 or higher ICANS. Baseline characteristics are summarized in table 1. Overall response rate for the entire cohort was 75.4%, with a median PFS of 11.9 months, median DOR of 13.2 months and mOS was not reached (NR). The median ORR for cilta-cel vs ide-cel was 94.4 % and 65.7% (p=0.01) respectively. The median PFS for cilta- cel vs ide-cel was NR vs 10.9 months (p=0.09) respectively (Figure 1), follow-up being very short for cilta- cel. Baseline characteristics, safety and efficacy data for the cohort and comparison between the two therapies are summarized in table 1. Conclusions In our single center experience, cilta-cel has shown superiority in terms of efficacy compared to ide-cel. Having said that, the authors do strongly recognize that longer manufacturing time for cilta-cel introduces a bias in favor of using ide-cel for patients with more aggressive/rapidly progressing disease, which may therefore result in inferior outcomes. The safety profile for both therapies is very similar and both offer promising results to patients with MM.

Management of Simple Ovarian Cysts

Dr. Chafitz is a Resident, Department of Obstetrics and Gynecology, Hackensack University Medical Center, Hackensack, NJ 07601, E-mail: [email protected]; Dr. Chemerinski is a Reproductive Endocrinology and Infertility Fellow, Rutgers-New Jersey Medical School, Newark, New Jersey; and Dr. McGovern is Associate Professor, Rutgers-New Jersey Medical School, Newark, New Jersey, and University Reproductive Associates, Hasbrouck Heights, New Jersey. All authors, faculty, and staff have no relevant financial relationships with any ineligible organizations regarding this educational activity. CME Accreditation Lippincott Continuing Medical Education Institute, Inc., is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Lippincott Continuing Medical Education Institute, Inc., designates this enduring material for a maximum of 2.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed answer form, answering at least seven of the 10 quiz questions correctly. Please visit http://cme.lww.com. This CME activity expires on June 29, 2025. NCPD Accreditation Lippincott Professional Development is accredited as a provider of nursing continuing professional development (NCPD) by the American Nurses Credentialing Center's Commission on Accreditation. Lippincott Professional Development will award 2.0 contact hours for this NCPD activity. This activity is also provider approved by the California Board of Registered Nursing, Provider Number CEP 11749 for 2.0 contact hours. Lippincott Professional Development is also an approved provider of continuing nursing education by the District of Columbia, Georgia, West Virginia, New Mexico, South Carolina, and Florida, CE Broker #50-1223. Your certificate is valid in all states. Instructions for earning ANCC contact hours are included on page 11 of the newsletter. This NCPD activity expires on June 5, 2026.

Isolated Left Ventricular Apical Hypoplasia: A Very Rare Congenital Anomaly Characterized by Multimodality Imaging and Invasive Testing.

HomeCirculation: Cardiovascular ImagingAhead of PrintIsolated Left Ventricular Apical Hypoplasia: A Very Rare Congenital Anomaly Characterized by Multimodality Imaging and Invasive Testing No AccessResearch ArticleRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsNo AccessResearch ArticleRequest AccessIsolated Left Ventricular Apical Hypoplasia: A Very Rare Congenital Anomaly Characterized by Multimodality Imaging and Invasive Testing Samuel D. Maidman, MD, William D. Salerno, MD, Dan G. Halpern, MD, Robert Donnino, MD and Muhamed Saric, MD, PhD Samuel D. MaidmanSamuel D. Maidman https://orcid.org/0000-0002-1376-5526 Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, NYU Langone Health. (S.D.M., D.G.H., R.D., M.S.) Search for more papers by this author , William D. SalernoWilliam D. Salerno Division of Cardiology, Hackensack University Medical Center, Hackensack Meridian School of Medicine, NJ (W.D.S.). Search for more papers by this author , Dan G. HalpernDan G. Halpern https://orcid.org/0000-0002-1656-798X Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, NYU Langone Health. (S.D.M., D.G.H., R.D., M.S.) Search for more papers by this author , Robert DonninoRobert Donnino Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, NYU Langone Health. (S.D.M., D.G.H., R.D., M.S.) Department of Radiology, NYU Grossman School of Medicine, NYU Langone Health. (R.D.) Division of Cardiology, Veteran Affairs NY Harbor Medical Center, Manhattan Campus (R.D.). Search for more papers by this author and Muhamed SaricMuhamed Saric Correspondence to: Muhamed Saric, MD, PhD, Adult Echocardiography Laboratory, 550 First Ave, New York, NY 10016. Email E-mail Address: [email protected] https://orcid.org/0000-0001-7682-3749 Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, NYU Langone Health. (S.D.M., D.G.H., R.D., M.S.) Search for more papers by this author Originally published30 Nov 2022https://doi.org/10.1161/CIRCIMAGING.122.014789Circulation: Cardiovascular Imaging. 2022;0:e014789FootnotesSupplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCIMAGING.122.014789.For Sources of Funding and Disclosures, see page XXX.Correspondence to: Muhamed Saric, MD, PhD, Adult Echocardiography Laboratory, 550 First Ave, New York, NY 10016. Email muhamed.[email protected]org Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.122.014789PMID: 36448445 Originally publishedNovember 30, 2022 Keywordscongenitalisolated left ventricular apical hypoplasiamultimodality imagingPDF download Advertisement SubjectsCongenital Heart DiseaseImaging

Effect of Daratumumab on Stem Cell Mobilization and Engraftment Kinetics Post Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

Background: High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care therapy for patients with newly diagnosed multiple myeloma. Daratumumab, an anti-CD38 monoclonal antibody, is now frequently being incorporated as a part of induction therapy in clinical practice, on the basis of data from several clinical trials.1-3 Few studies have evaluated the impact of daratumumab on stem cell mobilization and engraftment with conflicting results. Delayed neutrophil engraftment was noted in patients who received daratumumab as a part of induction therapy in one study.4 However, no delay was reported in another retrospective study5 and at least one clinical trial.6 Lower numbers of stem cells collected were reported uniformly in all three studies with daratumumab use. We evaluated the impact of daratumumab on stem cell yield with mobilization therapy as well as engraftment kinetics. Methods: We retrospectively evaluated 353 patients with newly diagnosed multiple myeloma treated at Hackensack University Medical Center between 2019-2021, on an IRB approved protocol. As per institutional guidelines, a combination of granulocyte colony stimulating factor (GCSF) with plerixafor was used as the mobilizing regimen for patients >70 yrs; cyclophosphamide, etoposide and dexamethasone (CdE) with GCSF was used for patients <70. Plerixafor could be added after chemotherapy mobilization for patients failing to achieve the desired collection goals. All patients received melphalan at a dose of 200mg/m2 administered intravenously on day -1. Time to engraftment (TTE) was calculated from the day of stem cell infusion to neutrophil and platelet engraftment, each defined as an absolute neutrophil count (ANC) of over 500/uL for three sequential tests and a platelet level over 20,000/uL without transfusion support, respectively. Goal for stem cell collection was defined as >8 x 106 CD34+ cells for patients >65 years, >12 x 106 CD34+ cells for patients <65. Statistical analyses were performed using STATA v16.0 (Stata Corp, TX, USA). The differences in median times to engraftment were analyzed using the Wilcoxon signed-rank test. Neutrophil and platelet recovery over time were calculated and plotted using Kaplan-Meier survival analyses and log-rank test for equality of survival function. Differences were considered significant at p-values <0.05. Results: 47 patients received daratumumab as a part of their induction therapy (Group A) compared with 306 patients who did not (Group B). Both groups were well balanced with regards to number of cycles of remission-induction therapy, age, sex, and mobilization regimens (Table 1). A higher number of CD34+ cells were collected for Group B, compared with Group A (12 x 10^6 vs 9.5 x 10^6, p<0.001); a lower number of collection days were required to reach collection goal for Group B compared with Group A (2 days vs 3 days, p=0.01); more CD34+ cells were collected per day for Group B compared with Group A (4.9 x10^6 vs 3.0 x 10^6, p=0.01). 73.5% patients met their collection goal for Group A, compared with 46% for Group B (p<0.001). A second mobilization attempt was required for 7 (14.9%) of patients in Group A compared to 10 (3.3%) for Group B. No difference was noted with regards to TTE for ANC (11 days for both groups, p=0.005) (Figures A); TTE for platelets was noted to be delayed by 1 day for Group A (14 days vs 13 days, p=0.0168) (Figures B). Rates of bacteremia did not differ between the two groups. Results are summarized in Table 1. Conclusions In our single-center study, a lower number of CD34+ cells were collected for patients who received daratumumab as a part of induction therapy for myeloma despite the use of standard mobilization regimens. No difference was found with regards to ANC engraftment. Platelet engraftment occurred one day earlier for patients who did not receive daratumumab for induction. These observations are consistent with results published in two prior studies.5,6 Depending on the target goal for CD34+ cell collection, daratumumab should be used with caution in the upfront setting for multiple myeloma. This is particularly important if tandem stem cell transplantation, salvage transplantation, or stem cell boost post high dose therapy are being considered as prospective treatment options for patients with multiple myeloma. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Outcomes of Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma Receiving Salvage Cytotoxic Therapy with Supportive Stem Cell Boost

Background Autologous hematopoietic stem cell transplant (ASCT) remains a cornerstone of therapy for eligible patients with multiple myeloma (MM) and can be incorporated as part of the initial therapy (early ASCT) or at the time of first relapse (delayed ASCT) [1]. Current guidelines recommend that adequate hematopoietic stem cells (HSC should be collected for a potential second ASCT, with a minimum goal of 2 million CD34+ cells/kg per transplant [2]. The stored HSC may be used for either a planned tandem transplant or future salvage ASCT. Less commonly, the previously stored HSC may be used for stem cell "boosts” following either dose intensive, non-myeloablative chemotherapy or for patients with "burned out” bone marrows secondary to extensive prior therapies. [3]. To our knowledge, there is a paucity of data on the effectiveness and survival outcome of patients with multiple relapsed MM who receive a stem cell boost following dose intensive chemotherapy. This study analyzes the clinical outcomes of multiply relapsed MM patients receiving multi-agent chemotherapy followed by a stem cell boost. Outcomes evaluated were overall response rate, proportion of patients who received a subsequent line of therapy, and overall survival. Methods This is a retrospective chart review performed at 2 institutions (Hackensack University Medical Center and MedStar Georgetown University Hospital). Fifty-nine (59) patients with MM aged ≥18 years old who underwent first ASCT from 1999 to 2021 and who collected sufficient s to allow for either tandem or salvage transplant or potential future stem cell boost were included in this study. Response to therapy was defined as stable disease or better on evaluation 1 month following stem cell boost. Patients who received another line of therapy less than 1 month post boost but did not have evidence of disease progression at that time, were excluded from ORR analysis. Overall survival (OS) was defined as the time from stem cell boost to date of death or last follow up. Statistical analysis was performed using STATA v16.0 (Stata Corp, TX, USA). Survival analysis was carried out using the Kaplan-Meier method and the log-rank test was used to compare survival curves. Results The patient characteristics who received a stem cell boost are shown in Table 1 (n=59): male gender (61 %), median age at diagnosis was 60 (range 37-81), median number of lines of therapy 6.3 5 Range 1-16). The patient who received only 1 prior line of therapy had aggressive relapse less than 100 days post melphalan-conditioned ASCT which necessitated use of urgent dose intensive chemotherapy. The stem cell dose used for the boost ASCT ranged from 0.4 to 9.8 X 10^6 CD34+ cells/kg (median 2.3). 1.6. Of the 49 evaluable patients, 28 (57.1%) had response to therapy 1 month post stem cell boost. Overall, 37 (62.7%) patients successfully received a subsequent line of therapy post stem cell boost. The median overall survival for the entire cohort was 129 days (range 1 - 1462 days) (Figure 1). OS was significantly longer in responding patients compared to those who did not respond (182 days vs 82 days, p=0.0081). Conclusions Dose intensive, non-myeloablative chemotherapy can improve survival in heavily pretreated, usually penta-refractory MM that require disease for refractory relapse. The administration of a stem cell boost utilizing previously collected HSCs may assist with hematopoietic recovery following dose intensive chemotherapy and in this subset of patients who have poor marrow reserve from prior therapy. This study serves to demonstrate the clinical outcomes of patients treated with multiagent chemotherapy followed by a stem cell boost. With an ORR of 57.1%, this approach can be effective in the appropriate clinical setting and significantly improves OS in patients who do respond to therapy (Figure 2). The goal of such therapy is to achieve disease control, and often serves as a "bridge” for patients to receive subsequent myeloma-directed therapy that may not be readily available at the time of relapse, such as clinical trial or chimeric antigen receptor T-cell (CAR-T) therapy. This data allows for treating oncologists to appropriately implement and inform patients of the therapeutic uses and clinical outcomes of treating such patients with dose intensive multiagent chemotherapy followed by a stem cell boost.

Assessing effectiveness of first-line carboplatin, pemetrexed, and pembrolizumab in patients with recurrent/metastatic lung adenocarcinoma.

e21045 Background: Randomized clinical trial data support the addition of immune checkpoint inhibitors to standard first-line platinum-doublet in patients with recurrent/metastatic non-small cell lung cancer. In the landmark KN189 Trial in which patients received carboplatin or cisplatin in combination with pemetrexed and pembrolizumab, the updated analysis (Gadgeel et al, JCO 2020) reported a median overall survival of 22 months. To explore the translation of this clinical trial-proven efficacy to clinical effectiveness in routine practice, we sought to explore patient outcomes with the combination of pemetrexed, carboplatin, and pembrolizumab as initial therapy for patients with recurrent or metastatic non-squamous non-small cell lung cancer. Methods: At two large, urban, academic medical centers (Hackensack University Medical Center and Memorial Sloan Kettering Cancer Center), we reviewed patient treatment data to identify all patient all patients with recurrent/metastatic non-squamous non-small cell lung cancer who received carboplatin, pemetrexed, and pembrolizumab as initial therapy for recurrent/metastatic NSCLC from June 2017 to December 2020. Patients with EGFR mutations or ALK gene fusions were excluded. From the medical record, we obtained baseline clinical characteristics, patient treatments and duration, as well as overall survival. Results: We identified 523 patients treated with carboplatin/pemetrexed/pembrolizumab, with 399 events occurring during the observation period. Baseline characteristics: 47% women and median age 66 (Interquartile range 59-72). The median overall survival from start of therapy was 11 months (95% confidence interval 9-12 months). Conclusions: In routine clinical practice, initiation of chemotherapy + immune checkpoint inhibitor as first-line therapy for patients with recurrent/metastatic NSCLC led to shorter median overall survival than reported in clinical trials. To further evaluate this finding, we will explore patient baseline characteristics including performance status, comorbidities, organ function as well as explore outcomes of a historical cohort of patients administered carboplatin and pemetrexed.

Judge rules against employee

Case name: Cascina v. Hackensack University Medical Center, et al., No. 19‐17571 (D. N.J. 10/01/21).

Judge rules against employee

Case name: Cascina v. Hackensack University Medical Center, et al., No. 19‐17571 (D. N.J. 10/01/21).

Impact of COVID-19 Pandemic on Utilization of the Inpatient Hospice Services (General Inpatient Hospice).

Background: Our institution has been offering the General inpatient hospice (GIP) services within the premises of our hospital since 2013. Our previous data had suggested increased acceptance of hospice and GIP care with this model. We wanted to study the impact of the current COVID-19 pandemic, on utilization of Hospice with this model of care.Objectives: Compare utilization of GIP at HUMC during the first COVID-19 surge, (3/1/2020–6/30/2020) to pre-COVID period (11/1/2019–2/29/2020).Methods: Using a retrospective chart review was done for GIP admissions from 11/2019 to 6/2020 at Hackensack University Medical Center (HUMC), an academic hospital in New Jersey which was approved by HUMC institutional review board. Data was collected for demographics and comorbidities. Descriptive statistics were reported. Results: The primary findings show increased hospice referrals during the study period (3.02%) compared to the pre-covid time period (2.63%), P = .0592. Furthermore, GIP admissions increased from 122/13 440 (.91%) in the pre-covid period to 146/11 480 (1.27%) during covid, P = .0055. There were 54 patients admitted to GIP with COVID-19. Descriptive statistics showed male and female distribution was almost equal (53.70% vs. 46.30%), and mean age of 82 years. In GIP patients with COVID-19, majority patients were white patients, (66.67%) age group of 76–95 years old and had < 3 comorbidities (85.19%), about half were with hypertension, next chronic condition was diabetes.Conclusions: COVID-19 outbreak increased both hospice referral and admission in our model of care. Availability of GIP in the hospital setting may help acceptance and facilitation of these essential end-of-life care services.

Feasibility and Effectiveness of Recruiting Latinos in Decídetexto-A Smoking Cessation Clinical Trial from an Emergency Department Patient Registry.

There is an underrepresentation of Latinos in smoking cessation clinical trials. This study describes the feasibility and effectiveness of recruiting Latino smokers in the U.S. from an emergency department (ED) patient registry into a randomized smoking cessation clinical trial. Recruitment occurred from the Hackensack University Medical Center ED. Potential participants were contacted from a patient registry. The primary outcome was whether the participant responded to a call or text. Secondary outcomes included the best day of the week, week of the month, and time of day to obtain a response. Of the 1680 potential participants, 1132 were called (67.5%), while 548 (32.5%) were texted. For calls, response rate was higher compared to text (26.4% vs 6.4%; p < 0.001). More participants were interested in the study when contacted by calls compared to text (11.4% vs. 1.8%) and more participants were enrolled in the study when contacted by calls compared to text (1.1% vs. 0.2%). Regression models showed that ethnicity, age, time of day, and week of the month were not significantly associated with response rates. Recruitment of Latinos from an ED patient registry into a smoking cessation clinical trial is feasible using call and text, although enrollment may be low.

Does Global Surgery Interest Influence the Choice of Surgical Residency Program?

Medical students actively seek global health opportunities. Surgical residents also show great enthusiasm for international missions, rotations and global surgery. Unfortunately, only 18% to 34% of all surgery residency programs offer such international opportunities. We surveyed fourth year medical students applying for surgery residency to determine if international surgery opportunities offered by a program would influence their match rank list. A 20 question survey was given to interviewees at our surgery residency program. Survey was optional and anonymous. We queried prior volunteerism, interest in global surgery and importance of international opportunities offered during residency. Hackensack University Medical Center, Hackensack New Jersey PARTICIPANTS: All candidates interviewing for general surgery residency at Hackensack University Medical Center from October 2019 to January 2020. A total of 97 fourth year medical students interviewed, with a 66% response rate to the survey. Mean age was 27 years. 92% of students had volunteered during college and/or medical school. 41% of students had volunteered internationally. Majority of students were interested in a surgery residency program offering international opportunity. 78% of students planned to volunteer internationally after residency, and two-thirds planned to include global surgery in future career. Half of the students reported they would rank a residency program higher if it offered an international opportunity. Students who were immigrants were significantly more likely to rank a program higher in the match if an international opportunity was offered, compared to students born in the US (p < 0.05). There is great interest in global surgery and international volunteer opportunities amongst fourth year medical students who apply for surgery residency. The majority of applicants have prior volunteer experience either locally or abroad. Majority of students plan to volunteer internationally after residency and are interested in academic global surgery careers. Students will rank surgery residency programs that offer international opportunities higher in the match.

Bridging the preclinical-clinical divide in response to COVID-19.

The COVID-19 pandemic posed unique challenges to educational institutions throughout the world, especially medical education programs. The usual demands of residency were heightened by increased patient volume and need for intensive care. Many hospitals, including Hackensack University Medical Center, enacted administrative changes including modifying staffing models to minimize disease exposure and remodeling hospital floors to increase the capacity of intensive care units. Many of these changes were enacted to allow for greater focus on patient care and social distancing, but they came at the expense of medical education, as traditional practices such as in-person lectures and participation in group clinical rounds were suspended to accommodate these changes. At a time when new information about SARS-CoV-2 and various treatment modalities was emerging rapidly, there was an urgent need for providing factual, relevant, concise educational materials to resident and attending physicians whose time was limited by the volume and urgency of COVID-19 patient care activities. This opened up an opportunity for students in our new medical school associated with the Hackensack Meridian Health network to provide this much needed informational resource. In March through June of 2020, first- and second-year students and medical science faculty at the Hackensack Meridian School of Medicine collaborated with resident and attending physicians at Hackensack University Medical Center via online web-conferencing. Each week, residents and attending physicians sent clinical questions to the medical school faculty that students would then research and convert into an educational presentation. The topics centered around actionable clinical queries. Students gathered relevant clinical studies and critically evaluated the methods, procedures, findings and conclusions of each report. Studies from hospitals and institutions around the world were emerging rapidly, most as preprints prior to peer-evaluation and often with a broad range of quality. Critical appraisal of data-gathering methods was essential to provide hospital staff with accurate information. Student presentations were supported by medical science faculty using standard evidence-based medicine methodology to ensure that a high-quality review had been conducted. After presentations concluded, residents and attendings posed further questions, reflected on what they were seeing clinically, and suggested new topics for discussion. This process allowed medical students to increase their skills in public speaking, critical appraising data and methodology, and presenting research in a concise, clear manner. These presentations also allowed frontline workers to receive up-to-date information in a setting of rapidly evolving knowledge of epidemiology, clinical presentation and disease management of COVID-19 patients. This innovative response to the pandemic provided a powerful opportunity to bridge medical education's preclinical-clinical divide. This example should serve as a prototype for sustained collaboration as different strains of SARS-CoV-2 emerge as a threat, as well as in post-pandemic times. This learning model can be applied to emerging diseases and is particularly useful for cutting-edge, novel research topics which significantly impact patient care.

Antifungal Drug Susceptibility and Genetic Characterization of Fungi Recovered from COVID-19 Patients.

Fungal infections are common complications of respiratory viral infections and are associated with the increased need for intensive care and elevated mortality. Data regarding microbiological and molecular characteristics of such infections in COVID-19 patients are scarce. Here, we performed a comprehensive analysis, including species identification, antifungal susceptibility testing, molecular resistance determinants analysis, typing, and retrospective clinical data review, of fungal isolates recovered from 19 COVID-19 patients, who were hospitalized at the Hackensack University Medical Center (HUMC) in Hackensack, New Jersey, USA, in the initial phase of the pandemic from April–May 2020. In total, 17 Candida albicans, two C. parapsilosis, and two Aspergillus fumigatus were analyzed. All Candida spp. isolates were susceptible to micafungin and azole drugs (fluconazole, voriconazole, posaconazole, itraconazole, isavuconazole). A. fumigatus isolates were susceptible to micafungin and all triazole drugs except fluconazole (intrinsic resistance). Multilocus sequence typing (MLST) of C. albicans isolates revealed 15 different sequence types (STs), which clustered below the clade-defining limit of p-distance < 0.04. Pulsed-field gel electrophoresis (PFGE) karyotyping revealed no chromosomal rearrangements in these isolates. A. fumigatus isolates were of different, non-related genotypes. We speculate that virus- and drug-induced immunosuppression (94.7% of the patients received corticosteroids), together with prolonged hospital stay (median duration of 29 days) and mechanical ventilation (median duration of 24 days) likely increased the susceptibility to secondary respiratory and bloodstream infections in the studied patient population. The presence of fungi in blood or respiratory tract fluid was a prognosticator for poor clinical outcome, which presented as an 89.5% 30-day mortality in our patient cohort.

Gene Expression Profiling (GEP) As a Prognostic Indicator of Multiple Myeloma, Irrespective of Disease Stage, Prior Treatment and Prior Transplant - a Single Center Experience

BackgroundMultiple myeloma (MM) risk is classified using fluorescence in situ hybridization (FISH) routine cytogenetics, and gene expression profiling (GEP). GEP is a clinically validated tool for prognostication of MM in newly diagnosed and relapsed patients (pts), its role in very heavily treated stages is less clear. A study (Nishihori et al, ASH, 2016) concluded that GEP is useful regardless of disease stage. We aim to determine the prognostic significance of GEP heavily pre-treated MM cohort.Methods299 pts with MyPRSTM GEP results at Hackensack University Medical Center (NJ) between 2012 and 2016 were included. High risk GEP was defined with the validated cutoff score of >45.2, high risk FISH was determined according to the mSMART classification as del17p, t(14,16), t(14,20). Chi-square tests were performed on categorical data and Wilcoxon rank sum tests on continuous data. Overall survival (OS) and progression free survival (PFS) were performed using Kaplan-Meier.ResultsMedian age was 63 years (range, 25-91), 170 pts (56%) were men, 81 pts (28%) had International Staging System (ISS) 3 and 191 pts (62%) had Durie-Salmon Staging (DSS) III. 245 pts (81%) had at least one bone marrow transplant (BMT). Median time from myeloma diagnosis to GEP was 30.1 (range 0.1-178.4) months. Most pts had GEP on diagnosis but 24% were heavily pretreated (range, 1-6 lines of treatment), and 13% had a BMT prior to GEP testing. 77 pts (25%) had high-risk disease based on GEP with a median score of 36.5 (range, 9.03-84.05). Molecular subtypes were hyperdiploidy (HY) 31%, cyclin family (CD)-2 20%, low bone disease (LB) 13%, proliferation (PR) 11%, MAF associated (MF) 10%, CD-1 8%, and MMSET associated (MS) 6%. Median OS and PFS were significantly inferior in patients with high-risk by GEP, 25 vs 33 months (p<0.021), 13 vs 21 months (p<0.004) respectively. Molecular subtypes were not individual predictors of OS (p<0.2). When MF, MS and PR subtypes were combined, they had inferior OS compared to other subtypes but this was not statistically significant (p<0.3).ConclusionsGEP can accurately predict risk status in heavily pre-treated and post-transplant MM pts. In conclusion, our data confirm that GEP is a good prognostic indicator in MM pts irrespective of disease stage and prior treatments. Further prospective studies with larger samples and correlating with baseline and intra-treatment GEP are needed. DisclosuresRichter:Janssen: Speakers Bureau; BMS: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vesole:Takeda: Speakers Bureau; Celgene: Speakers Bureau. Siegel:Celgene, Takeda, Amgen Inc, Novartis and BMS: Consultancy, Speakers Bureau; Merck: Consultancy. Biran:Takeda: Speakers Bureau; Celgene, Amgen: Consultancy, Speakers Bureau.

Reduced-Intensity Conditioning Is Successful in Matched Sibling Bone Marrow Transplantation As a Cure for Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is the most common genetic disease in this country, affecting 1 in every 72,000 individuals in the United States, with sickle cell trait found in 1 in 12 African-Americans. Without curative therapy, disease related mortality is as high as 14% in adolescents and young adults, with a decreased life expectancy compared to individuals without SCD. Hematopoietic stem cell transplantation (HSCT) is the only established cure, and matched sibling HCST have been performed for 30 years with great success. Unfortunately, only about 14% of SCD patients have a matched sibling. Most SCD HSCT protocols use myeloablative (MAB) conditioning in matched sibling transplants with average overall survival (OS) and disease-free survival (DFS) of 90% and 95% respectively, but with potential long-term complications including infertility following its use. Reduced Intensity Conditioning (RIC) has been used in young patients with malignancies with better tolerance and fewer complications. In an attempt to minimize risk and maximize cure, our study examined the use of a RIC regimen for both matched sibling and alternative donor HSCT in SCD patients ages 2-30.Primary Objective: To determine DFS after matched sibling or unrelated transplant after a conditioning regimen consisting of Alemtuzumab, Fludarabine, and Melphalan.Methods: The Institutional Review Board of Hackensack University Medical Center approved this study for human subjects. Strict stopping rules were established for graft rejection and death. Eligibility criteria included a diagnosis of SCD for patients receiving matched sibling donor HSCTs, but did not require any specific complications. For alternative donor HSCTs, eligibility criteria included specific complications associated with severe disease, and required a 9-10/10 unrelated donor or 5-6/6 UCB in the donor registry. All patients underwent partial exchange transfusions for a goal of HbS <45% at the start of conditioning. Conditioning initially consisted of Alemtuzumab beginning on d -22 followed by Fludarabine and Melphalan. However, Alemtuzumab was moved up to d -16 after 7 patients were enrolled to reduce graft vs host disease (GVHD). Due to increasing host chimerisms in 3 patients, the Alemtuzumab was moved back to d-22 after an additional 7 patients were enrolled. Post-HSCT, GVHD prophylaxis consisted of Tacrolimus (trough goal of 10-20) through d+100, mycophenolate mofetil through d+45, and steroids (for unrelated donors) through d+28. Patients were monitored closely for signs of infection with weekly PCRs for adenovirus, CMV and EBV. Donor chimerism by STR and HbS percentages by electropheresis were assessed at d+30, d+60, d+100, 1 year and 2 years post HSCT.Results: A total of 20 patients (17 related, 3 unrelated) were enrolled, with age at transplant ranging from 2.25 to 25.4 years. 3 patients were initially consented to the related arm, but then were found to be ineligible due to organ dysfunction or compliance issues. OS and DFS in patients with related donors were 100% and 94%, with one patient suffering secondary graft rejection. The OS and DFS in patients with unrelated donors were 66% and 33%, with one patient dying from GVHD complications and a second patient suffering secondary graft rejection. The unrelated patient with graft failure did receive a second HSCT off study, but died due to GVHD complications. Mean neutrophil engraftment occurred at d+14 and d+11 and platelet engraftment occurred at d+40 and d+26 for related and unrelated donors, respectively. The incidence of acute GVHD stage II-IV was 35% (7/20 patients), occurring in 6/17 (35%) related and 1/3 (33%) unrelated BMT patients. Chronic GVHD was noted in 20% of patients (4/20), occurring in 3/17 (18%) related and 1/3 (33%) unrelated BMT patients. Chimerisms ranged from 20-100% with HbS% of 0-62%.Conclusions : Our results show that a RIC regimen is well-tolerated with successful engraftment in patients undergoing matched sibling HSCT. However, the complications of GVHD & graft rejection in unrelated transplants greatly affected the DFS. The results are promising for continued use of this regimen for related HSCT even in SCD patients with minimal complications, but other alternatives need to be developed for unrelated HSCT. DisclosuresNo relevant conflicts of interest to declare.