bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic features and outcome of extra-nodal diffuse large B-cell lymphoma: An institutional experience from North India.
Authors: Nair Sukesh C , Gogia Ajay , Kumar Lalit , Sharma Atul , Biswas Ahitagni , Mallick Saumyaranjan 
Published: May 2020

e20079 Background: Primary extranodal diffuse large B cell lymphoma (DLBCL) forms upto 40-50% of all cases of DLBCL . Clinicopathological features and outcome of extranodal DLBCL patients especially in the rituximab era are scarce from developing countries. Methods: We carried out an ambispective analysis of newly diagnosed DLBCL patients (n = 417) over a period of 5 years (2014-2018).Of this total cohort 224 (53.7%) were found to have primary or predominant extranodal involvement. Prognostic factors were identified using Cox-regression analyses. Results: Median age was 50 years (18-86) with male female ratio of 2:1. B symptoms were seen in 48% patients and bulky disease in 39%. ECOG performance status of 0 or 1 was present in 50% and 63% presented with advanced disease. Bone was the most common site of extranodal involvement (32%) in our study followed by gastrointestinal tract ( 30%).Cell of origin (based on Hans algorithm) was available in 80% patients with Germinal center subtype (GCB) forming 44% and non-GCB forming 36% of all patients. Bone marrow involvement was present in 13 % patients. Low risk International Prognostic Index (IPI) was seen in 32 % and 41% were having intermediate risk IPI, the remaining being high risk. CHOP based treatment was used in 80 % of cases and rituximab was used in 76% of all cases. The overall response rate was 76% with a complete response rate (CR) of 65.5%. Presence of B-symptoms, central nervous system (CNS) involvement, non R-CHOP regimen and non-radiotherapy treatment protocols were associated with inferior CR rate. After a median follow up of 26 months, the 3-year event free survival and overall survival were 65 % and 82.7 % respectively. Involvement of specific extranodal sites (kidney, adrenals and CNS), high IPI score and use of non R-CHOP regimens were associated with poor EFS and OS on multivariate analysis Conclusions: This is one of the largest studies from India on extranodal DLBCL in the rituximab era. Involvement of specific extranodal sites, high IPI score and use of non R-CHOP regimens were associated with inferior survival.
Impact of immunoparesis on clinical outcomes following bone marrow transplantation.
Authors: Torgerson Nicholas , Odetola Oluwatobi , Hagen Patrick , Hossain Nasheed , Tsai Stephanie , Smith Scott E. , Stiff Patrick J. 
Published: May 2020

e20505 Background: Immunoparesis (hypogammaglobinemia) has been shown to impact outcomes in patients with newly diagnosed multiple myeloma (MM). Its impact in the post-transplant setting and potential risk of both infections and immune dysregulation impacting relapse is less clear. We sought to assess the role of immunoparesis both pre and post autologous stem cell transplant (ASCT) in newly diagnosed MM patients. Our primary outcome was the impact of immunoparesis on progression free survival (PFS) post-ASCT controlling for maintenance therapy. Methods: We evaluated all MM patients between 2008 and 2017 at Loyola University who underwent ASCT. Inclusion criteria included first ASCT and age > 18 years. We evaluated both the presence of and number of impacted immunoglobulin (Ig) classes pre-transplant and day 100, 6-months, and 12 months post-ASCT. Results: The most common MM isotype was IgG Kappa (41.01%). Immunoparesis pre-ASCT and post-ASCT at day 100, 6 months, and 12 months was seen in 75%, 89.5%, 80%, and 58.5% respectively. Median time from diagnosis to transplant was 7.75 months (5.98 – 13.73). When adjusting for pre-transplant response, conditioning regimen, and post-transplant maintenance, neither the absolute presence of or number of Ig-classes impacting was predictive of hazard of disease progression or death (OS) while ISS-stage, best response post ASCT, and time from diagnosis to transplant were (table). Conclusions: Contrary to studies in the pre-transplant setting, our analysis indicates that immunoparesis is not predictive of relapse or survival in the post-transplant setting, suggesting modification of disease process with treatment and ASCT. When controlled for maintenance therapy, immunoparesis does not increase risk of progression or decrease overall survival alleviating the concern for increased morbidity/mortality secondary to infections in the face of immunoparesis in the era of maintenance therapy. [Table: see text]
The effect that β-lactam antibiotics have on progression free and overall survival in multiple myeloma patients undergoing autologous stem cell transplantation.
Authors: McKenna Marshall , Feinman Rena , Ahn Jaeil , Wang Shuqi , Vesole David H. , Goldberg Stuart L. , Suero-Abreu Giselle Alexandra , Gonzalez Velez Miguel , Wang Jun Chih , Rehman Abdul , McKiernan Phyllis , Donato Michele , Paleoudis Elli Gourna , Siegel David Samuel DiCapua , Biran Noa 
Published: May 2020

e20518 Background: Gut microbiome dysbiosis is correlated with graft-versus-host disease (GVHD) in allogeneic stem cell transplant (allo-SCT) patients. In the allo-SCT population, antibiotics have been associated with increased risk for GVHD mortality and relapse due to loss of gut obligate anaerobes . It has been shown that antibiotics may negatively impact the efficacy of checkpoint inhibitors for patients with solid tumors. Based on these studies, we performed a retrospective analysis to determine if antibiotic treatment affects outcomes of multiple myeloma (MM) patients after autologous SCT (ASCT). Methods: This is a single institution retrospective study at Hackensack University Medical Center. A list of consecutive MM patients treated from 1/2012 to 12/2015 was obtained and an electronic medical record review of the first 217 who received ASCT was performed. Baseline characteristics, treatment history, transplant course and antibiotic treatment (including β-lactams, fluoroquinolones, macrolides, metronidazole, and vancomycin) were reviewed. Prophylactic antibiotics were excluded. Response was defined using the IMWG criteria. Median progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log rank tests were used to compare the difference in survival between stratified groups. The LASSO cox regression analysis method was used for multivariate analyses of PFS and OS. Results: Of the 217 patients, 205 patients were available for analysis. Median age at ASCT was 61. β-lactams were associated with decreased median PFS (1.95 vs 4.77 years (yrs), p < 0.01) and decreased median OS (7.51 vs 13.45 yrs, p = 0.01). Multivariate analysis adjusting for lasso-selected age, gender, complete remission (CR) after ASCT, and ISS demonstrated independent progression risk associated with β-lactam use (HR = 2.00, 95% CI, 1.28–3.12, p < 0.01). β-lactams were associated with worse OS in multivariate analysis adjusting for lasso-selected age, gender, CR after ASCT and high risk cytogenetics (HR = 1.89, 95% CI, 1.07–3.40, p = 0.03). Conclusions: In this preliminary study, β-lactams predicted for decreased PFS and OS compared to patients who did not receive β-lactams in MM patients undergoing ASCT. The study was limited by its retrospective nature but demonstrates one of the first evaluations of antibiotic effect on the ASCT population in MM. Prospective studies evaluating the impact of antimicrobials on patient outcomes and the gut microbiome are ongoing.
Triplet versus doublet therapy in multiple myeloma patients over 75 years.
Authors: Alam Zuhair , Grewal Ravleen , Girnius Saulius Kazmiems 
Published: May 2020

e20519 Background: Clinical trials in multiple myeloma (MM) typically enroll patients that are younger and less frail while 33% patients are over the age of 75. Advanced age/frailty is associated with worse prognosis, partly due to poor tolerability of therapy. Compared to doublets, triplets improve progression-free and overall survival (PFS and OS), but these outcomes are not well studied in older patients. Here, we compare doublet and triplet therapy in newly diagnosed MM patients over 75. Methods: The MMRF’s CoMMpass trial is an international, longitudinal, observational study capturing disease progression and response to treatment. Using the MMRF database, we compared doublet versus triplet therapy in patients over 75. Primary outcome was PFS while secondary outcomes included OS, quality of life (QoL) and fatigue. QoL was assessed using EORTC QLQ-C30 questionnaire and fatigue was captured by the MM eCRF survey. Results: 146 patients were eligible for analysis. Median age was 80 years. 27 (18%) were ISS 1, 38 (26%) were ISS 2, and 59 (40%) were ISS 3. Amongst doublets (n = 62), 48% received Bortezomib/Dexamethasone while 48% received Lenalidomide/Dexamethasone. Amongst triplets (n = 71), 35% received both proteasome inhibitors (PI) and immunomodulatory drugs (IMIDs), whereas 58% received PI-based therapy with no IMID. Mean PFS for doublets was 467 days and for triplets was 608 days, with difference of 141 days (p = 0.0663). Mean OS for doublets was 757 days and for triplets was 920 days. Difference of 163 days was not statistically significant (p = 0.1784). In doublets, QoL remained at a median of 50% from baseline to 5 years. In triplets, QoL improved from a median 58% to 83% from baseline to 5 years. With respect to fatigue, levels remained unchanged from baseline to 5 years in doublets (43 to 44%) and dropped from 37% to 29% in triplets. Conclusions: There is a trend towards improved PFS, as well as an improvement in QoL and fatigue in MM patients over 75 that are treated with triplets as compared to those treated with doublets. Limitations include lack of randomization and selection bias.
Quality-of-life (QOL) analyses in patients with multiple myeloma: Results from the selinexor (KPT-330) treatment of refractory myeloma (STORM) phase IIb study.
Authors: Jagannath Sundar , mehta jyotsna , Breeze Janis , Tremblay Gabriel , Li Lingling , Biran Noa , Shacham Sharon , Kauffman Michael G. , Shah Jatin J. 
Published: May 2020

e20522 Background: Selinexor, a novel oral selective inhibitor of nuclear export, was recently approved for use in relapsed/refractory multiple myeloma (MM). The efficacy and safety of selinexor and dexamethasone was evaluated in a phase 2b, single-arm, open-label, multicenter trial in patients with penta-exposed, triple-class refractory MM. Patient-reported outcomes were measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) assessment. While minimal clinically important differences (MCID) have been established for other FACT scales, there is no known, validated definition of MCID for the FACT-MM. This study reports results of QoL analyses in patients with MM enrolled in the STORM phase 2b trial and examines two approaches to calculate MCID for the FACT-MM. Methods: FACT-MM data were collected at baseline, on day 1 of each 4-week cycle, and at end of treatment (EOT) during the STORM phase 2b trial. Change from baseline was analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain. Two approaches for evaluating MCID were explored: the first based on patient-reported assessment of meaningful change, defined as 10% of the instrument range (Ringash 2007), and the second based on mean baseline differences between ECOG groups (0 vs 1 to 2) based on patient level data. Additional analyses were performed to identify trends among treatment responders and non-responders, including a difference-in-difference (DID) analysis to compare changes between baseline and EOT. Results: Eighty patients had sufficient data to be included in longitudinal QOL analyses. MCID analyses demonstrated that most patients did not experience decline during the first six cycles of treatment; this pattern was consistent with MCID defined either as 10% of the instrument range (range 54% to 75% of patients), or as an ECOG-based anchor (range: 54% to 73% of patients). The DID analysis found that the mean change in QoL of non-responders decreased significantly between baseline and EOT, while responders had no significant change. This difference between responders and non-responders was significant for the FACT-G. Conclusions: Most patients did not experience QoL decline during the early cycles of selinexor treatment during the STORM 2b trial. The MCID decline, evaluated by two approaches, was greater among treatment non-responders than responders. A DID approach demonstrated greater decline between baseline and EOT for non-responders. Clinical trial information: NCT02336815.
DREAMM-2: Assessing efficacy via indirect comparison of single-agent belantamab mafodotin versus selinexor plus dexamethasone combination in anti-CD38 exposed relapsed/refractory multiple myeloma (RRMM).
Authors: Popat Rakesh , Suvannasankha Attaya , Kapetanakis Venediktos , Prawitz Thibaud , Sarri Grammati , Hughes Rachel , Wang Feng , Hogea Cosima , Ferrante Shannon Allen , Willson Jenny 
Published: May 2020

e20527 Background: Single-agent belantamab mafodotin (GSK2857916) is a first-in-class immunoconjugate targeting B-cell maturation antigen that demonstrated deep and durable responses in heavily pretreated patients with RRMM in the pivotal DREAMM-2 study (NCT03525678; Lancet Oncol 2020). Methods: DREAMM-2 included patients with late-line RRMM treated with ≥3 prior lines of therapy, refractory to an immunomodulatory agent and a proteasome inhibitor, with prior exposure to an anti-CD38 antibody. Evidence from Phase II/III trials in a similar patient population was systematically identified following PRISMA guidelines. Based on the specificity of the DREAMM-2 population, selinexor plus low-dose dexamethasone (sel+dex) was identified as the only feasible comparator (STORM Part 2, NCT02336815). Matching-adjusted indirect comparisons (MAIC) were used to investigate the efficacy of single-agent belantamab mafodotin vs. sel+dex. Populations were matched for all clinically validated effect modifiers and prognostic factors with available data. MAIC were performed for overall response rate (ORR), time to response (TTR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS), as per NICE guidelines. Results: Single-agent belantamab mafodotin was more efficacious than sel+dex in terms of OS and DoR (Table). Results for ORR, TTR, and PFS showed no statistical difference between the two regimens. Conclusions: MAIC of single-agent belantamab mafodotin vs. sel+dex in this patient population with RRMM showed significantly improved efficacy on OS and DoR for belantamab mafodotin. Further validation is required owing to limited data availability. Additional safety analyses will further inform comparisons of the two. Clinical trial information: NCT03525678; NCT02336815. Funding: GlaxoSmithKline (207145). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. [Table: see text]
Daratumumab-induced lymphopenia predicts adverse events and outcomes in patients with myeloma.
Authors: Cottini Francesca , Williams Nita , Bumma Naresh , Khan Abdullah Mohammad , Chaudhry Maria , Devarakonda Srinivas S. , Efebera Yvonne Adeduni , Benson Don M. , Rosko Ashley Elizabeth 
Published: May 2020

e20534 Background: Daratumumab, a monoclonal antibody against CD38, is very effective in patients with Multiple Myeloma (MM). CD38 is expressed on MM cells but also on normal lymphocytes. Therapy-induced lymphopenia has been reported in 30-40% of patients; however its clinical significance is vastly unexplored. Methods: Here, we report the baseline characteristics and clinical course of 100 relapsed/refractory MM patients treated at the Ohio State University with Daratumumab as single agent or in combination. Data pertaining to patient demographics, MM characteristics, absolute lymphocyte count-ALC, infections, and hospital stays were collected. ALC of less or equal to 500 cells/µL is considered severe lymphopenia. Results: Fifty-nine percent of patients who completed treatment with Daratumumab (59%) developed severe lymphopenia. MM type (LLC and IgA), combination with immunomodulatory drugs (IMIDs), and lower baseline ALC count were statistically associated with severe lymphopenia, while stage, age, cytogenetics, number of prior lines of treatment, and autologous stem cell transplant were not. Patients with severe lymphopenia had higher rates of infections (52.5% versus 41.4%) and required hospital stays more frequently (83.8% versus 52.9%) than patients without severe lymphopenia. Upper respiratory tract infections and pneumonias were the most common infections. Sixty-one percent of severely lymphopenic patients recovered to ALC > 500 lymphocyte/μL while on therapy. The median time to recover was 14 days (average 43 days). Older patients have longer ALC recovery time (average: 52 days versus 24 days). No statistically significant difference in progression-free survival (PFS), overall survival (OS), or overall response rate (ORR) was noted between patients who did or did not develop severe lymphopenia. However, when the severe lymphopenic group was stratified based on ALC recovery, those with persistent lymphopenia had worst OS (p = 0.0019) and PFS (p < 0.0001), possibly due to better immune-mediated anti-tumoral effects. Conclusions: In our patient population, we discovered an elevated rate of severe lymphopenia, hospital utilization, and infections. Persistent severe lymphopenia is associated with shorter PFS and worst OS. Combination with IMIDs and low baseline ALC count are risk factors for severe lymphopenia while patients older than 65 has a longer ALC recovery time. These findings underline the importance of monitoring lymphocyte count and considering prophylactic measures in high-risk patients treated with Daratumumab.
Real-world stem cell mobilization (PBSC) patterns in MM pts receiving autologous transplant (ASCT).
Authors: Hari Parameswaran , Davila Omar , Pope Andrea , Hamadani Mehdi 
Published: May 2020

e20536 Background: PBSC mobilization (MOB) and apheresis is mandatory prior to ASCT and pose clinical, logistical, and financial challenges at transplant centers. This has resulted in considerable practice variation and a variety of local algorithms. Traditionally MOB was performed using G-CSF in the recovery phase after administration of chemotherapeutic agents such as cyclophosphamide (CTX). G-CSF alone (G) or G-CSF w/plerixafor (G+P) are other options. We compared the current US patterns of mobilization in a prospective observational study between OCT2017 and SEP2019. Methods: Consecutive pts (n = 690) undergoing MOB for upfront MM ASCT were prospectively enrolled from 20 participating centers. Specially designed data collection forms were used to collect resource utilization and complications in the peri-mobilization period. Based on a presurvey of center practices, 4 patterns of MOB were identified: CTX, G, G+P, or P Rescue of suboptimal G MOB. Results: CTX was the least common strategy (n = 52) followed by G (95) or G+P (252) or P Rescue (291). Presumed disease control and center preference were reasons for using CTX. Pt and disease characteristics were similar among groups with notable exceptions: CTX was less common in pts with higher SCr and more in those with higher beta2 microglobulin. CTX group had fewer pts in ≥VGPR status (31% vs. 60-71%). Triplet induction was used in 83% (RVD in 73% of pts) and resulted in ≥VGPR status in 61%. CTX was associated with 26% incidence of complications including a 4% hospitalization rate. Blood/platelet transfusions were needed in 15 and 12% respectively in CTX group but < 3% in other groups. A median of 8 million/kg CD34 cells were collected across all groups. Apheresis was completed in 2 days in 89% of G+P group vs. 70-75% of pts in the other groups. MOB was successful in 99% of cases overall with only 10 pts needing remobilization. 33% of CTX MOBand 63% of P Rescue group needed P resulting in 66% overall P use. With 98% pts still alive,clinical results of ASCT are not mature. Conclusions: CTX MOB is less used in clinical practice in the US for MM while P use was 66% in this large prospective study. CTX MOB seems to be preferred in some centers in those with suboptimal induction responses but was associated with higher complication rate. Planned G+P approach resulted in the fastest time to goal and less apheresis sessions. These data should inform overallMOB decision-making in the era of increasing apheresis needs for cellular therapies. [Table: see text]
Clinicopathologic profile of extramedullary plasmacytoma in Central Valley.
Authors: Valliani Salimah , Barakat Mohamad , Gill Harinder , Okudo Jerome , Abdulhaq Haifaa , Bukari Mohammed SANI 
Published: May 2020

e20551 Background: Extramedullary Plasmacytoma (EMP) occurs when neoplastic plasma cells cross the bone cortex to the surrounding soft tissue or spread hematogenously to other organs. The incidence rate of isolated plasmacytoma is reported to be 2-5% of plasma cell neoplasm. The skeletal system, head and neck are common organs involved. Our study evaluates the clinicopathologic characteristics of patients with EMP, with or without multiple myeloma (MM) in Central Valley, California. Methods: This is a retrospective review of 354 patients diagnosed with plasma cell dyscrasias, from January 2000 to January 2018. 33 patients had pathologically confirmed EMP and were evaluated for clinicopathologic data. Results: The incidence rate of EMP during the study period was 9%. Of the 33 patients diagnosed with EMP, 26 (78%) were associated with MM. The mean age at diagnosis was 62.6 years with no significant difference in mean age at diagnosis between patients with isolated EMP and EMP with MM (p = 0.23). Of the 33 patients, 11 (36.7%) were Hispanic, 11 (36.7%) were Caucasian whilst the rest constitute other minorities. This mirrored the 2010 population profile of the county. There are no statistically significant ethnic differences in the incidence of EMP with OR of 1.96 (p = 0.84). Compared to isolated EMP where aerodigestive system is most common site, bone with soft tissue (21%) is the most frequent site of involvement in EMP with MM [Table]. 9 (37%) patients were found to have IgG kappa as most common serum immunofixation finding in EMP with MM. FISH displayed high risk cytogenetics in 11 (45%) patients in the group. 91% of patients with EMP and MM were treated with chemotherapy alone or in combination with surgery or radiation. The median overall survival of patients with isolated EMP and EMP with MM was 46 months [95% CI: 11.2-80.9] and 55 months [95% CI: 16.3-93.7] respectively. Conclusions: The number of patients with isolated EMP is small for comparison with patients with EMP and MM. EMP occurs frequently with MM either at diagnosis or with disease progression. It tends to have high risk cytogenetics and may signify more aggressive disease. [Table: see text]