bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results from a phase 1b study of blinatumomab-pembrolizumab combination in adults with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
Authors: Giri Pratyush , Patil Sushrut , Ratnasingam Sumita , Prince H. Miles , Milliken Samuel , Briones Meijide Javier , Coyle Luke , Van Der Poel Marjolein , Mulroney Carolyn M. , Farooqui Mohammed Z. H. , Wong Hansen , Desai Rajendra , Zugmaier Gerhard , Mergen Noemi , Cannell Paul 
Published: June 2022

e19584 Background: This open-label, multicenter, phase 1b study evaluated the safety and efficacy of blinatumomab and pembrolizumab combination therapy in patients (pts) with R/R DLBCL (NCT03340766). Methods: Key inclusion criteria included adults with ECOG performance status ≤2 and life expectancy ≥12 weeks. In cycle 1, pts received a continuous intravenous (cIV) infusion of blinatumomab followed by step dosing to the target dose (TD; Table). After a 28-day treatment-free interval, cIV infusion of blinatumomab was administered for 28 days in cycle 2 with the same dose escalations as in cycle 1. Pembrolizumab 200 mg IV was administered once every 21 days starting on day 15 in cohort 1a, and on day 19 in cohorts 2a and 3a. Pts were premedicated with dexamethasone. Dose-limiting toxicities (DLT) were the primary endpoint. The maximum tolerated dose (MTD) was the highest dose level at which ≤1 of 6 or ≤2 of 10 pts experienced a DLT. Results: As of June 10, 2021, 31 pts were enrolled in cohorts 1a, 2a, and 3a (Table). DLTs occurred in 1 (10%) pt in cohort 1a (neutropenia) and 2 (40%) pts in cohort 3a (cognitive impairment, and elevated AST, ALP, and GGT levels). Treatment-emergent (TE) adverse events (AEs) were observed in 31 (100%) pts; grade ≥3 AEs occurred in 29 (94%) pts. The most frequent grade ≥3 TEAE attributed to blinatumomab was nervous system disorders (11 [35%]) and that attributed to pembrolizumab was blood and lymphatic system disorders (5 [16%]). Serious blinatumomab-related and pembrolizumab-related AEs were observed in 15 (48%) and 2 (6%) pts, respectively. Fourteen (45%) deaths occurred; none were treatment-related. Cohort 2a dose was determined as the MTD (Table). In cohort 2a, the objective response rate within 12 weeks of blinatumomab treatment was 30%; the median duration of response in responders (n = 8) was 176.5 (range: 28–680) days. Exposures of blinatumomab and pembrolizumab in this combination study were consistent with historical data for the individual agents. Conclusions: The cohort 2a dosing schedule with TD of 56 μg/day of blinatumomab was established as the MTD. The study was terminated after dose finding because the MTD of blinatumomab in combination with pembrolizumab was lower than the MTD of blinatumomab monotherapy, with no apparent efficacy gain. Clinical trial information: NCT03340766. [Table: see text]
Impact of high-dose melphalan followed by autologous stem cell transplant in producing MRD negative complete response in newly diagnosed multiple myeloma.
Authors: Ebraheem Mohammad , Cook Joselle , Kumar Shaji , Jevremovic Dragan , Dispenzieri Angela , Dingli David , Buadi Francis , Kapoor Prashant , Lacy Martha , Kourelis Taxiarchis , Warsame Rahma M. , Binder Moritz , Muchtar Eli , Hayman Suzanne R. , Go Ronald S. , Leung Nelson , Rajkumar S. Vincent , Kyle Robert A. , Gonsalves Wilson I. , Gertz Morie A. 
Published: June 2022

e20001 Background: High dose melphalan followed by autologous stem cell transplant (HDM-ASCT) remains the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM) despite advances in treatments. Achievement of complete response (CR) is associated with improved overall survival (OS) and progression-free survival (PFS); Minimal Residual Disease (MRD) negativity (-) using next generation flow cytometry with a sensitivity of 10-5 is strongly associated with improved PFS and OS. We investigated the rates of conversion to MRD(-), especially MRD(-) CR following HDM-ASCT in patients with NDMM. Methods: We retrospectively reviewed patients with NDMM who underwent early HDM-ASCT at Mayo Clinic Rochester from May 2018 to July 2019. Response assessment was conducted after induction and within 100 days post-ASCT based on 2016 IMWG criteria, except for using Mass-Fix instead of immunofixation. MRD was assessed in bone marrow using the established Euro Flow protocol with sensitivity of 10-5. The FISH assay was used to risk-stratify patients as high-risk (HR) and standard risk (SR) cytogenetics as per the mSMART guidelines. Primary outcome measure was the conversion to MRD(-) CR after ASCT. Secondary outcomes include the overall conversion to MRD(-) irrespective of IMWG response, the impact of HR cytogenetics and pre-ASCT IMWG response on conversion to MRD(-) CR. Results: Two-hundred and ten patients were included; 126 (60%) were male and median age 62 years (range 32–77 years). There were 78 (44%) patients with HR cytogenetics. Pre-ASCT, 23 patients (11%) achieved MRD(-) CR, and 66 (31%) patients achieved MRD(-) CR post ASCT. Of 187 patients not in MRD(-) CR pre-ASCT, 45 (24%) converted to MRD(-) CR. Table provides a breakdown of the conversion rate of pre-ASCT IMWG response category to MRD(-) CR post ASCT and patients with MRD(+) CR had the highest rate (78%) of conversion. The presence of HR cytogenetics did not impact rates of MRD(-) CR achievement post ASCT irrespective of pre-ASCT IMWG response (p = 1.0). Overall, irrespective of IMWG response, 43 (20%) patients were MRD(-) pre-ASCT (19 in VGPR, 24 in CR or better) and 102 (49%) patients were MRD(-) post-ASCT (36 in VGPR, 66 in CR or better). Among 85 patients in VGPR post-ASCT, 36 were MRD(-) of which 8 (22%) progressed, while 49 were MRD(+) of which 24 (49%) progressed (p = 0.014). Conclusions: Upfront HDM-ASCT in patients with NDMM leads to deeper responses with 24% converting to MRD(-) CR and more than doubling of the total rate of MRD(-) irrespective of IMWG response. [Table: see text]
Addition of carfilzomib as a third agent in lenalidomide-refractory multiple myeloma: Switching from doublet to triplet.
Authors: Cerchione Claudio , Nappi Davide , Catalano Lucio , Ronconi Sonia , Cangini Delia , Ceccolini Michela , Musuraca Gerardo , Martinelli Giovanni 
Published: June 2022

e20002 Background: 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. Methods: 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. Results: 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. Conclusions: 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. Clinical trial information: A108.
Body mass index and overall survival in multiple myeloma.
Authors: Wang Bei , Derman Benjamin Avi , Langerman Spencer , Stepniak Elizabeth , Johnson Julie , Zhang Wei , Jakubowiak Andrzej J. , Chiu Brian C 
Published: June 2022

e20007 Background: Elevated body mass index (BMI) is associated with a higher risk of multiple myeloma (MM), but its influence on survival is unclear. Studies evaluating BMI and mortality of MM have reported conflicting findings and most have limited data on clinical prognostic factors. We evaluated the associations between BMI at different life stages up to the time of diagnosis and overall survival (OS) in a cohort of newly diagnosed patients with MM. Methods: A total of 583 newly diagnosed MM patients were prospectively enrolled between 2010-2019 at the University of Chicago Medical Center. Epidemiology questionnaire and blood samples were collected at the time of diagnosis. We collected baseline clinical, laboratory, cytogenetic, and treatment data from electronic medical records. Vital status was ascertained using the National Death Index. Patients were followed through 31 December 2020 with an average follow-up length of 77.8 months. BMI was calculated using height and weight information collected from electronic health records and questionnaires. OS was defined as time from diagnosis until death from any cause. Chi-squared test and t-test were used to compare characteristics of patients by vital status. Hazard Ratios (HR) and 95% confidence intervals (CI) were derived from Cox proportional hazards models to examine the associations between BMI at different times and OS, adjusting for potential confounders. Stratified analyses were done to examine sex- and race-specific associations. Results: The median age at diagnosis was 63 years, 45% (n = 258) were female, and 27% (n = 150) were African Americans. Of the 572 MM patients, 176 (31%) deaths were identified during the follow-up. There was no significant association between elevated BMI at different time points (i.e., at diagnosis, 5 years before diagnosis, age 20, and maximum adulthood BMI) and OS after adjusting for age, race, sex, and prognostic variables (e.g., stage, serum lactate dehydrogenase levels). No association was found for both African Americans and European Americans. However, for women, obesity (BMI > = 30) at the time of diagnosis was associated with a better OS (HR = 0.25; 95% CI = 0.12-0.54 for obese vs. normal weight) whereas in men, obesity at the time of diagnosis was associated with worse OS (HR = 2.54; 95% CI = 1.18-5.49). Conclusions: We found no association between BMI and OS in MM, irrespective of race. Our data showed that, compared to subjects with normal BMI at the time of diagnosis, female patients with elevated BMI had better survival, whereas a higher BMI was associated with inferior OS among male patients. Our findings of an effect modification by sex are novel and warrant further investigations. These findings might have clinical significance because BMI is amenable to lifestyle modification.
Incidence and risk factors for bacterial infection in newly diagnosed multiple myeloma patients undergoing treatment with bortezomib, lenalidomide, and dexamethasone (RVD).
Authors: Pianko Matthew James , Bici Anisa , Nachar Victoria 
Published: June 2022

e20008 Background: Infection is an important cause of morbidity and mortality in newly diagnosed multiple myeloma (NDMM), but the risk of infection using novel treatment regimens is incompletely described in the literature. There are mixed trial results for antibacterial prophylaxis to reduce infection risk in newly diagnosed multiple myeloma and its use remains controversial. Methods: To evaluate the incidence of bacterial infection and early mortality in patients receiving bortezomib, lenalidomide, and dexamethasone (RVD) for NDMM, we performed a retrospective single-center cohort study of patients treated between 01/2014-01/2020. Demographic and clinical data were collected. Two cohorts were generated for those patients with or without bacterial infection during the follow-up period. A multivariate logistic regression was utilized to determine risk factors for bacterial infection. Variables with a P-value <0.2 on univariate analysis were considered for the model. For co-linear variables with a P-value <0.2 on univariate analysis, only one variable was included in the multivariable model. A receiver operating characteristic (ROC) curve was generated to assess the sensitivity and specificity of the model. Results: Of 144 patients, 21 patients (14.5%) experienced a bacterial infection of any grade. 11% of patients received pneumocystis prophylaxis, and 1 patient received levofloxacin prophylaxis. 11 (7.6%) patients experienced grade 3 (G3) or higher infection. One patient died in our cohort; there were no deaths from infection. G3 neutropenia occurred in 11% of patients with 2% experiencing any grade febrile neutropenia. Pneumonia and urinary tract infections were common, affecting 8(5.5%) and 6 (4.2%) patients, respectively. On multivariable analysis (Table), age, smoking history, history of diabetes, antibiotic use in the 60 days preceding 1st cycle of RVD, and high-risk cytogenetics (HR CG) were associated with a greater likelihood of experiencing a bacterial infection. The area under the ROC curve of the multivariable model was 0.829 (95% CI 0.729-0.934). Conclusions: The overall incidence of bacterial infection in NDMM patients receiving induction with RVD was low despite minimal use of antibacterial prophylaxis. Early mortality was uncommon and not attributable to infection. Clinical features may identify a subgroup of patients at greater risk of infection during induction therapy for MM and may impact clinical decisions to utilize antibacterial prophylaxis.[Table: see text]
Short- and long-term outcomes of multiple myeloma patients undergoing modern treatments proceeding to ASCT: A retrospective analysis.
Authors: Awada Hussein , Hajj Ali Adel , Ali Muhammad Faizan , Kumar Ashish , Adroja Shubham , Mahalwar Gauranga , Babar Arslan , Anwer Faiz 
Published: June 2022

e20012 Background: Multiple Myeloma (MM) accounts for approximately 10% of all hematological malignancies. MM patients have heterogeneous outcomes that depend on several demographic, genetic and clinical factors. Here, we report the demographics along with the short and long-term outcomes in a cohort of patients who underwent Autologous Stem Cell Transplant (ASCT) over a period of 5 years. Methods: In this retrospective cohort, we assessed all MM patients who underwent ASCT at the Cleveland Clinic during the period between January 1, 2016 and January 15, 2021. Demographic characteristics, ISS staging, Cytogenetic risk categorization, Pre-ASCT treatment, short-term in-hospital complications, response (defined per IMWG response criteria) before and up to12 months after ASCT, as well as maintenance therapy were collected by reviewing electronic health records. Continuous variables are presented as mean with standard deviation, while categorical variables are presented as percentages. Categorical variables are compared using the chi-squared test while continuous variables are compared using the ANOVA and t-tests. Results: 379 patients who underwent ASCT within the studied time period were identified (Table). Most common cytogenetic abnormalities were del(13) (RB) 25.07%, t(11;14) 17.94% and gain(1q) 16.62%. A Lenalidomide, Bortezomib and dexamethasone (RVd) regimen was the most common to elicit response pre-ASCT (59.05%). Complete response (CR) was achieved in 27.82%, very good partial response (VGPR) in 34.71% and partial response (PR) in 37.47% of all patients pre-ASCT as compared to CR in 43.05%, VGPR in 28.05%, PR in 24.73% and progressive disease (PD) in 4.17% 3 months post-ASCT. All patients received intermediate (140 mg/m2) or high-dose (200 mg/m2) Melphalan conditioning. Average length of hospital stay was 14.56 ± 2.11. Of all patients, thrombotic events were seen in 1.3%, bleeding in 1.8%, neuropathy in 5.34%, mucocutaneous toxicities in 47.99%, cytopenias in 98.39% and infections in 32.25%. RBC and platelet transfusions were required in 36.1% and 88.9% of patients, respectively. Progression-free survival (PFS) was 96.89% at 3 months, 93.77% at 6 months, 92.55% at 9 months, and 88.47% at 12 months post-ASCT. PFS up to 12 months was not statistically different across ISS stages (p = 0.881) or cytogenetic risk categories (p = 0.347). Most common cause of death was progressive MM (73.47%). Conclusions: Responses in MM are boosted by ASCT. Its most common complications are transfusion-dependent thrombocytopenia and infections. Most patients survive beyond 1 year with PD rate of only 11.53%. Advanced ISS stage and high-risk cytogenetics do not confer higher PD in the 1st 12 months post-ASCT.[Table: see text]
A retrospective study of the association of pre-autologous stem cell transplantation disease status with outcomes in patients with multiple myeloma: A single-center study.
Authors: Gutta Radhika , Balanchivadze Nino , Wani Kashmira , Sweidan Aroob , Springer Kylie , Kuriakose Philip 
Published: June 2022

e20013 Background: Autologous stem cell transplantation (ASCT) has improved long-term survival for many patients with multiple myeloma (MM), but not all patients respond to ASCT favorably, and many experience disease relapse. Our goal was to explore various disease parameters in patients with MM that might be associated with adverse outcomes after receiving ASCT. Methods: We performed a retrospective medical record review of adult patients with MM who underwent ASCT at Henry Ford Hospital between January 1, 2010 and November 1, 2020. Age, sex, international staging system stage, type of induction therapy, bone marrow cytogenetics and/or fluorescence in situ hybridization, International Myeloma Working Group (IMWG) treatment response criteria categories before ASCT, and the use of maintenance therapy were collected. Outcomes analyzed were time to relapse (TTR) and overall survival (OS). Cox regression analysis was performed. Results: A total of 321 patient records were analyzed: 194 (60.4%) patients were < 65 years old; 185 (57.6%) were men; 162 (50.5%) were Black, and 140 (43.6%) were White. IMWG treatment response categories before ASCT included 250 (78.2%) patients with partial response (PR) and very good partial response (VGPR) combined, and 40 (12.5%) with complete response (CR). There were 69 (21.4 %) patients classified with high-risk cytogenetics. Commonly used induction therapies included 96 (29.9%) patients receiving bortezomib/lenalidomide/dexamethasone, 21 patients (9%) receiving lenalidomide/dexamethasone, 80 patients (24.9%) receiving bortezomib/dexamethasone, and 30 patients (9.3%) receiving cyclophosphamide/bortezomib/dexamethasone, while other patients received a combination of other induction therapies. Mean time from ASCT and last follow-up date was 3.94 years. The overall mean TTR was 29.4 months and OS was 44.8 months. Univariate analysis showed that pre-ASCT treatment response status of combined PR/VGPR was associated with higher hazard of dying than CR (hazard ratio 3.03; 95% CI, 1.23-7.46); however, multivariate analysis showed that PR/VGPR status before ASCT was not significantly associated with increased TTR compared to CR (hazard ratio 1.29; CI, 0.65-2.59). Patients with pre ASCT CR status had longer OS than those with PR/VGPR status (hazard ratio 2.75; CI, 0.995-7.61; p < 0.05). No other variables, including cytogenetic risk were associated with a difference in OS or TTR. Conclusions: Being at CR status before receiving ASCT may indicate a reduced risk of death in MM patients compared to PR and VGPR status, regardless of upfront therapies. Since multiple factors, including treatment type, impact CR status in patients with MM, we believe that studying evolving risk-adapted front-line therapies will help guide optimized treatment strategies to improve overall survival.
Implications of 18F-FDG PET/CT findings before autologous stem cell transplant in patients with multiple myeloma.
Authors: Khan Muhammad Azeem , Markabawi Danny , Alberti Matthew , Burton Jeffrey , Maini Ruby , Catalfamo Vince , Badari Ambuga 
Published: June 2022

e20023 Background: The IMWG recommends using 18F-FDG PET/CT (PET) to monitor response to therapy in multiple myeloma (MM). Prior studies in patients who received chemotherapy before autologous stem cell transplant (ASCT) found that severe FDG uptake on PET was associated with inferior event free survival. However, novel agents and monoclonal antibodies have changed the landscape of MM and chemotherapy is no longer used as initial treatment making the role of PET before ASCT unclear. This study explores findings on pre-ASCT PET that may predict shorter remissions after ASCT. Methods: This was a retrospective cohort study. Patients were included if they had a PET at least 60 days before ASCT between 2014 and 2021. All patients achieved at least a partial response (PR) prior to ASCT. The primary endpoint, PFS was defined as time to progression on labs, imaging or bone marrow biopsy necessitating change in therapy or resulting in death after ASCT. The cytogenetic risk category (CG), number of bone lesions at diagnosis, presence of severe FGD uptake on PET (defined as SUV max ≥ 4.2) and persistence of lesions on PET was recorded. Patients who did not experience the event of interest were censored at their last date of clinic follow up. Hazard ratios (HR) for disease progression were estimated using Cox proportional hazards models. Results: 151 patients were included in our study. All patients underwent induction with a 3-drug regimen containing a proteasome inhibitor (PI) and/or an immunomodulatory agent (IMiD). 32% had high risk CG, 44% had > 3 bone lesions at diagnosis, 24% had severe FDG uptake and 29% had > 3 lesions on pre-ASCT PET. The presence of high-risk CG [HR 2.08 (1.03 – 4.17)] and severe FDG uptake on diagnostic PET [HR 6.43 (2.58 – 16.07)] was associated with more aggressive disease and shorter PFS. Patients with > 3 lesions in their pre-transplant PET had a statistically significant decreased PFS [HR 2.01 (1.02 – 3.96)] compared to those with ≤ 3 lesions. Conclusions: This study found that that persistence of > 3 lesions on pre-ASCT PET were an adverse finding associated with an increased risk of progression. To our knowledge these findings have not previously been shown in patients treated with PIs and IMiDs before ASCT. Significantly shorter PFS was observed in patients with high-risk CG and severe FDG uptake on initial PET, consistent with our knowledge of MM. In addition to established risk factors for aggressive disease, persistence of > 3 bone lesions on PET/CT could be used to identify a high-risk group of patients who may benefit from more intensive surveillance or therapy after ASCT. [Table: see text]