bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of elevated red cell distribution width and overall survival in multiple myeloma.
Authors: Rubinstein Sam , Sigworth Elizabeth , Chen Qingxia M , Chaugai Sandip , Cornell Robert F. , Warner Jeremy Lyle 
Published: May 2020

8534 Background: The most widely used multiple myeloma (MM) staging system, the Revised International Staging System (R-ISS), is based on lactate dehydrogenase, albumin, cytogenetics, and beta-2 microglobulin (B2M). B2M has limited clinical utility, is often only obtained to compute R-ISS, and is often a send-out test. Prior studies have shown that elevated red cell distribution width (RDW), a common test that is part of the routine complete blood count, is associated with reduced overall survival (OS) in MM. We hypothesized that a MM staging system could be constructed replacing B2M with RDW. Methods: Patients treated at Vanderbilt University Medical Center from 2000 to 2018 with cancer registry-confirmed MM diagnoses were included. OS was computed by registry-curated death and diagnosis dates; living patients were censored at date last known alive or of last follow up. A Cox proportional hazards model determining the independent effects of R-ISS, age, and RDW on OS was built. An alternate staging system (RDW-SS) was developed, replacing the B2M cutoffs in R-ISS with RDW (stage 1: RDW < 14.0% stage 2: RDW 14.0-15.5%; stage 3: RDW > 15.5%). Cox models comparing RDW-SS and R-ISS after adjustment for age and category of induction therapy (proteasome inhibitor [PI] and immunomodulatory drug [IMiD]), PI only, IMiD only, other) were built. Results: In 604 MM patients with available data, RDW was independently associated with OS after adjustment (HR = 1.069 per 1% RDW increase, p < 0.001). RDW-SS stages were associated with reduced OS (RDW-SS 2 HR 1.52, 95% CI 1.09 – 2.11, p = 0.01; RDW-SS 3 HR 2.13, 95% CI 1.37 – 3.28, p < 0.001) after adjustment; R-ISS stages were not (Table). Conclusions: RDW at MM diagnosis was independently associated with reduced OS, after adjustment for the clinical factors of age and treatment exposure; notably, R-ISS was not. The RDW-SS is simpler to obtain than R-ISS and may have improved prognostic value pending independent validation. If confirmed, mechanistic study of the etiology of this relationship is warranted. [Table: see text]
Pivotal DREAMM-2 study: Single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) refractory to proteasome inhibitors (PIs), immunomodulatory agents, and refractory and/or intolerant to anti-CD38 monoclonal antibodies (mAbs).
Authors: Lonial Sagar , Lee Hans Chulhee , Badros Ashraf , Trudel Suzanne , Nooka Ajay K. , Chari Ajai , Abdallah Al-Ola A. , Callander Natalie Scott , Sborov Douglas Weston , Suvannasankha Attaya , Weisel Katja , Voorhees Peter Michael , Hoos Axel , Zhi Eric , Baron January , Piontek Trisha , Jewell Roxanne C. , Opalinska Joanna , Gupta Ira , Cohen Adam D. 
Published: May 2020

8536 Background: Single-agent belantamab mafodotin (B-cell maturation antigen targeting immunoconjugate) showed clinically meaningful activity and manageable safety in patients with heavily pre-treated RRMM (DREAMM-2, NCT03525678, Lancet Oncol.2020). We report updated results (median follow-up 9 months). Methods: DREAMM-2 is an ongoing single-agent belantamab mafodotin (2.5 or 3.4 mg/kg) study in patients with RRMM after ≥3 prior therapy lines and refractory to an immunomodulatory agent, a PI, and refractory and/or intolerant to an anti-CD38 mAb. Primary endpoint: overall response rate (ORR; ≥partial response per independent review committee). Results: ORR was 31% in the 2.5 mg/kg (19% with ≥very good partial responses [VGPR]) and 35% (24% with ≥VGPR) in the 3.4 mg/kg groups (Table). Duration of response (DoR) was not reached (NR) in the 2.5 mg/kg and 6.2 months in the 3.4 mg/kg groups; 1-year overall survival (OS) estimate was 53%. Common Grade 3/4 AEs ( > 10% in either group) were keratopathy (2.5: 29%; 3.5: 24%), thrombocytopenia (2.5: 21%; 3.4: 32%), anemia (2.5: 20%; 3.4: 27%), pneumonia (2.5: 6%; 3.4: 13%), and neutropenia (2.5: 11%; 3.4: 16%). AEs were managed with dose delays (2.5: 54%; 3.4: 62%) and reductions (2.5: 34%; 3.4: 43%); discontinuations due to AEs were uncommon (2.5: 9%; 3.4: 12%). Conclusions: Single-agent belantamab mafodotin was well-tolerated, and clinically meaningful responses were sustained despite dose modifications with longer follow-up. Funding: GlaxoSmithKline (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT03525678 . [Table: see text]
Daratumumab + bortezomib, thalidomide, and dexamethasone (D-VTd) in transplant-eligible newly diagnosed multiple myeloma (TE NDMM): Baseline SLiM-CRAB based subgroup analysis of CASSIOPEIA.
Authors: Touzeau Cyrille , Moreau Philippe , Perrot Aurore , Hulin Cyrille , Dib Mamoun , Tiab Mourad , Caillot Denis , Facon Thierry , Leleu Xavier , van de Donk Niels W.C.J. , Broijl Annemiek , Zweegman Sonja , Levin Mark-David , Delforge Michel , Pei Lixia , Vanquickelberghe Veronique , De Boer Carla , Kampfenkel Tobias , Vermeulen Jessica , Sonneveld Pieter ,   on behalf of IFM and HOVON
Published: May 2020

8538 Background: In the phase 3 CASSIOPEIA study, D-VTd significantly improved outcomes vs VTd in TE NDMM pts at an 18.8-mo median follow-up. To allow earlier diagnosis and treatment of MM, the IMWG added 3 validated biomarkers (≥60% clonal bone marrow plasma cells, serum free light chain ratio ≥100, and > 1 focal bone lesion by MRI; “slim”) to the conventional “CRAB” diagnostic criteria. We present a subgroup analysis of CASSIOPEIA based on baseline slimCRAB criteria. Methods: TE NDMM pts were randomized 1:1 to 4 pre-ASCT induction and 2 post-ASCT consolidation cycles of D-VTd or VTd. The “slim-only” subgroup excludes pts with ≥1 conventional CRAB criterion based on data collected at baseline; the remaining pts were included in the “CRAB” subgroup. Results: Of 1085 randomized pts (543 D-VTd; 542 VTd), 81 were included in the slim-only subgroup (36 D-VTd; 45 VTd) and 1004 were included in the CRAB subgroup. In slim-only vs CRAB pts, 22% vs 54% had an ECOG score of ≥1, 4% vs 16% had ISS Stage III disease, and 11% vs 16% had high-risk cytogenetics. For D-VTd vs VTd pts in the slim-only group, these rates were 22% vs 22%, 8% vs 0%, and 6% vs 16%, respectively. Overall response rates (ORR) and rates of sCR, ≥CR, and MRD negativity were similar between slim-only and CRAB pts; for slim-only pts, rates were significantly higher for D-VTd vs VTd (Table). After an 18.8-mo median follow-up, progression-free survival (PFS) was not significantly different in slim-only vs CRAB pts, or in D-VTd vs VTd slim-only pts (Table). For D-VTd vs VTd CRAB pts, 18-mo PFS rates were 92% vs 84%, and 24-mo PFS rates were 89% vs 76%. Conclusions: Baseline characteristics indicate that slim-only pts were slightly fitter and of lower risk status vs CRAB pts; however, response rates, MRD-negativity rates, and PFS did not differ significantly between these groups. Among slim-only pts, significantly higher response and MRD-negativity rates were achieved with D-VTd vs VTd. Among CRAB pts, PFS rates were higher with D-VTd vs VTd. Clinical trial information: NCT02541383 . [Table: see text]
Efficacy of daratumumab in the treatment of multiple myeloma with high-risk cytogenetics: Meta-analysis of randomized phase III trials.
Authors: Giri Smith , Grimshaw Alyssa , Bal Susan , Godby Kelly Nicole , Kharel Prakash , Djulbegovic Benjamin , Usmani Saad Zafar , Facon Thierry , Moreau Philippe , Dimopoulos Meletios A. , Mateos Maria-Victoria , Costa Luciano J. 
Published: May 2020

8540 Background: The addition of Daratumumab (D) to backbone multiple myeloma (MM) regimens leads to improved response rates and progression free survival (PFS). Whether improved outcomes are also seen among patients with high-risk cytogenetics (HRC) remains unclear, particularly in first-line (FL) setting. Methods: We conducted a systematic search of bibliographic databases, clinical trials registries and meeting libraries from inception to December 2019, for phase III randomized trials that compared backbone MM regimens vs. same regimen plus D either in FL or relapsed/refractory (R/R) setting and reported outcomes by cytogenetic risk (HRC vs standard risk cytogenetics, SRC). We defined HRC as presence of t(4;14), t(14;16) or del(17p). The primary endpoint was PFS. We pooled relative log-hazard ratios using DerSimonian-Laird random-effects model. We assessed heterogeneity using Cochran’s Q and the I2 statistic. Results: Of 3,070 studies screened, 6 phase III trials were included. This included 3 trials in FL setting (Alcyone, Maia and Cassiopeia, 2,528 patients, 358 HRC) and 3 trials in R/R setting (Castor, Pollux and Candor, 1,533 patients, 222 HRC). The addition of D to FL backbone regimens among patients with HRC led to improved PFS (pooled HR 0.67; 95% CI 0.47-0.95, p = 0.02) with little heterogeneity (Cochran’s Q p = 0.77, I2= 0), similar to R/R setting (pooled HR 0.45; 95% CI 0.30-0.67, p < 0.01, Cochran’s Q = 0.63, p < 0.01, I2= 0). Similar results were seen in SRC MM patients in FL setting (pooled HR 0.45; 95% CI 0.37-0.54, p < 0.01, Cochran’s Q p = 0.49, I2= 0) and R/R setting (pooled HR 0.38; 95% CI 0.25-0.56; p < 0.01, Cochran’s Q p = 0.04, I2= 70%). Conclusions: Incorporating D to backbone regimens led to improved PFS among patients with HRC MM in both FL and R/R setting. Lack of substantial heterogeneity suggests benefit of D regardless of backbone regimen. D based regimens are appropriate choices in FL and R/R setting for both SRC and HRC patients. Longer follow up with mature overall survival data is needed to validate these findings. [Table: see text]
CTONG1104: Adjuvant gefitinib versus chemotherapy for resected N1-N2 NSCLC with EGFR mutation—Final overall survival analysis of the randomized phase III trial 1 analysis of the randomized phase III trial.
Authors: Wu Yi-Long , Zhong Wenzhao , Wang Qun , Mao Weimin , Xu Song-Tao , Wu Lin , Chen Chun , Cheng Ying , Xu Lin , Wang Jun , Li Xiao-Fei , Li Jian , Huang Cheng , Liu Zhidong , Xu Shun , Yang Jin-Ji , Yan Hong-Hong , Yang Xue-Ning , Liu Si-yang , Zhou Qing 
Published: May 2020

9005 Background: ADJUVANT-CTONG1104, a randomized phase 3 trial showed adjuvant gefitinib treatment significantly improved disease-free survival (DFS) vs standard doublet chemotherapy in patients (pts) with epidermal growth factor receptor ( EGFR) mutation-positive resected stage II-IIIA (N1-N2) non-small-cell lung cancer (NSCLC). 5-year survival rate of N1N2 were 38%-50% in IASLC staging system. Here, we present the final overall survival (OS) results from the study. Methods: From Sep 2011 to April 2014, 222 patients, aged 18-75 years, with EGFR activating mutation through completely resection and diagnosed as stage II-IIIA (N1-N2) NSCLC pathologically from 27 sites were enrolled. The enrolled patients were 1:1 randomized to receive adjuvant gefitinib (250 mg once per day) for 24 months (G, n=111) or vinorelbine (25 mg/m2, d1 and d8) plus cisplatin (75 mg/m2, d1) every 3 weeks for 4 cycles (C, n=111). The primary endpoint was DFS in the ITT population. Secondary endpoints included OS, 3 and 5-year DFS rate, 5-year OS rate. The subsequent therapy data were collected, including crossover from C to G, re-challenge TKI and other treatment. Data cut-off date was Jan. 13, 2020. Results: A median follow-up was 76.9 months. The median OS (mOS) was 75.5 months based on 95 (42.8%) events in ITT whole population. The mOS was 75.5m in G arm and 79.2m in C arm (HR 0.96, 95%CI 0.64-1.43, p=0.823). The 3, 5-year OS rate were 68.6%, 53.8% in G and 67.5%, 52.4% in C respectively. DFS in 3, 5-y were 40.3%, 23.4% in G and 33.2%, 23.7% in C, respectively (P3-y=0.395, P5-y=891). All predefined subgroups including age, gender, lymph node, EGFR mutation type had no significant difference in statistics but in favor of G arm in trend. Subsequent treatment especially targeted therapy contributed most to OS (HR = 0.46, 95% CI 0.26 – 0.83). Median OS of patients receiving subsequent target therapy was75.5m (n=35), 36.4m in other treatment (n=33; (P<0.001). For G mOS were 75.5 (n=15; target therapy) and 35.0 (n=18; other, p<0.001), for C 62.8m (n=20) and 46.8m (n=15; p=0.251). The RR was 26.7%, DCR 66.7%, mPFS 14.1m and mOS 19.6m for patients with rechallenged EGFR TKI in G arm (n=15). No novel unexpected SAE was observed during follow up. Conclusion The DFS survival advantage did not translate to OS difference in ADJUVANT trial. The OS with 75.5m was the best one of survival in completely resected N1N2 NSCLC comparing with historical data and sequent TKI treatment contribute to overall survival. Clinical trial information: NCT01405079.
Randomized phase III study of irinotecan/cisplatin (IP) versus etoposide/cisplatin (EP) for completely resected high-grade neuroendocrine carcinoma (HGNEC) of the lung: JCOG1205/1206.
Authors: Kenmotsu Hirotsugu , Niho Seiji , Tsuboi Masahiro , Wakabayashi Masashi , Ishii Genichiro , Nakagawa Kazuo , Daga Haruko , Tanaka Hiroshi , Saito Haruhiro , Aokage Keiju , Takahashi Toshiaki , Menju Toshi , Kasai Takashi , Yoshino Ichiro , Minato Koichi , Okada Morihito , Katayama Hiroshi , Asamura Hisao , Ohe Yuichiro , Watanabe Shun-ichi 
Published: May 2020

9006 Background: In the WHO classification, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are considered as high-grade neuroendocrine carcinoma (HGNEC) of the lung. Although there were no randomized trials evaluating adjuvant chemotherapy for patients (pts) with resected HGNEC, EP was considered to be a standard regimen for this population. A phase III study showed the superiority of IP to EP in pts with extensive stage SCLC (JCOG9511). Methods: Pts with completely resected HGNEC were randomized in a 1:1 ratio to receive either etoposide (100 mg/m2, days 1-3)/cisplatin (80 mg/m2, day 1) or irinotecan (60 mg/m2, days 1, 8, 15)/cisplatin (60 mg/m2, day 1), using the minimization method according to sex, pathologic stage, histology and institution. The primary endpoint was changed from overall survival (OS) to relapse-free survival (RFS) during the study period. We assumed a 3-year RFS of 59% of EP arm and 72% of IP arm (hazard ratio (HR) of 0.623). Planned sample size was 220 in total to give a power of 80% with a one-sided alpha of 5%, an accrual period of 6 years and a follow-up period of 3 years. Results: Between April 2013 and October 2018, 221 pts with a median age of 66 years, pathological stage I (54%), SCLC (53%), were randomly assigned to the EP arm (n = 111) or the IP arm (n = 110). In the second interim analysis, the predictive probability that IP would be superior to EP at the time of the primary analysis was 15.9%, which led to early termination of the trial. With a median follow-up of 24.1 months, 3-year RFS was 65.4% versus 69.0% with HR of 1.076 (95% CI, 0.666-1.738; log-rank test, one-sided P= 0.619). In the subgroup analyses of histology, 3-year RFS in SCLC was 65.2% versus 66.5% with HR of 1.029 (95% CI, 0.544-1.944), and 3-year RFS in LCNEC was 66.5% versus 72.0% with HR of 1.072 (95% CI, 0.517-2.222). Overall survival at 3 years was 84.1% versus 79.0% with HR of 1.539 (95% CI, 0.760-3.117). Proportions of treatment completion were 87.4% (EP) and 72.7% (IP). Incidences (EP/IP) of grade 3 or 4 febrile neutropenia (20.2/3.7%) or neutropenia (97.2/35.8%) were more common in EP. Grade 3 or 4 diarrhea (0.9/8.3%) or anorexia (6.4/11.1%) were more common in IP. One treatment-related death due to tracheal bleeding was observed in IP. Conclusions: This study failed to show the superiority of IP to EP in RFS for pts with completely resected HGNEC. EP is still a standard treatment for this population. Clinical trial information: UMIN000010298.
A phase I safety and feasibility study of neoadjuvant chemoradiation plus pembrolizumab followed by consolidation pembrolizumab in resectable stage IIIA non-small cell lung cancer.
Authors: Lemmon Christopher , Videtic Gregory M.M. , Murthy Sudish C. , Stephans Kevin L. , Shapiro Marc A. , Ahmad Usman , Raymond Daniel , Velcheti Vamsidhar , Bribriesco Alejandro , Pennell Nathan A. 
Published: May 2020

9009 Background: Patients (pts) with resectable stage IIIA non-small cell lung cancer (NSCLC) have high rates of recurrence despite concurrent chemoradiation (CRT) followed by surgery. Immune checkpoint inhibitor consolidation has improved outcomes in unresectable stage III pts. Here we report the addition of concurrent neoadjuvant pembrolizumab (P) to CRT in stage IIIA patients to determine the safety and feasibility of this approach. Methods: Pts with stage IIIA NSCLC deemed resectable by a thoracic surgeon received neoadjuvant CRT consisting of cisplatin, etoposide, and concurrent P (200mg every 3 weeks x 3) with 45 Gy in 25 fractions. Pts without progression underwent resection followed by 6 months of consolidation P. The primary objective was feasibility and safety (defined as ≤30% grade 3 or higher pulmonary toxicity or any grade 4/5 nonhematologic toxicity). Ten pts were to be enrolled in Part 1, and if 2 or fewer pts had events then an additional 10 pts were to be enrolled. Secondary objectives were progression free survival (PFS), overall response rate (ORR), and pathologic complete response rate (pCR). Results: The median age of 9 enrolled pts was 66 years (range 49-76). 67% were female. 8 pts were assessable for radiographic response with an ORR of 75%. One pt came off study for progression prior to surgery and one had pleural metastases found during surgery so resection was aborted. Six pts underwent complete resection with a pCR rate of 67% (4/6). Consolidation P was started on 4 pts, with 3 completing treatment and 1 declined further treatment after 3 cycles. Median follow-up is 19.6 months and median PFS has not been reached. None of the patients who underwent resection have recurred. Serious adverse events were reported in all 9 pts with most significant being 2 grade 5 events: 1 due to pneumocystis pneumonia after resection but prior to consolidation, and 1 due to cardiac arrest during the neoadjuvant phase. Grade 3 events included 1 episode each of pneumonitis, bronchopleural fistula, acute kidney injury, colon perforation, and febrile neutropenia. Conclusions: The addition of P to neoadjuvant CRT in resectable stage IIIA pts resulted in a high pCR rate at resection. Although the relationship between grade 5 events and the addition of P was not clear, the stopping rule for infeasibility was met. As other larger studies are underway, the trial was halted rather than amended. This investigator initiated trial was funded by Merck. Clinical trial information: NCT02987998.
Consolidation nivolumab/ipilimumab versus nivolumab following concurrent chemoradiation in patients with unresectable stage III NSCLC: A planned interim safety analysis from the BTCRC LUN 16-081 trial.
Authors: Yan Melissa , Durm Greg Andrew , Mamdani Hirva , Ernani Vinicius , Jabbour Salma K. , Naidoo Jarushka , Hrinczenko Borys , Leal Ticiana , Feldman Lawrence Eric , Kloecker Goetz H. , Fujioka Naomi , Fidler Mary J. , Hanna Nasser H. 
Published: May 2020

9010 Background: Consolidation PD-1/PD-L1 inhibition after chemoradiation (CRT) for unresectable stage III NSCLC improves overall survival. In stage IV NSCLC, the combination of nivolumab/ipilimumab improved overall survival compared to chemotherapy in patients with PD-L1 > 1% and performed favorably in patients with PD-L1 < 1%. The safety of consolidation nivolumab/ipilimumab after CRT has not been previously assessed. Methods: In this randomized, multi-center, phase II study, a total of 105 planned pts with unresectable stage IIIA/IIIB NSCLC will receive chemoradiation, then randomize 1:1 to either nivolumab 480mg IV q4 wks (Arm A) or nivolumab 3mg/kg IV q2 wks + ipilimumab 1mg/kg IV q6 wks (Arm B), for up to 24 wks. In this planned interim analysis, the safety of the first 50 patients, with 25 patients treated on each arm, is assessed. Results: From 9/2017 to 6/2019, the first 50 patients were accrued and analyzed for this planned safety analysis. Baseline characteristics for Arm A/B: median age 64/62, stage IIIA 17/16, stage IIIB 8/9, non-squamous 14/13, squamous 11/12. The median number of cycles completed in Arm A was 6 (range 1-6, cycle length q4 wks) and in Arm B was 4 (range 1-4, cycle length q6 wks). The rate of treatment-related adverse events leading to discontinuation of therapy was 16% in Arm A and 40% in Arm B. The percentage of patients with any > grade 3 adverse event (AE) was 32% in Arm A and 44% in Arm B. With respect to immune-related AE (irAEs), the percentage of patients with any ≥grade 2 was 44% in Arm A and 60% in Arm B; any ≥ grade 3 irAEs was 16% in Arm A and 32% in Arm B. The incidence of > grade 2 pneumonitis was 16% in Arm A and 36% in Arm B. The percentage of patients with > grade 3 pneumonitis was 4% in Arm A and 20% in Arm B. No treatment-related deaths were reported on either arm. Conclusions: In the post chemoradiation setting, the incidence of > grade 3 toxicity was greater in the consolidative nivolumab/ipilimumab arm, which resulted in a higher rate of treatment discontinuation than nivolumab alone. The Data and Safety Monitoring Board recommended continued enrollment without modification to the trial and the study currently remains open to accrual (66 of 105 patients have been enrolled as of 1/17/2020). Clinical trial information: NCT03285321.