bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of venetoclax in combination with azacitidine or decitabine in an outpatient setting in patients with untreated acute myeloid leukemia.
Authors: Manda Sudhir , Anz Bertrand Marquess , Benton Christopher , Broun E. Randolph , Yimer Habte Aragaw , Melear Jason M. , Cruz Jose C. , Fanning Suzanne , Sharman Jeff Porter , Kang Kingston , Svensson Anders , Pai Madhavi , Geils George F. , Renshaw John Scott , Donnellan William Bruce 
Published: June 2022

7044 Background: Venetoclax (Ven), a highly selective BCL-2 inhibitor, combined with hypomethylating agents (HMAs) azacitidine (Aza) or decitabine (Dec) is approved for the treatment of newly diagnosed acute myeloid leukemia (ND AML) in patients (pts) who are ineligible to receive intensive chemotherapy. Previous clinical studies initiated Ven + HMA in an inpatient setting due to concerns of tumor lysis syndrome (TLS). This Phase 3b, single-arm, multicenter, open-label study (NCT03941964) evaluated the efficacy and safety of Ven + HMA in a US community-based outpatient setting. Methods: Pts with ND AML who were ineligible to receive intensive chemotherapy, had no evidence of spontaneous TLS at screening, and were deemed an appropriate candidate for outpatient initiation of Ven + HMA by the investigator were eligible. Pts received Ven (400 mg) in combination with Aza (75 mg/m2) or Dec (20 mg/m2) for up to 6 cycles during the study period. Pts could continue receiving commercially acquired Ven after the study period. All pts received TLS prophylaxis. The primary endpoint was the composite complete remission (CR) rate (CR + CR with incomplete hematologic recovery [CRi]) per modified International Working Group criteria. Secondary endpoints included CR or CRi rates and transfusion independence (TI). TLS was assessed per Howard criteria (Howard. N Engl J Med. 2011;364:1844). Results: At the 19 Oct 2021 cutoff date, 60 pts were enrolled and treated (Ven + Aza, n=30; Ven + Dec, n=30). Efficacy outcomes are shown in the Table. The composite CR rate was 58%. CR and CRi rates were 13% and 45%, respectively. Most pts (>50%) maintained TI, and 41% and 57% of pts dependent on red blood cells or platelets, respectively, converted to TI. Bone marrow blast clearance was achieved in 42 pts (70%) at a median 26 days after treatment initiation. The most common (≥50%) AEs were anemia (75%), neutrophil count decrease (55%), white blood cell count decrease (52%), and nausea (50%). Serious AEs occurred in 67% of pts, most commonly (≥15%) febrile neutropenia (28%) and sepsis (15%). Two pts (3%) had TLS; neither event led to treatment discontinuation. Of pts who achieved blast clearance, 12/42 (29%) had a new event of myelosuppression post-blast clearance and prior to the next cycle. Conclusions: The results of this US community-based study indicate that Ven + HMA is an effective treatment option for pts with ND AML and, with appropriate TLS prophylaxis and monitoring, can safely be initiated in an outpatient setting. Clinical trial information: NCT03941964. [Table: see text]
Incorporating patient-reported outcome data into a hematopoietic cell transplant survival calculator.
Authors: Shaw Bronwen E. , Flynn Kathryn E. , Cusatis Rachel , D'Souza Anita , Hamilton Betty Ky , Horowitz Mary M. , Mattila Deborah , Phelan Rachel , Lee Stephanie , Brazauskas Ruta 
Published: June 2022

7045 Background: The Center for International Blood and Marrow Transplant Research (CIBMTR) provides a validated 1-year Overall Survival (OS) calculator to estimate outcomes for individual patients prior to allogeneic Hematopoietic Cell Transplant (HCT) to inform risk. The calculator considers pre-HCT clinical and demographic characteristics, but not patient-reported outcome (PRO)s. Pre-HCT PRO scores have been associated with OS. We hypothesized that adding the baseline PRO score to the calculator will enhance its performance in predicting OS. Methods: In addition to established covariates,we considered pre-HCT PRO scores, collected on five (published) prospective randomized clinical trials performed through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Measures used were the SF36 physical component score (PCS) and mental component score (MCS), and the FACT-BMT Trial outcome index (TOI). We also investigated inclusion of a single question from the SF36: In general, would you say your health is: excellent/very good/good vs fair/poor. Patients were ≥18. Results: 1,033 patients were included, 341 (33%) completed only the SF36, 339 (33%) only the FACT-BMT and 353 (34%) both, per study design. HCT occurred 2004-2014, and the population was diverse with respect to disease, stage, demographics, and transplant characteristics. When adjusted for clinical characteristics, the PCS was significantly predictive of mortality (HR=0.88, 95%CI 0.81-0.96, p=0.0021), while the MCS and TOI were not. The single general health question was also significantly associated with mortality (HR=0.52, 95%CI 0.35-0.74, p=0.0004). Addition of PRO scores to the calculator did not result in a significant change in the model’s predictive ability as measured by Harrell’s concordance statistic (Table). Conclusions: In this large analysis, we confirmed the significant, independent association of pre-HCT PRO scores with OS. We showed, for the first time in this setting, that a single general health question is as accurate as the full SF36 measure for predicting survival, but we did not find support for the hypothesis that adding PROs to the calculator improved its performance. Estimates of baseline PRO measure effect on mortality and model concordance statistics at 1-year post-HCT. [Table: see text]
Non-myeloablative allogeneic blood or marrow transplantation (AlloBMT) with post-transplant cyclophosphamide (PTCy) for peripheral T-cell lymphoma (PTCL): Improved outcomes with peripheral blood (PB) allografts and increased total body irradiation (TBI) to 400 cGV.
Authors: Sterling Cole Harris , Hughes Michael Sang , Tsai Hua-Ling , Fuchs Ephraim Joseph , Yarkony Kathryn , Varadhan Ravi , Gladstone Douglas Edward , Swinnen Lode J. , Jones Richard J. , Wagner-Johnston Nina D. , Ambinder Richard F. 
Published: June 2022

7047 Background: The use of PTCy for graft-versus host-disease (GVHD) prophylaxis has revolutionized alloBMT, but there is limited published experience in PTCL. Methods: All patients with PTCL who received a non-myeloablative alloBMT using PTCy-based GVHD prophylaxis between January 2004 and December 2020 at Johns Hopkins Hospital were analyzed. Standard population statistics were used. Results: Sixty-five patients were identified. The median age was 59 years (range, 24-75 years). Lymphoma histology included PTCL-not otherwise specified (n=24), ALK-negative anaplastic large cell lymphoma (n=14), angioimmunoblastic T-cell lymphoma (n=7), enteropathy-associated T-cell lymphoma (n=6), hepatosplenic T-cell lymphoma (n=4), and other (n=10). Eleven patients were in first complete remission (CR1, 17%). The remaining patients were in first partial remission (PR1) or underwent salvage therapy to at least PR prior to transplant. Forty-eight patients received an alloBMT from a haploidentical related donor (74%), 10 from a fully matched donor (15%), and 7 from a mismatched unrelated donor (mMUD, 11%). All patients received non-myeloablative conditioning with fludarabine, cyclophosphamide, and TBI. The graft source was bone marrow (BM) in the first 46 patients (71%). Because of relatively high relapse rates, in 2018 we began using PB and increased TBI from 200 to 400 cGy; the remaining 19 patients (29%) received this regimen. GVHD prophylaxis was PTCy, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. With a median follow up of 2.8 years, the 3-year progression-free survival (PFS) for the entire cohort was 39% (95% confidence interval [CI] 28-54%), and the 3-year overall survival (OS) was 43% (95% CI 31-58%). The cumulative incidence (CuI) of relapse and non-relapse mortality (NRM) at 1 year was 25% (95% CI 14-35%) and 12% (95% CI 4-20%), respectively. Among 29 cases of GVHD (45%), 2 were grade 3-4 acute GVHD (3%) and 3 were severe chronic GVHD (5%). Univariate analysis including age, histology, mMUD, PB/400cGy, and CR1 revealed only PB/400 cGy TBI as a significant predictor of survival, relapse, or NRM. Outcomes by source. Conclusions: AlloBMT with non-myeloablative conditioning and PTCy is safe and well-tolerated in patients with PTCL. Our preliminary data suggest increasing TBI dose to 400 cGy and using PB allografts may offer improved disease control and better survival outcomes, though additional studies are needed to confirm these findings. [Table: see text]
Anti–PD-1 antibody (sintilimab) plus decitabine as first-line treatment for patients with higher-risk myelodysplastic syndrome (MDS): Preliminary results from a single-arm, open-label, phase II study.
Authors: Wang Jing , Li Siqi , Jiang Hao , Chang Ying-Jun , Zhao xiao-Su , Jia jin-Song , Zhu xiao-Lu , Gong li-Zhong , Liu xiao-Hong , Yu wen-Jing , Huang xiao-Jun 
Published: June 2022

7052 Background: Hypomethylating agents (HMAs) are the preferred treatment for untreated patients (pts) with higher-risk MDS, but the survival of pts after HMAs treatment is poor. It has been demonstrated that the PD-1/PD-L1 expression was upregulated by HMAs in MDS pts, providing a strong rationale for combining HMAs with PD-1 antibody for MDS treatment. Therefore, this single-arm, open-label, clinical trial was performed to evaluate safety and efficacy of Sintilimab plus decitabine for pts with higher-risk MDS (ChiCTR2100044393). Methods: Adult pts with higher-risk MDS by the IPSS-R were enrolled. Patients received decitabine 20mg/m2 intravenously daily for 5 days and sintilimab 200mg IV starting on the first and 22nd day of a cycle every 42 days until unacceptable toxicity, relapse, or progression, for a maximum of 8 cycles. The primary endpoint was overall response rate (CR+PR+mCR). Simon’s optimal two-stage design was employed.If five or more pts in stage I (13 pts) achieved ORR, the study would enroll 34 additional pts in stage II (47 pts). Secondary endpoints included safety, and survival outcomes. The relationship between expression levels of immune-checkpoint and efficacy of the combination therapy, as well as other potential biomarkers were also explored via genomic profiling. Results: At data cut-off (January 31, 2022), 21 pts were enrolled with a median follow-up time of 5.8 months. The median age of pts was 64 years (range 30-83), and the other characteristics are summarised in Table.The ORR was 62%,with six pts reaching complete response (CR),four pts reaching marrow CR and three pts achieved marrow CR+ hematologic improvement (HI). In addition,four pts reaching HI. The most common grade 3 TEAEs( > 10%) were febrile neutropenia (76.2%) and pulmonary infection (38.1%). No grade 4 TEAEs and treatment-related deaths occurred. A total of 12 pts （57.1%）experienced immune-related adverse event, including rash (28.6%), pneumonia (9.5%), hypothyroidism (9.5%), elevated serum bilirubin (4.8%) and transpeptidase (4.8%), which were all resolved by glucocorticoid. In these 21 pts, the most frequently mutated genes are ASXL1（28.6%）, RUNX1 (14.3%) and TET2(14.3%). Updated biomarker data will be presented during the ASCO meeting. Conclusions: To the best of our knowledge, this is the first study to evaluate the efficacy and safety of sintilimab plus decitabine in pts with untreated higher-risk MDS. The preliminary results demonstrate that the combination therapy is relatively safe with anti-tumor activity. Clinical trial information: ChiCTR2100044393. [Table: see text]
Long-term utilization and benefit of luspatercept in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) from the MEDALIST trial.
Authors: Fenaux Pierre , Santini Valeria , Komrokji Rami S. , Zeidan Amer Methqal , Garcia-Manero Guillermo , Buckstein Rena , Miteva Dimana , Keeperman Karen , Holot Natalia , Zhang Jennie , Hughes Christina , Rosettani Barbara , Yucel Aylin , Platzbecker Uwe 
Published: June 2022

7056 Background: Luspatercept was previously shown to improve anemia in the phase 3 MEDALIST trial of pts with LR-MDS ineligible, intolerant, or refractory to erythropoiesis-stimulating agents (ESAs). Here, we report the long-term clinical value of luspatercept treatment (Tx) in pts from the MEDALIST study including dosing and rates of progression to acute myeloid leukemia (AML) and high-risk MDS (HR-MDS). Methods: Eligible pts were ≥ 18 y of age, had LR-MDS requiring regular red blood cell (RBC) transfusions, and were ineligible/intolerant or refractory to ESAs. Pts were randomized 2:1 to subcutaneous luspatercept or placebo every 3 wk for 24 wk. The primary endpoint was RBC transfusion independence (RBC-TI) ≥ 8 wk during wk 1–24. MEDALIST pts were eligible for enrollment into the long-term follow-up study. Median duration of Tx and cumulative duration of response were determined by Kaplan–Meier (KM) analysis. Total person-years for pts at risk of HR-MDS/AML progression was calculated from LR-MDS diagnosis to HR-MDS/AML diagnosis, or to last HR-MDS/AML follow-up date for pts who did not progress. Results: As of January 15, 2021, the median duration of Tx was 11.70 (95% CI, 8.97–16.33) mo for luspatercept pts and 5.52 (95% CI, 5.52–5.59) mo for placebo pts. Of those enrolled in MEDALIST, 106/153 (69.3%) pts receiving luspatercept and 64/76 (84.2%) receiving placebo escalated to the maximum dose of 1.75 mg/kg. During the entire Tx phase, RBC-TI ≥ 8 wk was observed in 74/153 (48.4%) and 12/76 (15.8%) pts in the luspatercept and placebo arms, respectively, with a median cumulative duration of response of 80.7 (95% CI, 53.71–154.14) wk and 21.0 (95% CI, 10.86–NE) wk, respectively. During the entire Tx period, RBC-TI ≥ 16 wk was observed in 48/153 (31.4%) and 6/76 (7.9%) pts in the luspatercept and placebo arms, respectively (Table). Among pts randomized to luspatercept, 13/153 (8.5%) progressed to HR-MDS/AML during the entire Tx period, compared with 5/76 (6.6%) for placebo. The total person-years for pts randomized to luspatercept at risk of progressing to HR-MDS/AML was 401.7 y vs 190.9 y for placebo. Conclusions: Pts receiving luspatercept had an extended period of clinical benefit and > 50% of pts continued to receive luspatercept for > 1 y, the majority of whom underwent dose escalations to achieve an optimal response. Pts experienced durable responses with luspatercept, with a median cumulative duration of RBC-TI response of approximately 20 mo. Pts receiving luspatercept also appeared to have a longer time to HR-MDS/AML progression than those receiving placebo.[Table: see text]
Outcomes of classic Hodgkin lymphoma, relapsed within one year of diagnosis, in the era of novel agents.
Authors: Desai Sanjal , Spinner Michael Alexander , David Kevin A. , Bachanova Veronika , Goyal Gaurav , Saba Raya , Dorritie Kathleen Anne , Azzi Jacques Mario , Harris Elyse , Fusco Brendon , Sumransub Nuttavut , Hatic Haris , Ibrahim Uroosa , Iyengar Siddharth , Rappazzo Katherine Cynthia , Baidoun Firas , Orellana-Noia Victor Manuel , Magid Diefenbach Catherine S. , Advani Ranjana H. , Micallef Ivana N. M. 
Published: June 2022

7515 Background: Primary refractory disease (PRD) and early relapse (ER) are predictors of poor prognosis in classic Hodgkin lymphoma (cHL). In this multicenter retrospective study, we describe outcomes of PRD and ER in pts with relapsed/refractory (R/R) cHL treated with salvage therapy (ST) and autologous stem cell transplant (ASCT). Methods: Of 14 sites, adult patients with R/R cHL who received ST and underwent ASCT were enrolled. PRD was defined as progression on frontline chemoimmunotherapy or within 6 months of diagnosis. ER was defined as relapse from 6 months-1 yr of diagnosis. Pts who relapsed >1 yr of diagnosis were called late relapses (LR). Study objectives were Overall response rates (ORR), CR rates, PFS, and OS. Results: Of 986 total pts, 160 had PRD, 365 had ER and 461 had LR. Significantly higher number of pts with PRD, but not ER, had bulky disease (41% vs 27%, p<0.01) and B symptoms (53% vs 38%, p<0.001) than LR. Higher proportions of pts with PRD and ER required >1 line of ST (44% vs 30% vs 23%, p<0.001) before ASCT and received BV maintenance (25% vs 24% vs 16%, p<0.05). When adjusted for B symptoms and Bulky disease, PRD and ER had significantly lower ORR (65% vs 76% vs 84%, p<0.001) and CR (37% vs 46% vs 57%, p<0.001) to first ST than LR. Pts with PRD and ER had significantly lower PFS (56.3%, 61.4%, vs 77.6%, p<.0001) and OS (93% vs 89% vs 94%, p=0.01) than LR. In pts with ER, Brentuximab/bendamustine (BBV) and brentuximab vedotin/nivolumab (BV/nivo) had a trend towards higher ORR (92% vs 92% vs 75%) but significantly higher CR (79.2% vs 76% vs 42%, p<0.01) than platinum based chemotherapy (PBC). In pts with PRD, BBV and BV/Nivo had a statistically insignificant trend towards higher ORR and CR than PBC. The table shows 2 yr PFS by type of ST in PRD, ER, LR. There was no difference in PFS by time to relapse in BV/nivo, CPI and miscellaneous agents. BV/Nivo had a significantly higher PFS than PBC in PRD (88% vs 48%, p<0.05) and ER (95% vs 57%, p<0.05). There was no difference in PFS of PBC and other ST in PRD, ER or LR. OS was not significantly associated with type of ST in either group. Conclusions: PRD and ER are associated with lower response to ST and survival after ASCT compared to late relapse. In pts with PRD and ER, BV/Nivo has high ORR and CR and leads to significantly higher PFS comparable to pts with late relapse and may be preferable ST regardless of time to relapse. [Table: see text]
Outcomes by BCL2 and MYC expression and rearrangements in untreated diffuse large B-cell lymphoma (DLBCL) from the POLARIX trial.
Authors: Morschhauser Franck , Jiang Yanwen , Jardin Fabrice , Herrera Alex Francisco , Sehn Laurie Helen , Herbaux Charles , Flowers Christopher , Phillips Tycel Jovelle , López Guillermo Armando , Magid Diefenbach Catherine S. , Gregory Gareth , Kim Austin Injae , Barbui Anna Maria , Balasubramanian Sandhya , Harris Will , Hirata Jamie , Paulson Joseph N. , Lee Calvin , Lenz Georg 
Published: June 2022

7517 Background: Overexpression of BCL2 and MYC, and translocation of MYC, BCL2, and BCL6, are associated with poorer outcomes in patients (pts) with DLBCL (Horn et al. Blood 2013). We previously reported progression-free survival (PFS) from POLARIX in subgroups of pts with DLBCL receiving Pola-R-CHP or R-CHOP, including pts with double expressor lymphoma (DEL; favoring Pola-R-CHP: hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.42–0.97), and double- or triple-hit lymphoma (DHL/THL; favoring R-CHOP: HR 3.81, 95% CI 0.82–17.64) (Tilly et al. NEJM 2022). In this prespecified exploratory analysis, we further analyzed immunohistochemistry (IHC) expression status of BCL2, MYC, and rearrangements (R) of BCL2, BCL6 and MYC as independent prognostic markers. We also explored the prognostic impact of DEL within treatment arms. Methods: BCL2 and MYC protein expression were assessed by IHC and identified as IHC+ (≥50% [BCL2]/≥40% [MYC]) or IHC−; MYC-R, BCL2-R, and BCL6-R were detected by fluorescence in situ hybridization (Tilly et al. NEJM, 2022). Exploratory multivariate Cox regression models were adjusted for treatment, stratification factors (IPI, bulky disease, geographic region), age >60 years, cell of origin, and biomarker evaluated, as appropriate. Results: The prevalence, univariate HR, and 2-year (yr) PFS estimates of BCL2+/MYC+ and BCL2-R/ MYC-R/ BCL6-R subgroups are presented (Table) except for BCL6-R, because all 4 PFS events in this subgroup were with Pola-R-CHP. Multivariate analyses results for Pola-R-CHP vs R-CHOP in pts with BCL2+ (HR 0.60, 95% CI 0.43–0.86) and in pts with MYC+ (HR 0.63, 95% CI 0.45–0.89) were similar to results of univariate analyses. Multivariate analyses of other subgroups were not performed due to the low pt number with BCL2-R/ MYC-R/ BCL6-R. While pts with DEL treated with Pola-R-CHP had improved PFS vs pts treated with R-CHOP (HR 0.64, 0.42–0.97), the prognostic impact of DEL vs non-DEL was more pronounced with R-CHOP (univariate HR 1.53, 95% CI 1.06–2.21; multivariate HR 1.29, 95% CI 0.88–1.91) vs Pola-R-CHP (univariate HR 1.10, 95% CI 0.72–1.69; multivariate HR 1.42, 95% CI 0.89–2.28). Conclusions: Multivariate analyses support the benefit of Pola-R-CHP in pts with BCL2+ and MYC+ DLBCL. The poor prognostic impact associated with DEL appears reduced in Pola-R-CHP- vs R-CHOP-treated pts. Clinical trial information: NCT03274492. [Table: see text]
Fixed-duration (FD) ibrutinib (I) + venetoclax (V) for first-line (1L) treatment (tx) of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Three-year follow-up from the FD cohort of the phase 2 CAPTIVATE study.
Authors: Wierda William G. , Barr Paul M. , Siddiqi Tanya , Allan John N. , Kipps Thomas J. , Trentin Livio , Jacobs Ryan , Jackson Sharon , Tedeschi Alessandra , Opat Stephen , Bannerji Rajat , Kuss Bryone J. , Moreno Carol , Croner Lisa J. , Szafer-Glusman Edith , Zhou Cathy , Szoke Anita , Dean James P. , Ghia Paolo , Tam Constantine Si Lun 
Published: June 2022

7519 Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of 1L I+V in CLL. The primary analysis (PA) evaluating FD tx with I+V was previously presented (Ghia et al., ASCO 2021). Here we present 3-y follow-up results from the FD cohort. Methods: Patients (pts) aged ≤70 y with previously untreated CLL/SLL received 3 cycles of I then 12 cycles of I+V (I 420 mg/d orally; V ramp-up to 400 mg/d orally). Responses were investigator assessed per iwCLL 2008 criteria. Undetectable minimal residual disease (uMRD; <10-4) was measured by 8-color flow cytometry. Serious AEs (SAEs) deemed related to I reported >30 d after last dose of study drug were collected. Results: 159 pts were enrolled (median age 60 y), including pts with high-risk features of del(17p)/ TP53 mutation (17%), unmutated IGHV (uIGHV; 56%), and complex karyotype (19%). 147 (92%) and 149 (94%) pts completed tx with I and V, respectively. With 1 y of additional follow-up since PA, median time on study was 39 mo (range 1-41). ORR was 96% and was consistent (96%-97%) in pts with high-risk features (Table).The primary endpoint of complete response (CR) including CR with incomplete bone marrow recovery (CRi) rate in pts without del(17p) (n=136) increased nominally from 56% (95% CI, 48-64) to 58% (95% CI 50-66); in all pts, CR rate increased from 55% (95% CI 48-63) to 57% (95% CI 50-65). In pts achieving CR, 93% had durable responses lasting ≥12 mo post-tx. Of pts with uMRD in peripheral blood at 3 mo post-tx, 66/85 (78%) evaluable pts maintained uMRD through 12-mo post-tx. At 36 mo, PFS was 88% (95% CI 82‒92) and OS was 98% (95% CI 94‒99); similar rates were seen in pts with high-risk features (Table). All pts are off tx; no new SAEs of any kind have occurred since the PA. Available data on relevant mutations in BTK, PLCɣ2, or BCL-2 at time of PD will be presented. As of January 2022, 12 pts were retreated with single-agent I after PD (tx duration range 3-29 mo); of evaluated pts, 7/9 had partial responses and 2/9 had stable disease. Conclusions: Fixed duration I+V continues to provide deep, durable responses and clinically meaningful PFS, including in pts with high-risk disease features, representing an all-oral, once-daily, chemotherapy-free FD regimen for previously untreated pts with CLL/SLL. With an additional 1 y of follow-up, no OS events or SAEs occurred. Manageable safety profile is unchanged as previously reported. To date, successful single-agent I retreatment responses are observed. Clinical trial information: NCT02910583. [Table: see text]