bluuebunny/crossref_metadata_2025_split huggingface dataset:
Letermovir prophylaxis and cytomegalovirus reactivation in adult allogeneic hematopoietic cell transplant recipients with graft versus host disease.
Authors: Wolfe Delaney , Zhao Qiuhong , Siegel Emma G , Puto Marcin M , Efebera Yvonne Adeduni , Tossey Justin C 
Published: June 2021

7004 Background: Cytomegalovirus (CMV) is the most common clinically significant infection after allogeneic hematopoietic-cell transplantation (allo-HCT) and is associated with increased mortality. The risk for CMV reactivation increases with HLA mismatch, high dose corticosteroids, and graft versus host disease (GVHD). GVHD contributes to significant morbidity and mortality and is treated with immunosuppressive therapies that further increase CMV infection risk. In a phase III trial, letermovir prophylaxis had a lower incidence of CMV infection post-allo-HCT in patients at high risk of CMV reactivation when compared to placebo when given up to day +100. There is a lack of data concerning the effectiveness of letermovir in patients who develop GVHD and may continue letermovir past day +100. Methods: This was a single-center, retrospective study conducted at The Ohio State University. Demographics and transplant details were collected from medical records. The primary outcome was incidence of clinically significant CMV infection (CS-CMVi) within 200 days of allo-HCT. Secondary outcomes included incidence of CMV viremia, duration of letermovir therapy, mortality, and risk factors for CS-CMVi. Early death without CMV was treated as a competing risk for CS-CMVi, while relapse was a competing risk for non-relapse mortality (NRM). Proportional subdistribution or Cox hazards models were used to evaluate the association between use of letermovir and risk of CS-CMVi, NRM, or overall survival (OS) adjusting for potential confounding factors, where use of letermovir and GVHD were treated as time-dependent variables. Results: A total of 262 CMV-seropositive patients who received an allo-HCT between June 1, 2016 and June 30, 2020 were included. Of these, 119 patients received letermovir prophylaxis. A total of 111 patients received treatment for CS-CMVi, which included 82 of 143 (57%) who did not receive letermovir compared to 29 of 119 (24%) who received letermovir. Incidence of CMV viremia was significantly reduced with the use of letermovir in all patients (HR 0.21, 95% CI 0.12–0.34, p < 0.001) and among patients with acute GVHD grade >2 within 200 days post-allo-HCT (HR 0.12, 95% CI 0.05–0.32, p < 0.001), adjusting for age, gender, GVHD prophylaxis and use of ATG or T-cell depleted graft. The median duration of letermovir therapy was 97 days. Nine patients were continued on letermovir indefinitely for recurrent CMV viremia. Patients who received letermovir had decreased NRM (HR 0.41, 95% CI 0.18-0.96, p = 0.04) and improved OS (HR 0.46, 95% CI 0.23-0.95, p = 0.04). Conclusions: Letermovir prophylaxis significantly decreased CS-CMVi and improved NRM and OS in this real-world analysis. In addition, patients with acute GVHD had significantly less CMV viremia, suggesting potential benefit in continuing letermovir prophylaxis in this patient population.
Second-line bosutinib (BOS) for patients (pts) with chronic phase (CP) chronic myeloid leukemia (CML): Final 10-year results of a phase 1/2 study.
Authors: Gambacorti-Passerini Carlo , Brümmendorf Tim H. , Kim Dong-Wook , Goh Yeow Tee , Dyagil Irina S , Pagnano Katia , Batai Arpad , Turkina Anna G. , Leip Eric , Purcell Simon , Leone Jocelyn M , Viqueira Andrea , Cortes Jorge E. 
Published: June 2021

7009 Background: BOS is approved for Philadelphia chromosome (Ph)+ CML resistant/intolerant to prior therapy and newly diagnosed Ph+ CP CML. In a phase 1/2 study, second-line BOS showed durable efficacy and manageable toxicity in pts with imatinib-resistant (IM-R) or -intolerant (IM-I) Ph+ CP CML. Methods: This final efficacy and safety analysis of the phase 1/2 study and extension study was based on ≥10 y of follow-up (FU). Ph+ CP CML pts who received BOS starting at 500 mg/d after prior treatment (Tx) with imatinib only were included. Results: 19% of pts were on BOS at y 10, and 13% were still on BOS at study completion after ≥10 y; 19% completed ≥10 y of FU. Median duration of Tx and FU were 26 and 54 mo, respectively. Median (range) dose intensity was 436 (87–599) mg/d. The most common primary reasons for permanent Tx discontinuation were lack of efficacy (unsatisfactory response or disease progression; 27%) and adverse events (AEs; 26%). In pts with a valid baseline assessment, cumulative complete cytogenetic response (CCyR), major molecular response (MMR) and MR4 rates (95% CI), respectively, were 50% (43–56), 42% (35–49) and 37% (30–44) (IM-R: 48% [41–56], 46% [37–55] and 39% [31–48]; IM-I: 53% [41–64], 36% [25–48] and 33% [22–45]). Responses were durable, with estimated probabilities of maintaining CCyR, MMR and MR4 > 50% after ≥10 y (Table). At 10 y, cumulative incidence of on-Tx progression/death was 24% and Kaplan-Meier (K-M) overall survival 72% (Table); 55 deaths (IM-R: n = 41; IM-I: n = 14) occurred on study, none BOS-related. Any grade Tx-emergent AEs (TEAEs) in ≥40% of pts were diarrhea (86%), nausea (46%) and thrombocytopenia (42%). Pleural effusion, cardiac and vascular TEAEs occurred in 13%, 12% and 11% of pts, respectively. 28% of pts had AEs leading to permanent Tx discontinuation; most common (≥2% of pts) were thrombocytopenia (6%), neutropenia (2%) and alanine aminotransferase increased (2%). Conclusions: These 10-y data are consistent with prior results of durable efficacy and manageable toxicity with second-line BOS and support long-term BOS use in CP CML pts after imatinib failure. Clinical trial information: NCT00261846 and NCT01903733. [Table: see text]
A registry-based, observational safety study of inotuzumab ozogamicin (InO) treatment in patients (pts) with B-cell precursor acute lymphoblastic leukemia (ALL) who proceeded to hematopoietic stem cell transplant (HSCT).
Authors: De Lima Marcos J.G. , Kebriaei Partow , Lanza Francesco , Cho Christina , Giralt Sergio , Popradi Gizelle , Hemmer Michael T , Zhang Xin , Shah Richa , Welch Verna L. , Vandendries Erik , Stelljes Matthias , Marks David I. , Saber Wael 
Published: June 2021

7017 Background: InO is a CD22-directed antibody-drug conjugate indicated for treatment of relapsed/refractory (R/R) ALL. InO has been associated with hepatotoxicity and hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), particularly post-HSCT. Registry data (Center for International Blood and Marrow Transplant Research [CIBMTR]) was analyzed to assess toxicity in pts with ALL who received InO prior to HSCT. Methods: CIBMTR patient data are being collected for a 5-year period after US approval of InO (Aug 2017 – Aug 2022). Data from US pts age ≥18 y treated with InO who proceeded to allogeneic HSCT were included. Using interim data at 3 y, we evaluated post-HSCT outcomes, including clinical status, overall survival, transplant-related (non-relapse) mortality (NRM), relapse, death after relapse (time from HSCT to death after the first 28 d from any cause with prior relapse/progression post-HSCT), and investigator-defined adverse events, including hepatic VOD/SOS. All statistical analyses are descriptive. Results: Data accrued from 18 Aug 2017 to 17 Aug 2020 for 131 adult pts (median age 40 y) who proceeded to first allogeneic HSCT: 31% in first complete remission (CR1), 46% in CR2, 13% in ≥CR3, 5% in 1st relapse, 2% in ≥3rd relapse, and 3% in primary induction failure. A majority (70%) had transplants from peripheral blood stem cells, and 47% involved an HLA-identical sibling or other related donor. Nearly half received myeloablative conditioning regimens. Before HSCT, 36% of pts received 1 cycle of InO, 46% had 2 cycles, and 17% had ≥3 cycles. Half (48%) received InO as a single agent. Median time from last dose of InO to HSCT was 2.0 mo (range: 0.4–26.2). At time of data-lock (11 Nov 2020), post-transplant data were available for 131 pts. Outcomes for these pts are shown in the Table. Among a subgroup of adults with active R/R ALL (n = 91) at time of HSCT (median of 4 lines prior therapy), VOD/SOS incidence within 100 d of HSCT was 18%. Conclusions: Incidence of VOD/SOS after first HSCT in InO-treated pts with R/R ALL in this study was similar to the 18–19% reported in pooled analyses of 2 clinical trials among InO-treated pts with R/R ALL (Marks et al, Biol Blood Marrow Transplant 2019) and in the INOVATE study (Kantarjian et al, Lancet Haematol 2017). The NRM at 1 y of 21% (23% R/R ALL) is lower than the NRM at 1 y of 38% reported in the pooled analyses of R/R ALL InO recipients.[Table: see text]
Health-related quality of life (HRQoL) in patients (pts) with myelodysplastic syndromes (MDS) in the Connect Myeloid Disease Registry.
Authors: Revicki Dennis A. , Grinblatt David L. , Komrokji Rami S. , Garcia-Manero Guillermo , Savona Michael R. , Scott Bart L. , Sekeres Mikkael A. , Flick E. Dawn , Makinde Adeola Y. , Kiselev Pavel , Louis Chrystal U. , Nifenecker Melissa , DeGutis Irene S. , Cogle Christopher R. 
Published: June 2021

7040 Background: At diagnosis, disease risk and transfusion burden (TB) can impact HRQoL in pts with MDS. The impact of disease status and higher transfusion requirements on HRQoL has not been well studied. We used data from the Connect Myeloid Disease Registry, an ongoing, prospective, observational cohort study that includes adult pts with lower-risk (LR) and higher-risk (HR) MDS, to investigate factors influencing baseline (BL) and subsequent HRQoL. Methods: BL and Month 6 (M6) data from pts enrolled from Dec 12, 2013 to Mar 6, 2020 (data cutoff) were analyzed. Pts were stratified by International Prognostic Scoring System (IPSS) risk (LR, HR), treatment (Tx) within 45 days post-enrollment (no Tx, best supportive care [BSC], active Tx), and TB 16 weeks post-BL (non-transfusion dependent [NTD], low TB [LTB]; 1−3 transfusions, high TB [HTB]: ≥4 transfusions). Pts completed EQ-5D, FACT-An trial outcome index (TOI), and FACT-Fatigue (FACT-F) questionnaires at BL and quarterly thereafter. Clinically meaningful change, based on minimally important differences, was defined as a change of ±0.07 for EQ-5D, ±6 for FACT-An TOI, and ±3 for FACT-F. Results: At data cutoff, 830 (489 LR, 341 HR) pts were enrolled. Median age was 74 years. 278 pts received no initial Tx, 161 BSC, and 378 active Tx. At BL, 470 were NTD, 197 LTB, and 163 HTB. Of 670 pts still on-study at M6, 462 completed the questionnaires at both BL and M6. At BL , clinically meaningful differences were observed in FACT-An TOI and FACT-F scores, but not EQ-5D, between LR- and HR-MDS and the Tx subgroups . From BL to M6, no clinically meaningful changes were observed in mean scores for each questionnaire. For the TB subgroups, meaningful differences were observed at BL in FACT-An TOI and FACT-F scores, but not EQ-5D (Table). From BL to M6, meaningful decreases in scores were reported by 26%, 30%, and 35% of NTD, LTB, and HTB pts in EQ-5D, 41%, 43%, and 48% for FACT-An TOI, and 40%, 42%, and 48% for FACT-F; increases were reported by 19%, 19%, and 20% pts for EQ-5D, 31%, 32%, and 39% for FACT-An TOI, and 30%, 39%, and 40% for FACT-F. Conclusions: This preliminary analysis suggests that pts with HR-MDS, and transfusion-dependent pts, generally had worse HRQoL at BL, providing further support to initiating active Tx in pts with TB. Possible limitations of the analysis are lower completion rates in pts with more severe disease, and EQ-5D may not capture changes in these subgroups at M6. A longer follow-up may help delineate the impact of Tx on HRQoL assessments in pts with MDS. Clinical trial information: NCT01688011. [Table: see text]
First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia.
Authors: Byrd John C. , Hillmen Peter , Ghia Paolo , Kater Arnon P. , Chanan-Khan Asher Alban Akmal , Furman Richard R. , O'Brien Susan M. , Yenerel Mustafa Nuri , Illés Árpád , Kay Neil E. , Garcia Marco Jose Antonio , Mato Anthony R. , Seymour John Francis , Leprêtre Stephane , Stilgenbauer Stephan , Robak Tadeusz , Patel Priti , Higgins Kara , Sohoni Sophia , Jurczak Wojciech 
Published: June 2021

7500 Background: Increased selectivity of the Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib (Aca) vs ibrutinib (Ib) may improve tolerability. We conducted an open-label, randomized, noninferiority, phase 3 trial to compare Aca vs Ib in patients (pts) with chronic lymphocytic leukemia (CLL). Methods: Previously treated CLL pts with del(17p) or del(11q) by central lab were randomized to receive oral Aca 100 mg BID or Ib 420 mg QD (stratified by del(17p) status, ECOG PS [2 vs ≤1], and number of prior therapies [1–3 vs ≥4]) until progression or unacceptable toxicity. Primary endpoint was progression-free survival (PFS) as assessed by IRC; secondary endpoints of all grade atrial fibrillation (AF), grade ≥3 infection, Richter transformation, and overall survival (OS) were assessed in hierarchical order. Results: 533 pts (Aca, n=268; Ib, n=265) were randomized (median age 66 y; median 2 prior therapies; del(17p) 45.2%; del(11q) 64.2%). At a median follow-up of 40.9 mo (range 0.0–59.1), Aca was noninferior to Ib with a median PFS of 38.4 mo in both arms (HR 1.00; 95% CI 0.79–1.27). Aca was statistically superior to Ib in all-grade AF incidence (9.4% vs 16.0%; P=0.023). Among the other secondary endpoints, incidences of grade ≥3 infection (Aca: 30.8%, Ib: 30.0%) and Richter transformation (Aca: 3.8%, Ib: 4.9%) were comparable between arms. Median OS was not reached in either arm (HR 0.82 [95% CI 0.59–1.15]), with 63 (23.5%) deaths in the Aca arm and 73 (27.5%) in the Ib arm. Among any-grade AEs in ≥20% of pts in either arm, Aca was associated with a lower incidence of hypertension (9.4%, 23.2%), arthralgia (15.8%, 22.8%), and diarrhea (34.6%, 46.0%) but a higher incidence of headache (34.6%, 20.2%) and cough (28.9%, 21.3%). AEs led to treatment discontinuation in 14.7% of Aca- vs 21.3% of Ib-treated pts. Among any-grade events of clinical interest, cardiac, hypertension, and bleeding events were less frequent with Aca (Table). Conclusions: In this first head-to-head trial of BTKis in CLL, Aca demonstrated non-inferior PFS with less cardiotoxicity and fewer discontinuations due to AEs vs Ib. Clinical trial information: NCT02477696. [Table: see text]
Real-world (RW) treatment (tx) patterns and outcomes of 3,455 previously untreated mantle cell lymphoma (MCL) patients (pts) in U.S. routine clinical practice.
Authors: Martin Peter , Wang Michael , Kumar Anita , Qi Keqin , Daly Katherine , Parisi Lori , Zhu Angeline , Salles Gilles A. 
Published: June 2021

7504 Background: MCL is a non-Hodgkin lymphoma with heterogeneous biology and outcomes. We characterized RW tx patterns and outcomes of MCL pts to identify factors associated with outcomes in the US. Methods: This retrospective study included adult MCL pts diagnosed Jan 2011-Nov 2020 in the nationwide Flatiron Health EHR-derived deidentified database. Pt characteristics, tx patterns, time to next tx (rwTTNT, defined as start of first-line [1L] tx to subsequent tx or death) and rwOS were evaluated. Results: 3455 pts were included, 85.3% from a community oncology setting. In 2946 (85.2%) pts with documented 1L MCL tx, median age was 69.5 y (range 27.7-85.3); 9.5% had blastoid/pleomorphic MCL. 262 (39.6%) and 235 (35.6%) of 661 pts with available MCL international prognostic index (MIPI) had intermediate and high risk, respectively. 150/1253 pts (12.0%) with available ECOG PS had PS ≥ 2. Chemoimmunotherapy was the most common 1L tx, including BR in 1223 (41.5%), R-CHOP in 512 (17.4%) and cytarabine (ara-C)-containing tx in 414 (14.1%). 667 pts received R maintenance (MR). In 1036 pts < 65 y, 243 pts received 1L stem cell transplant (SCT), mainly autologous. In 1L-treated pts, with median follow-up of survivors of 45.3 mos (range 0.03-117.2), median rwTTNT was 24 mos; 36-mo rwOS was 67%. The Table shows tx received and outcomes by age and SCT status. MVA analyses showed age ≥ 65 y, ECOG PS ≥ 2, LDH/ULN ≥ 1, WBC ≥ 10 × 109/L, bulky disease (≥ 5 cm) and blastoid/pleomorphic morphology were associated with shorter rwTTNT and rwOS; MR was independently associated with longer rwTTNT and rwOS. In pts < 65 y who were alive and did not initiate subsequent tx within 6 mos of 1L tx (“SCT-eligible”), 36-mo rwTTNT and rwOS were similar between pts treated with vs without SCT: 65% vs 59% and 86% vs 85%, respectively. Conclusions: In this large RW cohort of primarily community-based US practices, median 1L rwTTNT for MCL pts was ̃ 2 y. BR was the most commonly used 1L tx. SCT was uncommon even in pts < 65 y, suggesting RW considerations may influence SCT eligibility and availability. Also, SCT was not clearly associated with rwOS. As with other reports, older age and high-risk disease features were predictive of worse outcome in RW, while MR appeared to be associated with better outcomes. Outcomes across the board appear worse than prospective trials, suggesting a need to focus on developing tx that can be delivered effectively in the community setting.[Table: see text]
Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Elevate-TN four-year follow up.
Authors: Sharman Jeff Porter , Egyed Miklos , Jurczak Wojciech , Skarbnik Alan , Pagel John M. , Kamdar Manali K. , Munir Talha , Corbett Gillian , Fogliatto Laura Maria , Herishanu Yair , Banerji Versha , Coutre Steve E. , Walker Patricia , Karlsson Karin , Ghia Paolo , Janssens Ann , Wierda William G. , Patel Priti , Wang Min Hui , Byrd John C. 
Published: June 2021

7509 Background: Early results from ELEVATE-TN (NCT02475681) at a median follow-up of 28.3 mo demonstrated superior efficacy of acalabrutinib (A) ± obinutuzumab (O) compared with O + chlorambucil (Clb) in patients (pts) with treatment-naïve (TN) chronic lymphocytic leukemia (CLL) (Sharman et al. Lancet 2020;395:1278-91). Results from a 4-year update are reported here. Methods: Pts received A±O or O+Clb. Crossover to A monotherapy was permitted in pts who progressed on O+Clb. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Results: 535 pts (A+O, n=179; A, n=179; O+Clb, n=177) were randomized with a median age of 70 y; 63% had unmutated IGHV and 9% del(17p). At a median follow-up of 46.9 mo (range, 0.0–59.4; data cutoff: Sept 11, 2020), the median PFS was not reached (NR) for A+O and A pts vs 27.8 mo for O+Clb pts (both P<0.0001). In pts with unmutated IGHV, the median PFS was NR (A+O and A) vs 22.2 mo among O+Clb pts (both P<0.0001). In pts with del(17p), the median PFS was NR (A+O and A) vs 17.7 mo for O+Clb ( P<0.005). Estimated 48-mo PFS rates were 87% for A+O, 78% for A, and 25% for O+Clb. Median OS was NR in any treatment arm with a trend towards significance in the A+O group (A+O vs O+Clb, P=0.0604); estimated 48-mo OS rates were 93% (A+O), 88% (A), and 88% (O+Clb). ORR was significantly higher with A+O (96.1%; 95% CI 92.1–98.1) vs O+Clb (82.5%; 95% CI 76.2–87.4; P<0.0001); ORR with A was 89.9% (95% CI 84.7–93.5; P=0.035 vs O+Clb). Complete response/complete response with incomplete hematologic recovery (CR/CRi) rates were higher with A+O (26.8%/3.9%) vs O+Clb (12.4%/0.6%); 10.6%/0.6% had CR/CRi with A. Common adverse events (AEs) and AEs of interest are shown in the Table. Overall treatment discontinuation rates were 25.1% (A+O), 30.7% (A), and 22.6% (O+Clb); the most common reasons were AEs (12.8%, 12.3%, 14.7%, respectively) and progressive disease (4.5%, 7.8%, 1.7%). Most pts (77.4%) completed O+Clb treatment. Conclusions: With a median follow-up of 46.9 mo (̃4y), the efficacy and safety of A+O and A monotherapy was maintained, with an increase in CR since the interim analysis (from 21% to 27% [A+O] and from 7% to 11% [A]) and low rates of discontinuation.[Table: see text]
Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial.
Authors: Magid Diefenbach Catherine S. , Abrisqueta Pau , Gonzalez-Barca Eva , Panizo Carlos , Arguinano Perez Jose Maria , Miall Fiona , Bastos-Oreiro Mariana , Lopez-Guillermo Armando , Banerjee Lalita , McMillan Andrew , Hirata Jamie , Musick Lisa , Saha Sourish , Croft Brandon , Seymour Erlene Kuizon 
Published: June 2021

7512 Background: The combination of Pola-R-Len may enhance anti-tumor response in R/R DLBCL. We report the primary analysis of the R/R DLBCL cohort in a Phase 1b/2 study (GO29834; NCT02600897). Methods: Pts received induction with 6 x 28-Day (D) cycles (C) of: Pola 1.8mg/kg intravenous (IV; C1−6: D1); R 375mg/m2 IV (C1−6: D1) and oral Len 10–20mg (dose escalation) or recommended Phase 2 dose (RP2D) daily on D1–21. Pts with a response at end of induction (EOI) received 6 months (mo) consolidation with R 375mg/m2 (D1 every 2 mo) and Len 10mg (D1–21 monthly). Primary endpoints were safety/tolerability and positron emission tomography (PET)-complete response (CR) rate at EOI by independent review committee (IRC) by modified Lugano criteria. Results: At primary analysis (Sep 08, 2020), 57 pts were enrolled. Median age was 71 years (range 28–92); male (67%); Ann Arbor Stage III–IV (86%); International Prognostic Index 3–5 (60%); median 2 prior therapies; prior bone marrow transplant (11%); prior CAR-T therapy (5%); primary refractory (49%) and refractory to last therapy (65%). Grade 3–4 adverse events (AEs) were experienced by 75% of pts, most commonly, neutropenia (58%), thrombocytopenia (14%), infections (14%) and anemia (11%). AEs led to Len dose reduction in 25% and interruption in 63% of pts. One Grade 5 treatment-related AE (neutropenic sepsis) was reported. In total, 49 pts were treated at RP2D (Pola 1.8mg/kg + Len 20mg). IRC PET-CR rate at EOI was 29% (Table). A best overall response (BOR) assessed by investigator (INV) was seen in 36/49 (74%) pts with 17/49 (35%) pts achieving a CR; of these, 14/17 (82%) remain in remission at the cutoff date. Median duration of response (DOR) was 8.1 mo (95% confidence interval [CI]: 4.7–not evaluable [NE]). After a median follow-up of 9.7 mo, median progression-free survival (PFS) and overall survival (OS) were 6.3 mo (95% CI: 4.5–9.7) and 10.9 mo (95% CI: 7.4–NE), respectively. Conclusions: Our study of the novel triplet combination, Pola-R-Len, demonstrates a tolerable safety profile. This first efficacy report of Pola-R-Len shows promising activity in a difficult-to-treat R/R DLBCL population, particularly in pts achieving CR, a large proportion of whom remain in remission at the cutoff date. Further evaluation of Pola-R-Len and the impact of consolidation therapy is warranted to address the significant unmet need in this patient population. Clinical trial information: NCT02600897. [Table: see text]