bluuebunny/crossref_metadata_2025_split huggingface dataset:
Final results of NCCTG N0489: Epratuzumab and rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (ER-CHOP) in patients with previously untreated diffuse large B-cell lymphoma
Authors: Micallef I. N. , Maurer M. J. , Nikcevich D. A. , Cannon M. W. , Schaefer E. W. , Moore D. F. , Kurtin P. , Witzig T. E. 
Published: August 2020

8508 Background: A prior pilot study of epratuzumab (Immunomedics) and rituximab in combination with CHOP chemotherapy (ER-CHOP) in untreated patients with diffuse large B-cell lymphoma demonstrated feasibility and safety. This multicenter NCCTG phase II study was carried out to assess efficacy. Methods: Patients received immunochemotherapy on the following schedule: epratuzumab 360 mg/m2, rituximab 375 mg/m2, and standard dose CHOP every 3 weeks for 6 cycles. Weekly blood counts were obtained to monitor hematological toxicity. Primary endpoint was 12 month event free survival (EFS12). Secondary endpoints were response rate, progression free survival, functional CR (PET negative) and toxicity. Results: 107 patients were accrued from Feb 2006 to Aug 2007. 29 patients were ineligible resulting in 78 eligible patients. Baseline patient characteristics for the eligible patients included median age 61 (range 21–82); 59% were male. 81% had advanced stage; IPI was 0–1 in 17 pts (22%), 2 in 22 pts (28%), 3 in 29 pts (37%) and 4–5 in 10 pts (13%). Based on the revised IPI (R-IPI) 50% were poor/high risk (IPI 3–5). 71% had an elevated LDH. Performance score was 0–1 in 69 pts and 2–3 in 9 pts. The ORR was 95% (CR/CRu: 73%). For the low risk IPI (0–2), ORR was 95% (CR/CRu: 74%) and for the high risk IPI (3–5), ORR was 95% (CR/CRu: 72%). The EFS at 12 months was 80%. The 12 month progression free survival (PFS12) and overall survival (OS12) is 82% and 88% respectively. EFS12, PFS12 and OS12 by IPI risk category is shown ( Table ). Conclusions: ER-CHOP every 21 days is feasible and safe. The ORR, EFS and PFS compare favorably to studies using R-CHOP especially in the high-intermediate and high risk IPI subgroups. A randomized phase III trial of R-CHOP vs ER-CHOP is needed to prove that dual antibody targeting in combination with CHOP is better. [Table: see text] No significant financial relationships to disclose.
Multicenter analysis of 81 solid organ transplant (SOT) recipients with posttransplantation lymphoproliferative disease (PTLD): Examination of survival and prognostic factors
Authors: Evens A. M. , David K. A. , Helenowski I. , Kircher S. M. , Mauro L. , Gimelfarb A. , Hattersley E. , Shammo J. M. , Smith S. E. , Smith S. M. 
Published: August 2020

8510 Background: PTLD has a reported 3-year (yr) overall survival (OS) of 35–40% (Leblond, JCO 2001). The impact of rituximab (RTX) on the prognosis or outcome of PTLD is not known. Methods: We examined the clinical features, treatment, and outcomes among a large population-based cohort of SOT-related PTLD patients (pts) at 4 Chicago institutions (1/98–2/08). Prognostic factors were evaluated in univariate and Cox proportional hazards regression for survival. Results: 81 PTLD pts were identified (SOT: 47 kidney ± pancreas, 4 pancreas, 17 liver, 8 heart, 5 lung) with median age at diagnosis (dx) of 48 yrs (range 20–72). Median time from SOT to PTLD was 42 months (mo) (range 1–216 mo). PTLD dx (per WHO) were 55 monomorphic, 22 polymorphic and 4 plasmacytic, while 42 were EBV+ and 30 EBV-negative (9 unknown). 74% of pts (60/81) were treated with rituximab ± chemotherapy (and reduction of immune suppression). With 38-mo median followup for all pts, 3-yr progression-free (PFS) was 58% and 3-yr OS 62%, despite 16% of pts dying ≤ 6 weeks from dx. Most relapses (30/32) occurred ≤ 12 months from dx. Pts receiving RTX as part of therapy had 3-yr PFS of 69% and OS 71% (vs 21% (p=0.0002) and 33% (p=0.001), respectively, without RTX). Univariate analysis identified prognostic factors for PFS/OS (all <0.01): 1) PS, 2) serum albumin, 3) >1 EN site, 4) marrow involvement, 5) CNS disease and 6) RTX as part of initial therapy. Neither histology nor EBV status predicted outcome. On multivariate analysis, 4 factors remained significant ( Table 1a ). Further, a survival model based on 3 factors was constructed ( Table 1b ). Conclusions: This study represents the largest PTLD report in RTX-treated pts. We are the first to identify the prognostic significance of low albumin and a low PTLD relapse rate beyond 1 yr (6.3%). Further, it appears that the introduction of RTX has improved the survival of PTLD. In addition, clinical factors at dx identified pts with markedly divergent outcomes. [Table: see text] [Table: see text] No significant financial relationships to disclose.
Utilization of radiation therapy in early-stage Hodgkin disease and its impact on survival
Authors: Rineer J. , Schreiber D. , Wortham A. , Olsheski M. , Sroufe R. , Sura S. , Katsoulakis E. , Han P. , Choi K. , Rotman M. 
Published: August 2020

8511 Background: Despite numerous randomized trials confirming the benefit of consolidation radiation therapy (RT) in the management of early stage Hodgkin disease (HD), utilization of RT in this setting remains variable. We performed a population-based analysis to assess the utilization of RT and its impact on overall and cause specific survival. Methods: The surveillance, epidemiology and end results (SEER) registry was used to identify patients aged 15–75 years diagnosed between 1990–2004 with early stage (stage I-IIA/B) HD, excluding nodular lymphocyte predominant HD. Kaplan-Meier analysis was performed to evaluate the effect of RT on overall survival (OS) and cause-specific survival (CSS). Subgroup survival analyses were also performed by era of treatment (1990–1997 and 1998–2004), sex, and patient age (<30, 30–50, and >50 years). Results: A total of 9729 patients met inclusion criteria. Median age of all patients was 34 years. The majority (71.3%) had nodular sclerosis (NS) type HD. By clinical stage, 3399 (34.9%) were stage I, and 6330 (65.1%) were stage II. 5352 patients (55%) received RT. RT was more likely to be employed during the early era of treatment, in younger patients, females, non-Blacks, and in NS, mixed cellularity and lymphocyte-rich HD. For the entire cohort, RT was associated with a significant (p<0.001) improvement in OS and CSS (hazard ratio of 0.537 and 0.437, respectively). The benefit of RT for OS and CSS remained significant for all subgroups analyzed including the era of treatment, sex, and age (p≤0.001). Conclusions: In this large population-based series of early stage HD patients, the use of RT is associated with a significant OS and CSS benefit across all subgroups. Current efforts in clinical trials have aimed at decreasing the utilization of RT among this patient population. This shift in practice is reflected in the data presented here. The omission of RT from the treatment paradigm, however, appears to be related with diminished survival. No significant financial relationships to disclose.
Long-term follow-up of patients with follicular lymphoma (FL) receiving single agent rituximab at two different schedules in study SAKK 35/98
Authors: Ghielmini M. E. , Hsu Schmitz S. , Martinelli G. , Peccatori F. , Hess U. , Fey M. , Zucca E. , Stahel R. , Ketterer N. , Cerny T. 
Published: August 2020

8512 Background: In FL, rituximab as a single agent obtains a response rate of 50–70% with an EFS of 1–3 years depending on the population studied. Some patients respond to this treatment for a prolonged time, so we investigated, in a clinical trial, the proportion of long-term responders and the characteristics predicting long-term response. Methods: Between 1998 and 2002, chemotherapy naïve (n = 64) or pre-treated (n = 138) FL patients received 4 weekly doses of rituximab: those responding or with stable disease were randomized to either no further treatment (observation, n = 78) or 4 additional doses of rituximab given at 2 months intervals (consolidation, n = 73). Results: At a median follow up of 8.9 years, and with all living patients having been followed for at least 5 years, the median event-free survival (EFS: time until progression, relapse, second tumor or death) is 13 months for the observation and 24 months for the consolidation arm (p=0.0012). In the observation arm 10% had no event at 5-years, the figure dropping to 4% (3/78) at 8 years, while in the consolidation arm the EFS was 26% at 5 years and remained 18% (13/73) at 8 years. The only significant prognostic factor for EFS in a multivariate Cox regression was having received consolidation rituximab (hazard ratio = 0.58, CI = 0.44–0.87, p = 0.008), whereas being chemotherapy naïve, presenting with stage < IV and showing a VV phenotype at position 158 of the Fc receptor RIIIA were not any more significantly prognostic in this long term analysis, in contrast to previous data with shorter follow-up. No long-term toxicity from treatment was observed. There were 21 cases of second malignancy: 11 on observation, 10 receiving the consolidation arm. Conclusions: It appears that the EFS advantage of prolonged versus short course rituximab continues for many years after the end of treatment. This seems to hold true independently from previous treatment, stage or 158-phenotype of the Fc receptor. Patients treated with 8 doses of rituximab over 1 year have approximately 25% and 20% chance to remain in remission at 5 and 8 years respectively. [Table: see text]
A phase III study of VMPT versus VMP in newly diagnosed elderly myeloma patients
Authors: Palumbo A. P. , Bringhen S. , Rossi D. , Berretta S. , Montefusco V. , Peccatori J. , Galli M. , Carella A. , Omedè P. , Boccadoro M. 
Published: August 2020

8515 Background: In MM patients VMP is superior to MP. In relapsed-refractory patients the 4 drug combination VMPT induced a high proportion of complete responses (CR). Methods: 500 newly diagnosed MM patients ≥ 65 years were randomly assigned to receive VMPT (N=247) or VMP (N=253). Patients were treated with nine 5-week cycles of VMPT (bortezomib 1.3 mg/m2 days 1, 8, 15, 22; melphalan 9 mg/m2 days 1–4; prednisone 60 mg/m2 days 1–4 and thalidomide 50 mg days 1–35) or VMP (bortezomib, melphalan and prednisone at the same doses and schedules previously described). Primary end-point was progression-free survival (PFS). Assuming the hazard ratio (VMP vs VMPT) of 1.35, the total sample size is 500 (250/arm) subjects (power 80%, 2-side alpha 0.05). Results: 354 patients (median age 71 years), who received at least 1 cycle were evaluated: 177 VMPT and 177 VMP. Data were analyzed in intention-to-treat. The VGPR rate was 55% in the VMPT group and 45% in the VMP group (p<0.001). After a median follow-up of 14.5 months, the 3-year PFS was 74% in the VMPT group and 70% in the VMP group (HR=0.75, 95% CI 0.45–1.26, p=0.28). The 3-year overall survival (OS) was 88% in the VMPT group and 87% in the VMP group (HR=0.89, 95% CI 0.42–1.87, p=0.75). Subgroup analyses did not show any statistical difference between responses/PFS and either ISS or chromosomal abnormalities (t(4;14) or t(14;16) or del17) in both groups. Age > 75 years was associated with lower VGPR rate (p=0.02) in VMPT but not in VMP. Factors predictive of longer PFS were age ≤ 75 years (p=0.003) and the achievement of VGPR (p=0.0005) in VMPT but not in VMP. The incidence of grade 3–4 adverse events (AEs) was similar in both groups. In the VMPT patients and in the VMP patients, the more frequent AEs were neutropenia (36% vs 31%), thrombocytopenia (20% vs 19%), peripheral neuropathy (18% vs 12%) and infections (14% vs 10%), respectively. Conclusions: VMPT is superior to VMP in terms of response rates. Longer follow-up is needed to assess their effects on PFS and OS. Both regimens appeared to overcome the poor prognosis of ISS and chromosomal abnormalities. An update of these data will be presented. [Table: see text]
Phase II study of pegylated liposomal doxorubicin (PLD), low-dose dexamethasone (DEX), and lenalidomide (LEN) in patients with newly diagnosed (ND) multiple myeloma (MM)
Authors: Baz R. , Hussein M. A. , Sullivan D. , Raychaudhuri J. , Ochoa L. , Kosakowski K. , Nardelli L. , Dalton W. S. , Alsina M. 
Published: August 2020

8518 Background: We previously reported the results of a phase I/II trial of PLD, low dose DEX and LEN in patients with relapsed and refractory MM in which the MTD of LEN was 10 mg (for 21 of 28 days) and the overall response rate was 75% with 29% of patients achieving nCR or better (Ann Oncol 2006). Accordingly we evaluated this regimen in ND MM. Methods: We hypothesized that patients with ND MM would tolerate this combination better. Accordingly, patients received PLD (40 mg/m2 on day 1), DEX (40 mg on days 1–4) and LEN (25 mg Days 1–21) every 28 days (for 2 cycles beyond best response: 4–8 cycles). Prophylactic low dose aspirin, acyclovir and fluoroquinolone were recommended. Patients not eligible or not wishing to proceed with high dose therapy continued on the tolerated dose of LEN and DEX until disease progression or unacceptable toxicity. Results: Between 2/2008 and 8/2008, 31 of a planned 60 patients were enrolled. 2 patients were screen failures and are not included in subsequent analysis. The mean age was 64 years (41–82) and 58% were males. The median β2microglobulin was 2.8 mg/dL (34% had β2m>3.5). Using the modified SWOG criteria and after a median of 4 cycles of therapy, the overall response rate was 80% with 40% VGPR and better. Two patients had stable disease and 3 patients had progressive disease. Grade 3/4 hematologic toxicity was as follows: neutropenia (48%), anemia (10%), thrombocytopenia (7%). Grade 3/4 non-hematologic toxicity included: Fatigue (21%), infections and febrile neutropenia (20%, only 1 patient with febrile neutropenia), venous thromboembolic events (10%). 14 patients went off study including 8 patients to proceed with high dose therapy. Conclusions: The combination of PLD, LEN and DEX is an active regimen in patients with ND MM. Due to the unexpected higher rates of neutropenia and fatigue, the dose of PLD will be decreased to 30 mg/m2 every 28 days. Updated results will be presented at the time of the meeting. [Table: see text]
Role of T-cell immunity to embryonal stem (ES) cell antigen SOX2 in the progression of myeloma
Authors: Dhodapkar M. V. , Bolejack V. , Shaughnessy J. , Matthews P. , Pickering R. , Qu P. , Hoering A. , Crowley J. , Barlogie B. 
Published: August 2020

8522 Background: Clinical outcome in patients (pts) with asymptomatic plasma-proliferative disorders, monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic myeloma (AMM), is highly variable. There is a need to identify specific tumor or host related features that predict the risk of disease progression. In prior studies, we have shown that patients with MGUS commonly mount a T cell immune response against SOX2, an antigen critical for pluripotency of ES cells. Methods: Patients with MGUS/AMM were enrolled in a prospective observational clinical protocol (SWOG S0120). All patients underwent detailed staging evaluation at registration and were observed without therapy. The presence of T cell immunity to SOX2 in freshly isolated blood / marrow mononuclear cells was analyzed using an overlapping peptide library at study entry. Results: Anti-SOX2 T cell responses were detected in 39/109 (36%) pts tested. Progression to symptomatic MM was observed in only 2 of 39 patients with anti-SOX2 immunity compared to 17 of 59 pts lacking these responses, resulting in 2-yr progression-free survival 96 v 63% (p=0.003). Responses to viral antigens and polyclonal mitogens as controls were preserved in patients lacking SOX2 immunity indicating that the absence of immunity to SOX2 was not due to global immune-suppression. Immunity to SOX2 correlated with features of lower risk including serum-M component < 1.5 g/dL (p=0.008), marrow plasmacytosis < 10% (p<0.001) and normal serum free light chain ratio (p=0.01). Conclusions: These data demonstrate in the context of a prospective trial that T cell immunity to stem cell genes strongly correlates with a reduced risk of progression to clinical myeloma. These data point to SOX2 as a potential target for the prevention of disease progression in MGUS/AMM. No significant financial relationships to disclose.
Randomized phase III trial of pixantrone compared with other chemotherapeutic agents for third-line single-agent treatment of relapsed aggressive non-Hodgkin's lymphoma
Authors: Pettengell R. , Narayanan G. , Mendoza F. H. , Digumarti R. , Gomez H. , Cernohous P. , Gorbatchevsky I. 
Published: August 2020

8523 Background: Currently, treatment options for multiply relapsed aggressive NHL are limited, and response rates are disappointing. Pixantrone, a novel aza-anthracenedione with structural similarities to mitoxantrone, has potentially reduced cardiotoxicity and has demonstrated promising clinical activity in phase II studies in heavily pretreated NHL patients. Methods: PIX301 was a controlled, multicenter, open-label phase III study of ≥ third-line treatment of relapsed aggressive (de novo or transformed) NHL. All patients were required to have received ≥ 1 prior anthracycline-containing regimen, with the cumulative doxorubicin-equivalent dose limited to ≤ 450 mg/m2. Randomization was to pixantrone 85 mg/m2 on days 1, 8 and 15 of 28-day cycles, for up to 6 cycles, or to investigator's choice of a single-agent comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, or mitoxantrone; in the US only, gemcitabine and rituximab were permitted). The primary study endpoint was CR/CRu rate. Secondary objectives included safety, OS, and ORR. Originally planned to enroll 320 patients, PIX301 was amended to 140 patients due to slow enrollment. Results: 140 patients (70 per arm) were randomized. Median age was 60 on the pixantrone arm, 58 on the control arm; patients on both arms had received a median of 3 prior chemotherapeutic regimens. Based on independent review in the ITT population, the CR/CRu rate in patients treated with pixantrone was significantly higher than in those receiving other agents (20.0% vs. 5.7%, p-value = 0.02), and there were no CRs in the control group compared to 8 CRs in the pixantrone group. Conclusions: In this study, single-agent therapy with pixantrone achieved significantly superior CR/CRu and ORR rates in ≥ third-line treatment of relapsed/refractory aggressive NHL. [Table: see text] No significant financial relationships to disclose.
Tumor-infiltrating CD163-positive macrophages, clinicopathological parameters, and prognosis in classical Hodgkin lymphoma
Authors: Kamper P. , Bendix K. , Hamilton-Dutoit S. , Honoré B. , d'Amore F. 
Published: August 2020

8528 Background: Classical Hodgkin lymphoma (cHL) is characterized by a minority of neoplastic cells surrounded by a heterogeneous background of non-neoplastic cells. A possible prognostic role of LAMs in cHL and follicular lymphomas has been suggested. CD163 is a haemoglobin scavenger receptor expressed by monocytes/macrophages. A high CD163 expression has been observed in macrophages belonging to the “alternative activation” pathway suggested to have pro-tumoral effect. The aim of the present study was to correlate the expression of the tumor-infiltrating CD163+ LAMs with clinico-pathological features and prognosis in a cohort of previously untreated HL patients (pts). Methods: A tissue microarray (TMA) was constructed with paraffin embedded tissue specimens from 286 cHL cases. CD163 expression was assessed immunohistochemically and the degree of intratumoral LAM infiltration was scored semi-quantitatively. Clinical data were obtained from the Danish population-based lymphoma registry and clinical records. All pts were homogeneously treated with either chemo-radiotherapy (localised disease) or ABVD chemotherapy (advanced disease). Results: The median age was 37 yrs (range: 6–86 yrs). The M:F ratio was 1.2. The histological subtypes were: nodular sclerosis (NS)-type I, 167 cases (59 %); NS-type II, 71 (25%); mixed cellularity (MC), 44 (15 %); lymphocyte-rich, lymphocyte-depleted and cHL-NOS, each one case. Of 253 pts with assessable International Prognostic Score (IPS), 204 had a low-risk (≤ 2) and 49 a high risk (>2) profile. A high number of tumour-infiltrating CD163+ cells was associated with a significantly poorer overall and event-free survival (p=0.029 and p=0.018, respectively). Furthermore, a high expression of CD163 strongly correlated to stage IV disease (p=0.035), presence of B-symptoms (p=0.008), lymphocytopenia (p=0.003), hypersedimentation (p=0.009). In a multivariate analysis, IPS score > 2 remained the strongest predictor. Conclusions: In cHL, a high number of intratumoral CD163+ monocytes/macrophages correlates with adverse outcome and with clinical parameters reflecting underlying aggressive disease biology. No significant financial relationships to disclose.
Lenalidomide, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma (MM): Encouraging outcomes and tolerability in a phase II study
Authors: Anderson K. C. , Jagannath S. , Jakubowiak A. , Lonial S. , Raje N. , Alsina M. , Ghobrial I. , Knight R. , Esseltine D. , Richardson P. 
Published: August 2020

8536 Background: Lenalidomide (Revlimid, Len), bortezomib (VELCADE, Bz; maximum tolerated dose [MTD] 15 mg/1.0 mg/m2) ± dexamethasone (Dex; 20–40 mg; RVD) was well tolerated in a phase I study in relapsed/refractory MM patients (pts), with 58% ≥MR. This multicenter phase 2 study evaluated RVD efficacy and safety at the MTD. Methods: Patients received up to eight 21-day cycles of Len 15 mg (days 1–14), Bz 1.0 mg/m2 (days 1, 4, 8, 11), and Dex 40/20 mg (cycles 1–4/5–8, days of/after Bz dosing). After cycle 8, patients with stable/responding disease received maintenance (Len, days 1–14; Bz, days 1, 8; doses per end of cycle 8; Dex 10 mg, days 1, 2, 8, 9) until progression or unacceptable toxicity. Pts with significant peripheral neuropathy were excluded. Results: Among 64 pts, 38 (59%) had relapsed and 26 (41%) refractory/relapsed MM. Median number of prior therapies was two, including Len (8%), Bz (55%), Dex (92%), thalidomide (77%), and stem cell transplant (SCT, 36%). Forty-one pts (64%) completed 8 cycles, 33 continue on maintenance, 22 discontinued early (11 due to progressive disease). Toxicities were manageable, primarily grade (G) 1/2 myelosuppression; 2 developed DVT on aspirin, 2 G3 atrial fibrillation, 1 G3 peripheral neuropathy. One pt died on-study (fungal pneumonia, possibly due to Dex). Overall response rate (62 evaluable patients) was 84% ≥MR, including 21% CR/nCR, 68% ≥PR, which was independent of high-risk features and prior treatment ( Table ). Median duration of response is 24 weeks (range 6–81). Time-to-events data including median time to progression, progression-free survival, and 1-year survival rates will be presented. Conclusions: RVD is active and well tolerated in pts with relapsed/refractory MM, including pts who have received prior Len, Bz, thalidomide, and SCT. Durable responses have been observed and appear independent of adverse cytogenetics and other recognized risk factors. [Table: see text] [Table: see text]