bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dexabeam versus ICE salvage regimen prior to autologous transplantation for relapsed or refractory aggressive peripheral T-cell lymphoma: A retrospective evaluation of parallel patient cohorts of one center.
Authors: Mikesch Jan-Henrik , Kuhlmann Mareike , Demant Angela , Krug Utz , Schmidt Eva , Kessler Torsten , Schliemann Christoph , Pohlen Michele , Mohr Michael , Koehler Gabriele , Wessling Johannes , Mesters Rolf M. , Mueller-Tidow Carsten , Berdel Wolfgang E. , Thoennissen Nils Heinrich 
Published: March 2020

8548 Background: High-dose chemotherapy (HDT) followed by autologous stem-cell transplantation (ASCT) is considered standard in the treatment of patients with relapsed or refractory aggressive peripheral T-cell lymphoma (PTCL). However, the optimal salvage regimen before ASCT has not yet been established. Methods: We retrospectively analyzed 31 patients with relapsed or refractory aggressive PTCL after anthracycline based first-line chemotherapy who received either DexaBEAM (n=16) or ICE (n=15) regimen as first salvage chemotherapy followed by HDT and ASCT between 1996 and 2009. The median patient age was 46 years (range, 18-66) in the DexaBEAM group and 40 years (range, 17-59) in the ICE group. Patients were included independent of WHO stage and IPI score. Results: The overall response rate (OR) was significantly higher for patients treated with DexaBEAM (69%) as compared to the ICE group (20%; P=0.01), with higher complete response (CR; 38% vs. 7%) as well as partial response (PR; 31% vs. 13%) rate. Changing regimen due to failure of the first salvage therapy, 12 patients initially receiving ICE still achieved an OR of 58% (33% CR, 25% PR) with DexaBEAM as second salvage therapy, whereas in 3 patients receiving ICE after DexaBEAM failure only 1 patient achieved an OR (1 PR). Median progression-free survival (PFS) was significantly higher in the DexaBEAM group (6.4 vs. 2 months; P=0.01). Median overall survival (OS) was not different between the two groups (22.8 vs. 29.8 months; P=0.72), most likely due to the good response rate of patients to DexaBEAM as 2nd salvage regimen after failure of ICE chemotherapy. Major adverse event in both groups was myelosuppression with higher but tolerable treatment-related toxicity for patients in the DexaBEAM group. Conclusions: In this retrospective comparison DexaBEAM salvage chemotherapy was superior to ICE for patients with relapsed or refractory aggressive PTCL for remission induction prior to autologous transplantation, with higher but manageable treatment-related toxicity.
Phase I study of a novel humanized anti-CD20 antibody, BM-ca, in patients (pts) with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (B-NHL) pretreated with rituximab.
Authors: Tobinai Kensei , Ogura Michinori , Maruyama Dai , Suzuki Tatsuya , Kobayashi Yukio , Uchida Toshiki , Fukuhara Suguru , Oyama Takashi , Fukuzaki Tomoharu , Komatsu Yasuhiko 
Published: March 2020

8551 Background: BM-ca is a novel humanized type-I/II anti-CD20 antibody, which is effective against rituximab-resistant cell line RC-K8, and has more potent anti-cell-proliferation activity than rituximab or ofatumumab when combined with cancer chemotherapeutics. The aim of this study was to evaluate the safety, efficacy, and PK profile of BM-ca in pts with indolent B-NHL. Methods: A total of 12 pts {age: median 61 (50-73), number of prior regimens: median 2 (1-13)} with indolent B-NHL relapsed after or refractory to rituximab-containing therapy underwent treatment by IV infusion of BM-ca weekly for 4 weeks at a dose of 5, 10, or 15 mg/kg. Initially, 3 pts were to undergo BM-ca therapy at a dose of 5 mg/kg using the conventional 3+3 dose escalation design. To minimize infusion reactions (IRs), pts were pretreated with acetaminophen and d-chlorpheniramine maleate. Allopurinol and/or hydrocortisone were also administered if necessary. Infusion was started at 50 or 100 mg/h and was gradually increased to a maximum of 400 mg/h. Since no DLTs were observed, all 12 pts completed weekly 4 doses of BM-ca. Results: The most frequent AE was IRs (11 of 12 pts), which occurred mostly in the first infusion, and the highest grade of AE was neutropenia (grade 4 in one pt of 15 mg/kg after the last infusion). Anti-BM-ca antibodies were not detected. Of the 12 pts examined, 2 achieved CR (10 mg/kg) and 2 PR (15 mg/kg); these 4 pts had follicular histology. The remaining 8 pts including one each of extranodal marginal zone, nodal marginal zone, and small lymphocytic histology were judged to achieve SD. The CR states in 2 pts continued at least >14 and >11 months, respectively. The PK properties of BM-ca were comparable to those of other naked anti-CD20 antibodies including rituximab (AUC and Cmax were proportional to the doses; Vdss≈4 L; t1/2≈750 h). Since at 10 mg/kg the response was the best and no grade 4 AE observed, 10 mg/kg was suggested as a recommended phase II dose. Conclusions: Four weekly IV administration of BM-ca up to 15 mg/kg was well tolerated and safe with promising preliminary anti-lymphoma activity in pts with indolent B-NHL. Further evaluation is warranted. Clinical trial information: 000004805.
Long-term survival with 90yttrium ibritumomab tiuxetan and rituximab as treatment for relapsed or refractory diffuse large B-cell lymphoma.
Authors: Arnason Jon E. , Luptakova Katarina , Rosenblatt Jacalyn , Zwicker Jeffrey , Levine James D. , Boussiotis Vassiliki , Kim Michelle , Avigan David , Joyce Robin 
Published: March 2020

8558 Background: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) are salvaged with high dose chemotherapy followed by autologous stem cell rescue. Ibritumomab tiuxetan is an anti-CD20 antibody conjugated to the radionuclide 90yttrium. 90Y ibritumomab tiuxetan has demonstrated clinical efficacy in DLBCL with a favorable toxicity profile relative to transplant. Methods: This phase II trial investigated the overall response rate (ORR), event free survival (EFS), overall survival (OS) and toxicity of treatment with ibritumomab followed by rituximab in patients with relapsed or refractory DLBCL, not candidates for transplant. Patients were treated with an initial dose of rituximab (250 mg/m2) followed one week later by ibritumomab (0.4 mCi90Y/kg or 0.3 mCi90Y/kg based on plateles) followed by 4 weekly doses of rituximab (375mg/m2). All non-progressing patients received maintenance rituximab (375 mg/m2) weekly for 4 doses every 6 months for 4 cycles. Results: 25 patients were enrolled. Median age was 79 (range 45-95). 12 of 25 (48%) had stage 3 or 4 disease. 13 (52%) had 2 or more prior regimens. At 12 weeks 5 patients (21%) had a complete response (CR), 3 (13%) a partial response, 2 (8%) stable disease and 14 (58%) progressed for an ORR of 32% (8/25). At best response 7 patients obtained a CR. Median EFS was 2.5 months. Median OS was 8.1 months. No patient who obtained CR later relapsed, with follow up of 18.3-100.1 months. Deaths unrelated to treatment occurred in remission in 5 patients. 2 patients remain free of disease at 67.4 and 100.1 months. 11 (65%) patients had grade 3 or 4 thrombocytopenia, but no significant bleeding was observed. 9 (36%) patients had grade 3 non-hematologic toxicity. Grade 1 and 2 fatigue occurred in 41%. Patients who progressed through a rituximab containing regimen were at high risk of early progression. Conclusions: The ORR of ibritumomab as salvage therapy for DLBCL compares favorably to other regimens with acceptable toxicity. Those patients with disease refractory to rituximab are not likely to benefit. For a subset of patients not candidates for salvage with autologous transplant, this treatment can produce a durable remission. Clinical trial information: NCT00110149.
Markers of angiogenesis and hypoxia to cell of origin (COO) subtypes of DLBCL: Correlative studies from S0515, a phase II trial of R-CHOP plus bevacizumab.
Authors: Badari Ambuga R. , Abu Zaid Mohammad , Unger Joseph M. , Rimsza Lisa M. , Marron Marilyn , Fisher Richard I. , Miller Thomas P. , Stopeck Alison 
Published: March 2020

8562 Background: S0515 was a nonrandomized phase 2 trial of R-CHOP + bevacizumab in 64 patients with newly diagnosed DLBCL. No significant improvement in PFS or OS was observed compared with historic controls.Patients with higher baseline levels of plasma VCAM and urine VEGF had worse PFS and OS. Tumor-associated carbonic anhydrase, CA IX, is induced by hypoxia in various tumors and part of the hypoxia inducible factor -1/ hypoxia responsive element (HIF-1/HRE) system. We present additional correlative studies from S0515 including longitudinal plasma CAIX levels, and correlate expression of VEGF and VEGF receptors (VEGFR) to COO subtype [GCB vs. non-GCB] and urine VEGF and plasma VCAM. Methods: COO subtypes were determined by immunohistochemistry (IHC) using the Hans classification. VEGF and VEGFR expression was determined by IHC and scored on a scale of 0 (none) to +3 (strong). Plasma VCAM, CAIX, urine VEGF levels were measured by ELISA and samples collected at baseline and before cycles 4 and 8 of therapy. Results: Baseline CAIX levels did not predict PFS (p = 0.95) or OS (p=.66) or change with therapy. Patients with lower baseline CAIX levels (below the median) had a statistically significant increase in CAIX over the course of therapy (median 34.1 to 52.4, p=.002), whereas in patients with higher baseline CAIX, levels decreased (median 96.7 to 78.2, p=.20). CAIX correlated with plasma VCAM (P=.006), but not COO subtype. 33 lymphoma samples were classified as GCB (n = 21) or non-GCB (n=12). COO subtype did not predict difference in PFS (p=.56) or OS (p=.67). Median urine VEGF and plasma VEGF levels trended higher in non-GCB vs GCB tumors (181 vs 144pg/mL and 1499 and 821ng/mL, respectively). Lymphoma expression of VEGF did not correlate with plasma VCAM or urine VEGF. VEGR2 expression was higher in non-GCB vs GCB tumors (33% vs 5% expression). Conclusions: Plasma CAIX levels, a marker of hypoxia and HIF1alpha activation, increased only in those patients with lower baseline levels in response to therapy. COO by IHC did not predict PFS or OS. However, non-GCB tumors had higher expression of VEGFR2, plasma VCAM, and urine VEGF compared to GCB tumors consistent with increased angiogenesis. Clinical trial information: SWOG S-0515.
Association of 25-OH vitamin D deficiency with worse outcome for elderly patients with aggressive B-cell lymphomas treated with CHOP plus rituximab (R): An analysis of the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).
Authors: Bittenbring Joerg Thomas , Achenbach Marina , Altmann Bettina , Ziepert Marita , Reichrath Joerg , Geisel Juergen , Regitz Evi , Murawski Niels , Zwick Carsten , Held Gerhard , Pfreundschuh Michael 
Published: March 2020

8569 Background: Vitamin D deficiency was shown to be is associated with a worse outcome in patients with non-Hodgkin's lymphoma (Drake et al., 2010) To study whether this observation could be confirmed in patients with aggressive B-cell lymphomas treated uniformly within a prospective trial, we analyzed 25-OH vitamin D serum levels in patients treated within the RICOVER-60 trial of the DSHNHL. Methods: 25-OH Vitamin D serum levels were determined with a commercial chemoluminescence immunoassay in the serum from elderly patients of the RICOVER-60 trial which compared 6 or 8 cycles of CHOP, both with and without rituximab. Results: 193 of 359 pts (53.8%) had vitamin D deficiency (<10 ng/ml) and 165/359 patients (46.0%) had vitamin D insufficiency (10-30 ng/ml) according to current definitions. When treated with R-CHOP, patients with vitamin D levels ≤8 ng/ml had a 3-year EFS of 59% compared to 79% of patients with vitamin D serum levels >8 ng/ml; the respective figures for 3-year overall survival were 70% and 82%, respectively. In R-CHOP pts these differences were significant in a multivariable analysis adjusting for IPI risk factors with a hazard ratio (HR) of 2.1 (p=0.008) for EFS and a HR of 1.9 (p=0.040) for OS. In pts treated without R effects of vitamin D deficiency were significant only for OS (HR 1.8; p=0.025), but not with respect to EFS (HR 1.2; p=0.388). These results were confirmed in an independent validation set of 63 patients treated within the prospective RICOVER-noRx study. Conclusions: Vitamin D deficiency is a significant risk factor for patients with aggressive B-cell lymphomas treated with R-CHOP. The stronger adverse effect of vitamin D deficiency in patients receiving rituximab suggests that vitamin D deficiency interferes with the R mechanisms of this antibody. A prospective study evaluating the effects of vitamin D substitution on outcome of patients receiving R-CHOP is warranted. Supported by Deutsche Krebshilfe.
Infectious disease associations in advanced stage, indolent lymphoma (follicular, FL, and nonfollicular, nFL): A prospective trial of antibiotic therapy.
Authors: Portlock Carol S. , Hamlin Paul A. , Gerecitano John F. , Noy Ariela , Palomba Maria Lia , Walkley Janelle , Corcoran Stacie , Papanicolaou Genovefa A , Markowitz Arnold 
Published: March 2020

8571 Background: The antigen-drive association of gastric MALT with H. pylori (HP) is well recognized. Successful antibiotic (Ab) can result in lymphoma remission. We have studied a 3 mo course of clarithromycin (substituting lansoprazole/amoxicillin/clarithromycin, Prevpak, in the first 2 wks if HP +) in non-bulky, advanced stage indolent lymphoma as the first step to such a lymphoma treatment/prevention strategy. Methods: Patients with new diagnosis indolent lymphoma (FL and nFL), stages II (abdominal), III and IV fulfilling GELF criteria for observation were eligible. Stool HP done in all patients. Hepatitis B and C positive excluded. All patients had CT and PET prior to and 1 mo post Ab. Results: 32 evaluable patients were enrolled: 14 females, 18 males; median age, 53.5 years (36- 81); 22 FL, 10 nFL; stage II (2), III (16), and IV (14). HP + patients: 4 (3 FL, 1 nFL). We have observed lymphoma responses 1 mo post Ab in 7 of 32 (Table). With continued followup post Ab, best response to date in 9 of 32: PET CR ( 2 FL; 2 nFL); CT CR/PR ( 1/3 FL, 1/0 nFL). Median followup for all patients, 23.7 mos; and for those not needing lymphoma treatment, 54.9 mos. To date, no patient with PET CR has required lymphoma treatment (22.5+ to 62.8+ mos). Among 22 with FL, 8 have progressed, 3 had histologic transformation, possibly suggesting a different biology. Conclusions: H pylori eradication/3 mos clarithromycin has achieved lymphoma responses in advanced stage indolent lymphoma. PET negative CRs have been durable for 22.5 – 62.8 + mos following Ab alone. This prospective study may be a first step toward developing a lymphoma prevention strategy and deserves further clinical/biological study. Clinical trial information: NCT00461084. [Table: see text]
Use of stem cell transplantation (SCT) as initial therapy in multiple myeloma (MM) and impact of sociodemographic factors in the era of novel agents: Analysis of 137,409 patients using the National Cancer Data Base (NCDB).
Authors: Al-Hamadani Mohammed , Go Ronald S. 
Published: March 2020

8580 Background: Novel agents for MM became available in the past decade. Our study aim was to determine whether the rate of SCT utilization as part of initial therapy in patients with MM had changed in the US after the introduction of novel agents. We also determined the impact of various sociodemographic factors. Methods: De-identified patient level data were obtained from the NCDB bParticipant User File. NCDB is a nationwide oncology outcomes database, which comprises approximately 70% of all newly diagnosed cancer cases in the United States. Results: A total of 137,409 MM patients were included in the study. The median age was 68 years (range, 18-90+). The population was predominantly male (54%), white (79%), non-Hispanic (87%), and living in a metro (78%), low- or middle-income (annual income < $46,000; 63%), and low- or moderate-education (> 14% without high school diploma; 66%) areas. Most patients had minimal or no co-morbidities (Charlson-Deyo score of 0-1; 93%) and treated in the community setting (62%). The rate of SCT use as initial therapy consistently increased annually from 5% in 1998 to 12% in 2010. This was true for all socio-demographic subgroups except for those who were age > 75 years, treated in the Northeast, and the medically uninsured. Multivariate logistic regression showed that the following characteristics were significant main predictors of lower likelihood of SCT use (odds ratio): age > 65 years (0.18), non-white race (0.57), Hispanic ethnicity (0.68), lack of high education (0.89), annual income < $30,000 (0.76), diagnosed before the era of novel agents (1998-2003) (0.70), covered by a non-managed care insurance (0.57), treatment in a non-academic facility (0.28), residence at a non-metro area (0.88), and treatment facility located outside of the Midwest or West (0.62). In contrast, sex was not significant. Conclusions: Even after the introduction of novel agents, the rate of SCT as initial therapy in MM continues to increase annually in the US. Significant disparity exists in the rate of SCT use by demographic, social, and geographic factors as well as the type of treatment facility.
Changes in patient-reported outcomes in patients diagnosed with and treated for multiple myeloma in the Connect MM registry.
Authors: Pashos Chris L. , Shah Jatin J. , Terebelo Howard R. , Durie Brian G. , Abonour Rafat , Gasparetto Cristina , Mehta Jayesh , Narang Mohit , Thomas Sachdev , Toomey Kathleen , Swern Arlene S. , Sullivan Kristen A. , Street Thomas K. , Khan Zeba M. , Nourbakhsh Ali , Hardin James , Wildes Tanya Marya , Rifkin Robert M. 
Published: March 2020

8586 Background: Little is known about the impact of treatment on patient-reported outcomes (PROs) and health-related quality of life (HRQoL) in multiple myeloma (MM) patients (pts). The change in PROs of MM pts between baseline and 1 year was assessed relative to their baseline International Staging System (ISS) stage and Eastern Cooperative Oncology Group (ECOG) performance status (PS) score. Methods: Connect MM is a prospective US registry of MM pts initiated in 2009. Clinicians reported pt demographics, ECOG PS score, and ISS stage. PROs were collected at baseline and at 1 year utilizing the Functional Assessment of Cancer Therapy (FACT)-MM, EQ-5D, and Brief Pain Inventory (BPI). Changes in FACT-MM, EQ-5D, and BPI scores were analyzed by ISS stage and ECOG PS score in 636 pts meeting CRAB criteria from 189 centers. Results: Most pts were male (58%) and white (84%). Mean age was 66 years (± 11). Pts were treated in community (81%), academic (17%), or veterans/military (2%) settings. ISS stages of pts were: I (29%), II (35%), and III (35%). ECOG PS scores were 0 (37%), 1 (49%), 2 (11%), and 3 (3%). Improvements in overall HRQoL as shown by the FACT-MM and FACT-General (G) total scores, were observed across all ISS stages (P = 0.03 to < 0.0001) with no significant differences between stages. Improvements in FACT-MM and FACT-G total scores were observed with ECOG PS scores 1–3 (P = 0.03 to 0.005). Pts with poorer ECOG PS scores tended to have greater improvement in EQ-5D domains of mobility, self-care, and usual activities. HRQoL/functional ability improved in 4 of 5 FACT domains (except social/family; all others P < 0.0001), and in 4 of 5 EQ-5D domains (except pain/discomfort; all others, P = 0.01 to < 0.0001). BPI showed that overall average pain improved (P < 0.0005) over 1 year, but statistically significant differences by ISS stage or ECOG PS score were not observed. Conclusions: Connect MM data showed that overall HRQoL of MM pts improved between baseline and 1 year, with a consistent benefit observed across pts with different ISS stages and ECOG PS scores. Additional analysis should examine which disease- and treatment-related factors are associated with these HRQoL improvements.
Continued monoclonal protein response beyond day 100 after auto-transplantation for multiple myeloma.
Authors: Gonsalves Wilson I. , Gertz Morie , Lin Yi , Lacy Martha , Dispenzieri Angela , Hayman Suzanne R. , Buadi Francis , Dingli David , Kapoor Prashant , McCurdy Arleigh Robertson , Singh Preet Paul , Gupta Vinay , Kumar Shaji 
Published: March 2020

8587 Background: Patients (pts) undergoing an auto-transplant (ASCT) for multiple myeloma (MM) have disease assessment approximately 100 days later. This result may direct decisions of further therapy versus observation. However, some pts continue to experience a decline in their serum or urine monoclonal (M) - protein after day 100 without more therapy. Little is known about the prevalence and significance of this phenomenon. Methods: We identified 903 MM pts who underwent ASCT within 12 months (mos) of diagnosis (Dx) at our institution. Their day 100 post-ASCT M-protein from serum and urine electrophoresis with immunofixation as well as serum free light chains were compared to subsequent values during follow-up. The IMWG criteria were used to evaluate response. Results: Of the pts included, 510 (56%) were male and median age at ASCT was 59 (range 28-76). Median follow up from Dx and ASCT was 82 mos (95% CI; 75 - 86) and 74 mos (95% CI; 70 - 79) respectively. There were 453 (50%) pts seen in follow-up who had not achieved a CR at Day 100 nor initiated on maintenance therapy. Of these pts, 167 (37%) had a further decrease in their M-protein after day 100 at a median of 9.4 mos (95% CI; 8 – 10) post-ASCT. Given the time taken for maximal response, we assessed patients’ clinical response at one year post-ASCT. Compared to patients who did not have further clinical response between day 100 and 1 year, pts experiencing further response had a longer time to next therapy (TTNT) (43 mos vs. 17 mos, P < 0.001) as well as overall survival (OS) (96 mos vs. 62 mos, P < 0.001). Positive predictors for continued response included having an IgG isotype, evolution from a pre-existing MGUS, smoldering myeloma or solitary plasmacytoma and a Day 100 bone marrow plasma cell < 3%. In a multivariate analysis, elevated creatinine at Dx and lack of continued response predicted for shorter TTNT and OS post-ASCT. Older age and high-risk MM by FISH also predicted a shorter OS. Conclusions: In MM pts undergoing ASCT, continued M - protein response was seen in a third of the pts lacking a CR at day 100. This phenomenon appears prognostic and must be considered when interpreting studies evaluating post-ASCT response and the need for further therapy.