bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weekly MLN9708, an investigational oral proteasome inhibitor (PI), in relapsed/refractory multiple myeloma (MM): Results from a phase I study after full enrollment.
Authors: Kumar Shaji , Bensinger William , Zimmerman Todd M. , Reeder Craig B. , Berenson James R. , Berg Deborah , Hui Ai-Min , Gupta Neeraj , Di Bacco Alessandra , Yu Jiang , Shou Yaping , Niesvizky Ruben 
Published: March 2020

8514 Background: MLN9708 is an investigational, orally bioavailable, potent, reversible, specific inhibitor of the 20S proteasome that has demonstrated antitumor activity in in vivo models of MM. We report safety, activity and pharmacokinetics (PK) of weekly oral MLN9708 in a phase 1 trial in patients (pts) with relapsed and/or refractory MM after full enrollment (NCT00963820). Methods: Pts received MLN9708 (days 1, 8, 15; 28-day cycles) at 0.24–3.95 mg/m2 (dose-escalation phase) and at the MTD, 2.97 mg/m2, in relapsed and refractory (RR), bortezomib (btz)-relapsed, PI-naïve, and prior carfilzomib (CZ) expansion cohorts. Adverse events (AEs) were graded by NCI-CTCAE v3.0. Response was assessed by IMWG uniform criteria. Results: 60 pts (33 male, median age 64 yrs [40–79]) were enrolled, 32 in the dose-escalation phase and 31 to the expansion cohorts (11 RR, 10 btz-relapsed, 6 PI-naïve, 4 CZ; 2 RR and 1 btz-relapsed pts included from MTD dose-escalation cohort). Median time from MM diagnosis was 4.9 yrs (1.5–18.8). Median number of prior regimens was 6 (2–18), including btz, lenalidomide, thalidomide, and CZ in 83%, 95%, 52%, and 13%, respectively; 76% were refractory to last therapy (17% btz-refractory). At data cut-off (Nov 29, 2012) pts had received a median of 2 cycles (1–11); 5 pts remained on treatment. All-grade/grade ≥3 drug-related AEs were seen in 83%/52% of pts; common drug-related grade ≥3 AEs were thrombocytopenia (33%), diarrhea, neutropenia (17%), decreased appetite, fatigue, and lymphopenia (8%). 6 pts (10%) had drug-related PN (no grade ≥3). 5 pts discontinued due to drug-related AEs; 1 pt died on study due to an unrelated AE. By investigator assessment in 41 evaluable pts, responses included1 VGPR, 5 PR, 1 MR, and 15 with SD. MLN9708 was rapidly absorbed, with a terminal half-life of 4–12 days (supporting weekly dosing) and a proportional increase in plasma AUC with dose (0.8–3.95 mg/m2). PK data were similar across expansion cohorts. Conclusions: Current data suggest weekly oral MLN9708 is generally well tolerated with infrequent PN, and shows activity in this heavily pretreated population with prior exposure to immunomodulatory drugs and btz. Clinical trial information: NCT00963820.
Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with relapsed/refractory lymphoma.
Authors: Horwitz Steven M. , Flinn Ian , Patel Manish R. , Younes Anas , Foss Francine M. , Oki Yasuhiro , Sweeney Jennifer , Allen Kerstin , Dunbar Joi , Kelly Patrick Francis , Kahl Brad S. 
Published: March 2020

8518 Background: Phosphoinositide-3-kinases (PI3Ks) are pivotal in cell signaling and regulate a variety of cellular functions relevant to oncogenesis. IPI-145, a potent oral inhibitor of the PI3KEδ and PI3K-γ isoforms, is in clinical development for patients (pts) with hematologic malignancies. Early results in pts with relapsed/refractory lymphoma from an ongoing Phase 1 study are reported here. Methods: This dose-escalation study evaluates the safety, maximum tolerated dose (MTD), clinical activity, and pharmacokinetics (PK) of IPI-145. Expansion cohorts (EC) < MTD are allowed. IPI-145 is given orally twice daily (BID) in 28-day cycles. Tumor response is based on standard disease-specific criteria. Results: 55 pts have been dosed with IPI-145. PK, available through 50 mg BID, are linear with complete inhibition of PI3K-δ at doses > 15 mg BID and increasing suppression of PI3K-γ with increasing dose. In the 36 pts with lymphoma who received 15 mg to 75 mg BID, the median [range] number of cycles was 2.4 [0.1–10] and 67% remain on study. Treatment-related adverse events (TRAEs) occurred in 50% of pts with lymphoma. Neutropenia and increased ALT were the most common ≥ Grade 3 TRAEs (4 pts each) and were not associated with increasing dose. > Grade 3 ALT elevations were more common in lymphoma pts (18%) compared to non-lymphoma pts (5%). Among evaluable pts with lymphoma (n=27), early clinical activity was observed in T-cell (n=6, 1 CR, 1 PR, 1 SD) and aggressive/indolent B-cell (n=21, 2 CR, 9 PR, 5 SD) lymphoma pts at ≤ 75 mg BID. 92% of responses were observed by 3 months. Conclusions: IPI-145 appeared well tolerated and has shown clinical activity in pts with relapsed/refractory advanced B- and T-cell lymphoma across the range of doses examined. The single agent MTD has not been determined and dose escalation continues. Updated safety and efficacy data from pts with lymphoma enrolled in dose escalation or ECs evaluating 25 mg BID and a higher dose (< MTD) of IPI-145 will be presented. Clinical trial information: NCT01476657.
A phase II trial of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) for previously untreated stage I, II extranodal natural killer/T-cell lymphoma, nasal type (NTCL): A multicenter study of the Korean Cancer Study Group.
Authors: Kim Tae Min , Kim Dong-Wan , Kang Yoon-Koo , Cho Goon Jae , Song Hong-Suk , Kim Hyo Jung , Kim Byung Soo , Lee Jong-Seok , Kim Hawk , Yang Sung Hyun , Yuh Young Jin , Bae Sung Hwa , Lee Kyung-Hee , Jeon Yoon-Kyung , Kim Chul Woo , Heo Dae Seog 
Published: March 2020

8521 Background: Combination chemotherapy of IMEP was active as a first-line as well as a second-line treatment for NTCL in a retrospective analysis. Thus, we conducted a prospective, multicenter, phase II study of IMEP chemotherapy in previously, untreated stage I/II NTCL. Methods: Patients with chemo-naïve stage I/II NTCL were enrolled between December 2004 and February 2009 and they received 6 cycles of IMEP (ifosfamide 1.5 g/m2 on days 1 to 3; methotrextate 30mg/m2 on days 3 and 10; etoposide 100mg/m2 on days 1 to 3; and prednisolone 60mg/m2/day on days 1 to 5) followed by involved field radiotherapy (IFRT). Response was evaluated every 2 cycles of chemotherapy and 4 to 8 weeks after completion of IFRT using modified Response Evaluation Criteria in Solid Tumors. Results: Overall, 44 patients including 29 males were analyzed by the intent-to-treat principle. Overall response rates were 73% (complete remission [CR], 11 [27%] of 41 evaluable patients) after IMEP chemotherapy and 78% (CR, 18 [67%] of 27) after IMEP followed by IFRT. Grade 3 to 4 neutropenia and thrombocytopenia were documented in 33 (75%) and 7 (16%) patients, respectively. Only 8 (18%) patients experienced grade 3 febrile neutropenia. 2-year progression-free survival (PFS) and overall survival (OS) were 56% and 66%, respectively. High Ki-67 (≥ 70%) and Ann Arbor stage II independently reduced PFS (hazard ration [HR]=5.6, 95% confidence interval [CI] 1.8-17.6; P=.004) and OS (HR=4.8, 95% CI 1.9-12.2; P=.001), respectively. Conclusions: IMEP followed by IFRT is active and safe against patients with previously untreated stage I/II NTCL.
A pooled analysis of 1,546 patients with AIDS-related lymphoma (ARL): An assessment of prognostic factors by treatment era.
Authors: Barta Stefan K. , Samuel Michael , Xue Xiaonan , Lee Jeanette Y. , Mounier Nicolas , Kaplan Lawrence D. , Ribera Josep-Maria , Spina Michele , Tirelli Umberto , Weiss Rudolf , Galicier Lionel , Boue Francois , Wilson Wyndham Hopkins , Wyen Christoph , Dunleavy Kieron , Little Richard F. , Remick Scot C. , Goldfinger Mendel , Noy Ariela , Sparano Joseph A. 
Published: March 2020

8524 Background: Management of ARL evolved in the last 2 decades. We previously reported prognostic factors in a pooled analysis of 1,546 patients with ARL, and here present analysis of these factors over time to determine if their prognostic significance has changed. Methods: Following a systematic review, we assembled individual patient data from 19 prospective phase 2/3 clinical trials (published 1993-2010) for ARL (n=1,546). Factors analyzed include age, sex, histology, CD4 count, prior history of (h/o) AIDS, & age-adjusted (aa) IPI. The endpoint was overall survival (OS) expressed as the hazard ratio (HR) for death. We used separate Cox proportional hazard models adjusted for the other covariates to determine the significance of each variable in the following time periods: pre-cART [combination antiretroviral therapy] (<1996; n=388), early cART (‘96-‘00; n=694), modern cART (‘01-‘04; n=282) & current era (‘05-‘10; n=182). We also combined all enrollments in one Cox model to test for difference in association with OS over enrollment periods. Results: Rituximab use was limited in the early cART (20%) compared with the modern cART (83%) and current (93%) eras. Histology & sex were not significantly associated with OS in any time period. Increasing age was associated with worse OS in the pre-cART (HR 1.02; p<0.01) and current (HR 1.05, p=0.04) eras. A prior h/o AIDS increased risk of death during early cART (HR 1.31, p=0.047) but was not significant after 2000. Meanwhile, baseline CD4 count <50 was a poor prognostic factor during early (HR 1.78, p<0.01) and modern cART (HR 2.76, p=0.001) eras, but not in the current era. The aaIPI predicted worse OS in each time period (pre-cART: HR 1.54, p<0.0001; early cART: HR 1.49, p<0.0001; modern cART: HR 1.52, p<0.01; current era: HR 2.34, p<0.0001). No significant interaction between each prognostic factor with enrollment was found. Conclusions: In this pooled analysis of 1,546 patients with ARL, aaIPI was the only consistently significant prognostic factor and its effect was magnified in the current era. HIV-related factors gained prognostic relevance in the early and modern cART era but may not be as relevant with current treatment strategies.
Phase II study of chidamide (CS055), a new subtype-selective oral histone deacetylase inhibitor, in patients with relapsed or refractory peripheral T-cell lymphoma.
Authors: Shi Yuan-Kai , Dong Mei , Hong Xiao-Nan , Zhang Wei-Jing , Feng Ji-Feng , Zhu Jun , Yu Li , Ke Xiao-Yan , Huang Hui-Qiang , Shen Zhi-Xiang , Fan Yun , Li Wei , Zhao Xie-Lan , Qiu Lu-Gui , Huang He 
Published: March 2020

8525 Background: Chidamide (CS055) is a new benzamide type of histone deacetylase (HDAC) inhibitor with subtype selective activity against HDAC1, 2, 3 and 10. Chidamide has shown well-tolerated and favorable PK profiles in patients (pts) with advanced solid tumors and lymphomas. This phase II study was to evaluate the efficacy and safety of chidamide in relapsed or refractory peripheral T-cell lymphoma (PTCL). Methods: 102 PTCL pts were enrolled. In the exploratory trial, pts were randomized to receive chidamide 30mg or 50mg twice per week for 2 weeks, followed by 1 week of rest. In the pivotal trial, chidamide was administered 30mg twice per week w/o drug-free holiday. The primary endpoint was overall response rate (ORR). Responses were assessed using IWC criteria. Results: In the exploratory trial, 19 pts were enrolled with 9 and 10 to the 30mg and 50mg arms, respectively. ORR was 11.1% (1 CR) in the 30mg arm and 40.0% (1 CR, 1 CRu, 2 PR) in the 50mg arm. One pt in the 50mg arm experienced drug-related grade 4 thrombocytopenia. In the pivotal trial, 83 pts were enrolled. Most pts were stage III (35.2%) or IV (45.9%). 23 pts (29.1%) had confirmed responses out of 79 evaluable pts in the pivotal trial (8 CR, 3 CRu, and 12 PR). Responses of 19 pts (24.1%) maintained for ≥12 weeks. ORR with 27.8% was obtained by the Independent Review Committee. 68 pts (81.9%) experienced at least 1 AE in the pivotal trial, with 52.9% of AEs ≤ grade 2. The most common AEs were thrombocytopenia (50.6%), leucocytopenia (39.8%), neutropenia(21.7%), and fatigue (9.6%). 1 pt had a grade 3 QTc prolongation. 7 pts (8.4%) experienced at least one SAE, in which a grade 4 thrombocytopenia was considered to be drug-related. 2 pts with responses (CR) have received chidamide for > 43 months w/o evidence of cumulative toxicity. Conclusions: Chidamide as an oral single agent had significant and durable activity in pts with relapsed or refractory PTCL. Toxicities with the therapy were generally tolerable and manageable. The overall differences in pathological subtypes of pts enrolled and clinical profiles between chidamide and the two existing drugs, pralatrexate and romidepsin, will be discussed. Clinical trial information: ChiCTR-TNC-10000811.
Phase (Ph) I/II study of elotuzumab (Elo) plus lenalidomide/dexamethasone (Len/dex) in relapsed/refractory multiple myeloma (RR MM): Updated Ph II results and Ph I/II long-term safety.
Authors: Lonial Sagar , Jagannath Sundar , Moreau Philippe , Jakubowiak Andrzej J. , Raab Marc S. , Facon Thierry , Vij Ravi , Bleickardt Eric , Reece Donna Ellen , Benboubker Lotfi , Zonder Jeffrey A. , Deng Wei , Singhal Anil K. , Richardson Paul Gerard Guy ,   on behalf of the 1703 Study Investigators
Published: March 2020

8542 Background: Elotuzumab (Elo) is a humanized anti-CS1monoclonal antibody that enhances natural killer cell mediated antibody dependent cellular cytotoxicity of CS1 expressing myeloma cells. This study included a dose finding Ph I cohort (N=28) and a Ph II cohort (N=73). Here we update Ph II data and provide long term safety data from both cohorts. Methods: Patients (pts) treated with ≥1 (Ph I) or 1–3 (Ph II) prior therapies received Elo + Len/dex as described previously (Lonial JCO 2012; Richardson ASH 2012) until disease progression, unacceptable toxicity, or death. All pts received a premedication regimen including methylprednisolone, diphenhydramine or equivalent, ranitidine or equivalent, and acetaminophen to mitigate infusion reactions. Adverse events (AEs) in Ph I/II pts occurring ≤18 months (mo) (N=98) were compared to AEs with a >18 mo onset in a subgroup of pts treated >18 mo (n=49). This safety analysis excluded 3 Ph I pts treated with Elo 5 mg/kg. Results: In the Ph II cohort (median 63 yr), objective response rate (ORR) was 84%; 92% with 10 mg/kg (n=36) and 76% with 20 mg/kg (n=37). At a median follow-up of 20.8 mo, median progression free survival (PFS) was not reached (10 mg/kg) and 18.6 mo (20 mg/kg). Most common treatment emergent grade ≥3 AEs were lymphopenia (19%), neutropenia (18%), thrombocytopenia (16%) and anemia (14%). Most common grade 3/4 AEs emerging ≤18 vs >18 mo in Ph I/II cohorts are shown (Table). 15 pts discontinued due to AEs; none after 18 mo of treatment. There were 4 second primary malignancies; none were reported after 18 mo. Conclusions: Elo 10 mg/kg + Len/dex was generally well tolerated and resulted in a high ORR and encouraging PFS in pts with RR MM. AEs emergent after 18 mo of therapy were consistent with AEs during the initial 18 mo. Updated Ph II safety/efficacy data and long term safety data from Ph I/II cohorts will be presented.
Radiotherapy for nasal cavity and Waldeyer ring natural killer/T-cell lymphoma: Analysis in 131 patients.
Authors: Zhu Yuan , Liu Luying , Luo Jialing 
Published: March 2020

8553 Background: Theaim of this study was to evaluate the efficacy and prognosis of chemotherapy and radiotherapy for patients with nasal cavity and Waldeyer ring natural killer/T cell lymphoma. Methods: Records of 131 patients who received chemotherapy or radiotherapy or chemoradiotherapy at Zhejiang Cancer Hospital between 2000 and 2010, were retrospectively reviewed. Ninety-eight patients received chemoradiotherapy. Thirty patients received radiotherapy, and three patients received chemotherapy. All patients had pathology and immunohistochemistry diagnosis. According to the Ann Arbor Staging System, majority of patients were staged as IE stage (116/131). 14 patients presented with IIE stage, and 1 IIIE stage. Thirty-four patients had B symptoms. Results: 109 patients were with nasal cavity NK/T cell lymphoma, and 22 patients with Waldeyer ring NK/T cell lymphoma. Complete response (CR) was achieved in 116 (89%) patients. The 5-year overall survival (OS) rate and disease-free survival (DFS) rate for all patients were 62.7% and 53.5%, respectively. 5-year OS in patients with RT dose ³a50Gy and < 50Gy were 64% and 45.4% respectively (p =0.024). No survival difference was observed between patients with nasal cavity and Waldeyer ring, treated with radiotherapy and chemoradiotherapy, with or without B symptoms, CD56(+) and CD56(-), and between stage IE and IIE patients. On multivariate analysis, the level of lactate dehydrogenase (LDH) before treatment and dose of RT were correlated with prognosis (p<0.05). Conclusions: Radiotherapy, as the primary therapy, can result in a favorable outcome in the treatment of nasal cavity and Waldeyer ring natural killer/T cell lymphoma. The patients with the lower level of LDH before treatment, RT dose ≥50Gy had better prognosis. Addition chemotherapy to radiotherapy didn’t improve the survival.
Limited utility of surveillance imaging for detection of relapse in non-Hodgkin lymphoma.
Authors: Truong Quoc Van , Shah Nilay , Knestrick Mark , Curley Brendan F. , Craig Michael , Hamadani Mehdi 
Published: March 2020

8557 Background: Surveillance imaging with computerized tomography (CT) and positron emission tomography with CT (PET/CT) scans during follow-up after first-line therapies in patients with non-Hodgkin lymphoma (NHL) is commonly used in practice. However, most guidelines do not recommend surveillance imaging. We aimed to determine the value of routine imaging for the detection of first relapse in NHL patients in complete remission (CR) after first-line therapies. Methods: We retrospectively analyzed NHL patients referred to our center, who achieved CR after first-line therapies and subsequently relapsed. We evaluated whether the relapse was detected solely by routine CT or PET/CT or by patient-reported symptoms. Subgroup analysis was performed according to baseline histology (indolent vs. aggressive NHL). Data were also collected to determine the number of additional imaging, number of false positive scans, invasive procedures and iatrogenic complications, directly resulting from an abnormality detected on surveillance imaging. Results: Seventy-seven patients with first relapse of NHL between January 1, 2000 and December 31, 2010 were included. Majority of the relapses were detected by patient-reported symptoms as opposed to surveillance imaging (79.2% (n=61) vs. 20.8% (n=16); p<0.0001). There was no overall survival difference between the two groups (p=0.08). Patient-reported symptoms led to the detection of majority of relapses in aggressive (86.4% (n=45) vs. 13.6% (n=6); p<0.0001) and indolent NHL (69.7% (n=32) vs. 30.3% (n=10); p=0.037). There were greater number of scans done after a suspected relapse in the imaging versus symptoms group (1.94 versus 0.97; p=0.0004). Surveillance imaging led to 2 false positive scans/invasive procedures with one case of iatrogenic pneumothorax. Conclusions: Our limited retrospective analysis suggests that there is a limited role of surveillance imaging by CT or PET/CT for the detection of relapse in patients with NHL. There was no difference in survival outcome in our study between the two groups.
EBV-negative post-transplant lymphoproliferative disorder: Clinical characteristics, response to therapy, and survival.
Authors: Heil Daniel S. , Luskin Marlise Rachael , Stadtmauer Edward Allen , Schuster Stephen J. , Tsai Donald Edward , Reshef Ran 
Published: March 2020

8578 Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of solid organ transplantation. PTLD is frequently linked with Epstein-Barr virus (EBV) and it was suggested that EBV negativity is associated with a poor prognosis and lack of response to reduction of immunosuppression (RI). We conducted a case-control study to identify the characteristics, outcome and response to therapy of EBVpos and EBVneg PTLD over a 20-year period. Methods: We reviewed data on patients diagnosed with PTLD at U. Penn. between 1982 and 2012. We determined EBV positivity on tumor samples according to WHO criteria. We compared clinical and pathologic characteristics, response to therapy, and survival of EBVpos and EBVneg patients. Results: Of 222 patients diagnosed with PTLD, we verified the EBV status of 169 patients, of whom 35% were EBVneg and 65% were EBVpos. Mean follow-up was 46.7 months. Median time from transplant to PTLD was 23.1 mo. in EBVpos vs. 59.3 mo. in EBVneg (p=0.003) with 42% of EBVpos patients being diagnosed within the first year after transplant vs. 15% in the EBVneg group (p<0.001). EBVneg PTLD was more likely to occur in non-thoracic vs. thoracic transplants (p=0.006). 28% of patients with EBVpos PTLD presented with disease originating from the graft vs. 14% in the EBVneg group (p=0.03). In terms of histology, 36% of EBVpos patients had polymorphic PTLD vs. 7% of EBVneg patients (p<0.001). Of patients who were treated with RI alone (40% of patients in both groups), the overall response rates were 50% and 48% in EBVpos and EBVneg patients respectively (p=NS). Response rates to rituximab were also similar. There was no difference in the mortality risk between groups (HR=1.04; p=0.84). The 5-year survival rates were 47% and 51% in EBVpos and EBVneg PTLD respectively (p=NS). Conclusions: In a large single-center series, EBVneg PTLD was associated with late occurrence after transplant, monomorphic histology and similar outcome in comparison with EBVpos PTLD. Importantly, the response of EBVneg PTLD to RI and rituximab was no different than EBVpos PTLD. These results have implications for the management of solid organ transplant recipients with PTLD.
Measures of immune recovery following autologous stem cell transplantation for multiple myeloma and outcome.
Authors: Hegerova Livia , Gertz Morie , Lacy Martha , Dispenzieri Angela , Buadi Francis , Hayman Suzanne R. , Dingli David , Porrata Luis F. , Kumar Shaji 
Published: March 2020

8581 Background: Autologous stem cell transplant (ASCT) improves survival in patients with multiple myeloma (MM). Recent studies have elucidated the relationship in ASCT between absolute lymphocyte count (ALC) recovery and improved survival, highlighting the importance of immune recovery. We conducted a retrospective analysis of patients with multiple myeloma to observe the impact of different measures of immune recovery at day 100 post-ASCT on outcome. Methods: Retrospective analysis of data from the existing clinical databases identified 1184 patients with multiple myeloma that underwent ASCT at Mayo Clinic between 1987-2011. Markers of immune recovery analyzed on day 100 status-post ASCT included ALC, monocyte count, and immunoglobulin levels. Kaplan Meier analysis was performed to determine progression free survival (PFS) and overall survival (OS). Results: Among the 1184 patients, median age at diagnosis of multiple myeloma was 57 (range, 23-75 yr), and median age at time of transplantation was 59 (range, 24-75 yr); 59% were male. The median OS and PFS post-transplant were 80 months and 34 months respectively. 62% of patients were alive 5-years post-transplant. The median OS was not improved with normal vs. abnormal IgG levels at day 100 (p=.298). In contrast, monocyte recovery was a significant predictor of OS. Patients with normal monocyte counts of greater than 0.3 x 10⁹ cells/L at day 100 showed superior survival (65 vs. 37 months, p= .001). Similarly, patients with normal monocyte recovery at day 15 post-transplant showed a significant survival benefit (68 vs. 50 months, p=.007). Early ALC recovery, which has been shown to be a positive prognostic indicator at day 15 post-transplant, was not prognostic at day 100 (p= .960). Conclusions: The present study further elucidates prognostic indicators after ASCT for MM highlighting the importance of various markers of immune recovery. Immunoglobulin recovery was not associated with superior survival, while monocyte recovery at day 15 and day 100 post-transplant translated to an improved survival and requires further study. It may be hypothesized that early immune system reconstitution may have a positive effect against disease post-transplant.