bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of a novel oral isotype-selective histone deacetylase (HDAC) inhibitor in patients with relapsed or refractory Hodgkin lymphoma
Authors: Younes A. , Fanale M. , Pro B. , McLaughlin P. , Neelapu S. , Fayad L. , Wedgwood A. , Dubay M. , Backstrom J. , Martell R. E. 
Published: March 2020

8000 Background: MGCD0103 is a non-hydroxamate, isotype-selective, inhibitor of human HDACs. Abnormal regulation of HDAC activity is associated with malignant disease in humans, and small molecule HDAC inhibitors are a novel drug class with anticancer potential. Their proposed anti-Hodgkin activity is through regulation of aberrant gene expression at the transcriptional level by inhibiting proliferation, inducing apoptosis, and/or initiating differentiation in cancer cells. Methods: A phase II trial of MGCD0103 (110 mg 3x/week in 4- week cycles) is ongoing in patients (pts) with relapsed/refractory Hodgkin Lymphoma (RRHL). The primary endpoint is a composite of objective response and stable disease. Results: As of Dec 15th, 2006, 18 pts out of a planned 12–35 have been enrolled; median age 28 (range: 21–62). All pts were previously treated with autologous and/or allogeneic stem cell transplant. The median number of cycles received to date is 2 (range: 1–4). Seven pts have completed =8 weeks (2 cycles) of therapy and are evaluable for response analysis; 5 of these had tumor reduction ranging between 21% and 70% by CT, which is associated with a significant reduction in FDG-PET activity in 4 pts. Of the 18 pts, 5 have had dose reductions/discontinuations due to: mucositis (n=1); fatigue/nausea/diarrhea (n=1); nausea/vomiting (n=1); fatigue (n=1) and pancreatitis/hypotension (n=1). Significant HDAC inhibition (>20% of total activity), was seen in PBMCs from 7/9 pts with samples. Treatment is ongoing in 14 pts; including those with tumor reduction. Criteria have been met to expand to the second stage of the study (>1 response demonstrated in the first 12 patients). Conclusions: Preliminary results suggest that single-agent MGCD0103 demonstrates significant anti-tumor activity in RRHL and is well tolerated at a Phase II dose of 110mg in this ongoing trial. No significant financial relationships to disclose.
Prospective, multicenter, randomized GITMO-IIL trial comparing intensive (R-HDS) to conventional chemoimmunotherapy (CHOP-R) in high-risk follicular lymphoma (FL) at diagnosis
Authors: Ladetto M. , De Marco F. , Benedetti F. , Vitolo U. , Patti C. , Passera R. , Rambaldi A. , Gianni A. M. , Corradini P. , Tarella C. 
Published: March 2020

8006 Background: The GITMO-IIL trial evaluated if an intensified treatment with ASCT is better than conventional chemotherapy (both supplemented with Rituximab) in high-risk FL at diagnosis. Methods: Eligibility required a FL with aaIPI>1 or IIL>2 score and an age of 18–60. Primary endpoint was EFS. The analysis was intention to treat. Secondary endpoints were PFS, DFS, OS, rate and prognostic value of MR. R-HDS and CHOP-R have been already described (Ladetto et al ASH 2005, Rambaldi et al Blood 2002). Planned sample size was 240 to detect a 20% absolute increase in the 3-years EFS. However the trial was stopped at 136 pts due to R-HDS superiority in EFS at a planned interim analysis. Cross-over was allowed after CHOP-R failure. Centralized PCR-based molecular analysis was planned on BM cells. Results: Age, stage, LDH, bulky disease, B-symptoms ECOG PS, extranodal disease aaIPI, IIL and retrospectively assigned FLIPI were similar in the two arms. CRs were 59% with CHOP-R and 85% with R-HDS (p<0.001). At a median follow-up of 39 months EFS and PFS are 36% and 38% for CHOP-R and 66% and 72% for R-HDS. OS is 83% in each arm. 67% of relapsed R-CHOP pts underwent R- HDS. MRs were 44% after CHOP-R and 80% after R-HDS (p<0.001). MR was associated to a better PFS (p<0.001). Of note, 3yrs PFS of pts with or without MR was similar in the two arms (MR: 67% with CHOP-R and 76% with R-HDS) (no MR: 25% for CHOP-R and 32% for R-HDS). MR was the strongest independent prognostic factor for PFS, EFS and DFS by multivariate analysis. Conclusions: This is the first phase III trial including MR analysis in a high proportion of pts and comparing intensified versus conventional therapy in the rituximab age. This trial indicates that: a) R-HDS has a better EFS and PFS in truly high-risk FL patients; b) MR is the strongest outcome predictor available in FL; c) the similar outcome in pts achieving (or not achieving) MR, regardless of treatment received, indicates that the superior performance of R-HDS is mostly due to its superior MR rate. [Table: see text]
Rituximab compared to observation after high-dose consolidative first-line chemotherapy (HDC) with autologous stem cell transplantation in poor-risk diffuse large B-cell lymphoma: Updated results of the LNH98-B3 GELA study
Authors: Haioun C. , Mounier N. , Emile J. F. , Bologna S. , Coiffier B. , Tilly H. , Recher C. , Fermé C. , Morschhauser F. , Gisselbrecht C. 
Published: March 2020

8012 Background: Rituximab has been evaluated as a single agent and also in combination with chemotherapy in aggressive and indolent lymphomas with evidence of efficacy. More recently, rituximab maintenance therapy has been successfully used to keep responding patients in remission. We have shown that consolidative HDC improves outcome of poor risk responder-patients (pts) with aggressive lymphoma. Methods: The aim of the present study was to evaluate the potential benefit, as randomly compared to observation, rituximab - 375 mg/m2/week for 4 weeks - 2 months after HDC, in decreasing the relapse rate (second randomization: R2). A secondary objective was to improve the response rate before HDC using the intensified ACE chemotherapy regimen (doxorubicin 75mg/m2 d1, cyclophosphamide 1g/m2 d1-d2, etoposide 150mg/m2 d1-d3) as compared to the standard ACVBP induction regimen (R1). Four cycles were delivered every 15 days. In responding pts, HDC (mitoxantrone 45 mg/m2, cyclophosphamide 1500 mg/m2 × 4d, etoposide 250 mg/m2 × 4d and carmustine 300 mg/m2) was started between d80 and d90. Results: From 10/99 to 05/03 (closing date), 476 pts younger than 60 years with diffuse large B-cell lymphoma and aa-IPI 2 or 3 (aa-IPI 3: 29%). were enrolled. 237 pts were assigned to ACE and 239 to ACVBP. Complete response (CR+CRu) rates to induction treatment did not significantly differ between the 2 regimens (65% and 63%, respectively). Death rate during induction phase was 4% in both arms. Among the 331 pts who received HDC, 269 were randomized (R2) to receive either rituximab (n=139) or observation (n=130). 545 infusions of rituximab were administered with no clinically relevant infectious toxicity except two severe VZV infections. With a median follow-up of 4 years after R2, a trend toward a better 4y-EFS was observed in the rituximab group (80% vs 71%, p=0.098). In addition, a two-sided log-rank test stratified by aa-IPI, induction treatment and response after HDC was performed and confirmed the results of the unstratified analysis. Conclusions: We conclude that early and brief rituximab maintenance is feasible after HDC and may prolong remission status. [Table: see text]
Late treatment mortality and secondary cancers after autologous stem cell transplant for relapsed or refractory Hodgkin lymphoma (HL)
Authors: Dhani N. C. , Roberts T. , Pintilie M. , Kuruvilla J. , Franke N. , Nagy T. , Tsang R. , Keating A. , Crump M. 
Published: March 2020

8016 Background: Late treatment-related mortality and second cancers have an important influence on the long-term outcome of patients (pts) with HL. The incidence of treatment failure and causes of death were evaluated in pts with advanced HL receiving high-dose therapy and ASCT, to understand the impact of late events on overall survival (OS). Methods: From Dec 1986 to Nov 2005, 323 pts with relapsed/refractory HL after primary chemotherapy (plus radiation [RT]: 32%) received salvage chemotherapy to best response, followed by etoposide 60 mg/kg day -4 and melphalan 160–180 mg/m2 day -3 supported by autologous bone marrow (46%), mobilized peripheral blood stem cells (49%) or both (5%)on day 0; 24% received involved field RT post-ASCT. Risk of treatment failure and second cancer was estimated using competing risks methods. Results: Patient Characteristics: male: 61%; median age 33 years (range16–67). Number of salvage regimens pre-ASCT: 1: 72%; 2: 25%. Disease status post-salvage chemotherapy: CR 28%, PR 66%. After a median follow-up of 4.7 years post-ASCT (range 1–17), 174 pts (54%) have experienced treatment failure (relapse or treatment related death) and 154 pts (48%) have died, 75% following relapse and 20% from toxicity without relapse. Of the 30 deaths without relapse, 30% occured >5 years post-ASCT. Failure free survival at 3 and 10 years is 50% (95% CI, 44–55%) and 40% (33–46), and overall survival is 68% (63–73) and 39% (33- 46), respectively. There have been 29 second cancers (17 AML/MDS, 12 solid tumors) in pts alive without relapsed HL. The probability of a second cancer is 4.9% (2.8–7.8) at 3 years and 12% (8–17%) at 10 years. The hazard rates for second malignancy, leukemia and solid tumors for each 10-year age increment are 1.9 (p=0.0001), 1.9 (0.001) and 1.8 (0.03), respectively. Only 4 pts have relapsed beyond 5 years post- ASCT but the cumulative incidence of treatment-related death (from toxicity or second cancers) continues to increase from 9% (6–13) at 3 years to 15% (11–20) 10 yrs post-ASCT. Conclusions: In this single-institution series of uniformly treated patients with relapsed/refractory HL, late relapse of disease is uncommon, but late toxicities have a significant and ongoing impact on failure-free survival. No significant financial relationships to disclose.
A PETHEMA study of high-dose therapy/stem cell support (HDT), including tandem transplant, in primary refractory multiple myeloma (MM): Identification of two populations with different outcomes
Authors: Blade J. , Rosiñol L. , García-Sanz R. , Lahuerta J. , Hernández M. , Sureda A. , de la Rubia J. , Besalduch J. , García- Laraña J. , San Miguel J. 
Published: March 2020

8021 Background: It has been claimed that patients with primary refractory myeloma benefit from early HDT. However, the reported series have 2 shortcomings: 1) patients with “unresponsive-progressive disease” vs those “non-responding-non progressing” were not analyzed separately and 2) some included patients had MR or even PR according to the EBMT criteria. Aim: Response and survival after early HDT in the two populations of truly primary refractory MM Methods: From Oct 1999 to Dec 2004, 829 patients with MM received 6 cycles of VBMCP/VBAD and at least one transplant. 79 of the 829 patients were refractory to VBMCP/VBAD. These resistant patients were scheduled to receive a tandem transplant, the first with Bu-12/MEL-140 or MEL-200 and the second “autologous” with CVB or “allo- RIC” (if donor available) with Fluda/MEL-140. Response and progression were defined by the EBMT criteria. Results: 32 of the 79 primary refractory patients had progressive disease under the initial chemotherapy while 47 were “unresponsive, non-progressive”. The prognostic features, including cytogenetics, were similar in both groups. 70% of the patients responded to the first HDT (CR/nCR 8%, PR 48%, MR 13%). 37 patients were given a second transplant (26 “auto”, 11 “allo”). 41% who received a second “auto” up-graded their response (CR 9%, PR 14%, MR 18%) while 42% who underwent “allo-RIC” increased their response (CR 28%, PR 14%). Median survival of the whole series was 3 years. Patients progressing while on therapy had a shorter survival than the “no-change” group (median 2 yrs vs not reached, p=0.00002). Finally, the 47 “non-responsive, non-progressors” patients had similar survival than the 718 with chemosensitive disease intensified with HDT. Conclusions: 1) HDT in patients with primary refractory MM results in a low CR rate, 2) patients progressing while on initial therapy have a short survival despite the intensive approach and 3) patients with “non-responding, non-progressive” disease have similar survival than chemosensitive patients. Whether this good outcome is due to the impact of HDT or to the natural history of a more indolent disease remains to be determined. No significant financial relationships to disclose.
Outcome of patients relapsing early after autologous stem cell transplantation for multiple myeloma
Authors: Mahmood S. T. , Kumar S. , Lacy M. Q. , Dispenzieri A. , Hayman S. R. , Rajkumar S. V. , Litzow M. R. , Gertz M. A. 
Published: March 2020

8022 Background: Autologous stem cell transplant (ASCT) is the standard approach for eligible patients (pts) with multiple myeloma (MM). The median time to relapse after early ASCT is 2–3 yrs and overall survival (OS) is 4–5 yrs. Though various risk factors have been identified for early relapse, the outcome of this group of pts is not clearly described. With the advent of newer therapies, it is important to understand the natural history of MM in these pts to design treatment strategies. Methods: A total of 432 pts with MM, undergoing ASCT within 12 months (mos) of diagnosis, with a minimum follow up of 12 mos were studied. Clinical and laboratory data were obtained from a prospectively maintained database and clinical records. Pts were divided into 2 groups: early relapse (relapse <12 mos from ASCT) and late relapse (either relapsed >12 mos after ASCT or disease free at last follow up). Results: There were 94 pts (22%) in the early relapse group and among the late relapse group (N=338), 171 had relapsed beyond 12 mos and 167 were disease free at last follow up. The median time to ASCT was similar in all groups. The early relapse group had a significantly shorter median OS from diagnosis (23.9 vs. 82.2 months; P < 0.001) and from transplant (17.6 mos vs. not reached; P < 0.001). The median OS from relapse was 7.9 mos in this group compared to 39.6 months for the rest. In univariate analysis, elevated CRP, high BM plasma cell%, labeling index (PCLI) >1%, abnormal cytogenetics, presence of circulating PCs at harvest and lack of CR from ASCT predicted for early relapse. In multivariate analysis, an elevated PCLI (RR=2.9; P=0.002) and failure to achieve CR (RR 2.7; P=0.002) was associated with early relapse. Conclusions: Pts who relapse within 12 mos of an ASCT have a very short survival and should be offered trials evaluating novel therapies and combinations. Survival figures from this study represent the benchmark for the comparison of novel approaches in this population. Pts with poor prognostic factors have a short PFS after ASCT and should be considered for alternative approaches. Inability to achieve CR appears to predict shorter PFS and clinical trials evaluating maintenance therapy should be offered in these pts. No significant financial relationships to disclose.
I131-tositumomab monotherapy as frontline treatment for follicular lymphoma: Updated results after a median follow-up of 8 years
Authors: Kaminski M. S. , Estes J. , Tuck M. , Ross C. W. , Wahl R. L. 
Published: March 2020

8033 Background: Monoclonal antibody-based therapies are improving the outcome for patients (pts) with follicular lymphoma (FL). Radioimmunotherapy has been found to be effective for pts with relapsed/refractory disease, but even more so when used as frontline treatment. Methods and Results. We previously reported the results of a phase II, single-institution, study of anti-CD20 I-131- Tositumomab (Bexxar) given as a single agent and as a single one-week treatment for 76 pts with Stage 3 or 4 FL (NEJM 352:441, 2005). An overall response (OR) rate and complete remission (CR) rate of 95% and 75%, respectively, were observed. With a median follow-up of 5.1 yrs, 5-yr overall survival (OS) and progression-free survival (PFS) were 89% and 59%, respectively, with a median PFS reached at 6.1 yrs. We now report on this pt cohort after a median follow-up of 7.93 yrs. The 8-year and 10-yr OS is estimated (by KM) now at 86% and 8-yr PFS is 50% (95% CI: 38.8 - 61.7%). Only 3 additional relapses have occurred in the additional follow-up period (at 8.0, 8.3, and 9.2 years) in those with CRs. The 8-yr PFS for the 57 pts who achieved CR is now 64%. The median for PFS has now being reached for CRs at 9.2 yrs. When the impact of baseline FLIPI scores were analyzed, only 8-yr OS was significantly affected when low-risk (LR) and intermediate-risk (IR) categories were combined and compared to the high-risk (HR) category (92% vs. 75%; p = 0.029). The 8-yr PFS for LR + IR pts was 56% vs. 35% for HR pts (p = 0.317). 27 of the 76 total pts (35%) had HR scores. Of additional importance, no cases of MDS or AML have yet been observed. Other longterm toxicities including thyroid status and second non-hematologic cancers will be updated at the meeting. Conclusions. These data underscore the high degree of effectiveness and durability of remissions achieved with a single, one-week course of frontline Bexxar and should serve as a benchmark for comparison to other studies using more prolonged and toxic treatments, including those combining unlabeled or radiolabeled antibodies with chemotherapy. No significant financial relationships to disclose.
Bendamustine and rituximab (BR) are effective in the treatment of relapsed or refractory indolent and mantle-cell lymphomas: Long-term follow-up of a phase II study
Authors: Rummel M. J. , Atta J. , Welslau M. , Kofahl-Krause D. , von Gruenhagen U. , Schalk K. , Boeck H. P. , Banat A. G. , Knauf W. , Niederle N. 
Published: March 2020

8034 Bendamustine combines a purine-like benzimidazol and bifunctionally alkylating nitrogen mustard group. The aim of this multicenter- study was to evaluate the progression-free survival (PFS), response rate and toxicity of BR in patients with mantle-cell or low-grade lymphomas in 1st to 3rd relapse or refractory to previous treatment. A median of 4 courses per patient were administered to 63 pts. Bendamustine was given at a dose of 90 mg/m2 on day 1 and 2 combined with 375 mg/m2 Rituximab on day 1 for a max. of 4 cycles every 4 weeks. Histologies: 24 follicular, 16 mantle cell, 17 lymphoplasmacytoid, 6 marginal zone lymphoma. 57 of 63 pts responded to BR corresponding to an overall response rate of 90% with a CR-rate of 60%. In mantle cell lymphomas BR showed a considerable activity achieving a response rate of 75% with a CR-rate of 50%. In an updated analysis the median time of PFS was 30 months and the median duration of overall survival has not yet been reached. With a median follow-up period of 3 years two secondary neoplasms have been observed (bronchial carcinoma). No MDS was observed to date. These results demonstrate that the combination of Bendamustine and Rituximab is a highly active regimen in the treatment of low-grade lymphomas and mantle cell lymphomas. Based upon these encouraging results the Studiengruppe indolente Lymphome (StiL) initiated two Phase III trials that compare BR to established chemo-immunotherapy regimens: BR vs R-CHOP in untreated pts, and BR vs Fludarabine- R in relapsed pts. These studies should provide considerable guidance for the appropriate role of Bendamustine in the treatment of low-grade and mantle cell lymphomas. No significant financial relationships to disclose.
R-Dhaox, high dose chemotherapy (HDC) and rituximab maintenance as salvage treatment in relapsed/refractory (R/R) follicular (F) and mantle cells (MC) lymphomas (NHL)
Authors: Rupolo M. , Michieli M. , Spina M. , Bulian P. , Degan M. , Mazzucato M. , Abbruzzese L. , Tirelli U. 
Published: March 2020

8036 Second line regimens in NHL are mainly based on cisplatin (DDP). The substitution of DDP with oxaliplatin in DHAP- like regimens may result in lower toxicity and higher activity. In R/R CD20+ follicular (F) and mantle cell (MC) NHL the sinergistic activity of rituximab with chemotherapy and the maintenance immunotherapy obtain and prolong clinical and molecular remission. We assessed the tolerability and the activity in terms of clinical and molecular remission of R-Dhaox (rituximab 375 mg/m2 i.v., day 1, dexametazone 40 mg i.v. days 1–4, Oxaliplatin 130 mg/m2, day 2 and cytarabine 2,000 mg/m2 i.v. twice a day day 3) regimen for 4 courses in phase II study. The pts in response underwent to HDC with the scheme BEAM-R and further were treated with maintenance therapy with rituximab 375 mg/m2 i.v. 75+ from ABMT. After three monthly doses, pts were treated with further five every 4 months (for a total of two years). From June 2002 to September 2006, 31 pts were enrolled. 19 were male and 12 female. Median age was 51 (30–66). 21 (68%) pts were follicular G1-G2, 9 (29%) mantle cells and 1 a transformed follicular. The stage was III for 8 (26%) and IV for 23 (74%) pts. 22 (70%) pts were previous treated with rituximab and 30 (96%) with adryamicin based schedules. CD34+ harvest was after 4th cycle with a median collection of 5,5 ×106/Kg (2,1–20); 2 were positive for BCL-2 and 1 for BCL-1. Overall clinical response before ABMT was 94% for F and 100% for MC. 26 pts underwent ABMT with the schedule BEAM-R. At relapse 54% (12/22) of F were BCL-2 positive and 66% (6/9) of MC for BCL-1. Before ABMT 4/17 pts were BCL-2 positive and 1/9 for BCL-1. Among F, 3 pts relapsed after ABMT: 2 with reexpression of BCL-2 and 1 without. No relapse among MC, all negative for BCL-1 after ABMT. No pt showed severe or fatal infections during maintenance immunotherapy. Three- year projected free survival was 100% for MC and 68% for F NHL. These preliminary data suggested that R-DHAOX, HDC and rituximab maintenance is a novel approach highly effective for R/R F and MC NHL. No significant financial relationships to disclose.