A Prospective Randomized Study Comparing Dose Intensive Immunochemotherapy with R-ACVBP vs Standard R-CHOP In Younger Patients with Diffuse Large B-Cell Lymphoma (DLBCL). Groupe d'Etude Des Lymphomes De l'Adulte (GELA) Study LNH03-2B

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 109-109 ◽  
Author(s):  
Christian Recher ◽  
Bertrand Coiffier ◽  
Corinne Haioun ◽  
Christophe Fermé ◽  
Thierry Jo Molina ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Response Rate ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Hematological Toxicity ◽  
Intensive Chemotherapy ◽  
Free Survival ◽  
Younger Patients

Abstract Abstract 109 Two previous studies conducted in the prerituximab era have demonstrated the superiority of the intensive chemotherapy regimen ACVBP over standard CHOP in DLBCL (Tilly H et al. Blood 2003;102:4284; Reyes F et al. N Eng J Med 2005;352:1197). In order to investigate the role of intensive chemotherapy associated with rituximab, the GELA initiated in 2003 a multicenter, phase III open-label, randomized trial comparing efficacy and safety of R-ACVBP vs R-CHOP in younger DLBCL patients with an age-adjusted IPI (aaIPI) of 1. Patients and methods: Patients between 18 and 59y with DLBCL and aaIPI=1 were eligible. R-ACVBP consisted of 4 induction courses given every 2 weeks: rituximab (375 mg/m2) on d1, doxorubicin (75 mg/m2) on d1, cyclophosphamide (1200 mg/m2) on d1, vindesine (2mg/m2) on d1 and 5, bleomycin (10 mg) on d 1 and 5, prednisone (60 mg/m2) from d1 to d5, and intrathecal methotrexate (IT) (15 mg) on d2, G-CSF from d6 to d13. Patients then received a sequential consolidation therapy: 2 courses of methotrexate (3 g/m2) plus leucovorin rescue, 4 courses of rituximab (375 mg/m2), etoposide (300 mg/m2) and ifosfamide (1500 mg/m2) on d1, and 2 courses of cytosine-arabinoside (100 mg/m2, SC) for 4 days, each consolidation course being administered at a 14-day interval. Standard R-CHOP was delivered every 3 weeks for 8 cycles along with IT methotrexate at d1 of the first 4 cycles. The primary objective was to evaluate the efficacy of R-ACVBP compared to R-CHOP as measured by the event-free survival (EFS). Secondary endpoints were response rate, progression free survival (PFS), disease-free survival (DFS) for complete responders, overall survival, neuro-meningeal relapse rate and toxicities. Results are presented on an intend-to-treat basis. Response to treatment was evaluated according to 1999 Cheson criteria. Results: From December 2003 to December 2008, 380 patients were randomized in 73 hematology/oncology departments of the GELA. One patient withdrew his consent the day of randomization and 379 received at least one day of study treatment, 196 with R-ACVBP and 183 with R-CHOP. Median age was 47y (18-59). Patient characteristics were well-balanced in terms of demography and baseline disease status: male gender, 59%; stage III-IV, 55%; elevated LDH, 44%; mass>10 cm, 22%; B symptoms, 28%; number of extra-nodal sites >1, 26%; bone marrow involvement, 13%. Overall response rate was 90.3% in the R-ACVBP group and 88.5% in the R-CHOP group (p=0.57). Complete remission rate (CR+CRu), was 82.7% for R-ACVBP and 80.3% for R-CHOP (p=0.56). At the time of this final analysis, in June 2010, the median follow-up was 44 months. The 3-year EFS was 80.9% (95% confidence interval (CI) 74.5–85.9) in the R-ACVBP group and 66.7% (CI 59.2–73.2) in the R-CHOP group (p=0.0035, hazard ratio (HR) 0.559). Significant differences were also observed for PFS (86.8% at 3 years (CI 80.9–91.0) vs 73.4% (CI 66.1–79.3), p=0.0015, HR 0.482), DFS (91.3% at 3 years (CI 85.1–95.0) vs 80.3% (CI 72.8–85.9), p=0.0019, HR 0.393) and overall survival (92.2% at 3 years (CI 87.1–95.3) vs 83.8% (CI 77.2–88.6), p=0.0071, HR 0.439). Patients in the R-ACVBP group experienced more frequently a serious adverse event (42% vs 15% in the R-CHOP group). Grade 3–4 hematological toxicity was more frequent in the R-ACVBP group, with a higher proportion of patients receiving red cell (51% vs 7% for R-CHOP) or platelet transfusions (13% vs 1%) and/or experiencing febrile neutropenia (39% vs 9%). There were 3 deaths (1.5%) attributed to toxicity of study treatment in the R-ACVBP group and 2 (1.1%) in the R-CHOP group. Conclusions: Compared to standard R-CHOP, intensified immunochemotherapy with R-ACVBP significantly improves EFS, PFS, DFS and overall survival with increased but manageable hematological toxicity in younger patients with DLBCL. Disclosures: Coiffier: Roche: Honoraria, Research Funding; Genentech: Research Funding. Gisselbrecht:Roche: Research Funding. Bosly:Roche: Membership on an entity's Board of Directors or advisory committees. Tilly:Amgen: Honoraria.

Cladribine in Combination with Standard Daunorubicine and Cytarabine (DAC) as a Remission Induction Treatment Improves the Overall Survival in Untreated Adults with AML Aged < 60 y Contrary to Combination Including Fludarabine (DAF): A Multicenter, Randomized, Phase III PALG AML 1/2004 DAC/DAF/DA Study in 673 Patients-A Final Update.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2055-2055
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Grosicki ◽  
Slawomira Kyrcz-Krzemien ◽  
Kazimierz Kuliczkowski ◽  
Aleksander B Skotnicki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Remission Rate ◽  
Randomized Study ◽  
Phase Iii ◽  
Remission Induction ◽  
Induction Treatment ◽  
P Value ◽  
Who Grade ◽  
Free Survival

Abstract Abstract 2055 Poster Board II-32 This trial is a continuation of earlier Polish Adult Leukemia Group (PALG) studies on the use of purine analogues for therapy of AML patients (Leukemia 2004,18:989–97, updated at 7 y: ASH 2006, Abstr.N#2003, Ann Hematol. 2008, 87:361–7). The goal of the present study was to evaluate the efficacy of combination including fludarabine – DAF (daunorubicine 60 mg/m2/d iv, d 1–3; cytarabine (AraC) 200 mg/m2/d ci, d 1–7, and fludarabine 25 mg/m2 iv d 1–5) in untreated adult patients with AML, based on head to head comparison with DAC (DNR, AraC, Cladribine), and standard DA regimens (preliminary results: ASH 2008, abstr.#133). Primary end-points were: complete remission rate (CR) and overall survival (OS); secondary objectives were: toxicity and leukemia-free survival (LFS). Patients achieving CR received two courses of subsequent intensive consolidation: HAM (HD AraC, mitoxantrone) and HD AraC. Reduction of consolidation was accepted in patients treated with early alloBMT. In case of partial remission (PR) after the first induction course the same regimen was repeated. Patients with no remission (NR) or with PR after 2 induction courses were withdrawn from the study. Between 09.2004 and 05.2008, 673 adult untreated AML patients aged 18–60 y, median 47 y, sex: male 49,5%, female 50,5%, treated in 18 co-operating PALG centers were centrally randomized to either DAF (n=225), DAC (n=224) or DA (n=224) arm (1:1:1). PML/RAR alfa positive - FAB M3 cases were excluded. The study groups were well balanced in respect of age, sex, FAB subtype, and WBC. The results are summarized in the table. Outcome DAC (n = 223) DAF (n = 219) DA (n = 210) P Value (DAC vs DA) P Value (DAC vs DAF) CR 68 59 56 .013 .08 CR after 1 cycle 62 55 50,5 .017 16 3-yr OS 46 30 31 02 .02 2-yr LFS 47 40 39 NS NS Both, the entire CR rate and the CR rate after a single induction course were significantly superior in the DAC arm if compared with DA and DAF subgroups. With a median follow-up of 34 months (the longest observation time 5y) the OS rate equaled 46% for the DAC treated subgroup and was higher in comparison to the standard DA arm and the DAF arm. There were no significant differences in the leukemia free survival rates. The early death rates of 8,5–11%. were similar in the studied treatment subgroups. All patients developed WHO grade IV thrombocytopenia and agranulocytosis. The frequency and severity of infections, mucositis, vomiting, diarrhoea, alopecia, polyneuropathy as well as of cardiac, liver or kidney dysfunctions were comparable in particular arms. In conclusion, this updated results of randomized study prove that the incorporation of cladribine to the standard DA induction regimen (DAC) improves CR rate and the overall survival in adults with AML aged up to 60 y, without additional toxicity. This beneficial effect was not observed in patients treated using the DAF protocol with fludarabine added to the standard “DA 3+7” schedule. Disclosures: Robak: Celgene: Consultancy; Roche: Honoraria, Research Funding; Genmab: Research Funding; Cambridge Antibody Technology: Research Funding; GlaxoSmithKline: Honoraria. Warzocha:BMS: Consultancy, Honoraria; Celgene: Consultancy; Roche: Honoraria; Pfizer: Honoraria; Amgen: Honoraria.

Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 526-526 ◽  
Author(s):  
Barbara Eichhorst ◽  
Anna-Maria Fink ◽  
Raymonde Busch ◽  
Elisabeth Lange ◽  
Hubert Köppler ◽  
...  
Keyword(s):  
Adverse Events ◽  
Interim Analysis ◽  
Research Funding ◽  
Response Rate ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Abstract Introduction FCR is the current standard first line treatment regimen in advanced CLL (Hallek et al., Lancet, 2010), but is associated with significant side effects. The GCCLSG initiated an international phase III study in order to test the non-inferiority regarding efficacy and potentially better tolerability of BR compared to FCR in first-line therapy of physically fit pts without del(17p). Methods and Patients 688 CLL pts from 158 sites in five countries (Germany, Austria, Switzerland, Denmark and Czech Republic) were screened centrally for immunophenotype, genomic aberrations by FISH, IGHV sequenzing, comorbidity burden and renal function. 564 CLL pts with CIRS score ≤ 6, creatinine clearance > 70 ml/min and without del(17p) were enrolled between October 2008 and June 2011. Pts were randomly assigned to receive 6 courses of either FCR (N= 284; F 25mg/m2 i.v. d1–3, C 250 mg/m2 i.v. d1–3, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent courses; q 28 days) or BR (N=280; B 90mg/m2 i.v. d1+2, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent courses; q 28 days). The intent-to-treat population consisted of 561 pts, because three patients were excluded due to deferred treatment (1 pt decision, 1 treatment before randomization, 1 misdiagnosis). 22 % were Binet A, 38 % Binet B and 40 % Binet C. The median age was 62 years (yrs) (range 33 to 82), median CIRS score 2 (range 0-6). There were significantly more pts with unmutated IGVH in the BR arm (68%) in comparison to the FCR arm (55%; p=0.003). All other characteristics including median age were well balanced. A mean number of 5.27 courses was given in the FCR arm versus 5.41 courses in the BR arm (p=0.022). 70.6% (FCR) and 80.3% (BR) of pts received 6 courses (p=0.008). Dose was reduced by more than 10% in 27.3% (FCR) and 31.6% (BR) of all courses given (p = 0.012). Results The median observation time was 27.9 months (mo) in all pts alive. While response evaluation was missing in 14 pts, 547 pts (274 FCR; BR 273) were evaluable for response and all 561 pts (282 FCR; 279 BR) for progression-free survival (PFS), event-free survival (EFS) and OS. The overall response rate was identical in both arms with 97.8% (p=1.0). The complete response rate (CRR) (confirmed by central immunhistology) with FCR was 47.4% as compared to 38.1% with BR (p=0.031). MRD data were available at interim analysis from 192 pts (99 FCR; 93 BR) of the first 300pts. 71.7% of pts in the FCR and 66.7% in the BR arms achieved MRD-levels below 10-4 in peripheral blood at final staging (p=0.448). The complete MRD data set will be available by November. PFS was 85.0% at 2 yrs in the FCR arm and 78.2% in the BR arm (p=0.041). EFS was 82.6% at 2 yrs in the FCR arm and 75.7% in the BR arm (p=0.037).There was no difference in OS rate for the FCR vs BR arm (94.2% vs 95.8% at 2 years p=0.593). Hazard Ratio for PFS, EFS and OS was 1.385, 1.375 and 0.842 respectively. PFS was assessed in pts < 65 yrs and ≥ 65 yrs. While there was a significant difference in pts < 65 yrs between both treatment arm (median PFS for BR 36.5 mo vs not reached for FCR; p=0.016), the difference disappeared in elderly pts (not reached vs. 45.6 mo; p=0.757). A multivariate analysis including treatment arm, Binet stage, age, sex, comorbidity, serum TK, serum beta2-microglobulin (Beta2M), del(11q) and IGHV status identified treatment arm, Beta2M, del(11q) and IGHV as independent prognostic factors for PFS and EFS. FCR treated pts had significantly more frequent severe, CTC grade 3 to 5, adverse events during the whole observation period (90.8% vs 78.5%; p<0.001). Especially severe hematotoxicity was more frequent in the FCR arm (90.0% vs 66.9%, p<0.001). The higher rate of severe neutropenia (81.7% vs 56.8%, p<0.001) resulted in a significantly higher rate of severe infections (39.0% vs 25.4%, p=0.001) in the FCR arm, especially in the elderly (FCR: 47.4% vs BR: 26.5%; p=0.002). Treatment related mortality occurred in 3.9% (n=11) in the FCR and 2.1% (n=6) in the BR arm. Conclusion The results of this planned interim analysis show that FCR seems more efficient than BR in the first-line treatment of fit CLL pts with regard to higher CRR, as well as longer PFS and EFS. These advantages might be balanced by a higher rate of severe adverse events, in particular neutropenia and infections, associated with FCR. In light of these results, no firm recommendation of one regimen over the other can be given at the present time regarding the first-line use in CLL pts with good physical fitness. Disclosures: Eichhorst: Roche: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding. Gregor:Roche: Consultancy, Honoraria, Travel Support Other; Mundipharma: Travel Support, Travel Support Other. Plesner:Mundipharma: Research Funding. Trneny:Roche: Honoraria, Research Funding. Fischer:Roche: Travel grants Other; Mundipharma: Travel grants, Travel grants Other. Kneba:Roche: Consultancy, Research Funding. Wendtner:Roche: Consultancy, Research Funding; Mundipharma: Consultancy, Research Funding. Kreuzer:Roche: Honoraria; Mundipharma: Honoraria. Stilgenbauer:Roche: Consultancy, Research Funding, Travel grants Other; Mundipharma: Consultancy, Research Funding. Böttcher:Roche: Honoraria, Research Funding. Hallek:Janssen: Research Funding; Gilead: Research Funding; Roche: Research Funding.

Ixazomib, Dexamethasone and Rituximab in Previously Untreated Patients with Waldenström Macroglobulinemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2956-2956 ◽  
Author(s):  
Jorge J. Castillo ◽  
Joshua Gustine ◽  
Kirsten Meid ◽  
Toni Dubeau ◽  
Guang Yang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Time ◽  
Research Funding ◽  
Response Rate ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Induction Phase ◽  
Primary Therapy ◽  
Wild Type ◽  
Median Serum

Abstract Introduction: Waldenström's macroglobulinemia (WM) is an incurable B-cell lymphoma characterized by the accumulation of IgM-secreting lymphoplasmacytic cells in the bone marrow and other organs. Bortezomib in combination with rituximab and dexamethasone (BDR) is highly active as primary therapy in WM, though treatment-related neuropathy is common with BDR in WM, and often leads to premature treatment discontinuation. Ixazomib is an orally administered proteasome inhibitor with limited neuropathy that is active in myeloma, but has not been previously evaluated in WM Methods: Symptomatic, previously untreated patients with a clinicopathological diagnosis of WM were included in this prospective, single-arm phase II study evaluating ixazomib 4 mg PO on days 1, 8 and 15 + dexamethasone 20 mg PO/IV on days 1, 8 and 15 + rituximab 375 mg/m2 IV on day 1 (IDR) were administered for six 4-week cycles (induction) followed by six 8-week cycles (maintenance). Rituximab was held for the first two cycles of therapy to minimize risk of IgM flare. Zoster prophylaxis and proton pump inhibitors were administered throughout IDR therapy. The study was approved by the institutional review board at the Dana-Farber Cancer Institute, and registered under Clinicaltrials.gov ID NCT02400437. Results: Twenty-six WM patients were enrolled and were exposed to IDR therapy. The median age at WM diagnosis was 63 years (range 46-81 years) and the median age at initiation of therapy was 65 years (range 46-82 years). Baseline median hemoglobin was 10.2 g/dl (range 6.9-13.2 g/dL), median serum IgM level was 5,068 mg/dl (range 653-7,650 mg/dL), 46% of patients had lymphadenopathy and 12% had splenomegaly. The median bone marrow involvement was 55% (range 5-95%). The MYD88 L265P gene mutation was identified in all cases. CXCR4 gene mutations were identified in 15 patients (58%), of whom 10 (67%) had nonsense, and 5 (33%) frameshift mutations. Sixteen patients have completed the induction phase of therapy at this time. Following induction therapy, the median serum IgM level decreased to 2,316 mg/dl (range 287-5,820 mg/dL), median hemoglobin increased to 13.1 mg/dl (range 10.4-14.6 g/dL), and median bone marrow involvement decreased to 23% (range 0-76%). P-value <0.001 for all comparisons against baseline. Using consensus response criteria, the overall response rate was 88% (VGPR 6%, PR 44%, MR 38%) with a major response rate of 50%. Major responses (VGPR + PR) were observed in 47% of patients with CXCR4 mutations versus 64% in those who were wild-type CXCR4 (p=0.32). The median time to response was 8 weeks. The median time to response in CXCR4 mutant patients was 12 weeks versus 8 weeks in wild-type CXCR4 patients (log-rank p=0.03). Four patients have been taken off study; 2 for lack of response, 1 due to lack of clinical benefit with persistent failure to thrive while in PR, and 1 for progressive neuropathy while in PR although in part due to worsening of diabetic neuropathy. No other grade 3 or 4 adverse events were reported. Conclusion: These preliminary data suggest that the combination of IDR is an active and well-tolerated, neuropathy-sparing regimen in symptomatic untreated WM patients. Disclosures Castillo: Biogen: Consultancy; Otsuka: Consultancy; Abbvie: Research Funding; Pharmacyclics: Honoraria; Millennium: Research Funding; Janssen: Honoraria.

Paclitaxel plus carboplatin versus paclitaxel plus epirubicin as first-line treatment for metastatic breast cancer: Efficacy and safety results of a randomized, phase III trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1087-1087
Author(s):  
Zhongsheng Tong ◽  
Shufen Li ◽  
Yehui Shi ◽  
Xu Wang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Significant Difference

1087 Background: Paclitaxel/carboplatin combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, non-inferiority trial comparing paclitaxel/carboplatin (TP) with paclitaxel/epirubicin (TE) as first-line therapy for MBC. Progression-free survival (PFS) was the primary efficacy endpoint. Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Methods: From June 2009 to January 2015, 231 patients were randomly assigned, 115 of whom were randomized to TP and 116 to TE. Baseline characteristics were relatively well-balanced in the two treatments. Results: After a median follow-up of 29 months, no significant difference was observed between the two treatments in objective response rate (ORR) (38.3% vs. 39.7%, respectively). Both the progression-free survival (p=0.158) and overall survival (p=0.369) were very similar between the two treatments. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions, and alopecia. TP showed higher grades 3–4 alopecia and higher nausea (p<0.05). TE showed higher incidence of myelosuppression than TP (p<0.05) (Table). Those patients whose epirubicin cumulative dose was more than 1000 mg/m2 did not suffer worse cardiotoxicity. Conclusions: Our study suggests that TP arm is an effective therapeutic alternative for patients with MBC, especially in those previously exposed to epirubicin in the adjuvant setting. TP has some advantages, such as less cost and less side effects (myelosuppression and fatigue). Clinical trial information: NCT02207361. [Table: see text]

scholarly journals Baseline Suvmax Did Not Predict Histological Transformation from Follicular Lymphoma to Aggressive Lymphoma in the Phase III GALLIUM Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4160-4160 ◽  
Author(s):  
Farheen Mir ◽  
Sally F Barrington ◽  
Michel Meignan ◽  
Helen Brown ◽  
Tina Nielsen ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Aggressive Lymphoma ◽  
Histological Transformation

Abstract Introduction: Follicular lymphoma (FL) generally has an indolent clinical course, but there is a 1-2% annual rate of histological transformation (HT) into aggressive lymphoma. Nodal HT sites have a higher maximum standardized uptake value (SUVmax) than non-transformed sites, and patients with HT typically show greater variation in SUVmax between sites. Upfront identification of patients at high risk of HT would allow physicians to consider treatment intensification. The objective of this analysis was to assess the relationship between baseline SUVmax (bSUVmax) and HT in the GALLIUM study (NCT01332968). Methods In the randomized, phase III GALLIUM study, 1202 previously untreated patients with grade 1-3a FL were randomized to receive induction with either obinutuzumab (GA101; G)- or rituximab (R)-based immunochemotherapy. Patients who responded received maintenance therapy with the same antibody. The primary endpoint of investigator-assessed progression-free survival was significantly improved in the G arm relative to the R arm (hazard ratio 0.66; p=0.001). As an exploratory endpoint, the degree of 18-fluorodeoxyglucose (FDG)-avidity expressed by SUVmax was assessed in patients with baseline FDG positron emission tomography (FDG-PET) scans by an independent review committee. Results: Among 522 patients with available bSUVmax data, 13 (2.5%) experienced biopsy-confirmed HT to diffuse large B-cell lymphoma or Grade 3b FL after a median follow-up of 59 months. Patients with HT were older (median age 61 vs 56 years), and were more likely to have a poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status 2: 15.4% vs 2.6%), present with high-risk Follicular Lymphoma International Prognostic Index (FLIPI; 61.5% vs 40.3%), and have bone marrow involvement (76.9% vs 52.9%) than those without. More than 65% of patients showed bSUVmax >10, but only a minority of these experienced HT. Median (range) bSUVmax in patients with versus without HT was 12.4 (8.14, 27.95) versus 11.8 (3.05, 64.43), respectively. Median (range) baseline SUVrange (bSUVrange), defined as the difference between bSUVmax of the most and least FDG-avid lymphoma sites, was 6.6 (1.08, 23.91) versus 7.14 (0.00, 59.81), respectively (Figure). Conclusions: bSUVmax >10 is common in patients with previously untreated FL and is rarely associated with early HT. Neither bSUVmax nor bSUVrange predicted HT in GALLIUM, suggesting there may be little benefit in re-biopsy of lesions to exclude HT before commencing therapy. Better markers for identification of FL patients at risk of transformation are needed. Disclosures Mir: F. Hoffmann-La Roche: Employment. Barrington:F.Hoffmann-La Roche: Membership on an entity's Board of Directors or advisory committees; Department of Health (England): Research Funding; MRC: Research Funding; CRUK: Research Funding; EPSRC: Research Funding; National Institute of Health Research: Research Funding. Meignan:F. Hoffman-La Roche Ltd: Honoraria. Brown:PAREXEL, external business partner with Roche Products Ltd, Welwyn, UK: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Sahin:F. Hoffman-La Roche Ltd: Other: Ownership interests PLC. Trotman:F. Hoffman-La Roche: Other: Travel to meeting, Unremunerated member of Ad Board, Research Funding; Janssen: Other: Unremunerated member of Ad Board, Research Funding; Beigene: Research Funding; Takeda: Other: Unremunerated member of Ad Board; Celgene: Other: Unremunerated member of Ad Board, Research Funding; PCYC: Research Funding.

Risk Factors for CNS Relapse Among Patients with DLBCL Treated with EPOCH-R

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1500-1500 ◽  
Author(s):  
Mary Kathryn Malecek ◽  
Shaina Rozell ◽  
Benjamin A. Chu ◽  
Trifilio Steve ◽  
Natalie Galanina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Research Funding ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Cns Prophylaxis ◽  
Upper Limit ◽  
Cns Relapse ◽  
Increased Risk ◽  
Ecog Ps

Abstract Background: Central nervous system (CNS) relapse in pts with aggressive non-Hodgkin lymphoma (NHL) is a generally fatal complication, with median overall survival (OS) of less than six months (Abramson et al., 2010). Several studies have identified features associated with increased risk of CNS relapse, such as extranodal (EN) sites of disease, elevated lactate dehydrogenase (LDH), presence of B symptoms, and bone marrow involvement (Bernstein et al., 2009; van Besien et al., 1998). Moreover, multivariate analyses have suggested that LDH greater than 3x upper limit of normal (ULN) is strongly associated with increased risk of death or progression among patients with aggressive NHL (Zhou et al., 2014). Despite little evidence on its true efficacy, prophylaxis (ppx) intrathecal (IT) chemotherapy, most frequently with methotrexate (MTX), is often used to among pts thought to be at high risk for CNS relapse. Data on efficacy or need for CNS prophylaxis in patients receiving infusional therapy with etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (R-EPOCH) is not available. As R-EPOCH, is being increasingly used in pts with lymphoma, we sought to evaluate the role of IT chemotherapy when used with this regimen. Methods: We conducted a retrospective chart review analysis of patients with diffuse large B-cell lymphoma (DLBCL) who received R-EPOCH as frontline therapy, between 2005 and 2014. Use of IT ppx was at the discretion of the treating physician. We excluded patients under the age of 18, those receiving fewer than two cycles of R-EPOCH, those with CNS involvement at time of diagnosis, and those who received high-dose intravenous CNS ppx. Two-tailed Fisher's exact test was used to determine whether any of the following baseline features was associated with risk of CNS relapse: age>60, ECOG PS>1, LDH>normal and/or >3x ULN, presence of B symptoms, two or more EN sites, anatomic location of EN sites, international prognostic index (IPI) score > 1, bone marrow involvement, and HIV infection. In order to determine whether IT ppx was associated with any improvement in CNS and/or systemic control of disease, we compared, using Kaplan-Meier survival curves with log-rank analyses, the patterns of overall survival (OS), progression-free survival (PFS), and freedom from CNS progression (FFCP, in which death is not counted as an event) between patients receiving IT ppx and those not receiving it. Results: We identified 117 patients for analysis. Median age was 53 (range 19-80). 26% had ECOG PS>1; 76% had LDH above upper limit of normal (ULN). 38% had two or more EN sites of disease, and 68% had stage III-IV disease. 62 patients received IT ppx, and 55 did not. Of those receiving IT ppx, 95% received MTX, with the remainder receiving cytarabine. Those receiving IT ppx were more likely to have >1 EN site of disease, and IPI score >1 (Table 1). A total of seven had observed CNS relapse, occurring at a median of 6 months from time of NHL diagnosis (range 2-24 months). At a median follow up of 18 months, the 24-month PFS and OS were 80% and 83%, respectively. Median PFS and OS were not reached. The only factors associated with increased risk of CNS relapse were genitourinary EN disease and LDH >3x ULN (Table 2). There were no significant differences in OS, PFS, or FFCP among patients who did and did not receive CNS prophylaxis (Figure 1, panels A-C). Conclusions: The risk of CNS progression among DLBCL patients receiving R-EPOCH was similar to previous reports with R-CHOP, at 6%. GU location of EN disease and LDH >3xULN were associated with increased risk of CNS relapse. IT ppx was not associated with improved outcomes. Despite the common use of IT PPX in pts treated with R-EPOCH, our data suggest that this practice might not impact CNS progression and/or relapse, though randomized studies would be needed to answer this. Such studies are warranted in order to better determine what factors are associated with CNS progression, and whom, if anyone, may benefit from IT ppx. Figure 2. Figure 2. Disclosures Nabhan: Celgene Corporation: Honoraria, Research Funding. Petrich:Seattle Genetics: Consultancy, Honoraria, Research Funding.

scholarly journals Safety and Efficacy of Azacitidine with Venetoclax for Newly Diagnosed Intensive Chemotherapy Ineligible, and Relapsed or Refractory Acute Myeloid Leukemia in Arab Population: A Single-Center, Retrospective Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4423-4423
Author(s):  
Mohammmad Alwadi ◽  
Jude Howaidi ◽  
Abdullah M Alrajhi ◽  
Adel Alnakhli ◽  
Mohammed A. Marei ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Relapse Free Survival ◽  
Arab Population ◽  
Free Survival ◽  
Refractory Aml ◽  
Count Recovery

Abstract Background: Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukemia (AML) 75 years or older, or unfit for intensive chemotherapy. As precision therapy in AML expanded with the addition of venetoclax among others in the therapeutic armamentarium of AML, efficacy and safety reports in ethnic minorities are limited, with a background of well recognized inter-ethnic differences in drug response. Phase III data from VIALE-A, as well as VIALE-C, was limited for the Arab population as no site opened in the Arab world. We herein report our experience on the use of venetoclax with azacitidine in patients with newly diagnosed or relapsed/refractory AML in the Arab population. Methods: Retrospective-single center review on the use of Azacitidine with venetoclax in older patients (aged ≥60 years) with newly diagnosed AML, not eligible for intensive chemotherapy; secondary AML and relapsed or refractory AML. All patients self-identified of Arabic ethnicity. Patients who received previous BCL2-inhibitor therapy were excluded. Patients who received at least one dose of treatment (Azacitidine ≥3 days, &gt;14 days of venetoclax) were included in the intention to treat analysis. Patients typically received azacitidine 75 mg/m2 intravenously for 7 days with oral venetoclax 400 mg daily for induction, with appropriate dose adjustment for concomitant use of azoles. This is followed by the same regimen in consolidation, with adjustment according to response and side effects at the treating physician's discretion. The primary endpoint was overall survival. The secondary endpoints include response rate, safety, and relapse-free survival. Results: Between July 2019, and July 2021, we identified 19 patients; 13 (68%) had newly diagnosed AML (ND-AML), and 6 (32%) had relapsed or refractory AML (R/R AML). The median age was 70 years (17-82). In the ND-AML, most patients had an adverse ELN 2017 AML (69%) with 23% having either intermediate or adverse AML (Negative for CBF, NPM1, FLT3-ITD and biCEBPA, but missing NGS data for adverse mutations Tp53/ASXL1 and RUNX1). Only one patient was classified as intermediate-risk AML. The overall response rate in the ND-AML was 77%, with 46% achieving complete remission (CR), and 23% CR with incomplete count recovery (CRi) [Table]. One patient achieved PR after the first cycle (blast 7% by morphology and 1.5% by flow cytometry) and did not have a subsequent bone marrow evaluation, however had a full count recovery. Among the responders in the ND-AML cohort, 4 deaths were noted. One death was related to COVID-19 associated pneumonia, one due to graft failure (at day 42 post Haplo-SCT), one due to septic shock, and one was related to relapse disease. The overall survival and relapse-free survival for ND-AML were 5.6 months for both [Figure]. In the R/R AML, 66% had prior HMA exposure, and all patients did receive high-intensity chemotherapy. The median number of prior treatments was 3 (1-5). the response rate was 80% (4/5), with 60% achieving CR. All patients are still alive with a median follow-up of 7.6 months. One patient had progressive disease. One patient is early to evaluate and was not included in the response analysis [Table]. The 30-day mortality was zero in both ND-AML and R/R AML cohorts. Conclusions: In a majority of adverse risk ND-AML, and in heavily pretreated R/R AML, the response rate and overall survival is comparable to what has been previously reported. Our data support the use of this regimen in older patients with newly diagnosed AML, patients with relapsed or refractory disease, and those with adverse-risk features. This analysis is limited by the small number of patients, and by the lack of ELN 2017 favorable-risk AML. Future prospective and randomized studies are needed to clarify activity and safety in the Arab population, as well as in the high-risk AML subset. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Predictors of Central Nervous System (CNS) Involvement in North American Adult T-Cell Leukemia Lymphoma (ATLL) and Their Survival Pattern

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1400-1400
Author(s):  
Riya Patel ◽  
Shafia Rahman ◽  
Nishi Shah ◽  
Astha Thakkar ◽  
Ana Acuna-Villaorduna ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
North American ◽  
Research Funding ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
The United States ◽  
Publicly Traded ◽  
Cns Involvement

Abstract Introduction: North American-ATLL (NA-ATLL) is a distinct genomic and clinical entity when compared with Japanese ATLL. Despite the frequent CNS involvement by this entity there are no prognostication tools to identify variables associated with higher risk. We studied one of the largest NA-ATLL cohorts in the United States at a minority rich ethnically diverse New York City based tertiary care center to identify discrete variables that may be associated with CNS involvement. Additionally, we examined the predictive power of the previously validated International Prognostic Index (IPI) developed for Diffuse Large B-cell Lymphoma (DLBCL) in terms of CNS involvement as well as overall survival in our cohort. In our previous work, we assigned CNS involvement of ATLL if: 1) cerebrospinal fluid (CSF) cytology or flow cytometry was positive; 2) CNS imaging was positive for disease involvement or 3) physical exam was compatible with neurologic involvement. Methods and results: Of 65 NA-ATLL patients (pts), 20 (30.77%) had CNS involvement by ATLL meeting above mentioned criteria. The median age of all pts in our dataset was 59 years. Pts were divided into non- CNS involved NA-ATLL (non-CNS NA-ATLL) and CNS involved NA-ATLL (CNS NA-ATLL) groups. Parameters to predict CNS involvement were outlined as leukocytosis (&gt;11000 per microliter [μL]), elevated acute lymphocytic count (&gt;4000/ μL), elevated lactate dehydrogenase (LDH) (&gt;190 units/liter [u/l]), generalized lymphadenopathy (LAD) defined as involvement of 2 or more non-contiguous nodal sites, elevated corrected serum calcium levels (&gt;10.5 mg/deciliter), bone marrow (bm) involvement and serosal involvement defined as pleural or peritoneal involvement. These variables were chosen given our prior work identifying them as critical to predict OS in our general NA-ATLL population. We then performed the Fisher test of proportions to determine if the variables above mentioned were different between the CNS NA-ATLL and the non-CNS NA-ATLL. We did not find significant associations when analyzing gender (p=0.0535), leukocytosis (p= 0.4001), lymphocytosis (p =0.57), hypercalcemia (p= 0.7661), elevated LDH (p= 0.4898), generalized LAD (p=0.271), serosal involvement (p= 0.05088) or bone marrow involvement (p=1). We only found a strong association when examining ATLL subtypes, being the acute/lymphomatous variant strongly associated with CNS involvement (p=2.226e10 -5). To identify variables that can have an impact in OS in CNS NA-ATLL vs non-CNS NA-ATLL we calculated Kaplan Meier survival curves. We did not find any difference based on age (p=0.23), gender (p=0.95), leukocytosis (p= 0.074), lymphocytosis (p =0.21), hypercalcemia (p= 0.094), elevated LDH (p= 0.37), generalized LAD (p=0.28), and serosal involvement (p= 0.1) in the overall survival. The only significant association we found was bone marrow involvement in predicting poor OS in CNS NA-ATLL group (p= 0.038). Next, we determined IPI scores (age&gt;60, ECOG performance status&gt;2, Ann Arbor stage III/IV, serum LDH score &gt;190 u/L and more than 1 extra-nodal site) in our CNS NA ATLL and non-CNS NA ATLL cohorts. We sought to determine if: 1) this prognostication tool is predictive in NA-ATLL and 2) if these variables can be used to identify CNS involvement in our cohort. CNS pts with a higher IPI score (&gt;3) showed tendency towards a lower survival rate (p=0.089) than non-CNS pts (p=0.3). IPI score of 3 or more was not predictive of CNS involvement in our sample (p=1). Conclusions: NA-ATLL is a rare and protean disease with poor prognosis and CNS involvement is prevalent. With the variables used we did not find clear predictors of CNS associated disease other than patients presented with the lymphomatous and acute subtypes. We also observed than bone marrow involvement portends a dismal prognosis for individuals with CNS involvement. Future studies with a larger cohort could provider further insight on discovering predictors for CNS involvement in NA ATLL. Figure 1 Figure 1. Disclosures Shah: Celgene/BMS: Research Funding; Janssen: Research Funding. Gritsman: iOnctura: Research Funding. Shastri: GLC: Consultancy; Kymera Therapeutics: Research Funding; Guidepoint: Consultancy; Onclive: Honoraria. Verma: BMS: Research Funding; GSK: Research Funding; Incyte: Research Funding; Medpacto: Research Funding; Curis: Research Funding; Eli Lilly: Research Funding; Stelexis: Consultancy, Current equity holder in publicly-traded company; Novartis: Consultancy; Acceleron: Consultancy; Celgene: Consultancy; Stelexis: Current equity holder in publicly-traded company; Throws Exception: Current equity holder in publicly-traded company. Janakiram: Amgen: Honoraria.

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

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8508-8508
Author(s):  
I. N. Micallef ◽  
M. J. Maurer ◽  
D. A. Nikcevich ◽  
M. W. Cannon ◽  
E. W. Schaefer ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Hematological Toxicity ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

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.

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