Surgical Resection and Rituximab Show No Benefit in the Treatment of Primary Gastric Diffuse Large B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5110-5110
Author(s):  
Haiwen Huang ◽  
Tianwen Fu ◽  
Qiangli Wang ◽  
Ting Xu ◽  
Xiaochen Chen ◽  
...  

Abstract Objectives Clinically, primary gastric diffuse large B cell lymphoma (PG-DLBCL) is not encountered commonly. The optimal treatment of PG-DLBCL remains controversial. Whether patients should receive surgical resection, Rituximab or not was most concerned about. Here we analized 83 patients with PG-DLBCL retrospectivly and evaluated the effect of surgical option and Rituximab in the treatment of PG-DLBCL. Methods From January 2009 to December 2014, 83 cases of PG-DLBCL patients in the First Affiliated Hospital of Soochow University were retrospectively studied. Forty cases received surgical resection plus chemotherapy (group A) and 43 patients underwent chemotherapy alone (group B). The operation mode is decided by the surgeon according to the patients¡¯ current condition and the chemotherapy regimens of two groups were CHOP or R-CHOP. Patients¡¯ characteristics were listed in Table 1. The main outcomes of overall survival (OS) and the progression free survival (PFS) were analized by using the Kaplan-Meier (K-M) method. Results The K-M analysis showed that the 3-year PFS and OS in group A were 66.7% and 68.4%, respectively. On the other hand, the 3-year PFS and OS of group B were 82.6%and 85.7%, respectively. There is no significant difference between the two groups. For patients received CHOP or R-CHOP, the 5-year OS were 77.7% and 78.2% (p=0.178). And the 3-year PFS were 74.9% and 75.5% (p=0.347). The difference between the two groups was not statistically significant. In group A, the 5-year PFS of R-CHOP group and CHOP group is 62.5% and 71.2% £¨p=0.747£©, the 5-year OS of R-CHOP group and CHOP group is 64.2% and 73.6% (p=0.853). In group B, the 5-year PFS of R-CHOP group and CHOP group is 83.4% and 81.8% £¨p=0.706£©, the 5-year OS of R-CHOP group and CHOP group is 85.7% and 83.5% (p=0.753). The univariate analyses indicated that age and lactate dehydrogenase (LDH) level were related to prognosis. Multivariate analysis of prognostic factors with a Cox model showed that IPI was the only independent prognostic factor. Conclusions This study shows that PG-DLBCL patients have a similar long-term survival rate when adopted surgery plus chemotherapy. Therefore, resection of the primary tumor before systemic chemotherapy does not improve the survival of the patients with PG-DLBCL. At the same time, the addition of Rituximab to chemotherapy doesn¡¯t make difference for the survival of PG-DLBCL. More prospective clinical trials about the effect of surgical operation and rituximab are needed to confirm the results of our study. Table 1. Patients¡¯ baseline characteristics Patients £¨%£© P value With surgical resection(Group A, n£½40£© Without chemotherapy (Group B, n £½ 43 £© Gender Male 19£¨47.5%£© 24£¨55.8%£© 0.449 Female 21£¨52.5%£© 19£¨44.2%£© Age ¡Ü60 15£¨37.5%£© 22£¨51.2%£© 0.211 £¾60 25£¨62.5%£© 21£¨48.8%£© Ann Arbor Stage I/II 13£¨32.5%£© 7£¨16.3%£© 0.084 Stage III/IV 27£¨67.5%£© 36£¨83.7%£© ECOG £¼2 19£¨47.5%£© 22£¨51.2%£© 0.739 ¡Ý2 21£¨52.5%£© 21£¨48.8%£© Treatment plan R-CHOP 23£¨57.5%£© 24£¨55.8%£© 0.887 CHOP 17£¨42.5%£© 19£¨44.2%£© LDH ¡Ü245 24£¨60.0%£© 27£¨62.8%£© 0.794 £¾245 16£¨40.0%£© 16£¨37.2%£© IPI ¡Ü2 13£¨32.5%£© 15£¨34.9%£© 0.818 £¾2 27£¨67.5%£© 28£¨65.1%£© ECOG: Eastern Cooperative Oncology Group; CHOP: cyclophosphamide, doxorubicin, vincristine, prednisone; R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; LDH: lactate dehydrogenase Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1591-1591
Author(s):  
Nobuhiko Yamauchi ◽  
Kazunari Aoki ◽  
June Takeda ◽  
Yuki Funayama ◽  
Aiko Kato ◽  
...  

Abstract Abstract 1591 Introduction The use of fluorodeoxyglucose-positron emission tomography (PET) to aid the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) after treatment with rituximab-containing combination chemotherapy was investigated. Several studies report that less than 20 % of patients who are PET-negative and more than 85 % of PET-positive patients will experience lymphoma recurrence. Since therapy for DLBCL recurrence remains a major problem, the ability to accurately predict the risk of relapse in PET-negative DLBCL patients after chemotherapy would be extremely beneficial. In this study we focused on levels of serum soluble interleukin-2 receptor (sIL-2R) since several reports indicate that sIL-2R at the time of diagnosis is closely linked to the prognoses of DLBCL patients. We measured sIL-2R levels in DLBCL patients shortly after R-CHOP therapy and investigated whether there was any correlation with patient prognoses. Patients and Methods This was a retrospective pooled analysis of DLBCL patients treated with R-CHOP in our institute. Patients were included if they were under the age of 80, had an International Prognostic Index (IPI) score of more than two, and had received R-CHOP with curative intent. Patients who received salvage chemotherapies due to insufficient responses to R-CHOP were also included. We excluded patients with low IPI scores as their sIL-2R levels at the time of diagnosis were usually in the normal range. Patients were also excluded if R-CHOP could not be continued for reasons other than disease progression. sIL-2R and PET analyses were performed when patients first visited the institute after completing 6–8 cycles of R-CHOP. Patients were divided into three groups: Group A consisted of patients who had completed R-CHOP, were PET-negative and whose sIL-2R levels had returned to normal (<600 mg/dl); Group B consisted of patients who had completed R-CHOP and were PET-negative, but whose sIL-2R levels had remained high (>=600mg/dl); Group C consisted of patients who had switched to salvage therapies as well as those who remained PET-positive after completing R-CHOP. Overall survival (OS) was assessed using the Kaplan-Meier method and the log-rank test was used for comparisons within each group. A multivariate Cox regression analysis was used to adjust for IPI scores. Results From January, 2006 to January, 2012, a total of 178 DLBCL patients aged less than 80 years were referred to our institution, and 70 of these patients were included in this analysis. The median age of patients was 68 years (range 37–79 years), 96 % had advanced stage DLBCL, and 77 % had elevated lactate dehydrogenase levels. 30% of patients had ECOG performance status (PS) less than 2. The median sIL-2R level at the time of diagnosis was 2676 mg/dl (range 612–48000 mg/dl). The numbers of patients assigned to groups A, B, and C were 28 (40 %), 18 (26 %), and 24 (34 %), respectively. A Fisher's exact test showed no significant differences in IPI scores between the three groups (p=0.453). A Mann-Whitney test showed no significant differences in sIL-2R levels at the time of diagnosis between the three groups (A; median 2660 mg/dl, range 612–19000 mg/dl, B; 2905 mg/dl, 970–37100 mg/dl, C; 4347 mg/dl, 734–48000 mg/dl). Patients in groups A and B received 6–8 cycles of R-CHOP (median 7 cycles). Patients in group C received 1–4 salvage treatments (median 2 treatments) before or after completion of R-CHOP (median 6 cycles, range 2–8 cycles). After a median follow-up time of 36 months (range 5–60 months), 24 deaths had occurred (including 20 due to lymphoma), and the 3 year OS rate for the entire cohort was 65.5 % [95 % confidence interval (CI), 51.7–76.2 %]. The 3 year unadjusted OS rate of patients in groups A, B, and C was 95.2% [95%CI, 70.7–99.3%], 60.7% [95%CI, 31.3–80.6%] and 30.6% [95%CI, 12.5–51.0%], respectively (log-rank, p<0.001), (group A vs B; hazard ratio (HR), 10.8; 95%CI, 1.33–88.1; p=0.026, group B vs C; HR, 2.24; 95%CI, 0.91–5.54; p=0.079). Multivariate analysis including IPI score, revealed that 3 year OS for patients in group B was significantly inferior to that for patients in group A (HR, 6.26; 95%CI, 1.29–30.4; p=0.023), but was comparable with that for patients in group C. Conclusion DLBCL patients with an IPI score of more than 2 had an increased risk of relapse if their sIL-2R levels failed to return to normal following R-CHOP treatment, even if they completed 6–8 cycles of R-CHOP and were PET-negative. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS7579-TPS7579 ◽  
Author(s):  
Morton Coleman ◽  
Andres Forero-Torres ◽  
Vincent Ribrag ◽  
Ian Chau ◽  
Douglas James DeMarini ◽  
...  

TPS7579 Background: Aberrant activation of PI3Kδ is implicated in B-cell malignancies. INCB050465, a highly selective PI3Kδ inhibitor, is demonstrating preliminary efficacy in an ongoing phase 1/2 dose-escalation and expansion study as monotherapy for r/r DLBCL as well as for other r/r B-cell malignancies (ASH 2016; Abstract 4195). This phase 2 study will further evaluate the efficacy and safety of single-agent INCB050465 in pts with r/r DLBCL. Methods: In this phase 2, multicenter, open-label study (NCT02998476), eligible adults will have r/r DLBCL diagnosis, defined as receiving 1–5 prior treatments and be ineligible for high-dose chemotherapy or autologous stem-cell transplant (SCT). Pts will also have ≥1 measurable lesion (nodal ≥2 cm or extranodal > 1 cm in longest dimension); Eastern Cooperative Oncology Group performance status ≤2; adequate hematologic, hepatic, and renal function; no mediastinal large B-cell lymphoma or CNS metastases; no allogeneic SCT ≤6 months, or graft-versus-host-disease after allogeneic SCT, or autologous SCT ≤3 months, before first dose; and no prior treatment with PI3K inhibitors. Pts will be enrolled into 2 groups according to prior treatment with a Bruton’s tyrosine kinase (BTK) inhibitor (Group A [n = 100, no BTK inhibitor] or B [n≤20, received BTK inhibitor]). Both groups will receive INCB050465 20 mg orally QD for 8 wks; then 20 mg QW until disease progression, death, unacceptable toxicity, or consent withdrawal. The primary endpoint is the objective response rate in Group A (complete/partial response per independent review committee based on Lugano criteria). Secondary endpoints will include duration of response, progression-free survival, overall survival, and safety in Group A (these endpoints will be exploratory in Group B). Other exploratory assessments will include pharmacokinetics and association between genetic characteristics and treatment response in both groups. In a planned interim futility analysis of Group A, the study will be terminated if ≤13 of the first 40 treated pts respond (no futility analysis of Group B will be conducted). The study is currently recruiting (estimated completion date, March 2020). Clinical trial information: NCT02998476.


Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 54-58 ◽  
Author(s):  
Franck Morschhauser ◽  
Tim Illidge ◽  
Damien Huglo ◽  
Giovanni Martinelli ◽  
Giovanni Paganelli ◽  
...  

A prospective, multicenter, nonrandomized phase 2 trial was conducted to evaluate the efficacy and safety of a single dose of yttrium-90 (90Y) ibritumomab tiuxetan in elderly patients in first relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) ineligible for stem-cell transplantation. Patients had been previously treated with chemotherapy (group A, n = 76) or chemotherapy plus rituximab (group B, n = 28). Patients in group A were further divided into patients in whom induction therapy had failed (stratum AI, n = 33) and patients who had relapsed after achieving complete response (CR; stratum AII, n = 43). The overall response rate (ORR) was 52% and 53% in strata AI and AII, respectively, and 19% in group B, with CR/CRu rates of 24%, 39.5%, and 12%, respectively. Median progression-free survival was 5.9 months and 3.5 months in strata AI and AII, respectively, and 1.6 months in group B. Median overall survival was 21.4, 22.4, and 4.6 months in stratum AI, stratum AII, and group B, respectively. Two patients died from thrombocytopenic cerebral bleeding following administration of therapy. Nonhematologic adverse events were mild to moderate. 90Y-ibritumomab is active in patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) and its further evaluation in phase 3 studies is ongoing.


Blood ◽  
2011 ◽  
Vol 117 (6) ◽  
pp. 1958-1965 ◽  
Author(s):  
Seok Jin Kim ◽  
Hye Jin Kang ◽  
Jin Seok Kim ◽  
Sung Yong Oh ◽  
Chul Won Choi ◽  
...  

Abstract The aim of this retrospective cohort study was to analyze the impact of surgery on the outcomes and qualities of life (QOL) in patients with intestinal diffuse large B-cell lymphoma (DLBCL). We assessed 345 patients with either localized or disseminated intestinal DLBCL and compared them according to treatment: surgical resection followed by chemotherapy versus chemotherapy alone. In patients with localized disease (Lugano stage I/II), surgery plus chemotherapy yielded a lower relapse rate (15.3%) than did chemotherapy alone (36.8%, P < .001). The 3-year overall survival rate was 91% in the surgery plus chemotherapy group and 62% in the chemotherapy-alone group (P < .001). The predominant pattern in the chemotherapy group was local relapse (27.6%). When rituximab was used with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), there was no improvement of the outcomes in patients treated with primary surgical resection. The QOL of patients who underwent surgery and chemotherapy was lower than chemotherapy alone, but its difference was acceptable. Multivariate analysis showed that surgical resection plus chemotherapy was an independent prognostic factor for overall survival. Surgical resection followed by chemotherapy might be an effective treatment strategy with acceptable QOL deterioration for localized intestinal DLBCL. This study was registered at www.clinicaltrials.gov as #NCT01043302.


2019 ◽  
Author(s):  
Yan Qin ◽  
Shiyu Jiang ◽  
Peng Liu ◽  
Jianliang Yang ◽  
Sheng Yang ◽  
...  

Author(s):  
Basem Magdy William ◽  
Navneeth Rao Bongu ◽  
Martin Bast ◽  
Robert Gregory Bociek ◽  
Philip Jay Bierman ◽  
...  

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Emma Rabinovich ◽  
Kith Pradhan ◽  
R. Alejandro Sica ◽  
Lizamarie Bachier-Rodriguez ◽  
Ioannis Mantzaris ◽  
...  

AbstractAnti-CD19 chimeric antigen receptor T-cell therapies have shown striking clinical activity in diffuse large B-cell lymphoma but robust biomarkers predictive of responsiveness are still needed. We treated a multi-ethnic cohort of 31 diffuse large B-cell lymphoma patients with axicabtagene ciloleucel with an overall response rate of 71%. Analysis of various biomarkers identified a significant decrease in overall survival with elevated lactate dehydrogenase, measured both at time of cell infusion and before lymphodepletion. Lactate dehydrogenase was prognostic in a multivariate analysis [HR = 1.47 (1.1–2.0)] and a value of 400 U/L at time of infusion and a value of 440 U/L before lymphodepletion provided the best prognostic cutoffs for overall survival in our cohort. These data demonstrate efficacy of anti-CD19 chimeric antigen receptor T-cell therapy in a diverse inner city population and demonstrate novel lactate dehydrogenase cutoffs as prognostic biomarkers.


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