scholarly journals Efficacy of Yttrium-90 Iburitumomab Tiuxetan for Early Relapsed/Refractory Indolent B-Cell Lymphoma: A Single Institute Retrospective Analysis in the Rituximab Era

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5333-5333
Author(s):  
Keiichi Nakata ◽  
Shigeo Fuji ◽  
Ryo Nakata ◽  
Kazuhito Tsutsumi ◽  
Shuhei Kida ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Significant Prognostic Factor ◽  
Hematopoietic Stem ◽  
The Impact ◽  
Yttrium 90

Abstract Introduction: Indolent B-cell lymphoma is a type of non-Hodgkin's lymphoma that grows slowly and is not a curative disease. Yttrium-90 (90Y) iburitumomab tiuxetan is used in patients with relapsed/refractory indolent B-cell lymphoma, data is still limited in the rituximab era. In addition, previous studies did not assess the impact of early progression of disease within 2 years (POD24) which was reported to be associated with a poor prognosis in follicular lymphoma (Casulo et al, J Clin Oncol 2015) on the efficacy of 90Y iburitumomab tiuxetan. Thus, here we assessed the efficacy of 90Y iburitumomab tiuxetan in relapsed/refractory indolent B-cell lymphoma, and analyzed the impact of POD24 in this setting. Methods: We retrospectively analyzed the clinical outcomes of 51 patients with a relapsed/refractory indolent B-cell lymphoma who received 90Y iburitumomab tiuxetan at our institute from February 2009 to January 2018. POD24 was defined as progression within 24 months from the beginning of induction chemotherapy. Survival outcomes including overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier analysis and Cox proportional hazard models. Results: The median age was 64 years (range 37-88 years) at the time of receiving 90Y iburitumomab tiuxetan, and 29 (56.9%) were male. Disease subtypes were as follows: follicular lymphoma (n=44, 86.3%), mantle cell (n=4, 7.8%), marginal zone (n=2, 3.9%), and MALT lymphoma (n=1, 2.0%). The median number of previous regimens was 2 (range 1-9) and included rituximab-based therapy in all patients. Disease status at the time of receiving 90Y iburitumomab tiuxetan were as follows: complete remission (CR n=3, 5.9%), partial remission (PR n=13, 25.5%), stable disease (SD n=3, 5.9%), progression disease (PD n=32, 62.7%). The median follow-up time was 3.7 years (range 0.3-8.8 years) and overall response rate (ORR) was 94.1% (CR 56.9%, PR 37.3%). The ORR in patients with POD 24 was 95.0% (CR 60.0%, PR 35.0%), compared to 93.5% (CR 54.8%, PR 38.7%) with non-POD24. The 3-year OS and PFS rates for all patients receiving 90Y iburitumomab tiuxetan were 83.6% and 41.0%, respectively. POD24 was a significant prognostic factor for PFS in univariate analysis (1.2 years in patients with POD24 vs. 3.3 years in patients with non-POD24, (P=0.02) (Figure1). In multivariate analysis, POD24 was an independent prognostic marker of PFS (hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.22-0.87, P=0.02). Conclusion: 90Y iburitumomab tiuxetan was highly effective in patients with relapsed/refractory indolent B-cell lymphoma patients. However, in patients with POD24, duration of response was short. Thus, another treatment strategy including hematopoietic stem cell transplantation should be considered. Disclosures No relevant conflicts of interest to declare.

R-CHOP21 Vs R-CHOP14 in 950 Diffuse Large B-Cell Lymphoma Patients: Results of a Multicentre Retrospective Study Form Italian Lymphoma Foundation (FIL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1615-1615
Author(s):  
Luigi Rigacci ◽  
Benedetta Puccini ◽  
Maria Giuseppina Cabras ◽  
Luca Nassi ◽  
Alberto Fabbri ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
Bulky Disease ◽  
Symptomatic Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 1615 Background: Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. R-CHOP21 (C21) is considered the standard therapy but a large number of studies have tested R-CHOP14 (C14). Aims: The aim of our study was to evaluate retrospectively a cohort of patients (pts) treated with C21 or C14 and to compare the efficacy of the therapy. Methods: All pts with diagnosis of DLBCL or follicular grade IIIb lymphoma, treated with curative intent in 9 Italian Hematological Centers, were accrued. All patients treated with C14 used G-CSF as primary prophilaxis, and only elderly (over 70 years) patients treated with C21 used G-CSF as primary prophilaxis. Results: From january 2002 to june 2011, 950 pts were accrued, 643 pts were treated with C21 and 307 were treated with C14. The median age was 63 (range 19–89). The two cohorts of pts were balanced for all clinical characteristics a part for age (<60 or >60 years) with more aged pts in C21 arm (p 0.001), bone marrow positivity and more than 3 lymph node stations involved that were higher in C14 arm (p: 0.05 and p: 0.001). After induction therapy 751 pts (79%) obtained a complete remission: 501/643 (78%) after C21 and 250/307 (81%) after C14. The remaining pts obtained partial response in 110 and 48 or no response in 32 and 9 respectively for C21 and C14. After a median period of observation of 38 months 104 pts relapsed (14%), 68 (65%) in the C21 arm and 36 (35%) in the C14 arm. After a median observation period of 3 years, considering the two therapies, C21 vs C14, no differences were reported in OS (Figure 1), PFS (Figure 2) and DFS: 80% vs 84%, 69% vs 71% and 54% vs 56% respectively. In univariate analysis OS was lower in older pts (azard ratio (ar): 2.57), IPI 2 (ar: 2.09), IPI 3 (ar: 4.36), IPI 4–5 (ar: 6.36), bulky disease (ar: 1.70), symptomatic disease (ar: 2.23). In multivariate analysis factors which mantained significantly worst prognosis were older age (ar: 1.35), IPI 2 (ar: 1.95), IPI 3 (ar: 3.76), IPI 4–5 (ar: 5.01) and bulky disease (ar: 1.43). As expected hematological grade III/IV toxicity was more frequent in pts treated with C14. No differences in extra-hematological toxicity were observed. Secondary malignancies were reported: 7 in C21 and 3 in C14. After 3 years of median observation 188 pts are dead: 137 (73%) in C21 and 51 (27%) in C14 (not statistically significant, p:0.08). The large majority of pts are dead for disease progression or relapse. Conclusions: In conclusion our results confirm that C14 do not improve the results of the standard C21 in the whole lymphoma population. Dose dense therapy did not affect OS or PFS also analysing sub group of pts. As expected a higher frequency of neutropenia was observed in C21 arm but did not translate in increasing infection rate. Further prospective randomized studies are needed to verify this preliminary observations. Disclosures: No relevant conflicts of interest to declare.

Concurrent Follicular Lymphoma At Diagnosis Has a Negative Impact On The Outcome Of Patients With Diffuse Large B Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4260-4260 ◽  
Author(s):  
David Wrench ◽  
Hasan Rizvi ◽  
Andrew Wilson ◽  
Ciaran O'Riain ◽  
Andrew Clear ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Negative Impact ◽  
Tissue Sample ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract In contrast to either de novo diffuse large B cell lymphoma (dnDLBCL) or follicular lymphoma (FL) that transforms to DLBCL, the clinical course of DLBCL and FL presenting simultaneously (DLBCL/FL) is not well characterised. From 1 October 1975 to 31 December 2010, 819 patients were diagnosed with DLBCL at St Bartholomew’s Hospital. Twenty-seven patients with bone marrow (BM) involvement were excluded because of histologies other than FL or DLBCL in the BM (n=2) or unavailable BM samples (n=25). The remaining patients comprised the study population (n=792) which consisted of 45 histologically confirmed DLBCL/FL and 747 dnDLBCL. A pathological review was performed of all DLBCL/FL and all the positive BM samples. Remission duration (RD), progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) were compared in DLBCL/FL and dnDLBCL. DLBCL/FL comprised composite (both histologies in the same tissue sample; n=24) and discordant (both histologies in separate tissue samples; n=21) lymphoma. The majority (n=18, 75%) of composite DLBCL/FL were diagnosed on lymph node (LN) sampling with the remainder identified in tonsil (n=3) with single cases in testis, salivary gland and BM. Discordant DLBCL/FL, presented as DLBCL and FL involving LN and BM respectively in 16 cases (76%). Other combinations included DLBCL and FL in separate LNs (n=2) and one each of kidney + BM, mesentery + LN, bone biopsy + BM. At presentation, DLBCL/FL had more advanced stage (p<0.01), higher IPI (p=0.02) and lower Hb (p=0.02) than dnDLBCL in keeping with BM involvement rates of 19/45 (42%) and 32/747 (4%), respectively. Most DLBCL/FL (n=42; 93%) received anthracycline based combination chemotherapy (a single case received HD-MTX and 2 cases palliative / no treatment both of whom died within 3.5 months) and, since 2003, addition of rituximab (24% of cases) to CHOP (n=10) or CODOX-M/IVAC (n=1); with similar rates of anthracycline (82%) and rituximab (29%) use in dnDLBCL. The 44 documented responses in DLCBL/FL included complete response (CR, n=26; 59% similar to 66% in 696 patients with dnDLBCL and assessable responses), partial response (n=7) and stable disease/progression (n=11) with a shorter RD for DLBCL/FL (median 8.7 yrs) compared to dnDLBCL (median not reached), although this was not statistically different (p=0.09). PFS was significantly shorter for DLBCL/FL in comparison with dnDLBCL (2.0 versus 4.6 yrs, respectively; p=0.02) and DLBCL/FL not achieving CR had inferior OS (0.4 yrs) than those achieving CR (11.5 yrs; p<0.01). Relapse after CR occurred in 12/26 (46%) patients with DLBCL/FL and in 142/456 (31%; p=0.13) of those with dnDLBCL; 83% and 87% relapsed cases have died, respectively. With a median follow-up of 10 yrs, 71% patients with DLBCL/FL have died as compared to 65% patients with dnDLBCL, and no differences in median OS were observed (4.0 yrs for DLCBL/FL versus 5.5 yrs for dnDLBCL; p=0.28). Death was most commonly due to lymphoma, the rate being similar in patients with DLBCL/FL (56%) and dnDLBCL (52%). However, LSS was shorter for DLBCL/FL (6.3 yrs) than dnDLBCL (13.8 yrs; p<0.01) and, with the long follow-up, we found no differences in OS between DLBCL with concordant (DLBCL, n=32) or discordant (FL, n=18) BM involvement (p=0.38). This study, to the authors’ knowledge the largest series of concurrent FL and DLBCL, confirms the relative frequency of DLBCL/FL to DLBCL (45:747, 6%) and demonstrates that the simultaneous presence of FL negatively influences the outcome of patients with DLBCL, by shortening PFS and LSS. This data emphasizes the importance of thorough staging at diagnosis, including BM biopsies, and highlights the need for better management of this population, which has a worse prognosis than dnDLBCL and is frequently excluded from clinical trials. Disclosures: No relevant conflicts of interest to declare.

The prognostic significance of the number of extranodal sites in the patients with disseminated diffuse large B-cell lymphoma treated with R-CHOP

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8570-8570
Author(s):  
C. Yoo ◽  
B. Sohn ◽  
J. Kim ◽  
D. Yoon ◽  
J. Huh ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
B Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Stage Iii ◽  
Significant Prognostic Factor ◽  
Large B Cell Lymphoma ◽  
Large B Cell

8570 Background: The combination of rituximab and CHOP chemotherapy (R-CHOP) has improved survival of patients with diffuse large B-cell lymphoma (DLBCL). Recently, several reports have shown that standard International Prognostic Index (IPI) became less powerful prognostic predictor in patients with DLBCL in the era of R-CHOP. We evaluated the prognostic factors of DLBCL patients treated with R-CHOP. Detailed analysis was planned regarding the number of extranodal sites because of its higher frequency in Korea. Methods: Between January 2002 and May 2008, 126 patients with stage III/IV DLBCL treated with R-CHOP were identified. We performed the retrospective analysis of the clinicopathologic factors and verified the predictive power of standard IPI and revised IPI (R-IPI) which was reported by the study group of British Columbia. Various numbers of extranodal sites were analyzed for further stratification and we set E-IPI as the IPI when the number of extranodal sites is stratified in ≤2 vs >2. Results: In the univariate analysis, the number of extranodal sites (≤2 vs >2) was a significant prognostic factor for complete response (CR) (p=0.04), event-free survival (EFS) (p=0.01) and overall survival (OS) (p<0.001). Age was also significant for EFS (p=0.03). When the number of extranodal site was stratified differently (0 vs >0, or ≤1 vs >1), these were not associated with CR, EFS and OS. On the multivariate analysis, the number of extranodal sites (≤2 vs >2) remained significant for EFS (p<0.01, HR 2.6) and OS (p<0.01, HR 3.5). The standard IPI identified 3 risk groups with 2-year EFS; 68%, 55%, 56% (p=0.17) and 2-year OS; 85%, 68%, 58%, respectively (p=0.04). The R-IPI classified 2 risk groups with 2-year EFS; 65%, 50% (p=0.02) and 2-year OS 76%, 62%, respectively (p=0.04). The E-IPI represented 3 risk groups with 2-year EFS; 79%, 56%, 42% (p=0.01) and 2-year OS; 86%, 70%, 39%, respectively (p=0.001). The patient group with survival of less than 50% was only recognized by E-IPI. Conclusions: The number of extranodal sites (≤2 vs >2) is the most significant prognostic factor of EFS and OS. Although all three indices remain predictive, E-IPI is the best model to identify the prognostic group in this cohort with stage III/IV DLBCL treated with R-CHOP. No significant financial relationships to disclose.

scholarly journals Outcomes of Cardiac Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Taha Al-Juhaishi ◽  
Ghaith Abu Zeinah ◽  
Sadeer Al-Kindi
Keyword(s):  
B Cell ◽  
Survival Data ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
P Value ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Introduction: Cardiac lymphomas are very rare with diffuse large B-cell lymphoma (DLBCL) considered to be the most common histology. These lymphomas can be either local "primary cardiac" disease, or part of dissemination by systemic lymphoma. There is limited data regarding outcomes of patients with this disease. We sought to evaluate the outcomes of cardiac DLBCL in both pre- and rituximab eras using a large retrospective database. Methods: The public Surveillance, Epidemiology and End Results (SEER) database was used to identify all patients diagnosed with DLBCL and heart as the primary disease site. Data cutoff in the database was in 2016. Patients with missing date of diagnosis or survival data were excluded. Patients were divided into two groups based on diagnosis year, with rituximab cohort included all DLBCLs diagnosed in 2006 and later (2006 was FDA approval year of rituximab in untreated DLBCL). Treatment effect (surgery, radiation, chemotherapy) was analyzed when available. survival was estimated using the Kaplan-Meier method, and compared using Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. Results: Total of 106 patients were included in the final analysis, baseline characteristics are summarized in table 1. Median age at diagnosis was 69.5 years with only about 10% of patients being 50 years or younger. Most patients were white 71 (67%), had local stage I/II disease 68 (64.2%), and belonged to the rituximab era group 71 (67%). Most patients had chemotherapy 82 (77.4%), while only 25 (23.6%) had surgery, and 16 (15.1%) had radiotherapy. Median overall survival (OS) for the entire cohort was 22 months (0-292). Median OS was 16 months (95% CI, 0.55 -31) for the pre-rituximab group, and was 26 months (95% CI, 7.5 - 45) for the rituximab group which were not statistically different (p-value =0.340). Median lymphoma-specific survival (LCS) was 30 months (95% CI, 8.0 -52) for the pre-rituximab group, and was 36 months (95% CI, 16 - 158) for the rituximab group which were not statistically different (p-value =0.295). OS and LCS were also not different between the two era groups when stratified by chemotherapy (figure 1). On univariate analysis, Chemotherapy was associated with better OS [HR = 0.472, 95% CI (0.277-0.806); p-value = 0.006] but not LCS [HR = 0.690, 95% CI (0.341-1.396); p-value = 0.302]. Using a multivariate analysis model, both OS and LCS were associated with lymphoma stage, insurance status and age but not with diagnosis era or chemotherapy (table 2). Conclusion: Cardiac DLBCLs are rare and affecting mostly the elderly. No significant improvement in outcomes were noted in the current rituximab era. Age, disease stage, and having health insurance were associated with better outcomes. The role of chemotherapy needs further evaluation in larger studies. Disclosures No relevant conflicts of interest to declare.

Effects of FCGR3A and FCGR2A polymorphisms on outcomes of patients with diffuse large B-cell lymphoma treated with CHOP-like chemotherapy versus CHOP-rituximab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8567-8567
Author(s):  
J. Vose ◽  
F. Loberiza ◽  
J. Armitage ◽  
P. Bierman ◽  
R. Bociek ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Nucleotide Polymorphisms ◽  
Large B Cell Lymphoma ◽  
Treatment Type ◽  
The Impact ◽  
Large B Cell

8567 Background: The addition of rituximab to cyclophosphamide/ doxorubicin/ vincristine/ prednisone (R-CHOP) therapy for diffuse large B-cell lymphoma (DLBCL) has significantly improved the outcome for many patients (pts). We evaluated the impact of single nucleotide polymorphisms (SNPs) of Fc receptor (FcR) genes FCGR3A and FCGR2A on the outcomes of patients with DLBCL treated with R-CHOP compared to a historical control patientss treated with CHOP-like chemotherapy alone. Methods: 199 patients with DLBCL who had received CHOP or CHOP-like chemo (N=99) or R-CHOP (N=100) had tissue blocks assayed for FCGR3A and FCGR2A polymorphisms. The patient characteristics, progression-free survival (PFS), and overall survivals (OS) were compared and analyzed with respect to the polymorphisms. Results: In the univariate analysis, the probability of PFS of pts according to polymorphisms in the FCGR2A gene treated with CHOP-like chemotherapy; H/H (n=25), H/R (n=39), and R/R (n=35) and those treated with R-CHOP; H/H (n=24), H/R (n=41), and R/R (n=35) were both not statistically different; log-rank p=0.47 and p=0.86, respectively. The probability of PFS in the FCGR3A gene treated with CHOP-like chemotherapy; V/V (n=10), F/V (n=40), F/F (n=49) and those treated with R-CHOP; V/V (n=12), F/V (N=40), F/F (n=48) were also not statistically different; log-rank p=0.32 and p=0.22, respectively. In a multivariate analysis for risk of progression or death: FCGR2A : H/H vs. H/R or R/R by treatment type: CHOP-like [RR 0.63 (95% CI 0.37–1.08), p=0.10] and R-CHOP [RR 0.59 (0.36–0.96), p=0.04] and for FCGR3A V/V vs. F/V or F/F by treatment arm: CHOP-like [RR 0.75 (0.36–1.54), p=0.43] and R-CHOP [RR 2.28(0.70–7.44), p=0.17]. Conclusions: Generally, the addition of rituximab to CHOP chemotherapy results in better outcomes than patients who receive CHOP-like regimen regardless of polymorphisms. However, our study also suggests that a trend toward association of certain polymorphisms with clinical outcomes. Additional, larger studies are needed to confirm this data. This information may assist in targeting additional therapies in patients with less favorable outcomes. [Table: see text]

Combination of Rituximab with Initial Chemotherapy Improves Outcome of Primary Mediastinal B-Cell Lymphoma: A Retrospective Analysis of a Single Institution Cohort

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1283-1283 ◽  
Author(s):  
Abraham Avigdor ◽  
Tsvi Sirotkin ◽  
Noga Shemtov ◽  
Miriam Berkowicz ◽  
Yaron Davidovitz ◽  
...  
Keyword(s):  
B Cell ◽  
Retrospective Analysis ◽  
Predictive Value ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Historical Comparison ◽  
Pet Ct ◽  
Significant Difference ◽  
The Impact

Abstract Primary mediastinal B-cell lymphoma (PMBCL) is a relatively rare clinico-pathologic subtype of diffuse large B-cell lymohoma. The optimal management, the prognostic factors and the role of PET/CT scan in this entity remain a matter of debate. While several retrospective studies suggested that dose-dense regimens are more effective than standard CHOP, the impact of adding rituximab (R) on the outcome of patients (pts) with PMBCL has not been fully evaluated. In this retrospective analysis we reviewed the clinical and radiological records of 81 consecutive pts with PMBCL treated in Sheba Medical Center between August 1985 and October 2006. Chemotherapy in the pre-rituximab era (−R cohort) included VACOPB (n=47) or 6 courses of standard CHOP (n=5). Since October 2002, 6 cycles of R were added concurrent with the treatment in another 29 pts (+R cohort): R-VACOPB (n=21) and R-CHOP (n=8). Radiotherapy was not administered following initial chemotherapy to any of the pts. Median age at diagnosis was 31 years (yrs) (range 17–61). Stage I/II and bulky mediastinum (≥ 10 cm in diameter) were present in 88% and 33%, respectively, and extranodal involvement was evident in 44% of all pts. After a median follow-up of 85 months (range 9–240), the overall (OS) and progression-free (PFS) survival at 5 yrs for the entire cohort were 89% and 66%, respectively, with a plateau 1–2 yrs following treatment. PFS at 5 years was significantly better with +R (81%) than with -R cohort (58%, P=0.03). Five-year PFS in pts treated with R-VACOPB, R-CHOP, VACOP-B and CHOP were 84%, 74%, 62%, 20%, respectively (P=0.025). Yet, there was no significant difference in OS between +R and -R cohorts (96% vs. 88% at 5 yrs, p=0.29). Direct survival comparisons demonstrated that 5-yr OS and PFS were significantly better in VACOPB than in CHOP (P=0.04 and 0.05, respectively) and that R-VACOPB was significantly superior to VACOPB in terms of PFS (p=0.05). In contrast, there was no difference in 5-yr PFS between R-VACOPB and R-CHOP (p=0.44). Univariate analysis revealed that aaIPI was not predictive of OS (p=0.51). Age above 31 yrs (p=0.02) and pericardial effusion (p=0.04) were the only predictors of reduced OS. Furthermore, beginning in 2003, 16 consecutive pts in the +R cohort, who were scanned by PET/CT-FDG before starting and after completion of therapy, were also evaluated in the middle (mid-PET) of treatment. The estimated 3-year PFS rate for mid-PET negative pts (n=8) and for mid-PET positive pts (n=8) was 86% and 75%, respectively (P=0.48). In terms of treatment failure, the negative predictive value of mid-PET was 100%, while the positive predictive value was only 25%. In conclusion, our population-based historical comparison demonstrates that the addition of R to anthracycline-based therapy significantly improved PFS in pts with PMBCL. We observed superior PFS with VACOPB compared with CHOP, but this superiority was abrogated by the introduction of R as part of initial therapy. These findings merit further study in randomized prospective studies.

Pre-Clinical Evaluation of a Novel DNA Crosslinking Agent, Bo-1055 in B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5483-5483 ◽  
Author(s):  
Eloisi Caldas Lopes ◽  
Fabian Correa ◽  
Elizabeth Peguero ◽  
Srikanth R. Ambati ◽  
Jae Hung Shieh ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Crosslinking Agent ◽  
B Cell Lymphoma ◽  
Water Soluble ◽  
Therapeutic Window ◽  
Hematopoietic Stem ◽  
Normal Human

Abstract Some B-cell lymphoma including mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) remain incurable using conventional chemotherapeutic approaches. Therefore it is important that new treatment strategies be developed. We have evaluated the efficacy of a number of novel, third generation, DNA-directed alkylating agents that have DNA specific binding domain by linking DNA-affinic molecules to N-mustard pharmacophore via a urea, carbamate or hydrazinecarboxamide linker (Kapuriya et al. Bioorganic & Medicinal Chem. 19:471–485; 2011). One of these, the water-soluble ureidomustine BO-1055, was screened for toxicity against a panel of human lymphoma cell lines including MCL (JEKO-1, Z-138, HBL-2), DLBCL (OCILy10, OCILy19) and a spontaneous murine B-cell lymphoma. We also screened BO1055 against a panel of normal human cells including mesenchymal stromal cells (IC50 >10uM), bone marrow-derived endothelium (IC50 >10uM) lung basal epithelium, bronchial epithelium and myofibroblasts (IC50s >10uM) and purified cord blood CD34+ cells in suspension culture or colony-forming assay (for hematopoietic progenitor cells) (IC50 >10uM) and in cobblestone area-forming assay (for hematopoietic stem cells) (IC50 9.1uM). The mean IC50±SD (uM) in MCL cell lines was JEKO-1 (0.266±0.27), Z-138 (0.182±0.15), HBL2 (0.161±0.34), In DLBCL lines OCILy10 (0.117±0.21), OCILy19 (0.287±0.17) and murine B-cell lymphoma (0.463±0.39). Our results indicated that BO-1055 has a significant therapeutic window (50-100-fold) between its toxicity against human B-cell lymphomas compared to various normal human cell types. We evaluated BO-1055 cardiotoxicity in the HL-1 cardiomyocyte line and observed a 227-fold less cytotoxicity compared to Doxorubicin. Treatment with BO-1055 resulted in accumulation of cells in S-phase and up-regulation of proteins involved in DNA repair [MRE11, p-P95/NBS1 (ser343), RAD50, p-ATR (ser428)] while Bcl-6, an important B-cell lymphoma biomarker, was down-regulated. Xenograft experiments in NSG mice bearing JEKO-1 GFP/luciferase+ tumors treated with BO-1055 (30mg/kg) 3x/week showed complete tumor remission after 2 weeks of treatment as monitored by luciferase image. Our results suggest that BO-1055 has potent activity against B-cell lymphoma and present a strong rationale for its further therapeutic development as an alkylating agent due to his low toxicity against normal tissue and high toxicity against hematopoietic tumors. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Clinico-Genotypic Prognostic Index for De Novo Composite Diffuse Large B-Cell Lymphoma Arising from Follicular Lymphoma in the Rituximab Era

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5396-5396
Author(s):  
Ryan Mao Heng Lim ◽  
Natalie Pei Xin Chan ◽  
Lay Poh Khoo ◽  
Chee Leong Cheng ◽  
Leonard Tan ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Multivariate Model ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Double Hit ◽  
Large B Cell

Abstract Aim Composite follicular lymphoma with diffuse large B-cell lymphoma (FL/DLBCL) is an uncommon hematological neoplasm. The aim of this study was to examine clinico-pathological features of patients with FL/DLBCL and investigate relevant predictors of survival outcome. Methodology Patients with histologically-proven FL/DLBCL at diagnosis (n=106) and who were subsequently treated with Rituximab-based chemotherapy from 2002-2017 at the National Cancer Centre Singapore were retrospectively analyzed. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. Results The cohort consisted of 72 men and 34 women with a median age of 59 years (range, 24-82). The cell of origin by Han's algorithm was GCB in 37.7%, ABC in 58.5% and unknown in 3.8%. Eight patients (7.5%) were double-hit for c-MYC, BCL2 and/or BCL6 rearrangements. In a multivariate model inclusive of known clinico-pathological parameters at diagnosis, presence of B symptoms (p = 0.0122), stage 3 or 4 lymphoma (p = 0.0166) and double-hit genotype (p = 0.0045) were independently prognostic for worse overall survival (OS). These factors, excluding B symptoms, were similarly prognostic for progression-free survival (PFS). Including first-line treatment data in the multivariate model, lack of complete response (p < 0.0001) and use of chemotherapy regimens other than R-CHOP (p = 0.0360) alongside presence of B symptoms (p = 0.0022), were the only remaining independent prognostic variables for worse OS. Classification by cell of origin was not prognostic. A Clinico-Genotypic Index derived from point-wise addition of all five adverse parameters (score of 0, 1, 2, 3-4) revealed four prognostic risk groups accounting for 25%, 30%, 25% and 20% of the cohort, with a predicted 5-year OS of 100%, 95%, 57% and 19% respectively (p < 0.0001). Conclusion A Clinico-Genotypic Index derived from clinical and molecular factors can classify patients with composite FL/DLBCL into distinct prognostic groups. Han's algorithm has no prognostic value in this disease entity. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals MYD88 L265P Mutation Is a Possible Unfavorable Prognostic Factor in Patients with Diffuse B-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5051-5051 ◽  
Author(s):  
Anna A. Sidorova ◽  
Eugene E. Zvonkov ◽  
Andrey B. Sudarikov ◽  
Nataliya A. Severina ◽  
Alla M. Kovrigina ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Mutation Status ◽  
Myd88 L265p Mutation ◽  
The Impact ◽  
Myd88 L265p

Abstract INTRODUCTION Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Activated B-cell like (ABC) molecular subtype DLBCL is characterized by more aggressive behavior and poor clinical outcomes with standard R-CHOP chemotherapy. Approximately 30% of all patients (pts) with ABC DLBCL have recurrent mutation in the MYD88 gene (a change from leucine to proline at position 256 - L256P). We report the impact of the MYD88 mutation status on the clinical course and outcome of pts with ABC DLBCL. METHODS In present study MYD88 mutation status was investigated in untreated pts with ABC DLBCL. The diagnosis of ABC DLBCL was established according to the WHO 2008 classification. DNA from 41 cryopreserved and 12 formalin-fixed paraffin-embedded tumor samples were tested in our study. Sanger sequencing and real-time allele-specific PCR was used to assess MYD88 L265P mutation status. RESULTS We report data for 53 pts (34 male, 19 female) with a median age of 53 (18-74) years. MYD88 L265P mutation was detected in 26,4% (14/53) of pts. The international prognostic index (IPI) score was 4-5 in 7/14 (50%) of pts with MYD88 mutated DLBCL and 12/39 (30,8%) pts with MYD88 wild type DLBCL, whereas nearly half of all pts presented with Ann Arbor stage IV disease. The majority of pts 13/14 (93%) with MYD88-positive DLBCL had elevated lactate dehydrogenase levels versus 26/39 (66%) pts with MYD88 unmutated DLBCL. Extranodal was more common in pts with MYD88 mutation than in pts with MYD88 unmutated DLBCL (78,5% vs 54%). All pts received high-dose chemotherapy and were followed for 50,5 (11-95) month. Pts with MYD88 mutation had similar complete response rate comparing to pts without MYD88 mutation (78,6% vs 84,6%). The disease relapsed in 45,4% of pts with MYD88 mutation and in 24,2% of pts without MYD88 mutation. Mortality was in 45,4% of pts with MYD88 mutation and in 24,2% of pts without MYD88 mutation. Overall survival (OS) was better in pts with MYD88 unmutated DLBCL than in pts with MYD88 positive DLBCL (5-year OS, 73% vs 31%). CONCLUSION IPI high risk and extranodal involvement is common in ABC DLBCL pts with MYD88 L265P mutation. MYD88 L265P mutation can be a predisposing factor for poor OS probability in pts with ABC DLBCL. Disclosures No relevant conflicts of interest to declare.

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