Classification of Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) According to the Han's Criteria Defines Two Groups of Patients with Different Clinical Outcomes Following Systemic Rituximab-Multi Agent Anthracycline-Based Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 623-623 ◽  
Author(s):  
Julio Chavez ◽  
Mark Walsh ◽  
Francisco J Hernandez-Ilizaliturri ◽  
Anjana Elefante ◽  
Myron S. Czuczman
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Predictive Value ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Front Line ◽  
Free Survival ◽  
Line Therapy

Abstract Abstract 623 Gene expression profiling has successfully distinguished three subtypes of DLBCL with different biology and response to treatment: 1) germinal center B-cell (GCB); and 2) non-germinal center lymphomas, that include: activated B-cell-like (ABC) and Type 3 subtypes. Currently, immunohistochemical (IHC) analysis of lymphoma biopsy specimens appear to be a more widely applicable methodology (i.e. compared to gene microarray analysis) to use in order to differentiate between subtypes of DLBCL. While the clinical benefit of adding rituximab to CHOP or CHOP-like chemotherapy as a front line treatment of DLBCL is beyond dispute, it also requires a re-evaluation of previously accepted biomarkers of response to CHOP or CHOP-like chemotherapy alone. The predictive value of “IHC–defined” GCB phenotype in rituximab-chemotherapy-treated patients continues to be controversial, as retrospective studies have reported conflicting results. In an attempt to define the predictive value of using the Han's algorithm in newly diagnosed DLBCL patients undergoing frontline immunochemotherapy, we retrospectively analyzed differences in progression free survival (PFS) and overall survival (OS) between patients with GCB and non-GCB DLBCL treated with equivalent doses of rituximab and anthracycline-based therapy at our institution. Using the tumor registry and the pharmacy database, we identified patients with DLBCL treated at our Institution between 2000 and 2008. Demographic, clinical, pharmacologic and pathological characteristics were obtained for each patient. Patients were classified into GCB or non-GCB DLBCL according to the Han's algorithm based on the expression of CD10, Bcl-6 and MUM-1 in the large cell component of the tumor specimen. Cumulative doses of rituximab (R), cyclophosphamide (C), doxorubicin (H), vincristine (O), etoposide (E,; when used) and prednisone (P) were calculated for each patient, as well as the number of cycles, dose delays, and growth factor use. A total of 192 patients were included in the study. The average age was 58.65 years (F/M:73/119). Using the Hans algorithm, n=55 (28.6%) and n=57 (29.7%) were classified as non-GCB or GCB, respectively. Inadequate information was availabel to classify 80 patients (undetermined group). Clinical indictors such as clinical demographics, international prognostic index (IPI) score, extra-nodal disease, performance status, Ann Arbor stage, therapy delays, cumulative rituximab and chemotherapy doses were not significantly different between groups (non-GCB, GCB, and undetermined DLBCL). The majority of patients received R+CHOP (90%) or R+ dose adjusted–EPOCH. On follow-up, a total of 42 (21.8%) patients relapsed or were found to have primary-refractory disease. The complete remission rate to front-line therapy was 81% for the entire cohort of patients and was not different between patients with GCB or non-GCB DLBCL. On the other hand, significant differences in PFS and OS were observed between patients with non-GCB versus GCB DLBCL. The 5-year progression free survival (PFS) and overall survival (OS) were significantly better in the GCB DLBCL subtype (75.4% vs. 56.4%, p=0.017 and 84.2% vs. 70.9 %, p=0.037; respectively). As no differences in clinical parameters, CR rate, or rituximab-chemotherapy dose/schedule were observed between non-GCB and GCB DLBCL patients, it is possible that intrinsic biological pathways involved in lymphomagenesis and/or “resistance” of these subtypes of DLBCL may play a role in their responsiveness to rituximab-based immunochemoimmunotherapy. In summary, our data suggest that the Hans algorithm can predict the clinical outcome of patients with DLBCL undergoing front-line therapy with R-chemotherapy. Patients with non-GCB DLBCL while having a comparable initial complete response rate to R+CHOP had a shorter PFS and OS than GCB DLBCL patients. Non-GCB DLBCL represents a subgroup of DLBCL for which innovative therapeutic strategies targeting key regulatory pathways in the induction and/or maintenance setting are needed in an attempt to prolong PFS and improve OS. Disclosures: No relevant conflicts of interest to declare.

BCL6 Rearrangement Detected by FISH Analysis Is a Poor Prognostic Factor in the “Non-Germinal Center Phenotype” of Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4620-4620
Author(s):  
Jun Takizawa ◽  
Sadao Aoki ◽  
Akihito Momoi ◽  
Toshiki Kitajima ◽  
Masutaka Higashimura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Diffuse large B-cell lymphoma (DLBCL), which is the most common type of adult non-Hodgkin lymphoma, is considered to be heterogeneous in cytogenetics, immunophenotype and clinical feature. As the results of gene expression profiling, DLBCL can be divided into prognostically significant 3 subgroups of germinal center B-like (GCB), activated B-like and type 3. Chromosomal translocations affecting the BCL6 locus at the 3q27 locus are common in DLBCL, however, the prognostic significance of BCL6 rearrangement is still controversial. Methods: Twenty-six cases of DLBCL were examined with interphase fluorescence in situ hybridization (FISH) on touch preparations of lymph nodes using LSI BCL6 dual color probes (Vysis) for the incidence of BCL6 rearrangement and immunohistochemistry on paraffin section using CD10, BCL6 and MUM1 for subclassfying “GCB phenotype” and “non-GCB phenotype”. The correlation of BCL6 rearrangement with survival was investigated in two subgroups of DLBCL. Results: Of the 26 DLBCL cases, 6 cases (23%) were considered GCB phenotype and 20 cases (77%) non-GCB phenotype. BCL6 rearrangements were detected in 2 of 6 cases (33%) with GCB phenotype and 9 of 20 (45%) with non-GCB phenotype (total 11/26, 42%). ALL 6 cases with the GCB phenotype achieved sustained complete remission after chemotherapy and are alive. On the other hand, complete remission rate was 22% for the cases with BCL6 rearrangement but 73% for the cases without BCL6 rearrangement in the non-GCB phenotype (p=0.069). BCL6 rearrangement had a significant adverse effect on progression free survival within the non-GCB phenotype (P=0.016), but there was no significant correlation between BCL6 rearrangement and overall survival. Conclusion: FISH-based technique of the BCL6 rearrangements using touch preparations of lymph nodes could be developed for the retrospective analysis on survival. BCL6 rearrangement showed a poor prognostic effect particular in the non-GCB subgroup of DLBCL. Overall survival Overall survival Progression free survival Progression free survival

scholarly journals Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma

2020 ◽  
Author(s):  
Hsu-Chih Chien ◽  
Deborah Morreall ◽  
Vikas Patil ◽  
Kelli M Rasmussen ◽  
Chunyang Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Line Treatment ◽  
Electronic Health Record Data ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000–2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan–Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.

Survival of Limited Stage Peripheral T-Cell Lymphoma Is Similar To Diffuse Large B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2817-2817 ◽  
Author(s):  
Kerry J. Savage ◽  
Mukesh Chhanabhai ◽  
Nicholas Voss ◽  
Shenkier Tamara ◽  
Randy D. Gascoyne ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Limited Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of diseases with an overall poor prognosis. Little information is available regarding the outcome of PTCL patients who present with limited stage disease. We sought to determine the outcome of PTCL patients presenting with limited disease in comparison with a cohort of patients with limited stage diffuse large B-cell lymphoma (DLBCL). Methods: In a retrospective analysis we identified all patients with limited stage (non-bulky (<10cm) stage I/II disease no symptoms) PTCL diagnosed at the British Columbia Cancer Agency (BCCA) between 1983 and 2004. Patients were excluded if they had cutaneous anaplastic large cell lymphoma (CutALCL) (n=13), NK/T-cell lymphoma nasal type (n=9) or primary CNS/ocular involvement (n=6). Results: Thirty-seven patients with PTCL were identified according to the World Health Organization Classification: ALK-neg ALCL 8 (22%); PTCL-unspecified (PTCLUS) 28 (78%); enteropathy associated TCL (EATL) 1 (3 %). The majority received CHOP-type chemotherapy (n=31, 86%), most with brief chemotherapy followed by involved-field radiation (n=19, 61%). The 5 y OS and PFS was similar between PTCLUS and ALK-neg ALCL. There was no difference in survival between extranodal and nodal cases. The outcome of PTCL patients (including ALK-neg ALCL and PTCLUS) was compared to a cohort of limited stage DLBCL patients (excluding CNS/ocular lymphoma) (n=305) diagnosed over the same time period and treated similarly. There was no difference in 5 y OS or PFS (Figure 1,2). Interestingly, there were no late relapses observed in PTCLUS, in marked contrast to DLBCL. Conclusions: Limited stage PTCL is rare, however outcomes appear to be comparable to early stage DLBCL, supporting that they should be treated in a similar manner. Unlike limited stage DLBCL where late relapses occur, a plateau in the progression-free survival curve is observed, highlighting a distinct natural history for limited stage PTCL. Overall Survival Limited Stage PTCL vs DLBCL p=.18 Overall Survival Limited Stage PTCL vs DLBCL p=.18 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07 Progression-Free Survival Limited Stage PTCL vs DLBCL p=.07

Significance of c-myc Rearrangements in Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2030-2030
Author(s):  
Philip Bierman ◽  
Fausto Loberiza ◽  
Bhavana Dave ◽  
Warren Sanger ◽  
R. Gregory Bociek ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Overall Survival Rates

Abstract Rearrangements of the c-myc oncogene can be seen in 5–10% of patients with diffuse large B-cell lymphoma. However, studies examining the significance of this finding have yielded conflicting results. Therefore, we performed a retrospective analysis to determine the clinical significance of c-myc rearrangements in diffuse large B-cell lymphoma. The results of classical cytogenetic studies and FISH analyses were used to identify diffuse large B-cell lymphoma cases in the database of the Nebraska Lymphoma Study Group with or without c-myc rearrangements. Patients who were HIV positive and those with post-transplant lymphoproliferative disease were excluded. We identified 16 patients with diffuse large B-cell lymphoma and c-myc rearrangements. All patients were initially treated with doxorubicin- or mitoxantrone-containing chemotherapy regimens. The median age of these 16 patients was 61 years (range 40 to 80), and 5 (31%) were males. The International Prognostic Index (IPI) was 0–2 at diagnosis in 9 patients (56%), and 3–5 in 7 patients (44%). Eleven patients (69%) had bulky disease (≥ 5 cm) at diagnosis. No significant differences in outcome were identified when the 16 c-myc positive patients were compared with 97 c-myc negative diffuse large B-cell lymphoma patients in the same age range. The actuarial 5-year progression-free survival for the c-myc positive patients was 23% (95% CI 6% to 46%), as compared with 38% (95% CI 29% to 48%) for c-myc negative patients (p=0.17). The actuarial 5-year overall survival rates were 36% (95% CI 14% to 59%) and 47% (95% CI 36% to 56%), respectively (p=0.19). Classical cytogenetics and FISH analyses were also used to examine the 16 c-myc positive cases for bcl-2 rearrangements. Eight (50%) cases had rearrangements of bcl-2 in addition to c-myc rearrangements. These patients were similar to the c-myc positive/bcl-2 negative patients except for a higher likelihood of an elevated LDH level at diagnosis (88% vs. 25%; p=0.03). The actuarial 5-year progression-free survival for c-myc positive/bcl-2 positive patients was 0%, as compared to 33% (95% CI 6% to 66%) for patients with rearrangements of c-myc alone, and 37% (95% CI 28% to 47%) for c-myc negative patients. The actuarial 5-year overall survival rates were 12% (95% CI 1% to 42%), 47% (95% CI 12% to 76%), and 41% (95% CI 31% to 51%), respectively. A multivariate analysis, adjusting for IPI score, demonstrated that the relative risk (RR) of treatment failure was significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.86, 95% CI 1.32–6.23; p=0.008). Similarly, mortality was also significantly worse for the c-myc positive/bcl-2 positive patients, as compared to the c-myc negative patients (RR 2.69, 95% CI 1.18–6.11; p=0.02). In contrast, no significant differences in treatment failure or overall survival were demonstrated when c-myc positive/bcl-2 negative patients were compared with c-myc negative patients. Our results demonstrate that the c-myc rearrangement is not associated with poorer survival in patients with diffuse large B-cell lymphoma. However, patients with rearrangements of bcl-2 in addition to c-myc had significantly worse progression-free survival and overall survival.

The Impact of Activated Akt Expression On Clinical Outcome in Diffuse Large B-Cell Lymphoma: A Clinicopathological Study of 99 Cases.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2676-2676
Author(s):  
Jung Yong Hong ◽  
Moon Ki Choi ◽  
Young Saing Kim ◽  
Chi Hoon Maeng ◽  
Su Jin Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Clinical Impact ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Abstract 2676 Purpose Akt is a serine/threonine kinase that plays a central role in cell proliferation and growth. To define clinical impact of Akt expression in diffuse large B-cell lymphoma(DLBCL), we investigated the expression of phospho-Akt(p-Akt) in DLBCL and analyzed clinical impact of p-Akt expression on patient survival. Methods We evaluated the p-Akt expression in 99 DLBCL patients using tissue microarray(TMA) technology. Results Positive p-Akt expression was observed in 15.2% of the patients and significantly associated with elevated lactic dehydrogenase level (P = .044). Kaplan-Meier survival analysis showed that the patients with positive p-Akt expression showed substantially poorer overall survival (p-Akt+ vs p-Akt- 25.3 months [95% confidence interval(CI), 14.4–36.2 months] vs 192.6 months [95% CI, 131.3–253.9 months], P < .001) and progression-free survival (p-Akt+ vs p-Akt- 13.6 months[95% CI, 14.4–36.2 months] vs 134.5 months [95% CI, 131.3–253.9 months], P < .001), respectively. Multivariate Cox regression analysis revealed that patients with DLBCL with p-Akt positivity showed poorer overall survival with 3.2 fold (95% CI, 1.6–6.8, P = .002) risk for death compared to patients with DLBCL with p-Akt negativity. Conclusion Positive expression of p-Akt in DLBCL patients is associated with poorer overall and progression-free survival. Expression of p-Akt may act as an independent poor prognostic factor and might be a novel therapeutic target for DLBCL. Disclosures: No relevant conflicts of interest to declare.

Progression-free survival for subsequent relapses in patients with peripheral T-cell lymphoma (PTCL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8063-8063 ◽  
Author(s):  
Steven M. Horwitz ◽  
Richard Delarue ◽  
Matthew Alexander Lunning ◽  
Julie Vose ◽  
Bertrand Coiffier
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Front Line ◽  
New Agents ◽  
Free Survival ◽  
Treatment Responses ◽  
Line Of Therapy ◽  
Therapy Treatment

8063 Background: In B-cell lymphoma, overall response (ORR) is lower and progression free survival (PFS) is often shorter with each subsequent progression. However, this has not been described for PTCL. Methods: We undertook a retrospective analysis in two U.S. centers (MSKCC and UNMC) and in GELA studies. All data for PTCL were reviewed to collect data for each line of therapy: treatment, response, PFS, date of next treatment, and survival. When date of progression could not be defined we calculated PFS as the time to next treatment. Pts who did not progress, died during first line, or were untreated at progression 1 were excluded. Data were collected for 4 lines of treatment, front line and 3 progressions. Results: 254 pts were identified. 205 were analyzed (49 excluded for missing data): GELA 116, MSKCC 51, and UNMC 37. Diagnoses were PTCL NOS in 34% and 60%, AITL in 49% and 35%, ALCL Alk- in 3% and 5%, and others in 15% and 18% for GELA and US centers respectively. 67% were male, median age was 51 vs 58 y. Advanced stage was more frequent in GELA (79% vs. 56% for US); baseline IPI was ≥2 in 90% vs 71%. Multidrug regimens were given in 99% and 80% for front line, 67% and 66% for 2nd line, 61% and 50% for 3rd line, 53% and 54% for 4th line, for GELA and US. Significantly fewer pts received each subsequent line of therapy with 205 pts receiving 2nd line, 96 pts 3rd line and 38 pts 4th line. No pt ≥65 y received 4th line treatment. Responses and PFS are listed in the table. Conclusions: For pts with PTCL, similar to B-cell lymphomas, ORR and PFS decrease with each line of therapy. When evaluating the activity of therapies in relapsed PTCL, line of therapy is a consideration and this series provides a benchmark for comparison. Based on this dataset, it is possible that better responses will be seen as new agents are moved into earlier treatment paradigms. [Table: see text]

FCgammaRIIa Polymorphism Is Not Associated with Overall Response, Progression Free Survival and Overall Survival In Diffuse Large B-Cell Lymphoma Treated with Rituximab

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5078-5078
Author(s):  
Marcelo Bellesso ◽  
Sergio Paulo Bydlowski ◽  
Renata Oliveira Costa ◽  
Felipe Vieira Rodrigues Maciel ◽  
Debora Levy ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Lymphoma Cell ◽  
Free Survival ◽  
Overall Response ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 5078 Background: Low-affinity receptor for the Fcγ region of immunoglobulin G (IgG) (FcγR) is constitutively expressed on resting human neutrophils. These receptor, termed FcγRIIa display biallelic polymorphism which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. Rituximab is a chimeric monoclonal antibody directed against CD20, an antigen found in most B-cell malignancies. Multiple mechanisms have been proposed for the activity of Rituximab, including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and a direct proapoptotic effect. F(ab′)2 Rituximab homodimers were shown to be effective in inducing apoptosis of B-cell lymphoma cell lines in vitro. Recently, it have been established that ADCC is important as predominant mechanism of lymphoma cell clearance and that Fcγ receptors (FcγRs) are critical for the in vivo actions of Rituximab in non-Hodgkin lymphoma (NHL). A genomic polymorphism at amino acid 131 of FcγRIIA has been described whereby the presence of Histidine (H) rather than Arginine is associated with responses to the CD20-directed immunoglobulin G1 (IgG1) Rituximab among patients with indolent lymphoma. FcγRIIA genotype have been associated with a better clinical and molecular response in follicular lymphoma patients treated as first line therapy with Rituximab alone and in patients with diffuse large B-cell lymphoma (DLBCL) treated with the concomitant administration of Rituximab and CHOP (R-CHOP). Methods: Here we analyzed the role of specific polymorphism of activating FcγRIIA in 64 patients with DLBCL treated with R-CHOP concerning prediction complete response (CR), Progression Free Survival (PFS) and Overall Survival (OS) using a polymerase chain reaction-restriction fragment length polymorphism method. Results: The median age of the patients was 48.6 years. Out of the 64 patients (32%), were stage III-IV and 27 (42.5%) had more than 2 factors of the International Prognostic Index. Fity-six (89%) had CR and 7 (9.5%) had refractory disease (RD). Seven (11%) of the patients presented relapses. Deaths occurred in 6 (9.3%) patients with follow up of 19,5 months (range 21,3-50,1). The distribution of FcγRIIA polymorphism genotypes was: 15 (23,4%) HH, 30(46,9%) HR and 19(29,7%) RR, while considering only two groups (HH and R allele (HR and RR) was 15 (23,4%) and 49 (76,6%). There were no statistically significant differences in the genotypes groups according prognostic factors. In addition, there were not differences between response rate and FcγRIIA genotypes polymorphism: the CR in HH and HR/ RR were respectively 80% and 89%, p=0,377. It was not found differences regarding FcγRIIa. HH genotype presented a median PFS and OS. Thus, PFS HH genotype presented a median PFS 20,96 ± 10,49 months versus HR/RR median PFS 12,03 ± 7,71 months, p = 0,765, and OS 23,26 ± 10,42 months versus HR/ RR median OS 12,7 ± 7,42 months, p =0,98. Conclusions: Contrary to recent report we showed that FcγRIIA polymorphism is not associated to overall response, PFS and OS in patients with DLBCL treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.

Cell of Origin Determination in Diffuse Large B-Cell Lymphoma: Performance of Immunohistochemical (IHC) Algorithms and Ability to Predict Outcome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 950-950 ◽  
Author(s):  
Brian T. Hill ◽  
Angela M.B. Collie ◽  
Tomas Radivoyevitch ◽  
Eric D. Hsi ◽  
John Sweetenham
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
De Novo ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Free Survival

Abstract Abstract 950 INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) can be categorized by its cell of origin (CoO) as either being derived from a germinal center B-cell (GCB) or activated B-cell (ABC). Primary mediastinal DLBCL represents a third, distinct entity. This classification was initially defined by gene expression profiling (GEP), which remains the gold standard for such determination. Determination of CoO will likely become the basis for patient selection for clinical trials of targeted therapies. Several algorithms and methods have been developed that use immunohistochemistry (IHC) to differentiate GCB-DLBCL from non-GCB DLBCL. These include the Hans algorithm (utilizes staining for CD10, Bcl-6 and Mum1), the Choi algorithm (utilizes additional staining for GCET1 and FoxP1) as well as the Tally method (does not use Bcl-6 and utilizes LMO2 as a tie-breaker stain for otherwise equivocal cases). Recently, it has been recognized that IHC approaches to assign CoO may not be reproducible even at highly experienced laboratories. We sought to determine the performance of these IHC assays in our laboratory as a necessary step in developing trials based on CoO stratification. METHODS: We reviewed 108 adult (age ≥18) cases of de novo DLBCL, the majority of which were treated with chemoimmunotherapy (R-CHOP or R-CVP) at the Cleveland Clinic from 2000–2010. Diagnostic biopsies were available for all cases. IHC staining was performed on tissue microarrays (TMAs), and published algorithms (Hans, Choi and Tally) were applied to categorize cases as GCB or non-GCB. In addition, gene expression profiling was completed in a subset of these cases, for which frozen tissue was available. A linear predictor score for gene expression profiling (GEP) was used to assign cases in 31 of 33 cases with 2 technical failures at the array stage (overall success rate 84.8%). Clinical details including age, sex, International Prognostic Index (IPI) stage at diagnosis, treatment, progression free survival (PFS) and overall survival (OS) were captured for 69 of the 108 patients. Actuarial survival analysis was performed according to the Kaplan and Meier method, and the curves compared by the log-rank test. RESULTS: For the 69 patients with adequate clinical follow-up, the median age was 64 years old (range 18–88). There were 49% males and 51% females. The distribution of patients with stage I, II, III, and IV disease at the time of diagnosis was 20%, 14%, 20%, and 32% (14% had unknown stage). The 5-year overall survival of patients was 88%. Results of the Hans algorithm, Choi algorithm and Tally method were interpretable in 98 (90.7%), 95 (87.9%) and 88 (81.5%) of 108 cases, respectively. Inability to assign subtypes was due to suboptimal staining of the TMA (tissue loss or poor staining of an individual core). Using GEP to assign CoO, 42% of cases were classified as GCB, 42% as ABC and 14% were unclassifiable. The sensitivities of the Hans, Choi and Tally approaches to identify the CoO predicted by GEP were 0.83, 0.83, and 0.58 for correctly identifying GCB cases, respectively, and were 0.70, 0.70 and 0.80 for identifying non-GCB cases, respectively. The positive predictive values of the Hans, Choi and Tally approaches were 0.83, 0.83, and 1.0 for GCB and 0.78, 0.78, and 0.89 for non-GCB. As shown in the figure, 5-year overall survival was significantly superior for GCB relative to ABC cases using GEP (100% vs. 58.9%, P < 0.001) and for GCB vs. non-GCB cases for the algorithms of Hans (100% vs. 82.3%, P = 0.0197) and Choi (95.6% vs. 78.0%, P = 0.0482). The Tally method was not predictive of outcome, possibly due to insufficient power (5-year OS 94.4% for GCB vs. 80.7% for non-GCB, P = 0.1725). Similar findings were observed for progression-free survival. CONCLUSIONS: The Hans and Choi algorithms are reasonable methods for identifying PFS and OS differences based on CoO for de novo DLBCL treated with chemoimmunotherapy. The positive predictive value is universally high for all algorithms tested, but the sensitivity of IHC for identifying CoO was fair, particularly for the Tally method. IHC represents a valid biomarker to identify non-GCB cases. Clinical trials of DLBCL that stratify patients by IHC are feasible provided the performance characteristics of the algorithms are taken into consideration during study design. Disclosures: No relevant conflicts of interest to declare.

Is Interim/Mid-Treatment PET (interim PET, i-PET) Scan Predictive of Outcome in Diffuse Large B-Cell Lymphoma?.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2675-2675
Author(s):  
Dushyant Verma ◽  
Amol Takalkar ◽  
Runhua Shi ◽  
Glenn M. Mills ◽  
Srikanth Paladugu ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Free Survival ◽  
Interim Pet ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2675 Background: Initial treatment of diffuse large B-cell lymphoma (DLBCL) involves 6–8 cycles of chemo-immunotherapy and may be curative in 60–65% of patients. However, in the remaining patients, subsequent therapies appear inadequate for long lasting remission. A strategy to improve patient outcomes could involve early identification of patients who do not respond to treatment as expected and then employing different/aggressive treatment modalities in these patients. PET scan done during mid-treatment (interim PET, i-PET) may help identify these patients early. However, the value of i-PET in DLBCL is not established as there is controversy about its prognostic value and studies are ongoing to evaluate its benefit. Aims: To determine predictive value of i-PET on progression-free survival (PFS), overall survival (OS) in DLBCL patients. Methods: We performed retrospective analysis of DLBCL patients treated at LSU Health Shreveport, LA, between Jan 2002 – July 2012. All patients were treated with R-CHOP chemotherapy. PET-CT was performed at baseline at time of diagnosis, after 2 to 4 courses (i-PET) and at the end of therapy (final PET, f-PET). Results: Forty-four patients were evaluable for analysis. The median age was 55 years (range 21–84), 32 (73%) were males. Ann-arbor staging showed 5 patients each in stage I and II, 11 patients in stage III, 23 in stage IV, and the median IPI score was 3. Median time to i-PET was after 3 cycles of chemotherapy, and median days to i-PET after chemotherapy were 16. The median follow-up duration from start of chemotherapy was 23 months (range 4 – 89). The PET results were as follows: i-PET negative 30 (68%), i-PET positive 14 (32%) patients. Final PET results were: f-PET negative 33 (75%), f-PET positive 11 (25%) patients. The 3-year PFS was 96.3% and 35.7% for i-PET negative versus positive patients respectively (p<0.001), and the 3-year PFS for f-PET negative versus positive patients was 78.9%% versus 30.0% respectively (p<0.001). The 3-year OS was 79.4% and 62.6% for i-PET negative versus positive patients respectively (p=0.3306). The 3-year OS was 79.9% and 58.7% for f-PET negative versus positive patients respectively (p=0.021). Conclusion: Interim/mid-treatment PET (i-PET) scan is predictive of progression free survival but not overall survival for DLBCL patients. A final PET (f-PET) scan is predictive of progression free survival as well as overall survival for DLBCL patients. Larger prospective studies are needed to confirm these findings and could also look into the biology of i-PET positive patients by gene expressing profiling (GEP) and evaluate the role of novel agents in modifying the disease course. Disclosures: No relevant conflicts of interest to declare.

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