scholarly journals Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL

Blood ◽  
2019 ◽  
Vol 133 (9) ◽  
pp. 919-926 ◽  
Author(s):  
Magdalena Klanova ◽  
Laurie H. Sehn ◽  
Isabelle Bence-Bruckler ◽  
Federica Cavallo ◽  
Jie Jin ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Cns Relapse ◽  
Relapse Prediction ◽  
Expression Status ◽  
Dual Expression

Abstract Central nervous system (CNS) relapse carries a poor prognosis in diffuse large B-cell lymphoma (DLBCL). Integrating biomarkers into the CNS–International Prognostic Index (CNS-IPI) risk model may improve identification of patients at high risk for developing secondary CNS disease. CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study. Cell of origin (COO) was assessed using gene-expression profiling. BCL2 and MYC protein expression was analyzed by immunohistochemistry. The impact of CNS-IPI, COO, and BCL2/MYC dual-expression status on CNS relapse was assessed using a multivariate Cox regression model (data available in n = 1418, n = 933, and n = 688, respectively). High CNS-IPI score (hazard ratio [HR], 4.0; 95% confidence interval [CI], 1.3-12.3; P = .02) and activated B-cell‒like (ABC) (HR, 5.2; 95% CI, 2.1-12.9; P = .0004) or unclassified COO subtypes (HR, 4.2; 95% CI, 1.5-11.7; P = .006) were independently associated with CNS relapse. BCL2/MYC dual-expression status did not impact CNS relapse risk. Three risk subgroups were identified based on the presence of high CNS-IPI score and/or ABC/unclassified COO (CNS-IPI-C model): low risk (no risk factors, n = 450 [48.2%]), intermediate risk (1 factor, n = 408 [43.7%]), and high risk (both factors, n = 75 [8.0%]). Two-year CNS relapse rates were 0.5%, 4.4%, and 15.2% in the respective risk subgroups. Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk for developing CNS relapse. The study was registered at www.clinicaltrials.gov as #NCT01287741.

CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP

2016 ◽  
Vol 34 (26) ◽  
pp. 3150-3156 ◽  
Author(s):  
Norbert Schmitz ◽  
Samira Zeynalova ◽  
Maike Nickelsen ◽  
Roopesh Kansara ◽  
Diego Villa ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Risk Model ◽  
Risk Group ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Intermediate Risk ◽  
Data Set ◽  
Cns Relapse

Purpose To develop and validate a risk score for relapse in the CNS in patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods A total of 2,164 patients (18 to 80 years old) with aggressive B-cell lymphomas (80% DLBCL) treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy, who were enrolled in studies from the German High-Grade Non-Hodgkin Lymphoma Study Group and the MabThera International Trial, were analyzed for occurrence of relapse/progression in the CNS. The resulting risk model was validated in an independent data set of 1,597 patients with DLBCL identified in the British Columbia Cancer Agency Lymphoid Cancer database. Results The risk model consists of the International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI). In a three-risk group model, the low-risk group (46% of all patients analyzed), the intermediate-risk group (41%), and the high-risk group (12%) showed 2-year rates of CNS disease of 0.6% (CI, 0% to 1.2%), 3.4% (CI, 2.2% to 4.4%), and 10.2% (CI, 6.3% to 14.1%), respectively. Patients from the validation British Columbia Cancer Agency data set showed similar rates of CNS disease for low-risk (0.8%; CI, 0.0% to 1.6%), intermediate-risk (3.9%; CI, 2.3% to 5.5%), and high-risk (12.0%; CI, 7.9% to 16.1%) groups. Conclusion The CNS-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNS relapse/progression in patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Close to 90% of patients with DLBCL belong to the low- and intermediate-risk groups and have a CNS relapse risk < 5%; they may be spared any diagnostic and therapeutic intervention. In contrast, those in the high-risk group have a > 10% risk of CNS relapse and should be considered for CNS-directed investigations and prophylactic interventions.

scholarly journals Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1350-1358 ◽  
Author(s):  
Ash A. Alizadeh ◽  
Andrew J. Gentles ◽  
Alvaro J. Alencar ◽  
Chih Long Liu ◽  
Holbrook E. Kohrt ◽  
...  
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
Single Gene ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractSeveral gene-expression signatures predict survival in diffuse large B-cell lymphoma (DLBCL), but the lack of practical methods for genome-scale analysis has limited translation to clinical practice. We built and validated a simple model using one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI). LIM domain only 2 (LMO2) was validated as an independent predictor of survival and the “germinal center B cell–like” subtype. Expression of tumor necrosis factor receptor superfamily member 9 (TNFRSF9) from the DLBCL microenvironment was the best gene in bivariate combination with LMO2. Study of TNFRSF9 tissue expression in 95 patients with DLBCL showed expression limited to infiltrating T cells. A model integrating these 2 genes was independent of “cell-of-origin” classification, “stromal signatures,” IPI, and added to the predictive power of the IPI. A composite score integrating these genes with IPI performed well in 3 independent cohorts of 545 DLBCL patients, as well as in a simple assay of routine formalin-fixed specimens from a new validation cohort of 147 patients with DLBCL. We conclude that the measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with DLBCL.

BAL is a novel risk-related gene in diffuse large B-cell lymphomas that enhances cellular migration

Blood ◽  
2000 ◽  
Vol 96 (13) ◽  
pp. 4328-4334
Author(s):  
Ricardo C. T. Aguiar ◽  
Yoshihiro Yakushijin ◽  
Samir Kharbanda ◽  
Ravi Salgia ◽  
Jonathan A. Fletcher ◽  
...  
Keyword(s):  
Cell Migration ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cellular Migration ◽  
Cell Phenotype ◽  
Large B Cell

Clinical risk factor models such as the International Prognostic Index are used to identify diffuse large B-cell lymphoma (DLB-CL) patients with different risks of death from their diseases. To elucidate the molecular bases for these observed clinical differences in outcome, differential display was used to identify a novel gene, termed BAL (B-aggressivelymphoma), which is expressed at significantly higher levels in fatal high-risk DLB-CLs than in cured low-risk tumors. The major BAL complementary DNA encodes a previously uncharacterized 88-kd nuclear protein with a duplicated N-terminal domain homologous to the nonhistone portion of histone-macroH2A and a C-terminal alpha-helical region with 2 short coiled-coil domains. Of note, the BAL N-terminus and secondary structure resemble those of a recently identified human protein, KIAA1268. In addition, bothBAL and KIAA1268 map to chromosome 3q21, further suggesting that these genes belong to a newly identified family. BAL is expressed at increased levels in DLB-CL cell lines with an activated peripheral B cell, rather than a germinal center B cell, phenotype. This observation and the characteristic dissemination of high risk DLB-CLs prompted studies regarding the role of BAL in B-cell migration. In classical transwell assays, stable BAL-overexpressing B-cell lymphoma transfectants had significantly higher rates of migration than vector-only transfectants, indicating that the risk-related BAL gene promotes malignant B-cell migration.

CHOP-R + bortezomib as initial therapy for diffuse large B-cell lymphoma (DLBCL)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8031-8031 ◽  
Author(s):  
J. P. Leonard ◽  
R. R. Furman ◽  
Y. K. Cheung ◽  
J. M. Vose ◽  
P. W. Glynn ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
B Cell ◽  
International Prognostic Index ◽  
Elevated Serum ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Serum Lactate Dehydrogenase ◽  
Hematologic Toxicity ◽  
Combination Regimen

8031 Background: Bortezomib is a proteasome inhibitor with anti-tumor activity in B cell malignancies. These effects, which may relate to NF-kappaB associated pathways, could sensitize tumor cells to standard chemotherapy-based regimens and enhance efficacy. We report findings of a phase I/II trial of dose-escalated bortezomib + standard CHOP-rituximab in DLBCL patients (accrual of the MCL cohort of this study remains ongoing). Methods: Patients with previously untreated DLBCL (n=40) received CHOP-21 + rituximab (375 mg/m2 each cycle) plus bortezomib at 0.7 mg/m2 (Arm 0, n=4), 1.0 mg/m2 (Arm 1, n=8) or 1.3 mg/m2 (Arm 2, n=28 including phase I and all phase II) on days 1 and 4 of each cycle Results: Median age (n=40) was 58 years (range 21–86), thirty-five subjects (88%) had stage III/IV disease at study entry, and 29 (73%) had elevated serum lactate dehydrogenase (LDH). Patients generally had unfavorable baseline international prognostic index (IPI) scores of 2 in 16 subjects (40%) and 3–5 in 19 subjects (48%). Median follow-up is 21 months (range 9 - 35 months). Treatment was generally well tolerated. Peripheral neuropathy occurred in 22 subjects (55%), with 45% grade 1, 5% grade 2 and 5% grade 3. Grade 4 hematologic toxicity included thrombocytopenia (15%) and leukopenia (15%). Four subjects (3 over age 75 and all with high risk IPI) died prior to first response assessment. Intent to treat (ITT) overall response rate (n=40) is 90% with 68% CR/CRu. For the evaluable subset (n=36), ORR was 100% with CR/CRu 75%. Kaplan-Meier estimate (n=40) of 2-year progression-free survival is 72%. Of all 19 enrolled (ITT) patients in the high-intermediate or high-risk IPI groups, 14 (74%) were alive without progression at last assessment. Correlation of outcome with cell of origin type (activated B cell vs germinal center) is ongoing. Conclusions: Bortezomib can be administered with acceptable toxicity in conjunction with CHOP-R chemotherapy. Efficacy findings with this combination regimen in newly-diagnosed DLBCL are encouraging and warrant further study. No significant financial relationships to disclose.

Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

2007 ◽  
Vol 25 (17) ◽  
pp. 2426-2433 ◽  
Author(s):  
Silvia Montoto ◽  
Andrew John Davies ◽  
Janet Matthews ◽  
Maria Calaminici ◽  
Andrew J. Norton ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Advanced Stage ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Purpose To study the clinical significance of transformation to diffuse large B-cell lymphoma (DLBCL) in patients with follicular lymphoma (FL). Patients and Methods From 1972 to 1999, 325 patients were diagnosed with FL at St Bartholomew's Hospital (London, United Kingdom). With a median follow-up of 15 years, progression occurred in 186 patients and biopsy-proven transformation in 88 of the 325. The overall repeat biopsy rate was 70%. Results The risk of histologic transformation (HT) by 10 years was 28%, HT not yet having been observed after 16.2 years. The risk was higher in patients with advanced stage (P = .02), high-risk Follicular Lymphoma International Prognostic Index (FLIPI; P = .01), and International Prognostic Index (IPI; P = .04) scores at diagnosis. Expectant management (as opposed to treatment being initiated at diagnosis) also predicted for a higher risk of HT (P = .008). Older age (P = .005), low hemoglobin level (P = .03), high lactate dehydrogenase (P < .0001), and high-risk FLIPI (P = .01) or IPI (P = .003) score at the time of first recurrence were associated with the diagnosis of HT in a biopsy performed at that time. The median survival from transformation was 1.2 years. Patients with HT had a shorter overall survival (P < .0001) and a shorter survival from progression (P < .0001) than did those in whom it was not diagnosed. Conclusion Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.

scholarly journals Diffuse large B-cell lymphoma: An institutional analysis

2018 ◽  
Vol 07 (03) ◽  
pp. 200-202 ◽  
Author(s):  
Ajay Gogia ◽  
Chandan K. Das ◽  
Lalit Kumar ◽  
Atul Sharma ◽  
Akash Tiwari ◽  
...  
Keyword(s):  
Retrospective Study ◽  
High Risk ◽  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma. We conducted a retrospective study to analyze the clinicopathological characteristics, cell of origin, response to therapy, and the outcome of patients with DLBCL. Materials and Methods: This was a retrospective study which included all patients with DLBCL registered at our center, between May 1, 2013, and July 31, 2015. The data regarding demography, clinical presentation, histopathology, stage, prognostic index, treatment, and treatment-related outcome were collected from prospectively maintained clinical case records of the patients. Results: In the study, we included 267 patients. The median age is 49 (20–81) years with male: female ratio of 2:1. B symptoms were seen in 124 (45%) of patients. Early Stages (I and II) were seen in 130 (52%) patients, while advanced Stages (III and 1V) were seen in 119 (48%) patients. Bulky disease (>7.5 cm) was seen in 30% of cases, and bone marrow was involved in 12%. Extranodal involvement is present in 35% of cases. Cell of origin data was available in 160 (60%) of cases, of which 88 (55%) were germinal center and 72 (45%) were activated B cell in origin. The distribution according to the international prognostic index (IPI) was as follows: low risk 40%, intermediate risk 45%, and high risk in 15%. Rituximab was used in 45% of cases. The overall response rate was 84% with a complete response (CR) rate of 70.5%. The CR rates were better with RCHOP compared with CHOP (77% vs. 61.5%, P = 0.001) and good-risk IPI (83.3% vs. 65.2%, P < 0.001) compared with intermediate- and high-risk IPI. Median follow-up period was 24 months, and 2-year event-free survival (EFS) was 70%. The presence of B symptoms, high IPI, failure to attain CR, poor PS, and nonrituximab-based chemotherapy were significantly associated with lower EFS. Conclusions: This is the first study from India, which investigated the impact of chemotherapy with or without rituximab in context of cell of origin. Adding rituximab to CHOP showed better response rate and EFS irrespective of cell of origin.

Impact of Central Nervous System International Prognostic Index on the treatment of Diffuse Large B Cell Lymphoma

2020 ◽  
Author(s):  
Mohammad Ma'koseh ◽  
Mohammad Ma’koseh ◽  
Faris Tamimi ◽  
Alaa Abufara ◽  
Lana Abusalem ◽  
...  
Keyword(s):  
High Risk ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Intrathecal Chemotherapy ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Selection Of

Abstract Background The central nervous system international prognostic index [CNS-IPI]is being usedwidely for the identification of patients with diffuse large B cell lymphoma [DLBCL]with highrisk of CNS relapse. The aim of our study is to confirm the value of the CNS-IPI in predicting CNS relapse in our young study population and to evaluate the impact on selection of patients for CNS prophylaxis. Methods We retrospectively reviewed patients with pathological diagnosis of DLBCL who were treated with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone] regimen from January 2004 till December 2016 with no evidence of CNS involvement on diagnosis. Different demographic, disease characteristics and treatment given including the use of intrathecal chemotherapy prophylaxis were collected. Correlation between CNS-IPI and CNS relapse was examined through chi square test. Median time to CNS relapse and median overall survival [OS] after CNS relapse were estimated using the Kaplan-Meier plots. Results 354 patients were included. Median age was 46 years. 52 [15%] patients were given intrathecal chemotherapy [ITC] prophylaxis, of whom CNS-IPI was high in 7[13%]. Overall, 5% of the patients [n = 17] developed CNS relapse.The median survival after CNS relapse was 7 months. The rate of CNS relapse in patients with low, intermediate and high risk CNS-IPI was 0.6%, 3% and 22% respectively [p = < 0.001].On multivariate analysis, involvement of bone marrow [p = 0.039]and renal or adrenal glands[p = 0.023]significantly correlated with CNS relapse. Considering theCNS-IPI and high risk anatomical sites [breast, uterus, testis and epidural space], 26% of our patients with DLBCLwould have needed prophylaxis. Conclusion Although CNS-IPI helps in better selection of DLBCL patients for CNS prophylaxis, it will significantly and possibly unnecessarily increase the number of patients exposed to prophylaxis. More investigational biomarkers and methods are necessary to better refining high risk patients.

Safety of same day HD-MTX with induction therapy for DLBCL with concurrent CNS disease or as prophylaxis for high risk of CNS relapse.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19545-e19545
Author(s):  
Brett Barlow ◽  
Haris Hatic ◽  
Charles Douglas Bodine ◽  
Amitkumar Mehta ◽  
Gaurav Goyal ◽  
...  
Keyword(s):  
High Risk ◽  
Induction Chemotherapy ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Treatment Delays ◽  
Cns Disease ◽  
Cns Relapse ◽  
End Of Treatment

e19545 Background: High-dose methotrexate (HD-MTX) at a dose between 2.5 to 5 gm/m2 is commonly administered in conjunction with standard induction chemotherapy to patients with Diffuse Large B Cell Lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse, as defined by the Lymphoma International Prognostic Index (CNS-IPI). Optimal timing of HD-MTX in relation to induction chemotherapy is unknown. A recent study suggested that HD-MTX intercalated with R-CHOP cycles was associated with increased toxicity and treatment delays without improvement in survival or CNS relapse compared with end of treatment MTX (Wilson et al 2020). This retrospective study evaluates the toxicities and treatment delays associated with HD-MTX administered on day 1 of cycles of chemo-immunotherapy. Methods: This single center retrospective cohort study included 45 patients (pts) with DLBCL with concurrent CNS disease or at high risk of CNS relapse who received HD MTX on day 1 of chemo-immunotherapy at our center. Data was abstracted from chart review and included variables describing clinical and treatment characteristics, time to MTX clearance, toxicities experienced and treatment delays. Results: 31 pts received HD-MTX on the day of R-CHOP chemotherapy, 6 pts received HD-MTX on the day of R-EPOCH (Rituximab, Etoposide, Doxorubicin, Vincristine, Cyclophosphamide, and Prednisone), and 8 pts received HD-MTX with R-MiniCHOP (dose reduced R-CHOP). Same day HD MTX with chemo-immunotherapy was associated with acute kidney injury (AKI; 17-25%), treatment delays >7 days (13-17%), and grade 2 mucositis (11-50%). The burden of toxicities was numerically higher in patients treated with R-EPOCH vs. R-CHOP (Table). Clinical outcomes are summarized in table below. Conclusions: In our heterogeneous population of pts, we describe that the incidence of toxicities and treatment delays experienced with same day HD-MTX are higher with R-EPOCH than with R-CHOP. Comparative studies with intercalated or end of treatment MTX will determine if the incidence of treatment delays, toxicities and de-escalations are higher with same day HD-MTX administration. [Table: see text]

The t(14;18) Is Associated with Germinal Center Phenotype Subset of the Diffuse Large B-Cell Lymphoma Patients in Egypt.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4124-4124
Author(s):  
Hasan A. Abdel-Ghaffar ◽  
Sherin M. Abdel-Aziz ◽  
Doaa A. Shahin ◽  
Ezzat S. Sobki Board ◽  
Nadia I. Attwan ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Biological Variables ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is a generic term for clinically and biologically heterogeneous group of tumors. Identification of high risk patients at presentation will allow effective trials of treatment. Therefore, t(14;18) detection using interphase Florescence in Situ Hybridization (FISH) and Biomed multiplex polymerase chain reaction (PCR) was done on formalin fixed paraffin embedded lymph node archives from pathology department, National Cancer Institute, Cairo, Egypt. Diagnosis were confirmed by pathological review using the diagnostic criteria defined in the revised European-American Classification of Lymphoid Neoplasm / WHO classification. The study was carried out on 26 patients with lymph screen CD 19 +/ CD 5 - / CD 10 ± correlating t(14;18) with the immunophenotypic biological variables, Immunohistochemistry, and the standardized international prognostic index (IPI) with a median follow up for 5 years. Comparison of FISH and PCR techniques showed identical specificity with advantageous sensitivity of FISH over the PCR. Nine patients out of eleven with t(14;18) were associated with Germinal Center (GC) phenotype (CD10+ /Bcl-6 +). However, Only two out of fifteen with non GC phenotype(CD10- /Bcl-6 -) were associated t(14;18). The mean 5 years survival time of patients with t(14;18) was significantly lower (31.18 ± 3.06 month) compared to those without translocation (54.32 ± 2.54 month) (P=0.001). Interestingly, patients with t(14;18) showed Bcl-2 positive (100%) compared to 46.6% in patient without t(14;18) (P=0.004). There is a significant correlation between t(14;18) and the clinicopathological risk criteria of IPI(P=0.01). In our study we demonstrated a detection of t(14;18) by FISH was found to be superior to PCR. The high risk group of GC phenotype together with Bcl-2 expression were associated with t(14;18) and could be used to tailor treatment.

Combination Antibody Therapy With Epratuzumab and Rituximab in Relapsed or Refractory Non-Hodgkin's Lymphoma

2005 ◽  
Vol 23 (22) ◽  
pp. 5044-5051 ◽  
Author(s):  
John P. Leonard ◽  
Morton Coleman ◽  
Jamie Ketas ◽  
Michelle Ashe ◽  
Jennifer M. Fiore ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Antibody Therapy ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose To explore the safety and therapeutic activity of combination anti–B-cell monoclonal antibody therapy in non-Hodgkin's lymphoma (NHL). Patients and Methods Twenty-three patients with recurrent B-cell lymphoma received anti-CD22 epratuzumab 360 mg/m2 and anti-CD20 rituximab 375 mg/m2 monoclonal antibodies weekly for four doses each. Sixteen patients had indolent histologies (15 with follicular lymphoma) and seven had aggressive NHL (all diffuse large B-cell lymphoma [DLBCL]). Indolent patients had received a median of one (range, one to six) prior treatment, with 31% refractory to their last therapy and 81% with high-risk Follicular Lymphoma International Prognostic Index scores. Patients with DLBCL had a median of three (range, one to eight) prior regimens (14% resistant to last treatment) and 71% had high intermediate–risk or high-risk International Prognostic Index scores. All patients were rituximab naïve. Results Treatment was well tolerated, with toxicities principally infusion-related and predominantly grade 1 or 2. Ten (67%) patients with follicular NHL achieved an objective response (OR), including nine of 15 (60%) with complete responses (CRs and unconfirmed CRs). Four of six assessable patients (67%) with DLBCL achieved an OR, including three (50%) CRs. Median time to progression for all indolent NHL patients was 17.8 months. Conclusion The full-dose combination of epratuzumab with rituximab was well tolerated and had significant clinical activity in NHL, suggesting that this combination should be tested in comparison with single-agent treatment.

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