Multicenter Phase II Trial of Immunotherapy With the Humanized Anti-CD22 Antibody, Epratuzumab, in Combination With Rituximab, in Refractory or Recurrent Non-Hodgkin's Lymphoma

2006 ◽  
Vol 24 (24) ◽  
pp. 3880-3886 ◽  
Author(s):  
Sandra J. Strauss ◽  
Frank Morschhauser ◽  
Juergen Rech ◽  
Roland Repp ◽  
Philippe Solal-Celigny ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Objective Response ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose A multicenter, single-arm study examining efficacy and toxicity of epratuzumab combined with rituximab was conducted in patients with recurrent or refractory non-Hodgkin's lymphoma. Patients and Methods Sixty-five patients were enrolled; 34 patients with follicular lymphoma (FL), 15 patients with diffuse large B-cell lymphoma (DLBCL), and 16 patients with other lymphomas. The patients had received a median of two prior therapies (range, 1 to 4); 23% had received rituximab. Epratuzumab was given at 360 mg/m2 intravenously over 60 minutes followed by infusion of 375 mg/m2 rituximab, weekly for 4 consecutive weeks. Results Combination therapy was well tolerated without greater toxicity than rituximab alone. The objective response (OR) rate was 47% (30 of 64) in assessable patients (46%; 30 of 65 in all patients), being highest in FL (64%; 21 of 33) and DLBCL (47%; seven of 15), and with 24% (eight of 33) and 33% (five of 15) achieving complete response (CR) or complete response unconfirmed (CRu) in these two groups, respectively. Two of six patients with marginal zone lymphoma responded to treatment (one CR). There was a trend for the response rates to be higher in patients with low prognostic index scores (statistically significant with respect to the Follicular Lymphoma International Prognostic Index score in FL patients), with 12 FL patients and three DLBCL patients in groups 0 to 1 having OR (CR/CRu) rates of 83% (33%) and 100% (100%), respectively. The median duration of response was 16 months for FL, with five patients currently progression free for 18 months to 30 months, and 6 months for DLBCL, with two patients currently progression free for 12 months and 18 months. Conclusion Epratuzumab combined with rituximab was well tolerated, demonstrating promising antilymphoma activity that warrants additional study.

scholarly journals The C5R protocol: a regimen of high-dose chemotherapy and radiotherapy in primary cerebral non-Hodgkin's lymphoma of patients with no known cause of immunosuppression [see comments]

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 2922-2929
Author(s):  
JY Blay ◽  
D Bouhour ◽  
C Carrie ◽  
E Bouffet ◽  
M Brunat-Mentigny ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Cranial Radiotherapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

In most reported series, less than 20% of patients with primary cerebral non-Hodgkin's lymphoma (PCL) and no known cause of immunodepression are alive and disease-free 5 years after the initial diagnosis. Whether chemotherapy improves the outcome of these patients remains unclear. We report a pilot study of a protocol (C5R) with 5 courses of chemotherapy followed by cranial radiotherapy in 25 adult patients with PCL and no known cause of immunodepression. The median age was 51 years (range, 16 to 70 years) and the median performance status was 2 (range, 1 to 4) in this series. Fourteen patients (56%) achieved a complete response and 4 (16%) achieved a partial response 1 month after the completion of the treatment. Four patients died in the first month of treatment because of progression (n = 1) or toxicity (n = 3). In 3 patients, the treatment could not be performed because of patient refusal (n = 1) or severe infections (n = 2). Myelosuppression was the most frequent side effect; febrile neutropenia occurred in 96%, 89%, 69%, and 74% of the patients after the second, third, fourth, and fifth courses of chemotherapy, respectively. Grade 4 thrombocytopenia occurred in 20% of the patients. With a median follow-up of 24 months, the projected survival of the group at 2 and 5 years is 70% and 56%, respectively. The 4 early deaths occurred in the subgroup of 6 patients greater than 60 years of age with an international prognostic index (IPI) greater than 3. In the 19 remaining patients (76% of this series) less than 61 years of age or with an IPI less than 4, the projected overall survival at 2 and 5 years is 88% and 70%, respectively. The C5R protocol is a highly efficient regimen in nonimmunosuppressed patients with PCL less than 61 years of age or with an IPI less than 4.

scholarly journals The C5R protocol: a regimen of high-dose chemotherapy and radiotherapy in primary cerebral non-Hodgkin's lymphoma of patients with no known cause of immunosuppression [see comments]

Blood ◽  
1995 ◽  
Vol 86 (8) ◽  
pp. 2922-2929 ◽  
Author(s):  
JY Blay ◽  
D Bouhour ◽  
C Carrie ◽  
E Bouffet ◽  
M Brunat-Mentigny ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Cranial Radiotherapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract In most reported series, less than 20% of patients with primary cerebral non-Hodgkin's lymphoma (PCL) and no known cause of immunodepression are alive and disease-free 5 years after the initial diagnosis. Whether chemotherapy improves the outcome of these patients remains unclear. We report a pilot study of a protocol (C5R) with 5 courses of chemotherapy followed by cranial radiotherapy in 25 adult patients with PCL and no known cause of immunodepression. The median age was 51 years (range, 16 to 70 years) and the median performance status was 2 (range, 1 to 4) in this series. Fourteen patients (56%) achieved a complete response and 4 (16%) achieved a partial response 1 month after the completion of the treatment. Four patients died in the first month of treatment because of progression (n = 1) or toxicity (n = 3). In 3 patients, the treatment could not be performed because of patient refusal (n = 1) or severe infections (n = 2). Myelosuppression was the most frequent side effect; febrile neutropenia occurred in 96%, 89%, 69%, and 74% of the patients after the second, third, fourth, and fifth courses of chemotherapy, respectively. Grade 4 thrombocytopenia occurred in 20% of the patients. With a median follow-up of 24 months, the projected survival of the group at 2 and 5 years is 70% and 56%, respectively. The 4 early deaths occurred in the subgroup of 6 patients greater than 60 years of age with an international prognostic index (IPI) greater than 3. In the 19 remaining patients (76% of this series) less than 61 years of age or with an IPI less than 4, the projected overall survival at 2 and 5 years is 88% and 70%, respectively. The C5R protocol is a highly efficient regimen in nonimmunosuppressed patients with PCL less than 61 years of age or with an IPI less than 4.

scholarly journals International Prognostic Index for aggressive non-Hodgkin's lymphoma is valid for all malignancy grades

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1460-1463 ◽  
Author(s):  
J Hermans ◽  
AD Krol ◽  
K van Groningen ◽  
PM Kluin ◽  
JC Kluin-Nelemans ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Hodgkin’S Lymphoma ◽  
Performance Status ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Population Based ◽  
Hodgkin's Lymphoma ◽  
Intermediate Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

An International Prognostic Index (IPI) for patients with aggressive non-Hodgkin's lymphoma (NHL) has recently been published. The IPI is based on pretreatment clinical characteristics and developed on clinical trial patients, classified as intermediate grade according to the Working Formulation (WF). We applied this IPI in a population-based registry of NHL patients. This registry does not have the restrictions that usually hold for patients in clinical trials, eg, with respect to age and performance status. Moreover, it covers all the three WF classes (low, intermediate, and high). The IPI turned out to be of prognostic value for response rate and survival in our unselected cohort of 744 patients, as well. In each of the three WF classes separately, the four IPI classes showed going from low to high substantially decreasing response rates and survival percentages. For our cohort of WF intermediate grade patients 5-year survival levels were lower in all four IPI classes (59%, 34%, 14%, and 10%, respectively), probably reflecting the selection of clinical trial patients in the original study (73%, 51%, 43%, and 26%).

Elderly patients with aggressive non-Hodgkin's lymphoma: disease presentation, response to treatment, and survival--a Groupe d'Etude des Lymphomes de l'Adulte study on 453 patients older than 69 years.

1997 ◽  
Vol 15 (8) ◽  
pp. 2945-2953 ◽  
Author(s):  
Y Bastion ◽  
J Y Blay ◽  
M Divine ◽  
P Brice ◽  
D Bordessoule ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Aggressive Lymphoma ◽  
Prognostic Parameters ◽  
Aggressive Disease ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE To clarify disease characteristics and optimal treatment for elderly patients with non-Hodgkin's lymphoma (NHL), we performed a randomized trial in 453 patients older than 69 years with aggressive lymphoma. PATIENTS AND METHODS Two hundred twenty patients received cyclophosphamide 750 mg/m2, teniposide (VM-26) 75 mg/m2, and prednisone 40 mg/m2/d for 5 days (CVP) and 233 patients received CVP plus pirarubicin (THP-doxorubicin) 50 mg/m2 (CTVP), each for six courses every 3 weeks. RESULTS The median age was 75 years. Most patients had clinically aggressive disease; 30% had one and 53% two or three adverse prognostic parameters as defined by the International Prognostic Index. More patients on the CTVP arm had an elevated lactic dehydrogenase (LDH) level, but the two groups were otherwise well balanced. CTVP treatment was more frequently associated with leukopenia, thrombocytopenia, and infectious complications. Death during chemotherapy occurred in 16% and 21% of patients on the CVP and CTVP arms, respectively (not significant). Forty percent of patients achieved a complete response (CR): 47% on CTVP and 32% on CVP (chi2 = 20.98, P = .0001). The median time to treatment failure (TTF) was 7 months for CTVP versus 5 months for CVP (log-rank test, P < .05). The median survival time was 13 months in both groups; however, the 5-year survival rate was 26% with CTVP versus 19% with CVP (chi2 = 4.68, P < .05). Lymphoma progression was the primary cause of death. CONCLUSION Elderly patients with aggressive lymphoma have an aggressive disease with adverse prognostic parameters at the time of diagnosis. Slightly longer survival was observed for patients treated with an anthracycline-containing regimen.

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.

Development and Measurement of Guideline-Based Indicators for Patients With Non-Hodgkin's Lymphoma

2011 ◽  
Vol 29 (11) ◽  
pp. 1436-1444 ◽  
Author(s):  
Lianne Wennekes ◽  
Petronella B. Ottevanger ◽  
John M. Raemaekers ◽  
Harry C. Schouten ◽  
Marjorie W.E. de Kok ◽  
...  
Keyword(s):  
The Netherlands ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Aggressive Lymphoma ◽  
Diagnostic Process ◽  
Non Hodgkin’S Lymphoma ◽  
Improvement Potential ◽  
Non Hodgkin's Lymphoma

Purpose Patients with cancer are not always treated according to available guidelines. Factors such as age and comorbidities are frequently used as arguments for nonadherence. The aim of this study was to measure guideline adherence with guideline-based indicators for patients with non-Hodgkin's lymphoma (NHL) and to examine the need for improvement, considering relevant arguments. Methods A RAND-modified Delphi procedure was used to systematically develop NHL indicators. We evaluated their improvement potential (defined as < 90% score) in a random sample of patients with NHL (N = 431) diagnosed in 2006-2007 in 22 hospitals in the Netherlands with data from medical records. Multilevel logistic regression analyses were used to estimate the relationship between indicator scores and factors: comorbidity index (combined with age), stage, patient's objections, and lymphoma type. Scores were adjusted for significant factors. Results Of the 20 indicators developed, 16 had improvement potential. Scores were lowest for assessment of International Prognostic Index, 21%; imaging of neck, thorax, and abdomen and bone marrow examination during the diagnostic process, 23%, and after chemotherapy, 37%; adequate pathology reporting, 11%; and multidisciplinary discussion of patients, 21%. Scores for eight indicators were better for patients with a low Charlson index, stage III or IV disease, no objections to care, and aggressive lymphoma. After adjustments, adherence to all but one indicator (administration of the combination of rituximab and cyclophosphamide-doxorubicin-vincristine-prednisone) remained < 90%. Conclusion In the Netherlands, almost all indicators for NHL needed improvement. This should be evaluated in other countries as well. International efforts should be undertaken to improve the quality of care of this often curable malignancy.

Central Nervous System (CNS) Relapse in Agressive Non-Hodgkin’s Lymphoma; Does CNS Prophylaxis Work?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 520-520 ◽  
Author(s):  
Steven H. Bernstein ◽  
Joseph Unger ◽  
Micheal LeBlanc ◽  
Richard I. Fisher
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hodgkin’S Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Hodgkin's Lymphoma ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Central Nervous System (CNS) relapse of aggressive non-Hodgkin’s lymphoma is a devastating clinic event. Significant controversy exists however, as to whether CNS prophylaxis affects the risk of CNS relapse and if so, which patients should be offered CNS prophylaxis. To address these questions we analyzed the twenty year follow up data of SWOG 8516, a prospective randomized trial comparing CHOP (n=225 patients), MACOP-B (n= 218), ProMACE-cytaBOM (n=233), and m-BACOD (n=233) for patients with newly diagnosed intermediate or high grade non-Hodgkin’s lymphoma. Patients that received ProMACE-cytaBOM who were bone marrow (BM) positive at baseline and BM negative after 4 cycles of treatment, received prophylactic cranial irradiation (XRT). Patients that received MACOP-B who were BM positive at baseline received intrathecal methotrexate and Ara-C (IT chemo) twice weekly for six doses. In contrast, no patient that received CHOP or m-BACOD received any CNS prophylaxis. Patient clinical characteristics were well balanced between these four arms. Results: Of the 515 patients who relapsed with documented lymphoma, 348 (68%) relapsed only in nodal areas; 167 patients (32%) had extranodal relapse, the most common site of which was the CNS (n=34, 3.8%). Among the 34 patients with CNS relapse, 31 (91%) presented with isolated CNS relapse, 2 (6%) presented with CNS and nodal relapse and 1 (3%) presented with CNS, nodal and other extranodal relapse. 97% of all CNS relapses occurred by year 2, compared to only 73% of non-CNS relapses (p= .002). Survival after CNS relapse was significantly worse compared to that of patients with non-CNS relapse (2 year estimate 9% vs. 30%, respectively; p= .002). Using logistic regression analysis, significant differences in the incidence of CNS relapse were evident in patients with > 1 extranodal sites (5.7% vs. 2.7%, p=.03) and in patients with higher International Prognostic Index (IPI) scores (6.3% in high IPI, 4.8% in high intermediate, 3.4% in low-intermediate and 1.6% in low IPI, p=.02). There was no evidence that patients receiving any type of CNS prophylaxis (i.e., either cranial XRT or IT chemo) had different rates of CNS relapse compared to patients who did not receive any CNS prophylaxis (5.2% vs. 3.6%, p=.40). In separate analyses, there was no evidence that patients receiving cranial XRT had different rates of CNS relapse than other patients (p=.65) and no evidence that patients receiving IT chemo had different rates of CNS relapse than other patients (p=.48). Finally, if the analysis is restricted to the 238 patients that were BM positive at diagnosis, 96 patients had CNS prophylaxis and 142 did not. The rate of CNS relapse in those patients that received CNS prophylaxis was no different than that seen in the patients that did not receive CNS prophylaxis (5.2% vs. 4.2%, p=.72). Conclusion: CNS relapse almost always occurs within 2 years of initial treatment, is usually isolated, and portends a poor prognosis. Patients with > 1 extranodal sites or those having a high IPI score have a higher incidence of CNS relapse. There is no evidence to suggest however, that CNS prophylaxis with either cranial radiation or intrathecal MTX/Ara-C decreases the risk of CNS relapse.

R-CHOP Every Two Weeks with Pegylated Filgastrim Support for the Treatment of CD20+ Aggressive Non Hodgkin's Lymphoma: Feasibility of Delivery On Time.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4773-4773
Author(s):  
Shatha Y. Farhan ◽  
Tim Kasunic ◽  
George Divine ◽  
Philip Kuriakose ◽  
Nalini Janakiraman
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Treatment Delay ◽  
Hodgkin's Lymphoma ◽  
Hematologic Toxicity ◽  
Bulky Disease ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Abstract 4773 Introduction Several studies have shown that modifying CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, prednisone 100 mg) by adding rituximab (R) and/or shortening the time between cycles to 14 days improves survival in patients with aggressive non hodgkin's lymphoma (NHL). However, in some of the 14-day trials few patients withdrew from studies because of treatment delay more than 2 weeks. We implemented a two-stage phase II trial to assess the feasibility of delivering R-CHOP on time every two weeks with pegylated filgastrim (Neulasta) support for the treatment of CD20+ aggressive NHL. Patients and Methods Previously untreated patients with intermediate or high grade CD20+ NHL were assigned to receive R-CHOP every 2 weeks with pegylated filgastrim support. Lymphoblastic and mantle cell lymphoma were excluded. After 4 cycles, the patients who achieved complete response (CR) received 2 more cycles. Those who achieved a partial response (PR) were re-evaluated after receiving six cycles. If they were found in CR they got two more cycles (8 total). However, if they were found to be in PR they received radiotherapy or other therapy per treating physician. This interim report of this study reflects 16 patients enrolled so far between 8/4/05 till 8/8/09. Results Fourteen patients received two or more cycles and are considered evaluable. Their mean age was 60 years (range: 47-77). Thirteen patients had Diffuse Large B cell Lymphoma (DLBL) and one patient had DLBL transformed from follicular lymphoma. Ten patients (71.4%) had an International Prognostic Index (IPI) low to low-intermediate and four (28.6%) had high intermediate to high IPI, two had a bulky disease and six had stage IV disease, three had stage III, the rest had stage I and II. Treatment delay was defined as more than two week delay in delivering the scheduled chemotherapy in two or more cycles due to absolute neutrophil count <500/microL or Platelets <75,000/microL. Nine patients received 6 cycles, two received 8, another two patients received 5 and one received 7 cycles (87 cycles total). Therapy was delivered on time without any delay in 8 patients (57% of patients). Only one patient (7.1%) met the defined criteria and had treatment delay >2 weeks for 2 cycles secondary to neutropenic fever (2.73% of 73 cycles, since the first cycle in each patient was not susceptible to delay). The study met the criteria (<=2 delays among the first 10 patient) for progression to the second stage. Five patients (6.84% of 73 cycles) had >1 week delay for non hematologic reasons (stroke, gastritis, ovarian cancer, perforated colon and drug allergy). Eleven patients had grade 3-4 neutropenia, five had grade 3anemia and one had grade 3thrombocytopenia. One patient had grade 2neuropathy. Median follow up time was 21.1 months. Overall response rate (CR+ PR) was 14/14 (100%), however one patient relapsed after 7 months and underwent stem cell transplantation. Conclusions It appears feasible and safe to deliver RCHOP every two weeks with pegylated filgastrim support in patients with CD20+ aggressive NHL. However in this group of 14 patients, there were some delays due to non hematologic toxicities and the delay due to hematologic toxicity was encountered in only one patient. Disclosures: No relevant conflicts of interest to declare.

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