Response to Tositumomab and Iodine 131I-Tositumomab (BEXXAR) Based on International Prognostic Index (IPI) Score.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4630-4630
Author(s):  
Sridhar E. Pal ◽  
Eric S. Winer ◽  
Kevin Chin ◽  
Alisa Dungy ◽  
Beth Higgins ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Response Duration ◽  
Overall Response ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Access Program

Abstract Purpose: The therapeutic efficacy of Bexaar (tositumomab and131I tositumomab) in the treatment of follicular lymphoma patients who have relapsed or had refractory disease after rituximab has been demonstrated. A retrospective review has reported durable complete responses in patients who were both rituximab refractory and naive.1 Results of an expanded access program reported a 59% overall response rate with a median duration of 15 months in patients with relapsed or refractory NHL.2 We report results on 33 patients treated in the expanded access program and have attempted to identify patient characteristics predictive of response or outcome. Methods: From April 1999 to November 2001, 33 patients with refractory NHL were enrolled in an IRB-approved expanded access trial at Tufts New England Medical Center. Patients were dosed with 450 mg of tositumomab and a total body exposure of 75cGy with 131I-tositumomab. Results: Of 33 treated patients, 24 had follicular lymphoma, 6 had transformed to diffuse large cell lymphoma, and 3 had small lymphocytic lymphoma. Median prior therapies was 2 (range 1–6), with 18 rituximab refractory and 15 rituximab naïve. Of 33 evaluable patients, the overall response rate was 67%, with 59% (13/22) of responders achieving CR. Median progression free survival (PFS) of the responders was 19 months, compared to a median PFS of 4 months with their last therapy. Median overall survival was 44 months in the 22 responders compared to 23 months in non-responders (p=.002). Among all patients, 28 of 33 eventually developed progressive disease, and 17 deaths had occurred during this study period. Median time to ANC nadir was 41 days and PLT nadir occurred at a median of 34 days. Two patients developed AML/MDS, and no patient required long term treatment for thyroid dysfunction. When prognostic factors were considered, 15 patients had an International Prognostic Index (IPI) score of 4–5. The median survival in this group was 24 months, while patients with Intermediate risk IPI scores of 2–3 (18 pts) had not yet reached median survival at 42+ months. Duration of response was 12 months in the high-risk IPI group compared to 42 months in the intermediate-risk group (p=.0017). Prior rituximab was also an independent predictor of outcome, with a median response duration of 12 months in rituximab exposed vs 38 months in rituximab naïve patients (p=.03), although there was not a statistically significant difference in response rates between the two groups. Because or number of transformed patients was small, it was impossible to correlate response based on histology. Conclusions: We report an overall response rate of 67% with a response duration of 19 months in responders. Median overall survival for responders was in excess of 44 months. Response duration was higher for patients with low -intermediate IPI scores and in rituximab naïve patients. A response duration of 12 months in the high IPI group in this retrospective analysis suggests that Bexaar therapy may be associated with an improved outcome compared to other therapies. Further prospective studies stratifying patients based on IPI score are underway.

scholarly journals Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3698-3704 ◽  
Author(s):  
Myron S. Czuczman ◽  
Luis Fayad ◽  
Vincent Delwail ◽  
Guillaume Cartron ◽  
Eric Jacobsen ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Overall Response Rate ◽  
Response Rate ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Free Survival ◽  
Overall Response ◽  
Median Progression Free Survival ◽  
Grade 3

Abstract New treatments are required for rituximab-refractory follicular lymphoma (FL). In the present study, patients with rituximab-refractory FL received 8 weekly infusions of ofatumumab (CD20 mAb; dose 1, 300 mg and doses 2-8, 500 or 1000 mg; N = 116). The median age of these patients was 61 years, 47% had high-risk Follicular Lymphoma International Prognostic Index scores, 65% were chemotherapy-refractory, and the median number of prior therapies was 4. The overall response rate was 13% and 10% for the 500-mg and 1000-mg arms, respectively. Among 27 patients refractory to rituximab monotherapy, the overall response rate was 22%. The median progression-free survival was 5.8 months. Forty-six percent of patients demonstrated tumor reduction 3 months after therapy initiation, and the median progression-free survival for these patients was 9.1 months. The most common adverse events included infections, rash, urticaria, fatigue, and pruritus. Three patients experienced grade 3 infusion-related reactions, none of which were considered serious events. Grade 3-4 neutropenia, leukopenia, anemia, and thrombocytopenia occurred in a subset of patients. Ofatumumab was well tolerated and modestly active in this heavily pretreated, rituximab-refractory population and is therefore now being studied in less refractory FL and in combination with other agents in various B-cell neoplasms. The present study was registered at www.clinicaltrials.gov as NCT00394836.

Modified Magrath IVAC Regimen as Second-Line Therapy for Relapsed and Refractory Aggressive Non-Hodgkin Lymphoma in Developing Countries: The Experience of a Single Center in Brazil.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4588-4588
Author(s):  
Luis F. Pracchia ◽  
Juliana Pereira ◽  
Marcelo Belesso ◽  
Beatriz Beitler ◽  
Dalton A. Chamone
Keyword(s):  
Hodgkin Lymphoma ◽  
Median Overall Survival ◽  
Overall Response Rate ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Grade 3 ◽  
Relapsed Disease

Abstract In this retrospective study we described the response and toxicity of a modified Magrath IVAC (mIVAC) regimen in 25 patients with refractory/relapsed aggressive non-Hodgkin lymphoma (NHL). The mIVAC consisted of ifosfamide 1,500mg/m2 (one-hour infusion beginning at 9:00; D1 to D5), mesna 300mg/m2 (bolus at hours 9:00, 13:00, 17:00; D1 to D5), citarabine 2,000 mg/m2 (two one-hour infusions beginning at 8:00 and 16:00; D1 and D2) and etoposide 60 mg/m2 (one-hour infusion beginning at 10:00; D1 to D5). Treatment was repeated every four weeks for a maximum of six cycles. Patients who achieved partial remission or complete remission after at least three courses were offered autologous stem cell transplantation (ASCT), if eligible. The median age was 37 years (range 18 to 59 years). Twenty-two (88%) patients had diffuse large B-cell lymphoma, fourteen (56%) had relapsed disease and 10 (40%) were considered high-intermediate and high risk by age-adjusted International Prognostic Index. The overall response rate was 68% (95% CI: 46%–90%). A total of 64 cycles were given, with a median of three courses per patient. Grade 3/4 neutropenia was observed after 85,6% of the courses, and grade 3/4 thrombocytopenia was observed after 87,5% of the courses. Grade 3/4 neutropenic fever occurred after 28% of the courses. Non-hematologic toxic effects were rare, predominantly grade 1/2. No toxic deaths were observed. Fifteen (88%) of the 17 responding patients underwent ASCT. With a median follow-up of 14 months, the median overall survival time for mIVAC sensitive patients was 16 months. This regimen may be feasible for patient with relapsed and refractory aggressive NHL in countries with inadequate numbers of hospital beds.

Low Absolute Lymphocyte Count Predicts Chemotherapy Response and Survival In Peripheral T-Cell Lymphoma, NOS

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3135-3135
Author(s):  
Yu Ri Kim ◽  
yun Deok Kim ◽  
Jin Seok Kim ◽  
June-Won Cheong ◽  
soo Jeong Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Factor ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Independent Prognostic Factor ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Overall Response

Abstract Abstract 3135 Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS) is heterogenous groups of aggressive T-cell lymphoma and treatment outcome is dismal. Lymphopenia is an independent prognostic factor for survival for B-cell lymphoma. The ALC at diagnosis on survival in T-cell lymphoma has not been studied. Thus, we studied the role of ALC at diagnosis on clinical outcome in patients with PTCL, NOS. Between 2001 and 2009, 32 patients with PTCL, NOS reviewed for the study. Median patient age was 57 (range 34–78) years. Median ALC at the time of diagnosis was 1.54 (range 0.41–12.64×109/L). Patients were divided two groups according to ALC count 1.0 ×109/L. Ten patients (31%) had lower ALC at diagnosis. Median follow up duration was 299 days (range 11–2164 days). Overall response rate was 61.5% (16 of 26 patients) and complete response (CR) rate was 42% (11 of 26 patients). Only two patients reached CR in low ALC group.There was no significant difference in overall response rate because of small number of patients. Superior overall survival was observed with an ALC 1.0 × 109/L (N = 22) versus an ALC < 1.0 × 109/L (N=10) (median OS: not reached vs 242 days, OS rates at 5 years, 57% vs 0%, p =0.016, respectively). Multivariate analysis demonstrated ALC to be an independent prognostic indicator for OS (Hazard Ratio 3.5, 95% confidence intervals 1.2–10.2; p<0.019) when compared to the International prognostic index (IPI) and Prognostic Index for PTCLU (PIT). This study suggested that low ALC is an independent prognostic factor for survival in patients with PTCL, NOS. Disclosures: No relevant conflicts of interest to declare.

SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group

Blood ◽  
2012 ◽  
Vol 120 (15) ◽  
pp. 2973-2980 ◽  
Author(s):  
Yok-Lam Kwong ◽  
Won Seog Kim ◽  
Soon Thye Lim ◽  
Seok Jin Kim ◽  
Tiffany Tang ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Remission Rate ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Newly Diagnosed ◽  
Natural Killer T Cell ◽  
Grade 3 ◽  
Killer T Cell

Abstract Natural killer/T-cell lymphoma is rare and aggressive, with poor outcome. Optimal treatment remains unclear. A novel regimen dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) showed promise in phase 1/2 studies with restrictive recruitment criteria. To define the general applicability of SMILE, 43 newly diagnosed and 44 relapsed/refractory patients (nasal, N = 60, nonnasal, N = 21; disseminated, N = 6; male, N = 59; female, N = 28) at a median age of 51 years (23-83 years) were treated. Poor-risk factors included stage III/IV disease (56%), international prognostic index of 3 to 5 (43%), and Korean prognostic scores of 3 to 4 (41%). A median of 3 (0-6; total = 315) courses of SMILE were administered. Significant toxicities included grade 3/4 neutropenia (N = 57; 5 sepsis-related deaths); grade 3/4 thrombocytopenia (N = 36); and nephrotoxicity (N = 15; 1 acute renal failure and death). Interim analysis after 2 to 3 cycles showed complete remission rate of 56%, partial remission rate of 22%, giving an overall response rate of 78%. On treatment completion, the overall-response rate became 81% (complete remission = 66%, partial remission = 15%). Response rates were similar for newly diagnosed or relapsed/refractory patients. At a median follow-up of 31 months (1-84 months), the 5-year overall survival was 50% and 4-year disease-free-survival was 64%. Multivariate analysis showed that international prognostic index was the most significant factor impacting on outcome and survivals.

scholarly journals Eprenetapopt (APR-246) and Azacitidine in TP53-Mutant Myelodysplastic Syndromes

2021 ◽  
pp. JCO.20.02341 ◽  
Author(s):  
David A. Sallman ◽  
Amy E. DeZern ◽  
Guillermo Garcia-Manero ◽  
David P. Steensma ◽  
Gail J. Roboz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Allele Frequency ◽  
Myelodysplastic Syndromes ◽  
Median Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Variant Allele ◽  
Variant Allele Frequency ◽  
Overall Response

PURPOSE Approximately 20% of patients with TP53-mutant myelodysplastic syndromes (MDS) achieve complete remission (CR) with hypomethylating agents. Eprenetapopt (APR-246) is a novel, first-in-class, small molecule that restores wild-type p53 functions in TP53-mutant cells. METHODS This was a phase Ib/II study to determine the safety, recommended phase II dose, and efficacy of eprenetapopt administered in combination with azacitidine in patients with TP53-mutant MDS or acute myeloid leukemia (AML) with 20%-30% marrow blasts (ClinicalTrials.gov identifier: NCT03072043 ). RESULTS Fifty-five patients (40 MDS, 11 AML, and four MDS/myeloproliferative neoplasms) with at least one TP53 mutation were treated. The overall response rate was 71% with 44% achieving CR. Of patients with MDS, 73% (n = 29) responded with 50% (n = 20) achieving CR and 58% (23/40) a cytogenetic response. The overall response rate and CR rate for patients with AML was 64% (n = 7) and 36% (n = 4), respectively. Patients with only TP53 mutations by next-generation sequencing had higher rates of CR (69% v 25%; P = .006). Responding patients had significant reductions in TP53 variant allele frequency and p53 expression by immunohistochemistry, with 21 (38%) achieving complete molecular remission (variant allele frequency < 5%). Median overall survival was 10.8 months with significant improvement in responding versus nonresponding patients by landmark analysis (14.6 v 7.5 months; P = .0005). Overall, 19/55 (35%) patients underwent allogeneic hematopoietic stem-cell transplant, with a median overall survival of 14.7 months. Adverse events were similar to those reported for azacitidine or eprenetapopt monotherapy, with the most common grade ≥ 3 adverse events being febrile neutropenia (33%), leukopenia (29%), and neutropenia (29%). CONCLUSION Combination treatment with eprenetapopt and azacitidine is well-tolerated yielding high rates of clinical response and molecular remissions in patients with TP53-mutant MDS and oligoblastic AML.

scholarly journals Survival in Early Phase Immuno-Oncology Trials: Development and Validation of a Prognostic Index

2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Daphne Day ◽  
Christina Guo ◽  
Yada Kanjanapan ◽  
Ben Tran ◽  
Anna Spreafico ◽  
...  
Keyword(s):  
Phase I ◽  
Patient Selection ◽  
Odds Ratio ◽  
Overall Response Rate ◽  
Response Rate ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Phase I Trials ◽  
Free Survival ◽  
Overall Response

Abstract Background Immuno-oncology (IO) is rapidly evolving in early drug development. We aimed to develop and prospectively validate a prognostic index for patients treated in IO phase I trials to assist with patient selection. Methods The development cohort included 192 advanced solid tumor patients treated in 13 IO phase I trials, targeting immune checkpoint and/or co-stimulatory molecules. A prognostic scoring system was developed from multivariate survival analysis of 10 clinical factors, and subsequently validated in two independent validation cohorts (n = 152 and n = 80). Results In the development cohort, median age was 57.5 years (range = 20.4–84.8 years). Median progression-free survival and overall survival (OS) were 13.4 and 73.6 weeks, respectively, 90-day mortality was 16%, and overall response rate was 20%. In multivariate analysis, Eastern Cooperative Oncology Group performance status greater than or equal to 1 (hazard ratio [HR] = 3.2, 95% confidence interval [CI] = 1.8 to 5.7; P &lt; .001), number of metastatic sites greater than 2 (HR = 2.0, 95% CI = 1.3 to 3.1; P = .003), and albumin less than the lower limit of normal (HR = 1.8, 95% CI = 1.2 to 2.7; P = .007) were independent prognostic factors; comprising the Princess Margaret Immuno-oncology Prognostic Index (PM-IPI). Patients with a score of 2–3 compared with patients with a score of 0–1 had shorter OS (HR = 3.4, 95% CI = 1.9 to 6.1; P &lt; .001), progression-free survival (HR = 2.3, 95% CI = 1.7 to 3.2; P &lt; .001), higher 90-day mortality (odds ratio = 8.1, 95% CI = 3.0 to 35.4; P &lt; .001), and lower overall response rate (odds ratio = 0.4, 95% CI = 0.2 to 0.8; P = .019). The PM-IPI retained prognostic ability in both validation cohorts and performed better than previously published phase I prognostic scores for predicting OS in all three cohorts. Conclusions The PM-IPI is a validated prognostic score for patients treated in phase I IO trials and may aid in improving patient selection.

Yttrium-90 (90Y) ibritumomab tiuxetan for treatment of relapsed or refractory non-hodgkin’s lymphoma: The Western Pennsylvania Cancer Institute experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12511-12511
Author(s):  
S. Jasthy ◽  
N. Sudan ◽  
B. Haq ◽  
J. Lister
Keyword(s):  
B Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response Duration ◽  
Disease Stage ◽  
Ibritumomab Tiuxetan ◽  
Overall Response ◽  
Yttrium 90

12511 Background: Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) radioimmunotherapy is an effective agent for treatment of CD20+ B-cell lymphoma (NHL).It is approved for treatment of relapsed or refractory, follicular or transformed B cell lymphoma. An overall response rate ranging from 74% to 82% has been reported. Median response duration of 11.5 to 28.1 months has been reported. Methods: We identified, retrospectively, 37 patients treated at our institution with relapsed or refractory NHL who were treated with 90Y ibritumomab tiuxetan at a dose of 0.3mCi/kg or 0.4mCi/kg. Response rate and survival were assessed. Median age was 60 years (range 28–82 years) of which 65% were male. Follicular lymphoma was present in 57% (n = 21) and diffuse large B-cell lymphoma in 22% (n = 8) of patients. Advanced disease (stage III or IV) was present in 84% (n = 31) of patients. All of the patients had received at least one prior regimen and 68% (n = 25) had received ≥ 3 regimens before 90Y ibritumomab tiuxetan. Results: Overall response rate was 65% (24/37); CR 43% (16/37); PR 19% (7/37); SD 3% (1/37). Duration of response was 13.3 months (range 4 to 48 months) with response duration greater than 12 months in 35% (n = 13) of the patients. Of responders, 67% (16/23) had failed to respond to prior immediate therapy. The only toxic event was pancytopenia, which predictably occurred after treatment. No patients died of toxicity and all toxicity was reversible. Conclusions: 90Y ibritumomab tiuxetan was well tolerated and effective for our patients.We document durable response in our patients with relapsed or refractory NHL and with advanced stage disease. Further study of ibritumomab tiuxetan using different doses and in combination with chemotherapy is warranted. No significant financial relationships to disclose.

IPILIMUMAB IN PATIENTS WITH DISSEMINATED MELANOMA: THE N.N. PETROV NATIONAL MEDICAL RESEARCH CENTER OF ONCOLOGY EXPANDED ACCESS PROGRAM EXPERIENCE

2018 ◽  
Vol 64 (3) ◽  
pp. 388-393
Author(s):  
Yekaterina Anokhina ◽  
V. Rubinchik ◽  
Yekaterina Yaremenko ◽  
Gulfiya Teletaeva ◽  
Dilorom Latipova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Medical Research ◽  
Research Center ◽  
Expanded Access ◽  
Risk Of Death ◽  
National Medical ◽  
Expanded Access Program ◽  
Access Program

Ipilimumab (IPI) provides a ten-year overall survival in almost 20 % of selected patients participated in several phase II-III trials. However, the expanded access program (EAP) looks more like routine practice than like clinical trials& This is why the results of such application could be different. Here we present the long-term follow-up data of single center EAP. Ninety-six patients with disseminated melanoma progressing after at least one lines of drug therapy were included at the N.N. Petrov National Medical Research Center of Oncology. Sixty-seven (70 %) patients had stage IV M1c, 35 patients (36 %) had elevated LDH before initiating IPI therapy. All patients received IPI 3 mg / kg IV every 3 weeks for a maximum of 4 cycles. Totally, 320 cycles (mean - 3.3 per patient) were conducted. Grade 3-4 immuno-mediated adverse events (imAE) observed in 18 (19 %) patients. Three patients died of adverse events, possibly associated with ongoing therapy. The median time to progression was 3 (95 % CI, 2.4 to 3.5) mo., the median overall survival was 13 (95 % CI, 8.3 to17.6) mo. Previous immunotherapy with dendritic cell vaccines decreased the risk of death by 48 % (Log-rank p = 0.049). The wild type BRAF status increased three-year overall survival from 29 to 68 % (p = 0.042). Our data confirms long-term safety and efficacy of IPI in patients with pretreated disseminated melanoma in the close to real practice setting.

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