scholarly journals FCR (Fludarabine, Cyclophosphamide, Rituximab) Followed By 90yttrium Ibritumomab Tiuxetan for the Treatment of Relapsed Grades 1 and 2 Follicular Lymphoma. Long Term Efficacy and Safety Results of 9 Cases

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5452-5452
Author(s):  
Francesco Pisani ◽  
Maria Laura Dessanti ◽  
Diana Giannarelli ◽  
Ramy Kayal ◽  
Francesco Marchesi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
Partial Remission ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Ibritumomab Tiuxetan ◽  
Free Survival ◽  
Term Efficacy

Abstract Background: This retrospective analysis is focused on the efficacy and safety of radioimmunotherapy (RIT) with Zevalin® in nine patients with recurrent follicular lymphoma (FL) who were treated in a consolidation setting after having achieved complete remission or partial remission with FCR. Methods: The median age was 63 years (range 46-77), all patients were relapsed with histologically confirmed CD20-positive (grade 1 or 2) FL, at relapse they received FCR every 28 days: F (25mg/m2x 3 days), C (1gr/m2 day 1) and R (375mg/m2 day 4) for 4 cycles. Who achieved at least a partial remission, with<25% bone marrow involvement, was treated with 90Yttrium Ibritumomab Tiuxetan 11.1 or 14.8 MBq/Kg up to a maximum dose 1184 MBq, at 3 months after the completion of FCR. The patients underwent a further restaging at 12 weeks after 90Y-RIT with total body CT scan, FDG-PET/CT and bilateral bone marrow biopsy. Results: Nine patients have completed the treatment: FCR followed by 90Y-RIT (6 patients at 14.8 MBq/Kg, 3 patients at 11.1 MBq/Kg). After FCR 7 patients obtained CR and 2 PR; after 90Y-RIT two patients in PR converted to CR 12 weeks later. With median follow up of 86 months (range 20-107) since FCR and 79 months (range13-97) since RIT, 3 deaths were observed not related to lymphoma: one for acute renal failure, one for ictus cerebri and one for sepsis; all three deceased patients obtained CR before 90Y-RIT and died still in CR. The median overall survival (OS) and progression free survival (PFS) have not been reached , current analysis has shown that either OS or PFS are 67% at 7 year. The most common grade 3 or 4 adverse events were hematologic, one patient developed herpes zoster infection after 8 months following valacyclovir discontinuation; another patient developed fungal infection. Conclusions: These results confirm the long term efficacy and safety of 4 cycles of FCR followed by consolidation with 90Y-RIT in patients relapsed with grades 1 and 2 FL and suggest that this regimen could be an option to be used for treatment in this setting of patients, specially at age of 60-75 with no unexpected toxicities. Figure 1. Progression free survival from RIT Figure 1. Progression free survival from RIT Disclosures No relevant conflicts of interest to declare.

Long-Term Follow-Up of Autologous Bone Marrow Transplantation for Follicular Lymphoma in First Remission: Bone Marrow Involvement at Harvest and PCR Detectable Disease after Ex Vivo Purging Predict Relapse.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3041-3041
Author(s):  
Jennifer R. Brown ◽  
John G. Gribben ◽  
Yang Feng ◽  
Donna Neuberg ◽  
Peter Mauch ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
Ex Vivo ◽  
Bone Marrow Involvement ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Rank Test ◽  
Free Survival ◽  
First Remission

Abstract ASCT improves progression-free and likely overall survival in patients with relapsed follicular lymphoma. Randomized trials of ASCT as upfront therapy have generally also found an improvement in progression-free survival, but this benefit has been counterbalanced by an increase in second malignancies. We report the long-term outcome of two sequential prospective clinical trials of autologous bone marrow transplantation for advanced stage follicular lymphoma patients under 60 in first remission. In the 1st study 83 previously untreated patients received 6–8 cycles of CHOP induction and in the 2nd study 20 patients received 4 cycles of high-dose CHOP induction (cyclophosphamide 1.5 g/m2 d1–2 with g-csf support). The median age of the patients was 42 (range 19–57). 17% had high FLIPI scores, 58% intermediate and 25% low; all patients were under 60 and 21% had missing data required in the FLIPI. 96% had stage III or IV disease. 77 of 83 patients on the 1st study, and 19 of 20 on the 2nd study (N=96 total), achieved a protocol-defined minimal disease state after CHOP induction (< 2 cm masses, <20% bone marrow involvement). 35% of patients achieved CR after induction. Nine patients required IFRT to achieve protocol eligibility. Marrow was purged in vitro with anti-B1 (CD20), B5 and J5 (CD10) monoclonal antibodies and complement. Subjects were conditioned with cyclophosphamide and total body irradiation prior to re-infusion of purged bone marrow. Two early treatment-related deaths were observed. The 12 year relapse-free survival is 42.7% (95% CI 32.3–52.7%) and overall survival 60.7% (95% CI 49.5–70.1%). 44 patients (45.8%) have relapsed with follicular lymphoma of whom 24 have died of disease and 15 are alive. The median survival following relapse is 6.1 years (95% CI 4.1–9.0). 27 patients (28%) have developed a second malignancy, at a median 8.7 years following ABMT, including 10 cases of MDS/AML, 2 non-MDS hematologic malignancies, 8 solid tumors and 10 non-melanoma skin cancers. 9 patients (9.4%) have died of a secondary malignancy. Age, stage, FLIPI, hemoglobin, LDH, number of nodal sites, IFRT, and induction therapy were not predictive of PFS or OS. Histologic evidence of residual bone marrow disease at harvest was associated with a 12 year PFS 33.9% (95% CI 20.5–47.9%), compared to 50% (95% CI 34.8–63.5%) for those without marrow involvement (p= 0.02, log-rank test). 70 patients with known detectable bcl-2/IgH translocations prior to therapy had post-purging bone marrow samples analyzed by PCR; 30 of these 70 were negative. The 12 year RFS for PCR negative patients is 66.7% (95% CI 47–81%), compared to 26.3% (95% CI 14–41%) for those with PCR detectable disease (p= 0.001, log-rank test). In Cox proportional hazards regression analysis evaluating the impact of pre-transplant factors on PFS, only histologic bone marrow involvement at harvest (HR 2.27, 95% CI 1.31–3.93, p<0.004) and PCR positivity after ex vivo purging (HR 4.18, 95% CI 1.99–8.80, p= 0.0002) were independent predictors of outcome. These results, showing that 42.7% of patients are in ongoing complete remission and 60.7% are alive at twelve years following ABMT, suggest that a subset of follicular lymphoma patients can experience prolonged survival with ABMT in first remission.

Myeloablative therapy and unpurged autologous bone marrow transplantation for poor-prognosis neuroblastoma: report of 34 cases.

1991 ◽  
Vol 9 (6) ◽  
pp. 962-969 ◽  
Author(s):  
G Dini ◽  
E Lanino ◽  
A Garaventa ◽  
D Rogers ◽  
S Dallorso ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Partial Remission ◽  
Autologous Bone Marrow Transplantation ◽  
Progression Free Survival ◽  
Autologous Bone Marrow ◽  
High Dose ◽  
Free Survival ◽  
Autologous Bone

From October 1984 to November 1987, 34 patients aged from 1 year 1 month to 7 years 7 months with resistant or relapsed neuroblastoma (NB) (group 1, 10 patients), unselected disseminated NB (group 2, 14 patients), or selected disseminated NB (group 3, 10 patients) received myeloablative therapy (MAT) followed by unpurged autologous bone marrow transplantation (ABMT) at the end of an intensive protocol, which included high-dose chemotherapy and surgery to the primary tumor. Median time from diagnosis to MAT and ABMT was 6 months (5 months from last relapse to MAT and ABMT in the relapsed patients). The MAT regimen included vincristine, fractionated total body irradiation (TBI), and melphalan. Seventeen patients were grafted in complete remission (CR), five in very good partial remission (VGPR), 10 in partial remission (PR), and two in progressive disease (PD). The acute toxic death rate was 2.9%. The overall progression-free survival was 29%. The median progression-free survival was 20 months for the 17 patients grafted in CR, 6 months for the five patients grafted in VGPR, and 12 months for the 10 patients grafted in PR.

Extranodal Diffuse Large B Cell Lymphoma In The Rituximab Era and The Risk of Central Nervous System (CNS) Relapse. A Single Center Experience From 2008-2012

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4330-4330
Author(s):  
Christina Tsao ◽  
Kate Fisher ◽  
Ji-Hyun Lee ◽  
Julio C Chavez ◽  
Samir Dalia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Musculoskeletal Involvement

Abstract Background Diffuse large b-cell lymphoma (DLBCL) with CNS relapse or progression has a poor prognosis. Prior studies noted certain factors which increased the risk of CNS relapse: bone marrow involvement, type as well as number (1+) of extra-nodal sites, age over 60, and increasing International Prognostic Index (IPI) score. However, these were prior to the advent of rituximab (R), which has been suggested to lower CNS relapse when used in combination with CHOP therapy. To our knowledge, no one has looked at the incidence of CNS relapse with regards to extranodal disease in the rituximab era. Methods Retrospective chart review of patients with DLBCL treated with multiagent induction therapy including rituximab from July‘08 to Jan’12 at Moffitt Cancer Center. Age, stage, IPI score, extra-nodal site, number of nodal sites, and use of intrathecal prophylaxis (IT), were evaluated for their impact on the risk of developing CNS relapse. For those who had complete response to initial therapy, time to progression(TTP) for CNS relapse was measured from completion date of first set of chemo cycles to date of CNS relapse (those who did not CNS relapse were censored at last follow up). TTP was censored at 6 years. Progression free survival(PFS) was measured from date of diagnosis to date of CNS or systemic relapse or death (those who were alive without relapse were censored at last follow up). Overall survival (OS) was measure from date of diagnosis to date of death. Stratified Kaplan Meier curves(with log rank p-values) and Cox PH models(with Wald p-values) were used to explore potential risk factors associated with relapse. Results Sixty-four patients with DLBCL who received induction therapy were evaluated: median age (range) = 65 (24-93) years; male =56%; IPI scores at diagnosis: 1 (43.8%), 2(21.9%), 3(15.6%); median length of follow up from time of diagnosis = 32 months. All the patients received a regimen containing rituximab, and 92% of patients received R-Chop as treatment. IT prophylaxis with methotrexate was used in 28% of the patients. Incidence of CNS relapse in our study population= 17.3% (n=9) The risk of CNS relapse varied depending on the extranodal site. Those with bone marrow and/or musculoskeletal involvement had an increased risk, with 78% of the CNS relapses occurring in patients with one or both of these sites of involvement. The hazard ratio (HR) for CNS relapse for patients with bone marrow and musculoskeletal involvement was 2.53 and 2.74, respectively (p=0.20 and p=0.13). Other extranodal sites of disease such as visceral organs, genital urinary tract, nasopharynx, or skin did not seem to significantly contribute to the risk of CNS relapse. Patients with bone marrow involvement also had an inferior overall survival (HR=3.05, Wald p=0.02) (see figure 1). Though not statistically significant (log rank p=0.126), those receiving IT methotrexate prophylaxis appear to have longer PFS than those who did not, with 83% alive without relapse at 6 years compared to 43% (see figure 2). Conclusions Despite the addition of rituximab to multiagent chemotherapy, those with bone marrow and musculoskeletal involvement still had a significantly higher risk of CNS relapse. There is a trend which suggests intrathecal prophylaxis with methotrexate can improve progression free survival and is still possibly beneficial in high risk DLBCL patients even in the rituximab era. Larger prospective studies are needed to determine the true benefit of prophylactic IT therapy in this population. Disclosures: No relevant conflicts of interest to declare.

Follicular Lymphoma International Prognostic Index 2: A New Prognostic Index for Follicular Lymphoma Developed by the International Follicular Lymphoma Prognostic Factor Project

2009 ◽  
Vol 27 (27) ◽  
pp. 4555-4562 ◽  
Author(s):  
Massimo Federico ◽  
Monica Bellei ◽  
Luigi Marcheselli ◽  
Stefano Luminari ◽  
Armando Lopez-Guillermo ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Free Survival ◽  
Study Population ◽  
Index 2

Purpose The aim of the F2 study was to verify whether a prospective collection of data would enable the development of a more accurate prognostic index for follicular lymphoma (FL) by using parameters which could not be retrospectively studied before, and by choosing progression-free survival (PFS) as principal end point. Patients and Methods Between January 2003 and May 2005, 1,093 patients with a newly diagnosed FL were registered and 942 individuals receiving antilymphoma therapy were selected as the study population. The variables we used for score definition were selected by means of bootstrap resampling procedures on 832 patients with complete data. Procedures to select the model that would minimize errors were also performed. Results After a median follow-up of 38 months, 261 events for PFS evaluation were recorded. β2-microglobulin higher than the upper limit of normal, longest diameter of the largest involved node longer than 6 cm, bone marrow involvement, hemoglobin level lower than 12 g/dL, and age older than 60 years were factors independently predictive for PFS. Using these variables, a prognostic model was devised to identify three groups at different levels of risk. The 3-year PFS rate was 91%, 69%, and 51% for patients at low, intermediate, and high risk, respectively (log-rank = 64.6; P < .00001). The 3-year survival rate was 99%, 96%, and 84% for patients at low, intermediate, and high risk, respectively (P < .0001). Conclusion Follicular Lymphoma International Prognostic Index 2 is a simple prognostic index based on easily available clinical data and may represent a promising new tool for the identification of patients with FL at different risk in the era of immunochemotherapy.

scholarly journals Nonmyeloablative allogeneic transplantation with or without 90yttrium ibritumomab tiuxetan is potentially curative for relapsed follicular lymphoma: 12-year results

Blood ◽  
2012 ◽  
Vol 119 (26) ◽  
pp. 6373-6378 ◽  
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
William D. Erwin ◽  
Barry I. Samuels ◽  
Martin Korbling ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Survival Rates ◽  
Conditioning Regimen ◽  
Low Frequency ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Ibritumomab Tiuxetan ◽  
Free Survival ◽  
Innovative Strategies

In 2008, we reported favorable 5-year outcomes of nonmyeloablative allogeneic stem cell transplantation after fludarabine, cyclophosphamide, rituximab (FCR) conditioning for relapsed and chemosensitive follicular lymphoma. However, innovative strategies were still needed to treat patients with chemorefractory disease. We therefore subsequently performed a trial in which 90Y-ibritumomab tiuxetan (0.4 mCi/kg) was added to the fludarabine, cyclophosphamide conditioning regimen (90YFC). Here, we report updated results of the FCR trial and outcomes after 90YFC. For the FCR group (N = 47), since the last update, one patient developed recurrent disease. With a median follow-up of 107 months (range, 72-142 months), the 11-year overall survival and progression-free survival rates were 78%, and 72%, respectively. For the 90YFC group (N = 26), more patients had chemorefractory disease than did those in the FCR group (38% and 0%, P < .001). With a median follow-up of 33 months (range,17-94 months), the 3-year progression-free survival rates for patients with chemorefractory and chemosensitive disease were 80% and 87%, respectively (P = .7). The low frequency of relapse observed after a long follow-up interval of 9 years in the FCR group suggests that these patients are cured of their disease. The addition of 90Y to the conditioning regimen appears to be effective in patients with chemorefractory disease. This trial was registered at www.clinicaltrials.gov as NCT00048737.

scholarly journals Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study

2021 ◽  
Vol 5 (17) ◽  
pp. 3354-3361
Author(s):  
Christian Buske ◽  
Wojciech Jurczak ◽  
Juan-Manuel Sancho ◽  
Edvard Zhavrid ◽  
Jin Seok Kim ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Induction Period ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Advanced Stage ◽  
Phase 3 ◽  
Double Blind ◽  
End Points ◽  
Term Efficacy

Abstract Rituximab biosimilars are a cornerstone of treatment of advanced-stage follicular lymphoma (FL). This double-blind, parallel-group, phase 3 trial randomized (1:1) adults (≥18 years) with stage III to IV indolent B-cell lymphoma, including grades 1 to 3a FL, to receive CT-P10 or rituximab (375 mg/m2 IV), with cyclophosphamide, vincristine, and prednisone, every 3 weeks for 8 cycles (induction period). Patients achieving complete response (CR), unconfirmed CR, or partial response (PR) received CT-P10 or rituximab maintenance for 2 years (375 mg/m2, every 8 weeks). Primary end points were previously reported, proving noninferiority of efficacy and pharmacokinetic equivalence of CT-P10 to rituximab. Secondary end points included overall response rate (PR+CR) during the induction period per 2007 International Working Group (IWG) criteria, survival analyses, and overall safety. Between 28 July 2014 and 29 December 2015, 140 patients were randomized (70 per group). Median follow-up was 39.9 months (interquartile range, 36.7-43.5). Per 1999 IWG criteria, 4-year Kaplan-Meier estimates (95% confidence interval [CI]) for CT-P10 and rituximab were 61% (47% to 73%) and 55% (36% to 70%) for progression-free survival (hazard ratio, 1.33 [95% CI, 0.67-2.63]; P=.409), respectively, and 88% (77% to 94%) and 93% (83% to 97%) for overall survival (5.29 [0.84-33.53]; P=.077). Overall, 90% (CT-P10) and 86% (rituximab) of patients experienced treatment-emergent adverse events. Long-term safety profiles were similar between groups. Findings confirm favorable outcomes for CT-P10–treated patients with advanced-stage FL and demonstrate comparable long-term efficacy and overall safety between CT-P10 and rituximab. This trial was registered at www.clinicaltrials.gov as #NCT02162771.

Clinical and Prognostic Relevance of Magnetic Resonance Imaging of the Spine in Newly Diagnosed Multiple Myeloma Patients Receiving Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4885-4885
Author(s):  
Patrizia Tosi ◽  
Alessandro Petrucci ◽  
Lucia Pantani ◽  
Elena Zamagni ◽  
Paola Tacchetti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Resonance Imaging ◽  
Focal Lesions ◽  
Free Survival ◽  
Focal Pattern

Abstract Abstract 4885 Magnetic resonance imaging (MRI) of the spine has demonstrated to be a useful tool for a correct staging of multiple myeloma (MM), as it is more sensitive than plain x-rays in detecting vertebral lesions. Furthermore, both pattern of bone marrow involvement (focal, diffuse or normal), and number of focal lesions can be detected, and this could contribute to better define the prognosis and the outcome of newly diagnosed patients. In the present study we prospectively evaluated the clinical and prognostic role of spinal MRI in 152 newly diagnosed MM patients (89M, 63F, median age = 56yrs) that subsequently received high-dose chemotherapy and autologous stem cell transplantion, either single (n=43) or double (n=109). Pattern of marrow involvement was normal in 11% of the cases, diffuse in 20% and focal in 69%, with 34% of the patients showing > 7 focal lesions. Patients with a diffuse pattern or a focal pattern with > 7 lesions showed a significantly higher bone marrow plasma cell infiltration (p=0.04) and beta2 microglobulin values (p= 0.04) as compared to patients with a focal pattern with < 7 lesions. Response rate to the assigned treatment program was similar in the three groups of patients, with > VGPR obtained in 63% of the patients with a diffuse pattern, and in 70% of those with a focal pattern. Median progression-free survival (PFS) was significantly longer in patients with < 7 focal lesions as compared to those with >7 lesions or a diffuse pattern (55 vs 46 months p=0.05). Normalization of MRI was more frequently obtained in patients with < 7 lesions (67% vs 38% in patients with > 7 lesions, p=0.005); patients achieving a normal MRI pattern showed a significantly longer PFS (67 months) as compared to patients failing to achieve a negative MRI at the end of treatment (p=0.0000). According to our data, MRI confirms its prognostic role in newly diagnosed MM receiving high-dose therapy and autologous stem-cell transplantation; a diffuse pattern of bone marrow involvement or a focal pattern with > 7 lesions are predictive of a more aggressive outcome of the disease; furthermore normalization of MRI pattern after therapy is predictive of a longer progression-free survival Disclosures No relevant conflicts of interest to declare.

Fludarabine Plus I-131 Tositumomab as Initial Treatment for Follicular Lymphoma: Half of Patients In Remission at Over 10 Years Median Followup.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1785-1785
Author(s):  
Peter Martin ◽  
Morton Coleman ◽  
Richard R. Furman ◽  
Shankar Vallabhajosula ◽  
Dong Sun Kim ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Initial Treatment ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Front Line ◽  
Free Survival ◽  
Sequential Combination ◽  
Intent To Treat

Abstract Abstract 1785 Background: The sequential combination of chemotherapy and radioimmunotherapy has been shown to be effective front-line treatment for patients with follicular lymphoma (FL). We report ten-year followup results of a phase II trial of abbreviated fludarabine followed by tositumomab and I-131 tositumomab in patients with untreated follicular lymphoma. Methods: Patients with untreated follicular lymphoma received fludarabine 25 mg/m2/d for five days every five weeks for three cycles followed in six to eight weeks by tositumomab and I-131 tositumomab. Results: Thirty-eight patients were enrolled. One patient was withdrawn due to ineligible histology. The median age of eligible patients was 53 years, median time from diagnosis was 3.5 months, and 43% of patients had a high-risk FLIPI score. Two patients did not receive radioimmunotherapy; one patient had a myocardial infarction during fludarabine and was not evaluable, and one patient had persistent cytopenias following three cycles of fludarabine. All 35 patients that completed the regimen responded (ORR 100%). With a median follow-up of 128.5 months for all 37 eligible patients, the 10-year intent-to-treat overall survival is 69% and the progression-free survival is 51%. Seventeen patients have progressed (range 2–102 months). Sixteen patients remain in remission with no evidence of disease more than ten years from enrollment. Only four patients have relapsed beyond five years. Four patients have developed MDS (range 16–84 months), one of whom evolved to AML. Conclusions: Fludarabine followed by tositumomab and I-131 tositumomab is very effective at inducing long-lasting complete remissions in FL. The efficacy and long-term safety of sequential chemotherapy plus radioimmunotherapy should continue to be evaluated in the context of the range of therapeutic options for the initial treatment of follicular lymphoma. Disclosures: Furman: GSK: Speakers Bureau. Leonard:GSK: Consultancy.

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