Abbreviated Chemotherapy With Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab for Untreated Follicular Lymphoma

2005 ◽  
Vol 23 (24) ◽  
pp. 5696-5704 ◽  
Author(s):  
John P. Leonard ◽  
Morton Coleman ◽  
Lale Kostakoglu ◽  
Amy Chadburn ◽  
Ethel Cesarman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
Standard Dose ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Complete Response ◽  
To Receive

Purpose To evaluate the safety and efficacy of a sequential chemotherapy plus radioimmunotherapy (RIT) regimen in previously untreated follicular non-Hodgkin's lymphoma. Patients and Methods Thirty-five patients received an abbreviated course (three cycles) of fludarabine followed 6 to 8 weeks later by tositumomab and iodine I 131 tositumomab. Results After fludarabine, 31 (89%) of 35 patients responded, with three (9%) of 31 patients achieving a complete response (CR). After the full regimen of fludarabine and iodine I 131 tositumomab, all 35 patients responded; 30 (86%) of 35 patients achieved CR, and five (14%) of 35 achieved partial response. After a median follow-up of 58 months, the median progression-free survival (PFS) had not been reached (95% CI, 27 months to not reached), but it will be at least 48 months. The 5-year estimated PFS rate is 60%. Baseline Follicular Lymphoma International Prognostic Index (FLIPI) was significantly associated (P = .003) with PFS. Five of six patients with more than 25% bone marrow involvement at baseline achieved adequate bone marrow cytoreduction to receive standard-dose iodine I 131 tositumomab. Ten (77%) of 13 patients with baseline bone marrow Bcl-2 positivity demonstrated molecular remissions at month 12. Toxicities were manageable and principally hematologic. Two (6%) of 35 patients developed human antimurine antibodies (HAMA) after RIT. Conclusion Use of abbreviated fludarabine before iodine I 131 tositumomab can reduce bone marrow involvement, when needed, to allow the use of RIT and can suppress HAMA responses. This sequential treatment regimen is highly effective as front-line therapy for follicular lymphoma, particularly for low- or intermediate-risk FLIPI patients.

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 Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy

Blood ◽  
2019 ◽  
Vol 134 (4) ◽  
pp. 353-362 ◽  
Author(s):  
Emanuele Zucca ◽  
Stephanie Rondeau ◽  
Anna Vanazzi ◽  
Bjørn Østenstad ◽  
Ulrich J. M. Mey ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Complete Response ◽  
Clinical Cancer Research ◽  
International Prognostic Index Score ◽  
First Line Therapy ◽  
Phase 2 Trial ◽  
Grade 3

Abstract The SAKK 35/10 phase 2 trial, developed by the Swiss Group for Clinical Cancer Research and the Nordic Lymphoma Group, compared the activity of rituximab vs rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1 of weeks 1-4 and repeated during weeks 12-15 in responding patients) or rituximab (same schedule) in combination with lenalidomide (15 mg orally daily for 18 weeks). Primary end point was complete response (CR)/unconfirmed CR (CRu) rate at 6 months. In total, 77 patients were allocated to rituximab monotherapy and 77 to the combination (47% poor-risk Follicular Lymphoma International Prognostic Index score in each arm). A significantly higher CR/CRu rate at 6 months was documented in the combination arm by the investigators (36%; 95% confidence interval [CI], 26%-48% vs 25%; 95% CI, 16%-36%) and confirmed by an independent response review of computed tomography scans only (61%; 95% CI, 49%-72% vs 36%; 95% CI, 26%-48%). After a median follow-up of 4 years, significantly higher 30-month CR/CRu rates and longer progression-free survival (PFS) and time to next treatment (TTNT) were observed for the combination. Overall survival (OS) rates were similar in both arms (≥90%). Toxicity grade ≥3 was more common in the combination arm (56% vs 22% of patients), mainly represented by neutropenia (23% vs 7%). Addition of lenalidomide to rituximab significantly improved CR/CRu rates, PFS, and TTNT, with expected higher, but manageable toxicity. The excellent OS in both arms suggests that chemotherapy-free strategies should be further explored. This trial was registered at www.clinicaltrials.gov as #NCT01307605.

The Clinical Impact of Minimal Bone Marrow Involvement on the Outcome of Patients with Follicular Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2966-2966
Author(s):  
Daisuke Kato ◽  
Satoshi Yoshioka ◽  
Tomohiro Yabushita ◽  
Yoshimitsu Shimomura ◽  
Yuichiro Ono ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Morphological Evidence ◽  
Stage Disease ◽  
Igh Rearrangement ◽  
The Impact ◽  
Index Table

Abstract Introduction: Follicular lymphoma (FL) is the second most common type of non-Hodgkin cell lymphoma, and usually manifests as a disseminated disease. Bone marrow (BM) involvement, which occurs in 40-70% of cases, is often seen in follicular lymphoma and thought to be associated with less favorable prognosis. Diagnosis of BM involvement has traditionally been based on morphological findings, and BM involvement has been determined using histology alone in most clinical trials. Immunocytologic or molecular studies, such as flow cytometry (FCM) and polymerase chain reaction (PCR), have become more readily available, and their usage has clearly documented minimal BM involvement reproducibly. In this study, we evaluated the impact of BM involvement detected by FCM and PCR on the outcome of patients treated for FL. Methods: Patients who were diagnosed with biopsy-proven FL between 2004 and 2015 at our institution were included in the study. All patients had received a staging bone marrow examination before treatment with immunotherapy-based regimen. Immunocytologic [FCM] and/or molecular [PCR] studies were always performed if the patients did not have morphological BM involvement. We used 4- or 6- color FCM, and performed PCR analysis of Bcl-2/IgH rearrangement and/or IgH rearrangement detected by modified BioMed-2 protocol. A total of 90 patients were included, and the median follow-up duration was 36 months (range, 6|122 months). The BM status was classified using into 3 categories: morphological, minimal, and negative BM involvement. Minimal BM involvement was defined as BM involvement detected by FCM or PCR without morphological evidence. Morphological and minimal BM involvements were detected in 37 (41%) and 38 (42%) patients, respectively. The primary outcome measure was progression-free survival (PFS). PFS curves were plotted using the Kaplan-Meier method and compared by the log-rank test. Multivariate analyses were performed using a Cox linear regression model. There were significant differences in gender, LDH levels, stage, nodal sites, and FL International Prognostic Index (FLIPI) between patients with and without morphological BM involvement (Table1). Results: The 3-year PFS rate for patients with negative BM involvement was significantly better than that for patients with minimal or morphological BM involvement (84.8% vs. 40.3% vs. 60.5%; p= 0.043) (Figure 1). There was no statistical difference in 3-year PFS between patients with morphological BM involvement and those with minimal BM involvement. The difference of 3-year PFS rate between patients with minimal BM involvement and those with negative BM involvement was significant for patients with FLIPI low-intermediate risk (88.9% vs. 51.5%; p= 0.032) and those with advanced stage disease (90.0% vs. 33.6%; p= 0.027), but there were no significant differences in patients deemed FLIPI high risk and those with limited stage disease. Multivariate analysis revealed that BM involvement, including morphological and minimal involvement, was a significant poor prognostic factor (hazard ratio 4.885 [95% confidence interval 1.16-20.56], p = 0.0305). Conclusion: At the start of treatment, bone marrow involvement was seen in most FL patients. Patients without any BM involvement had an excellent prognosis. Patients with minimal BM involvement had an equally poor prognosis as those with morphologic BM involvement. Table 1 FLIPI: Follicular Lymphoma International Prognostic Index Table 1. FLIPI: Follicular Lymphoma International Prognostic Index Table 2 BM state positive: including morphological and minimal bone marrow involvement. Table 2. BM state positive: including morphological and minimal bone marrow involvement. Figure Figure. Disclosures Ishikawa: Mundipharma KK: Research Funding.

scholarly journals BONE MARROW IN FOLLICULAR LYMPHOMA PROGNOSIS

2016 ◽  
Vol 15 (3) ◽  
pp. 99-102 ◽  
Author(s):  
N. N. Tupitsyn ◽  
N. A. Falaleeva ◽  
A. V. Mozhenkova ◽  
A. I. Pavlovskaya
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Follicular Lymphoma ◽  
Histological Study ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Prognostic Role ◽  
Long Time

Background. Bone marrow is the mostfrequent metastatic site in follicular lymphoma, 40-70 % cases. It’s unfovourable prognostic role is stated in the index FLIPI-2 (Follicular Lymphoma International Prognostic Index-2). Objective. To study both prognostic role of bone marrow involvement and it’s relation to erythropoiesis peculiarities in follicular lymphoma was the purpose of this research. Materials and methods. Histological study was performed in 269 follicular lymphoma patients. Erythropoiesis peculiarities were studied in that patients according to standard myelogram analysis. Results. Bone marrow involvement was noted according to trephine biopsy section staining in 37,9 % of follicular lymphoma case (102 from 269). Bone marrow involvement did not influenced the prognosis (overall survival) in all period of observation (p = 0,18). Longterm survival (more than 48 months) was negatively influenced by bone marrow involvement (p = 0,04). Intertrabecular pattern of follicular lymphoma growth in bone marrow was negative prognostic factor (p = 0,02). We noted negative correlation between bone marrow involvement and the elevation of orthochromic normoblasts in bone marrow of patients with follicular lymphoma. In cause of bone marrow such elevation was noted in 67 %, and in the absense of involvement - in 78 % (p = 0,043). Elevation of orthochromic normoblasts did not influenced the overall survival of follicular lymphoma patients (p = 0,89). Conclusion. Bone marrow involvement in follicular lymphoma plays prognostically unfavourable role in long-time observation periods (later than 48 months). The most unfavourable are the intertrabecular patchy lesions. Involvement of bone marrow is in opposite relations to elevation of orthochromic normoblast, but the latter sign is of no prognostic significance.

Tositumomab and Iodine I-131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma: Median 10 Year Follow-up Results.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3759-3759 ◽  
Author(s):  
Mark S. Kaminski ◽  
Melissa Tuck ◽  
Judith Estes ◽  
Arne Kolstad ◽  
Charles Warren Ross ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Hormone Replacement ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Therapeutic Regimen ◽  
Risk Scores ◽  
Hematologic Toxicity ◽  
Label Use

Abstract Abstract 3759 Poster Board III-695 Purpose Tositumomab and iodine I 131 tositumomab (Bexxar® Therapeutic Regimen) has been found effective in relapsed/refractory follicular lymphoma. We now report updated results of a single center, single-arm, Phase II trial of a single one-week course of this treatment for 76 previously untreated, stage III and IV, follicular lymphoma patients (reporting period June 1996 to May 2009). Patients and Methods Patients had a median age of 49 years (range 23 to 69) and received a dosimetric dose followed by a single total body dose of 75 cGy iodine I-131 tositumomab one week later. Seventy percent had stage IV disease and 70% of patients had histological grade 1 follicular lymphoma, 29% had grade 2, and 1 patient had mantle-cell lymphoma. Bone marrow involvement was present in 64% of patients; 43% of patients had at least one tumor 3 5 cm in diameter; LDH was elevated in 30%. Overall, 35% of patients had high risk Follicular Lymphoma International Prognostic Index (FLIPI) scores and 50% had intermediate risk scores. Patients entered long-term follow-up after disease progression or after 2 years on study. Response, second malignancy occurrence and thyroid medication use were assessed every 6 months for 5 years and yearly thereafter up to 12 years post treatment. Results As previously reported (NEJM 352:441, 2005), the overall response rate was 97% with 57 patients (75%) achieving a complete remission. Hematologic toxicity, although common, was modest to moderate (grade 4 neutropenia in 5% of patients and no grade 4 thrombocytopenia). After a median of 10 years follow-up (range 0.7 to 12.3 years), the median duration of response was 6 years (95% CI: 2.5, 10.8), with approximately 40% remaining progression-free at 10 years. For the 57 complete responders, median progression-free survival was 10.9 years (95% CI: 8.3, NR). Ten-year overall survival was approximately 82%. Five cases (7%) of hypothyroidism occurred 0.5 to 2.9 years after treatment and were managed with thyroid hormone replacement. Eleven patients (14%) were diagnosed with second malignancies including 4 skin neoplasms (2 basal cell and 2 squamous cell) and 7 visceral neoplasms (3 breast, 2 prostate, 1 endometrial cancer, 1 glioblastoma). One case of myelodsyplastic syndrome was diagnosed about 8 years after treatment. Conclusion A single course of treatment with Bexxar therapeutic regimen can commonly produce durable responses, especially durable complete responses lasting over a decade in patients with untreated follicular lymphoma. Further studies comparing this monotherapy to other regimens, including combination therapies, are warranted. Disclosures: Kaminski: GlaxoSmithKline: Honoraria, Patents & Royalties, Research Funding, Speakers Bureau. Off Label Use: Radioimmunotherapeutic for treatment of frontline treatment of follicular lymphoma. On-label use is for relapsed/refractory patients. Horner:GlaxoSmithKline: Employment. Williams:GlaxoSmithKline: Employment. Vleisides:GlaxoSmithKline: Employment. Wahl:Nordion: Honoraria; GlaxoSmithKline: Patents & Royalties.

Fractionated 90Y-Ibritumomab Tiuxetan Radioimmunotherapy As an Initial Therapy of Follicular Lymphoma: An International Phase II Study in Patients Requiring Treatment According to GELF/BNLI Criteria

2014 ◽  
Vol 32 (3) ◽  
pp. 212-218 ◽  
Author(s):  
Tim M. Illidge ◽  
Sam Mayes ◽  
Ruth Pettengell ◽  
Andrew T. Bates ◽  
Mike Bayne ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Complete Response ◽  
Initial Therapy ◽  
Hematologic Toxicity ◽  
Ibritumomab Tiuxetan ◽  
Free Survival

Purpose We report an international, multicenter phase II trial to evaluate the efficacy and toxicity of fractionated 90Y-ibritumomab tiuxetan (90Y-IT) as initial therapy of follicular lymphoma (FL). Patients and Methods A total of 74 patients, with a median age of 61 years (range, 28 to 80 years), were recruited requiring initial therapy by Groupe d'Etude des Lymphomes Folliculaires (GELF)/British National Lymphoma Investigation (BNLI) criteria. Among them, 78% had stage III-IV disease, 32% intermediate, and 44% high-risk (according to FL International Prognostic Index). Treatment consisted of two doses of 90Y-IT (11.1 MBq/kg) administered 8 to 12 weeks apart. Patients with more than 20% lymphoma infiltration of bone marrow (BM) received one infusion per week for 4 consecutive weeks of rituximab (375 mg/m2) and proceeded to fractionated radioimmunotherapy (RIT) only if a repeat BM biopsy demonstrated clearing of lymphoma to less than 20% involvement. The primary end point was end of treatment response of the intention-to-treat population. Secondary objectives were safety and progression-free survival (PFS). Results Initial overall response rate (ORR) was 94.4% (68 of 72 patients) with combined complete response (CR/CRu) of 58.3% (42 of 72 patients). Nine patients subsequently improved response making an ORR of 95.8% (69 of 72 patients) and CR/CRu of 69.4% (50 of 72 patients). At a median follow-up of 3.1 years (range, 0.2 to 5.2 years) estimated 3-year PFS is 58%, treatment-free survival 66%, and overall survival 95%. Median PFS is 40.2 months. Thirty patients have experienced disease progression and 24 have required further treatment. The treatment was well tolerated with few (2.8%) grade 3 or 4 infectious episodes or adverse events and manageable hematologic toxicity. Conclusion Fractionated RIT using 90Y-IT is an effective initial treatment for advanced-stage FL in patients with higher tumor burden requiring treatment.

Prognostic impact of concordant and discordant cytomorphology of bone marrow involvement in patients with diffuse, large, B-cell lymphoma treated with R-CHOP

2013 ◽  
Vol 66 (5) ◽  
pp. 420-425 ◽  
Author(s):  
Hyoeun Shim ◽  
Jae-Il Oh ◽  
Sang Hyuk Park ◽  
Seongsoo Jang ◽  
Chan-Jeoung Park ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
International Prognostic Index Score ◽  
Large B Cell Lymphoma

BackgroundBone marrow involvement confers a poor prognosis in patients with diffuse, large, B-cell lymphoma (DLBCL). However, the prognostic significance of concordant and discordant bone marrow involvement in these cases differs. We analysed this further in patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) at a single institute.Design and MethodsThe cytomorphology of bone marrow involvement was evaluated in 632 patients who were diagnosed with DLBCL in primary tissues and had received R-CHOP therapy. Bone marrow trephine biopsies and clot sections were analysed, along with the immunohistochemical analysis of CD20, CD79a and CD3.ResultsBone marrow involvement was identified in 80 of our DLBCL patient subjects (12.7%). Of these, 32 (40%) showed discordant bone marrow involvement, and 48 (60%) showed concordant involvement. Kaplan–Meier survival analysis showed that progression-free survival and overall survival was poorer in the concordant group (p<0.001). Multivariate analysis, adjusted for the International Prognostic Index score, showed that concordant involvement was an independent predictor of progression-free survival (p<0.001) and overall survival (p=0.011). Discordant involvement was not a negative prognostic factor independent of the International Prognostic Index.ConclusionsPrognostication based on bone marrow involvement cytomorphology is a useful indicator of progression-free survival and overall survival, independent of the International Prognostic Index score, in DLBCL patients. Accurate staging based on morphology should thus be included in bone marrow examinations of such cases.

Obinutuzumab short-duration infusion (SDI) in previously untreated advanced follicular lymphoma: Results from the end of induction analysis of the phase IV GAZELLE study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7545-7545
Author(s):  
Miguel Angel A. Canales Albendea ◽  
Thomas A. Buchholz ◽  
Koji Izutsu ◽  
Takayuki Ishikawa ◽  
Laura Maria Fogliatto ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Complete Response ◽  
Primary Analysis ◽  
Open Label ◽  
Secondary Endpoints ◽  
To Receive ◽  
Phase Iv

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]

Phase III Study of R-CVP Compared With Cyclophosphamide, Vincristine, and Prednisone Alone in Patients With Previously Untreated Advanced Follicular Lymphoma

2008 ◽  
Vol 26 (28) ◽  
pp. 4579-4586 ◽  
Author(s):  
Robert Marcus ◽  
Kevin Imrie ◽  
Philippe Solal-Celigny ◽  
John V. Catalano ◽  
Anna Dmoszynska ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Response Duration ◽  
Complete Response ◽  
Phase Iii ◽  
Term Outcome ◽  
Bulky Disease ◽  
Long Term Outcome ◽  
Trial Treatment

PurposeTo compare the long-term outcome of patients with previously untreated follicular lymphoma (FL) needing therapy, after treatment with cyclophosphamide, vincristine and prednisone (CVP) versus CVP plus rituximab (R-CVP) and to evaluate the predictive value of known prognostic factors after treatment with R-CVP.Patients and MethodsPatients with previously untreated CD20-positive stage III/IV FL were randomly assigned to eight cycles of R-CVP (n = 159) or CVP alone (n = 162). The median follow-up period was 53 months.ResultsThe primary end point—time to treatment failure (TTF), which included patients without a response after four cycles as an event—was significantly prolonged in patients receiving R-CVP versus CVP (P < .0001). Improvements in all other end points, including overall and complete response rates (P < .0001), time to progression (TTP; P < .0001), response duration (P < .0001), time to next antilymphoma treatment (P < .0001), and overall survival (OS; P = .029; 4-year OS: 83% v 77%;) were achieved with R-CVP versus CVP alone. Univariate analyses demonstrated an improvement in TTP with R-CVP versus CVP irrespective of the Follicular Lymphoma International Prognostic Index (FLIPI) subgroup, the International Prognostic Index (IPI) subgroup, baseline histology, and the presence or absence of B symptoms or bulky disease. By multivariate analysis, FLIPI retains a strong predictive power for TTP in the presence of the trial treatment effect.ConclusionAnalysis of all outcome measures, including OS, confirm the benefit of adding R to CVP in the front-line treatment of FL.

The Follicular Lymphoma International Prognostic Index (FLIPI) as Part of a Proposed Prognostic Model for Follicular Lymphoma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation (ASCT).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 12-12 ◽  
Author(s):  
Grant E. Keeney ◽  
Theodore A. Gooley ◽  
Oliver W. Press ◽  
John M. Pagel ◽  
Stephen H. Petersdorf ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Median Number ◽  
Hematopoietic Stem ◽  
Prior Chemotherapy ◽  
Five Factors ◽  
Grade 3

Abstract The FLIPI has recently been demonstrated to correlate with survival in patients (pts) with newly diagnosed follicular lymphoma (FL). No such index has been developed or evaluated to predict outcome for FL pts in the setting of myeloablative therapy and ASCT, despite data suggesting that ASCT may improve overall and progression-free survival (PFS). We examined the factors that contribute to the FLIPI as well as other factors assessed at time of transplant for their association with overall survival (OS) in 189 pts undergoing ASCT for FL. Baseline characteristics included: median age = 47 years (range, 24 – 64), stage III–IV = 94%, &gt;4 nodal areas = 7.7%, elevated LDH = 30%, &gt;5 cm maximal bulk of disease = 18%, chemoresistant disease = 13%, median number of prior chemotherapy regimens = 2. The FL histologies included: Grade 1 (49%), Grade 2 (31%), Grade 3 (13%), and transformation to diffuse large B-cell lymphoma (6%). Patients were conditioned with chemotherapy-only (21%), chemo+TBI (45%), or radioimmunotherapy +/− chemo (34%). Among all pts, the five-year estimated OS and PFS are 58% and 39%, respectively, with a median follow-up among surviving pts of 8 years (range, 1 – 18). The five factors that were found to be most significantly associated with OS include two FLIPI factors [age, hazard ratio for death (HR) = 1.37 per ten-year increase in age; elevated LDH, HR = 1.57] and three other clinical factors [&gt;1 maximal extranodal site of disease, HR = 1.67; ≥2 prior chemotherapy regimens, HR = 1.99; chemoresistant disease, HR = 2.8]. Patients with 0 – 1 adverse factors (with age dichotomized as &lt; 45 vs. ≥ 45) had an estimated 5-year OS of 79%, those with 2 factors 50%, 3 factors 41%, 4 or 5 factors 13% (Figure). Although prospective validation of this proposed model is required, this approach may be used to counsel FL pts regarding expected outcome following ASCT, to compare data between trials, and to design future studies. Figure Figure

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