scholarly journals Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study

2019 ◽  
Vol 37 (31) ◽  
pp. 2815-2824 ◽  
Author(s):  
Emmanuel Bachy ◽  
John F. Seymour ◽  
Pierre Feugier ◽  
Fritz Offner ◽  
Armando López-Guillermo ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Long Term Results ◽  
Induction Treatment ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
To Receive

PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582 ) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (> 18 years of age) with previously untreated high–tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m2, once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P < .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.

scholarly journals Short Course of Bendamustine and Rituximab Followed By 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naive Follicular Lymphoma (FOL-BRITe): Final Report of Response Rates and Progression Free Survival

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1793-1793 ◽  
Author(s):  
Cristiana A Costa ◽  
Bassem I Zaki ◽  
Stephanie P Yen ◽  
Eric S Winer ◽  
Helen Ryan ◽  
...  
Keyword(s):  
Partial Response ◽  
Follicular Lymphoma ◽  
Myeloid Leukemia ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
To Receive

Abstract Background: Y90-Ibritumomab tiuxetan (90YIT) is approved for use for follicular lymphoma (FL) patients who have achieved a complete or partial response to frontline chemotherapy; however, its use after bendamustine and rituximab (BR) has not been reported. BR has proven to be a superior frontline therapy over R-CHOP in the treatment of FL and is a widely used initial treatment strategy. This analysis focuses on the long-term outcomes and safety of untreated follicular lymphoma patients treated with a short induction course of BR for 4 cycles followed by consolidation with 90YIT. Methods: Patients greater than 18 years with chemotherapy-naïve FL (grade 1-2 and 3a) requiring treatment were eligible. All patients had Stage II-IV disease and had adequate hematologic, liver, and renal function. Treatment consisted of an initial dose of rituximab 375 mg/m2. One week later, bendamustine 90 mg/m2 was administered on days 1 and 2, and rituximab 375 mg/m2 was given on day 1. BR was given for 4 cycles every 28 days. Patients were restaged 4-6 weeks after the last dose of BR. Patients were eligible for consolidation with 90YIT if they obtained at least a partial response after induction, had a platelet count greater than 100,000/mm3, a granulocyte count greater than 1,500/mm3, and bone marrow infiltration less than 25%. 90YIT was given 6-12 weeks after completion of the last cycle of BR. The primary endpoint is complete and unconfirmed complete response (CR/CRu) rate after sequential therapy with BR followed by 90YIT. Secondary endpoints are overall response rate after 4 cycles of BR, conversion rate from partial response (PR) after BR to CR/CRu after 90YIT, progression-free survival, and safety. The 1999 NHL Working Group Criteria was used to assess response. Results: From October 2010 to May 2014, forty-four patients were enrolled in this study (NCT01234766). 39 patients initiated treatment, and 5 were screen failures. Median age was 57 years [range 31-75]. The study enrolled FLIPI low (18%), intermediate (44%), and high (38%) risk patients; 33 of 39 (85%) were Grade 1-2 and 6 (15%) were Grade 3a. Twenty-two of 39 patients achieved CR/CRu (56%) and 16 of 39 patients had a PR (41%) for an overall response rate (ORR) of 97%. One patient had stable disease (SD). Four patients were not randomized to receive 90YIT: one in CR and one in PR were unable to receive 90YIT due to thrombocytopenia, one only achieved SD after BR, and one declined treatment. Thirty of 35 evaluable patients were in CR/CRu (86%), 4 remained in PR (11%) after 90YIT and one progressed during 90YIT, for an ORR of 97%. The number of patients in PR after BR who reached CR/CRu immediately after 90YIT were 10 of 16 (63%). Three (19%) additional patients converted to CR/CRu during follow-up, the latest occurring 16 months after 90YIT. After a median follow up of 30 months, 25 patients (71%) remain in CR/CRu, 10 patients (29%) have progressed/relapsed with a 24-month PFS of 80% (95% CI 63-90) [Figure]. The median PFS was not reached. Grade 3-4 hematologic toxicities during the 90YIT period included: neutropenia (34%), leukopenia (37%), thrombocytopenia (40%), lymphopenia (15%), and anemia (6%). There were no incidences of febrile neutropenia. One patient developed JC Virus/Progressive Multifocal Leukoencephalopathy, 13 months after receiving the last dose of rituximab and 90YIT on study. One patient developed chronic myeloid leukemia 11 months after, one patient developed acute myeloid leukemia 15 months after, and one patient developed uterine cancer 52 months after all study treatment. One patient died to progression of the lymphoma, 35 months after treatment. There have been no reported cases of myelodysplasia. Conclusions: In this 2.5 year report of patients that received BR followed by 90YIT, the CR/CRu rate of patients completing all study therapy is 71% and the 24-month PFS is 80%. There is a high rate of conversion in partial responders to CR/CRu (81%), some occurring more than one year after treatment with 90YIT. The durable PFS is comparable to what is reported in the FIT trial (Morschhauser et al. JCO 2013) and the phase II Spanish intergroup study (Canales et al. ASH 2013). BR followed by 90YIT is a well-tolerated regimen for follicular lymphoma with high response rates that is a safe and highly effective as first-line therapy. Long-term safety reflects the natural history of patients with indolent lymphomas. Figure Figure. Disclosures Lansigan: Pharmacyclics: Consultancy; Teva: Research Funding; Celgene: Consultancy; Spectrum: Consultancy, Research Funding.

scholarly journals Long-Term Results of the FOLL05 Trial Comparing R-CVP Versus R-CHOP Versus R-FM for the Initial Treatment of Patients With Advanced-Stage Symptomatic Follicular Lymphoma

2018 ◽  
Vol 36 (7) ◽  
pp. 689-696 ◽  
Author(s):  
Stefano Luminari ◽  
Angela Ferrari ◽  
Martina Manni ◽  
Alessandra Dondi ◽  
Annalisa Chiarenza ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Long Term Results ◽  
Advanced Stage ◽  
Free Survival ◽  
Time To Treatment ◽  
Time To Treatment Failure

Purpose The FOLL05 trial compared R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone) with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-FM (rituximab plus fludarabine and mitoxantrone) regimens without rituximab maintenance as initial therapy for patients with advanced-stage follicular lymphoma (FL). A previous analysis with a median follow-up of 34 months showed a superior 3-year time to treatment failure, the primary study end point, with R-CHOP and R-FM versus R-CVP and showed R-CHOP to have a better risk-benefit ratio in terms of toxicity than R-FM. We report a post hoc analysis of this trial after a median follow-up of 7 years. Patients and Methods Of the 534 enrolled patients, 504 were evaluable. At the time of analysis, the median follow-up was 84 months (range, 1 to 119 months). Results The 8-year time to treatment failure and progression-free survival rates were 44% (95% CI, 39% to 49%) and 48% (95% CI, 43% to 53%), respectively. The hazard ratio for progression-free survival adjusted by FL International Prognostic Index 2 versus R-CVP was 0.73 for R-CHOP (95% CI, 0.54 to 0.98; P = .037) and 0.67 for R-FM (95% CI, 0.50 to 0.91; P = .009). The 8-year overall survival (OS) rate was 83% (95% CI, 79% to 87%), with no significant differences among study arms. Overall, we observed a higher risk of dying as a result of causes unrelated to lymphoma progression with R-FM versus R-CVP. Conclusion With an 83% 8-year OS rate, long-term follow-up of the FOLL05 trial confirms the favorable outcome of patients with advanced-stage FL treated with immunochemotherapy. The three study arms had similar OS but different activity and toxicity profiles. Patients initially treated with R-CVP had a higher risk of lymphoma progression compared with those receiving R-CHOP, as well as a higher risk of requiring additional therapy.

Updated Results of the PRIMA Study Confirms the Benefit of 2-Years Rituximab Maintenance In Follicular Lymphoma Patients Responding to Immunochemotherapy.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1788-1788 ◽  
Author(s):  
Gilles Andre Salles ◽  
John Catalano ◽  
Pierre Feugier ◽  
Fritz C Offner ◽  
Reda Bouabdallah ◽  
...  
Keyword(s):  
Adverse Events ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Induction Treatment ◽  
First Line ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Treatment Characteristics

Abstract Abstract 1788 The GELA-sponsored intergroup PRIMA Phase III study was designed to investigate the potential benefit of 2-years of rituximab maintenance in high tumour burden follicular lymphoma patients responding to one of three non-randomised first line immunochemotherapy treatments. The results of the pre-planned interim analysis with 24 months median follow-up were positive and demonstrated a significant reduction in the risk of progression for patients randomized to rituximab maintenance (Salles et al., ASCO 2010). We present here the updated efficacy and safety results after an additional year of follow-up, when all randomized patients had completed the observation/maintenance period. From December 2004 until April 2007, 1217 patients were enrolled from 223 centres. Complete data are available for 1193 patients who had the following pre-induction treatment characteristics: median age 56 years [range 22–87]; 52% male; 90% Ann Arbor stage III-IV; 33% B symptoms; 55% bone marrow involvement; 4% ECOG performance status >1; 34% elevated LDH; 32% β2-microglobulin≥3mg/L; FLIPI score 0–1 (21%), FLIPI 2 (36%), FLIPI 3–5 (43%). Most patients (74%) received R-CHOP induction (22% R-CVP, 4% R-FCM). Patients responding to induction therapy were stratified based on their immunochemotherapy regimen and response [CR/CRu versus PR], and randomized to observation or rituximab maintenance, 1 infusion (375 mg/m2) every 8 weeks for 2 years. A total of 1018 randomised patients were analyzed according to the ITT principle (513 observation/505 rituximab maintenance). All initial pre-treatment characteristics were well balanced between arms and the response status at time of randomization was CR=39%; CRu=31% and PR=29% (others 1%). After a median follow-up of 36 months, 3-year progression free survival was 60.3% (95% confidence interval [CI] 55.8 – 64.5%) in the observation arm and 78.6% (95% CI 74.7 – 82%) in the rituximab maintenance arm, respectively (stratified Log-Rank, P<.0001; hazard ratio [HR]=0.55, 95% CI 0.44 – 0.68). In pre-planned analyses of patient subgroups categorized by age, sex, FLIPI score, induction chemotherapy and response to induction, the effect of rituximab maintenance was found to be consistent with the overall study results. In a Cox regression multivariate analysis, older age (P=.0013), male sex (P=.013), higher FLIPI group (P<.0001), R-CVP induction treatment (P=.003) and rituximab maintenance (P<.0001) were all significant variables associated with inferior progression free survival. A significant reduction in the number of patients starting a new anti-lymphoma treatment (HR=0.60, 95% CI 0.47 – 0.76) or starting a new chemotherapy (HR=0.62, 95% CI 0.47 – 0.81) was also observed for rituximab maintenance. Regarding response to treatment, 52% of the patients that were in PR at the time of randomization converted to CR or CRu at the end of 2-year maintenance in the rituximab maintenance arm compared to 30% of patients in the observation arm (P=.0001). As a result, 361 out of 482 patients evaluated (75%) in the rituximab maintenance arm were in CR or CRu as compared to 268 out of 491 patients evaluated (55%) in the observation arm (P< .0001). At the time of the data cut-off, 30 patients (6%) had died in the observation arm compared to 26 patients (5%) in the rituximab maintenance arm (HR=0.87, 95% CI 0.51 – 1.47). The most common adverse events reported were infections, which occurred in 24% and 39% of the patients in the observation and rituximab maintenance arms respectively. Grade 3–4 adverse events were reported in 17% of patients in the observation arm and 24% in the rituximab maintenance arm (neutropenia 1% vs 4%; infections 1% vs 4%, respectively) but these lead to treatment discontinuation in only 8 and 19 patients, respectively. In conclusion, after an additional year of follow-up, these data demonstrate a sustained benefit of 2 years of rituximab maintenance therapy after immunochemotherapy, resulting in improved progression free survival and complete response rates. No additional or unexpected toxicities were observed. All randomized patients have an excellent survival to date and longer follow-up will explore factors affecting overall survival in these patients. The PRIMA results indicate that rituximab maintenance should be considered in all follicular lymphoma patients who have responded to first line immunochemotherapy. Disclosures: Salles: Roche: Consultancy, Honoraria. Off Label Use: The use of rituximab maintenance in follicular lymphoma patients. Catalano:Celgene: Research Funding; Roche: Honoraria, Research Funding, Travel Grants. Feugier:roche: Consultancy, Honoraria. Belada:Roche: Consultancy, Honoraria. Tilly:Amgen: Honoraria. Leppa:Roche: Honoraria. Soubeyran:Roche: Honoraria, Research Funding. Hagenbeek:roche: Consultancy. Lister:Allos: Consultancy; Bioconnections: Consultancy; Astra Zeneca: Consultancy; Tenet: Consultancy; GSK: Chairman of Safety Monitoring Committee. Lopez-Guillermo:Roche: Consultancy, Honoraria. Seymour:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel support; Bayer-Schering: Honoraria, Travel Support.

scholarly journals Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial

2020 ◽  
Vol 38 (3) ◽  
pp. 248-256 ◽  
Author(s):  
Hanneke C. Kluin-Nelemans ◽  
Eva Hoster ◽  
Olivier Hermine ◽  
Jan Walewski ◽  
Christian H. Geisler ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Random Assignment ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Mantle Cell ◽  
Grade 3

PURPOSE In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209 ), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years ( P < .001) and 7.1 years ( P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe.

Radiation ±cisplatin for bulky stage IB cervical carcinoma; Long-term follow-up of a GOG trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5015-5015
Author(s):  
F. B. Stehman ◽  
S. Ali ◽  
D. G. Gallup ◽  
H. Key
Keyword(s):  
Cervical Carcinoma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stage Ib ◽  
Long Term Follow Up ◽  
Weekly Cycles ◽  
To Receive ◽  
Weekly Cisplatin

5015 Purpose: To confirm that concurrent cisplatin (CT) with radiation (RT) is associated with improved long-term progression-free survival (PFS), overall survival (OS), and decreased morbidity compared to RT stage IB bulky carcinoma of the cervix, when both groups’ therapy is followed by hysterectomy. Methods: Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT+RT. Radiation dosage was 40 Gray (Gy) in 20 fractions followed by a single low dose-rate intracavitary application of 30 Gy to Point A. Chemotherapy consisted of cisplatin 40 mg/M2 every week for up to six weekly cycles. Total extrafascial hysterectomy followed the completion of RT by 3–6 weeks. Results: Preliminary results have been published, at which time there many censored observations and limited follow-up. Patient and tumor characteristics were well-balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is 101 months. The relative risk for progression was 0.61 favoring CT+RT (95% confidence interval [CI]: 0.43–0.85, p < 0.004). At 72 months 71% of patients receiving CT+RT were predicted to be alive and disease-free when adjusting age and for tumor size compared to 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI: 0.43–0.91, p < 0.015) favoring CT+RT. At 72 months, 78% of CT+RT patients were predicted to be alive compared to 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT+RT. There was no detectable difference in the frequency of late adverse events. Conclusion: Concurrent weekly cisplatin with RT significantly improves long term PFS and OS when compared to RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens must be compared. Key Words: Cervical carcinoma, chemoradiotherapy. No significant financial relationships to disclose.

Long-Term Results of the HD2000 Trial Comparing ABVD Versus BEACOPP Versus COPP-EBV-CAD in Untreated Patients With Advanced Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi

2016 ◽  
Vol 34 (11) ◽  
pp. 1175-1181 ◽  
Author(s):  
Francesco Merli ◽  
Stefano Luminari ◽  
Paolo G. Gobbi ◽  
Nicola Cascavilla ◽  
Caterina Mammi ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cumulative Risk ◽  
Progression Free Survival ◽  
Long Term Results ◽  
Entire Group ◽  
Second Malignancies ◽  
Free Survival ◽  
Post Hoc

Purpose The randomized HD2000 trial compared six cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), four escalated plus two standard cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and six cycles of COPP-EBV-CAD (cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxorubicin, vincristine, procarbazine, vinblastine, and bleomycin; CEC) in patients with advanced-stage Hodgkin lymphoma. After a median follow-up of 42 months, patients who received BEACOPP were reported to have experienced better progression-free survival (PFS) but not better overall survival (OS) results than those receiving ABVD. We here report a post hoc analysis of this trial after a median follow-up of 10 years. Patients and Methods Three hundred seven patients were enrolled, 295 of whom were evaluable. At the time of our analysis, the median follow-up for the entire group was 120 months (range, 4 to 169 months). Results The 10-year PFS results for the ABVD, BEACOPP, and CEC arms were 69%, 75%, and 76%, respectively; corresponding OS results were 85%, 84%, and 86%. Overall, 13 second malignancies were reported: one in the ABVD arm and six each in the BEACOPP and CEC arms. The cumulative risk of developing second malignancies at 10 years was 0.9%, 6.6%, and 6% with ABVD, BEACOPP, and CEC, respectively; the risk with either BEACOPP or CEC was significantly higher than that reported with ABVD (P = .027 and .02, respectively). Conclusion With these mature results, we confirm that patients with advanced Hodgkin lymphoma have similar OS results when treated with ABVD, BEACOPP, or CEC. However, with longer follow-up, we were not able to confirm the superiority of BEACOPP over ABVD in terms of PFS, mainly because of higher mortality rates resulting from second malignancies observed after treatment with BEACOPP and CEC.

scholarly journals Prolonged rituximab maintenance in follicular lymphoma patients: long-term results of the SAKK 35/03 randomized trial

2020 ◽  
Vol 4 (23) ◽  
pp. 5951-5957
Author(s):  
Alden A. Moccia ◽  
Christian Taverna ◽  
Sämi Schär ◽  
Anna Vanazzi ◽  
Stéphanie Rondeau ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Randomized Trial ◽  
Long Term Results ◽  
Short Term ◽  
Free Survival ◽  
Long Term Treatment ◽  
Significant Difference ◽  
Term Maintenance

Abstract The Swiss Group for Clinical Cancer Research (SAKK) conducted the SAKK 35/03 randomized trial (NCT00227695) to investigate different rituximab monotherapy schedules in patients with follicular lymphoma (FL). Here, we report their long-term treatment outcome. Two-hundred and seventy FL patients were treated with 4 weekly doses of rituximab monotherapy (375 mg/m2); 165 of them, achieving at least a partial response, were randomly assigned to maintenance rituximab (375 mg/m2 every 2 months) on a short-term (4 administrations; n = 82) or a long-term (up to a maximum of 5 years; n = 83) schedule. The primary end point was event-free survival (EFS). At a median follow-up period of 10 years, median EFS was 3.4 years (95% confidence interval [CI], 2.1-5.5) in the short-term arm and 5.3 years (95% CI, 3.5-7.5) in the long-term arm. Using the prespecified log-rank test, this difference is not statistically significant (P = .39). There also was not a statistically significant difference in progression-free survival or overall survival (OS). Median OS was 11.0 years (95% CI, 11.0-NA) in the short-term arm and was not reached in the long-term arm (P = .80). The incidence of second cancers was similar in the 2 arms (9 patients after short-term maintenance and 10 patients after long-term maintenance). No major late toxicities emerged. No significant benefit of prolonged maintenance became evident with longer follow-up. Notably, in symptomatic patients in need of immediate treatment, the 10-year OS rate was 83% (95% CI, 73-89%). These findings indicate that single-agent rituximab may be a valid first-line option for symptomatic patients with advanced FL.

Chemotherapy plus radiotherapy (CT-RT) versus RT alone for patients with anaplastic oligodendroglioma: Long-term results of the RTOG 9402 phase III study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2008b-2008b ◽  
Author(s):  
J. Gregory Cairncross ◽  
Meihua Wang ◽  
Edward G. Shaw ◽  
Robert B. Jenkins ◽  
Bernd W. Scheithauer ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Long Term Results ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Entire Cohort ◽  
Phase Iii Study

2008b Background: Anaplastic oligodendrogliomas, pure (AO) and mixed (AOA), are chemosensitive tumors, especially if co-deleted for chromosomes 1p and 19q, but whether addition of CT to RT prolongs overall survival (OS), is unknown. Methods: In the RTOG 9402 Phase III trial, patients (pts) with AO/AOA were randomly assigned to PCV [procarbazine, CCNU (lomustine) and vincristine] followed by immediate RT vs. immediate RT alone. Early analysis showed no OS benefit for the PCV+RT group but combined therapy was associated with a longer progression-free survival (PFS). It also showed that the finding of 1p/19q co-deletion was associated with a longer OS independent of treatment. The current analysis has a median follow up of 11.3 years (yrs). Results: Two hundred ninety-one patients were randomized, 148 to PCV+RT and 143 to RT. PCV+RT was associated with longer PFS [2.5 vs. 1.7 yrs, hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.53, 0.88), P = 0.003] and the 1p/19q co-deletion with a longer Median Survival Time (MST) [8.7 vs. 2.7 yrs, HR 0.41, 95% CI (0.30, 0.55), P < 0.001]. For the entire cohort, there was no difference in MST by treatment [4.6 yrs for PCV+RT vs. 4.7 yrs for RT, HR 0.79, 95% CI (0.60, 1.04), P = 0.1]. However, patients with 1p/19q co-deleted tumors lived much longer after PCV+RT (n = 59) than after RT (n = 67) [14.7 vs. 7.3 yrs, HR 0.59, 95% CI (0.37, 0.95), P = 0.03]. There was no difference in MST by treatment in pts without the 1p/19q co-deletion [n=137; 2.6 vs. 2.7 yrs, HR 0.85, 95% CI (0.58, 1.23), P = 0.39]. Re-operation rates upon progression were similar between treatment arms in co-deleted pts (43%, PCV+RT vs. 54%, RT) but salvage CT rates were higher in the RT arm [57% vs. 81% (P = 0.04)]. Conclusions: PCV followed by immediate RT was a highly effective therapy for patients with 1p/19q co-deleted AO/AOA. In this setting, 1p/19q co-deletion was both prognostic and predictive, and the early PFS benefit in co-deleted cases was a harbinger of their longer OS. [This work was supported by RTOG grants U10 CA21661 and U10 CA32115, NCCTG grant U10 CA25224, ECOG grants CA17145 and CA21115, SWOG grant CA32102, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI)]

scholarly journals Tandem Autologous Followed By Nonmyeloablative Allogeneic Transplantation in Relapsed High Risk Follicular Lymphoma Leads to Excellent Long Term Progression-Free Survival after 8 Years of Follow-up

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4677-4677
Author(s):  
Magalie Tardif ◽  
Imran Ahmad ◽  
Nadia M. Bambace ◽  
Lea Bernard ◽  
Lambert Busque ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Median Time ◽  
Progression Free Survival ◽  
Disease Status ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival

Abstract Many new therapeutic agents have been approved for follicular lymphoma (FL) but none appear to be curative. Despite novel agents, some patients (pts) experience early relapse, become chemorefractory or suffer transformation into more aggressive lymphomas. Options for these pts are limited. High dose chemotherapy with autologous stem transplant (ASCT) prolongs progression free survival (PFS) and overall survival (OS) in FL pts in first relapse and registry data shows favorable outcome with ASCT in cases of histologic transformation. However, ASCT is usually not curative. Myeloablative allogeneic transplant (MT) has produced long term PFS but is hampered by significant non relapse mortality (NRM) while nonmyeloablative transplant (NMT) has a higher relapse rate compared to MT especially in high risk pts. Finally, many transplant studies have excluded these high risk pts such as those with chemorefractory or transformed disease. We hypothesized that a tandem transplant consisting of an ASCT followed by a NMT would confer the same benefit as a MT without the associated high NRM by separating the high dose chemotherapy from graft versus host disease (GVHD) while preserving the graft versus lymphoma effect. The goal of our study was to improve long term PFS in high risk FL pts. We therefore initiated a prospective protocol in April 2003, for pts with high risk relapsed FL as defined by chemorefractory disease, early 1st relapse, >1st relapse or transformation into aggressive histology. At least one therapy was attempted to document chemosensitivity prior to ASCT. However, regardless of disease status prior to transplant, pts underwent ASCT followed 3 months later by an outpatient NMT from an HLA-identical sibling. NMT comprised 5 days of fludarabine 30 mg/m2/day and cyclophosphamide 300mg/m2/day followed by an infusion of >2x106CD34+ cells/kg. GVHD prophylaxis, chosen to take advantage of the low incidence of acute (a) GVHD and the putative protective effect of chronic (c) GVHD, consisted of tacrolimus starting on day (D) - 8 to achieve levels of 8-12 nmol/L then tapered off by D+100 or D+180 depending on disease risk and of mycophenolate mofetil 1g bid from D+2 to D+50. We previously reported on 27 pts with a follow-up (f/u) of 3 years (yrs). We now report a larger cohort of 40 pts with a median f/u of 8 yrs. Up until July 2015, 40 pts were enrolled with a median age of 50 yrs (34-65). Pts had previously been treated with a median of 3 lines of therapy (2-6). Median time from diagnosis to ASCT was 33 months. Disease status at ASCT was: 14 CR, 16 PR and 10 refractory. Conditioning for ASCT included BEAM/BEAC (n=39), and Cy-TBI (n=1). In addition, 4 pts received radiotherapy after ASCT to sites of previously bulky disease. Median time between ASCT and NMT was 138 days (75-238). Pre NMT disease status was: 25 CR, 12 PR and 3 refractory. Engraftment was prompt in all pts after ASCT and median neutrophil and platelet recovery were respectively 13 days (0-19) and 0 day (0-18) post NMT. Seven pts (18%) developed aGVHD: 2 grade II and 5 grade III. Overall, 29 pts (73%) developed cGVHD: 1 mild, 13 moderate and 15 severe according to NIH revised criteria. Median time to discontinuation of immunosuppression was 22 months. To date, 2 pts have progressed at 11 and 59 months post NMT (one died from relapse and one is now in CR after chemotherapy and DLI) and 5 pts died from either GVHD related complications (n=4) or unknown cause (n=1). All pts alive at last f/u were in CR. With a median f/u of 8 yrs in surviving pts (1-12), OS is 95% at 3 and 5 yrs and 82% at 8 yrs. PFS is 92% at 3yrs, 89% at 5 yrs and 80% at 8 yrs. NRM and relapse rate at 8 yrs are 18% and 6% respectively. Based on our current results in 40 pts, we conclude that ASCT followed by sibling NMT for high risk relapsed FL is associated with excellent disease response and PFS. Furthermore, this tandem strategy appears to be safe and well tolerated. The incidence of cGVHD remains high but could in part explain the impressive PFS in this high risk cohort. This approach should now be further explored in a multi institution setting, include matched unrelated donors and consider the addition of rituximab post-transplant to reduce the incidence and severity of cGVHD with the hope that relapse will not be increased. Figure 1 Figure 1. Disclosures Busque: Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

Long-term results of the GEINO 1401 TRIAL: Randomizing patients to stop or to continue temozolomide until 12 cycles.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2013-2013
Author(s):  
Marta Domenech ◽  
Carles Fabregat-Franco ◽  
Carlos Mesia ◽  
Anna Esteve ◽  
Sonia Del Barco Berron ◽  
...  
Keyword(s):  
Methylation Status ◽  
Progression Free Survival ◽  
Long Term Results ◽  
Control Group ◽  
Measurable Disease ◽  
Previously Treated ◽  
And Control ◽  
To Receive

2013 Background: We previously presented our results of the GEINO 1401 trial that randomized patients diagnosed with glioblastoma and treated with chemoradiotherapy and adjuvant temozolomide (TMZ) followed by six cycles of TMZ, to receive an extended use of TMZ up to 12 cycles or to control. We found no differences in 6-months neither progression free survival (PFS) nor overall survival (OS). In this report we actualize our results and analyse long-term survivor patients (LTSP). Methods: The trial NCT02209948 randomized (ratio 1:1) 159 patients diagnosed with glioblastoma who had been treated with standard therapy to stop treatment or to continue up to 12 cycles of TMZ. Patients were stratified based on their O6-methylguanine-DNA-methyltransferasa (MGMT) methylation status and presence or absence of measurable disease at inclusion. We update here OS outcomes and analyse the data of LTSP defined as an OS over 30 months from diagnosis. Results: At a median follow-up of 20 months, 82.4% of the patients had died and 89.9% had progressed. The median OS from randomization was 22.0 months for the control arm and 18.2 for the experimental arm: HR 0.957 (95%CI 0.806-1.136, p = 0.615). At 2 years from randomization there were a 61% of survivors in the TMZ group and 62% in the control group. There were a 49.7% of LTSP showing no differences between TMZ and control group. We found a higher prevalence of methylated MGMT in LTSP, but no differences were shown in patients with or without measurable disease at inclusion, status of IDH and the use of bevacizumab after progression. Conclusions: Adding 6 cycles of TMZ after the first 6 adjuvant cycles confers no additional benefit in OS. Nearly 50% of the patients included in GEINO 1401 who had been previously treated with TMZ 6 cycles without progressing were LTSP. Clinical trial information: NCT02209948.

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