RESPONSE ORIENTED MAINTENANCE THERAPY IN ADVANCED FOLLICULAR LYMPHOMA. RESULTS OF THE INTERIM ANALYSIS OF THE FOLL12 TRIAL CONDUCTED BY THE FONDAZIONE ITALIANA LINFOMI.

2019 ◽  
Vol 37 ◽  
pp. 153-154 ◽  
Author(s):  
M. Federico ◽  
D. Mannina ◽  
A. Versari ◽  
S. Ferrero ◽  
L. Marcheselli ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Interim Analysis

scholarly journals Safety Profile of Idelalisib in Patients with Refractory Follicular Lymphoma: Interim Analysis of a Noninterventional Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-50
Author(s):  
Gilles Salles ◽  
Ka Lung Wu ◽  
Sofya Kovalchuk ◽  
Santiago Mercadal ◽  
Annalisa Chiarenza ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Safety Profile ◽  
Interim Analysis ◽  
Research Funding ◽  
Stage Iii ◽  
Disease Stage ◽  
Stevens Johnson Syndrome ◽  
Risk Of Death ◽  
Registration Trial ◽  
Grade 3

Introduction: Idelalisib, a selective oral inhibitor of PI3Kδ, was approved by the FDA and EMA as monotherapy for patients with advanced follicular lymphoma (FL) based on positive efficacy and safety results from the registration phase 2 trial in patients with indolent non-Hodgkin lymphoma (iNHL) refractory to 2 prior regimens (NCT01282424; 101-09). Phase 3 studies of idelalisib in earlier lines of treatment for iNHL were terminated prematurely due to an increased risk of death and higher incidence of serious adverse events (AEs) associated with idelalisib. Herein, we present the preplanned interim results as of June 8, 2020, of the safety of idelalisib monotherapy in patients with refractory FL treated in the EU from one of the largest noninterventional trials of idelalisib. Methods: This was a noninterventional, partially retrospective cohort study conducted in 10 European countries (EUPAS19618; NCT03568929). Eligible patients were adults aged ≥18 years treated with idelalisib for refractory FL, per the Summary of Product Characteristics and treatment guidelines, in routine clinical practice. Data was collected from patients' medical records and anonymized. Safety events were evaluated and included treatment-emergent AEs (TEAEs), health outcomes of interest (HOIs) requested by the EMA (bowel perforations, Grade ≥3 diarrhea/colitis, progressive multifocal leukoencephalopathy, pneumonitis, Grade ≥3 rash, infections, Stevens-Johnson syndrome, transaminase elevations, and hepatocellular injury), and deaths. TEAEs were defined as AEs that occurred between first dose and 30 days after last dose. Data were summarized using descriptive statistics. Rates per person-year were calculated as the number of patients experiencing an AE divided by the person-time at risk. Results: For the 158 patients included in this analysis, median age was 67 years and 84 (53%) were male. A summary of patient and disease characteristics at baseline are presented in Table 1. At treatment initiation, 47 (30%) patients had grade 2 FL and 105 (66%) had Ann Arbor stage III/IV disease, though these characteristics were not captured for 42% and 20% of patients, respectively; 149 (94%) had ≥2 prior therapies. The median duration of idelalisib exposure was 165 (range 11-1321) days, and patients were observed for a median of 323 (range 12-1676) days. In total, 144 (91%) patients experienced a TEAE, with a rate of 3.36 per person-year. The proportion of patients experiencing Grade 3/4, severe, common, and HOI TEAEs are presented in Table 2. Diarrhea of any grade was the most common TEAE, and infections were the most common treatment-emergent HOI. During the TEAE period, 19 (12%) patients died (Table 2). The proportion of common TEAEs reported in this analysis were lower compared with a subgroup analysis of patients with FL from the registration trial (Salles Haematologica 2017; DOI: 10.3324/haematol.2016.151738), including diarrhea 27% vs 51%, cough 9% vs 32%, fever/pyrexia 10% vs 29%, pneumonia 5% vs 11%; treatment-emergent Grade 3/4 diarrhea/colitis and transaminase elevations were also lower in this analysis: 8% vs 17% and 4% vs 14%. This comparison is limited due to differences in study populations, namely that patients in the registration trial had more advanced disease (stage III/IV, 66% vs 83%) and had a higher median number of prior therapies (3 vs 4). Conclusions: This interim analysis of the safety of idelalisib in patients with refractory FL in this large noninterventional safety study provides an estimate of potential final study findings. The AE profile from this study appears to corroborate the known safety profile of idelalisib. No new safety signals were detected. Disclosures Salles: Bristol Myers Squibb: Consultancy, Other; Genmab: Consultancy; Gilead: Consultancy, Honoraria, Other: Participation in educational events; Epizyme: Consultancy; Abbvie: Consultancy, Honoraria, Other: Participation in educational events; Autolus: Consultancy; Amgen: Honoraria, Other: Participation in educational events; Celgene: Consultancy, Honoraria, Other: Participation in educational events; Debiopharm: Consultancy; Takeda: Consultancy, Honoraria, Other; Novartis: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Other; Janssen: Consultancy, Honoraria, Other: Participation in educational events; Karyopharm: Consultancy; Kite: Consultancy, Honoraria, Other; MorphoSys: Consultancy, Honoraria, Other. Pettengell:Celgene: Honoraria; MEI Pharma: Honoraria; Roche Ltd: Honoraria; Takeda: Honoraria. Vandenberghe:Celgene: Other: sponsorship to attend Lugano lymphoma meeting in 2019; Abbvie: Other: travel grants, Research Funding; Gilead: Other: travel grants, Research Funding; Janssen: Other: travel grants; Roche: Other: travel grants, Research Funding. Corradini:Kiowakirin: Consultancy, Honoraria; Incyte: Consultancy; Gilead: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other; BMS: Other; Servier: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other; Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other; Takeda: Consultancy, Honoraria, Other; AbbVie: Consultancy, Honoraria, Other. De Belder:Gilead Sciences Europe, Ltd.: Current Employment. Shah Gupta:Gilead Sciences, Ltd.: Current Employment. van Troostenburg:Gilead Sciences GmbH: Current Employment. Rajakumaraswamy:Gilead Sciences, Inc.: Current Employment. Ramroth:Gilead Sciences, Ltd.: Current Employment.

POLATUZUMAB VEDOTIN (POLA) + OBINUTUZUMAB (G) + LENALIDOMIDE (LEN) IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL): PHASE IB/II INTERIM ANALYSIS

2019 ◽  
Vol 37 ◽  
pp. 175-176 ◽  
Author(s):  
C. Diefenbach ◽  
B. Kahl ◽  
L. Banerjee ◽  
A. McMillan ◽  
R. Ramchandren ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Interim Analysis ◽  
Phase Ib

Rituximab maintenance therapy for follicular lymphoma

The Lancet ◽  
2011 ◽  
Vol 377 (9772) ◽  
pp. 1150-1151
Author(s):  
Haiyang Zhou ◽  
Beibei Zhang ◽  
Jian Zhang ◽  
Wu Ni ◽  
Zhiqian Hu
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Rituximab Maintenance

Chimeric Anti-CD20 Monoclonal Antibody (Rituximab; Mabtheraâ) in Remission Induction and Maintenance Treatment of Relapsed /Resistant Follicular Non-Hodgkin’s Lymphoma : A Phase III Randomized Intergroup Clinical Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 586-586 ◽  
Author(s):  
Marinus H.J. Van Oers ◽  
Martine Van Glabbeke ◽  
Ivana Teodorovic ◽  
Cynthia Rozewicz ◽  
Richard Klasa ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Follicular Lymphoma ◽  
Interim Analysis ◽  
Hodgkin’S Lymphoma ◽  
Maintenance Treatment ◽  
Initial Diagnosis ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Remission Induction ◽  
Non Hodgkin's Lymphoma

Abstract Background. In view of a) the efficacy of Rituximab (R) monotherapy in relapsed low grade lymphoma; b) the feasibility to combine R with cytostatic drugs c) the potential of such combinations to clear minimal residual disease, in 1999 we started a phase III clinical trial in patients with relapsed follicular non-Hodgkin’s lymphoma, with 2 main objectives. First: to compare CHOP and R-CHOP as to response rate and response quality. Second: to establish the effect of maintenance treatment with R on progression-free survival (PFS ). Study design. Patients with stages III or IV follicular lymphoma at initial diagnosis and relapsed after or resistant to a maximum of two non-anthracycline containing systemic chemotherapy regimens, were randomized to remission induction with either 6 cycles of standard CHOP (once every 3 weeks) or CHOP + R (375 mg /m2 at day 1 of each cycle of CHOP). Those with a complete or partial remission after 6 cycles of therapy underwent a second randomization to no further treatment or maintenance treatment with R (375 mg/m2 once every 3 months until relapse or for a maximum period of two years). Results. In February 2004, a preplanned second interim analysis by the IDMC was performed. At that time 461 patients had been included. Of these, 369 could be evaluated for response (188 CHOP; 181 R-CHOP). The groups did not differ as to age, sex, performance status, time from initial diagnosis, number and type of, and best overall response to prior chemotherapy. Both treatment arms yielded similar PR rates: CHOP 53.7%; R-CHOP 52.5 %. However, there was a highly significant difference in CR rates: CHOP 18.1% versus R-CHOP 30.4 % (p=0.0004). 319 patients have been randomized for maintenance treatment. Of these, 268 were evaluable (132 observation; 136 R maintenance). 1 year and 3 year PFS were 54.9% and 31.2% respectively in the observation arm, and 80.2 % and 67.7% in patients with R maintenance treatment (p< 0.0001). There is as yet no impact on OS: the observed difference (in favor of R maintenance) was not significant for an interim analysis (p=0.03). There were no differences in toxicity between CHOP and R-CHOP induction treatments. Maintenance treatment was associated with minimal toxicity. Because the planned second interim analysis revealed that the primary endpoints for both the induction and maintenance part of the study had been reached, the formal criteria for stopping the trial have now been met. Conclusion. In patients with relapsed/resistant follicular lymphoma R-CHOP remission induction results in a highly significant increase in CR rate as compared to CHOP. Moreover, this is the first trial to show that in these patients Rituximab maintenance treatment achieves a considerable improvement in PFS.

Tolerability and Efficacy of Bortezomib Added to CVP-R for Previously Untreated Advanced Stage Follicular Lymphoma: Interim Analysis of a Phase II Study by the NCIC Clinical Trials Group.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1576-1576 ◽  
Author(s):  
Laurie H Sehn ◽  
David A Macdonald ◽  
Sheldon H. Rubin ◽  
Morel Rubinger ◽  
Kevin R Imrie ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Interim Analysis ◽  
Standard Dose ◽  
Single Agent ◽  
Acceptable Level ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Grade 3

Abstract Background: Despite recent improvements in therapy, follicular lymphoma (FL) remains incurable with standard treatment, warranting investigation of new approaches. Bortezomib, the first-in-class proteasome inhibitor has demonstrated promising efficacy as a single agent in heavily pretreated patients (pts) with FL. This is the first study to evaluate the safety and efficacy of the addition of bortezomib to cyclophosphamide, vincristine, prednisone and rituximab (CVP-R). Methods: This is a phase II multi-center open-label trial adding bortezomib (1.3 mg/m2 day 1&8) to standard dose C(750 mg/m2) V(1.4 mg/m2, capped at 2 mg) P(40 mg/m2 × 5) –R(375 mg/m2) for up to 8 cycles in pts with newly diagnosed stage III/IV FL requiring therapy. Planned accrual is 90 patients. A two-stage design was employed with a planned interim analysis of the first 28 patients to ensure an acceptable level of neurotoxicity (defined as less than 5/28 patients with grade 3/4 neurotoxicity after the first 4 cycles) and meaningful response rate (more than 12/28 patients with a complete response following 8 cycles), prior to enrolling remaining patients. Results: Median age of the first 28 patients was 55 years (range, 30–73). Fifty percent were male and 79% had stage IV disease. FLIPI score at study entry: low 14%, intermediate 43%, high 43%. Overall, the combination of bortezomib and CVP-R was extremely well tolerated. To date, no pts have developed grade 4 neurotoxicity and only 1/28 (4%) has developed grade 3 neurotoxicity within the first 4 cycles (neuropathic pain which resolved without need for treatment modification). The incidence of grade 1 and 2 neurotoxicity was 54% and 25% respectively. Only 3 pts discontinued therapy prematurely (2 pt refusal, 1 progressive disease). Ninety-four percent of planned bortezomib treatments in the first four cycles and 93% of vincristine doses were administered without dose reduction. Hematologic toxicity was mild, with no pts experiencing grade 3/4 anemia or thrombocytopenia. Only 2 episodes of febrile neutropenia occurred and no grade 3/4 infections were noted. Although it is too early to report on efficacy in this ongoing trial, response objectives for stage I have been met, and enrollment to stage 2 is underway. Conclusions: The addition of bortezomib to standard dose CVP-R is very well tolerated, with an acceptable level of neurotoxicity, without compromising the delivery of bortezomib or vincristine. This ongoing study will provide toxicity and efficacy data to facilitate the development of a planned phase III trial.

A Phase III Study to Determine the Efficacy and Safety of Lenalidomide in Combination with Melphalan and Prednisone (MPR) in Elderly Patients with Newly Diagnosed Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 613-613 ◽  
Author(s):  
Antonio Palumbo ◽  
Meletios A. Dimopoulos ◽  
Michel Delforge ◽  
Martin Kropff ◽  
Robin Foa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Board Of Directors ◽  
Primary Endpoint ◽  
Interim Analysis ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Time To Progression ◽  
First Line ◽  
Advisory Committees

Abstract Abstract 613 Background: Lenalidomide (Revlimid®) is an oral immunomodulatory agent with clinical efficacy in patients with multiple myeloma (MM). In patients with relapsed/refractory MM, lenalidomide plus dexamethasone improved time to progression (TTP) and overall survival (OS) in comparison with dexamethasone alone. In newly diagnosed MM patients, the current study compares the efficacy and safety of melphalan, prednisone and lenalidomide (MPR) with that of MP alone. Methods: Key inclusion criteria were: ≥65 years of age, newly diagnosed and symptomatic MM. 459 patients were randomly assigned to receive MPR followed by lenalidomide maintenance therapy or MPR followed by placebo maintenance therapy or MP followed by placebo maintenance therapy (Figure 1). The study induction and maintenance phases were followed by an open label lenalidomide extension and a follow-up phase. All patients received aspirin 100 mg/day as thrombo-prophylaxis. The primary endpoint of the study is progression free survival (PFS). The secondary endpoints are OS, time-to-progression, response rate, time to response, response duration, time-to-next anti-myeloma therapy, safety, quality of life and exploratory assessment of cytogenetic abnormalities. Primary comparison is based on the intent-to-treat population comparing PFS between MPR followed by lenalidomide with MP followed by placebo; secondary comparisons are between MPR followed by lenalidomide and MPR followed by placebo, and between MPR followed by placebo and MP followed by placebo. Results: The first patient was enrolled in February 2007. A pre-planned interim analysis to evaluate the efficacy and safety was performed at 50% information. An independent central adjudication committee determined the assessment and timing of progressive disease prior to the interim analysis. At the interim analysis, it was determined by the Data Monitoring Committee (DMC) that the study had crossed the O'Brien Fleming superiority boundary for the primary endpoint, demonstrating a highly statistically significant improvement in PFS for patients treated with MPR compared with MP as first-line treatment for MM patients. The topline results will be availabel at the time of the meeting. Conclusions: MPR is an effective and safe regimen for front-line use in MM. PFS was significantly improved in patients who received MPR followed by lenalidomide maintenance compared with those who received MP followed by placebo maintenance. MPR followed by lenalidomide maintenance is a new therapeutic option and can be considered a new standard for patients older than 65 years old. Disclosures: Palumbo: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmion: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Lenalidomide is not approved for first line use in multiple myeloma. Dimopoulos:Celgene: Honoraria. Delforge:Janssen-Cilag: Consultancy, Honoraria; Celgene: Honoraria, Speakers Bureau. Kropff:Ortho Biotech: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Foa:Celgene: Membership on an entity's Board of Directors or advisory committees. Yu:Celgene: Employment. Herbein:Celgene: Employment. Mei:Celgene: Employment. Jacques:Celgene: Employment. Catalano:Celgene: Research Funding.

Cost Effectiveness Analysis of Rituximab Maintenance In Patients with Untreated High Tumour Burden Follicular Lymphoma After Response to Immunochemotherapy: A UK National Healthcare Services Perspective.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3833-3833
Author(s):  
Konstantinos Papadakis ◽  
George A Follows ◽  
John Boyer ◽  
Zahid Bashir ◽  
Philip Ball ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cost Effectiveness ◽  
Cost Saving ◽  
Maintenance Therapy ◽  
Willingness To Pay ◽  
Follicular Lymphoma ◽  
Health State ◽  
National Healthcare ◽  
Chemotherapy Induction ◽  
The Cost

Abstract Abstract 3833 Introduction: The PRIMA Phase III study demonstrates that rituximab (R) maintenance therapy after induction immunochemotherapy in previously untreated follicular lymphoma (FL) significantly improves progression-free survival (PFS) with little additional toxicity (Salles et al., 2009). Utilising clinical evidence from PRIMA, this economic analysis evaluated whether R-maintenance therapy in FL patients after response to R-chemotherapy induction is a cost-effective option compared to observational (Obs) practices in the UK National Healthcare System. METHODS: A transition state (Markov) model was developed with FL patients having a complete/partial response to 1st line R-chemotherapy induction being assigned across 4 health states reflecting their disease status; progression-free in 1st line maintenance (PF1), progression-free in 2nd line, progressive disease (PD) or Death. The model was developed over a 25 year horizon to capture the lifetime of an average patient. This required extrapolation of PFS beyond the PRIMA trial follow-up period (median 38.37 months; PFS hazard ratio 0.55; 95% CI [0.44-0.68]; Clinical Study report addendum) using the best parametric fit (Gompertz). The monthly probability of dying in PF1 was based on the maximum of either the observed PFS deaths in PRIMA or background mortality. The disposition of 1st line R-maintenance patients after progression was based on ESMO guidelines (Dreyling et al., 2010) and PRIMA. Due to extensive censoring of overall survival in PRIMA (95% and 97% in the respective R and Obs arms), the probabilities of progressing or dying in second-line or third line were obtained from the EORTC 20981 trial (van Oers et al., 2010). Predicted time in each health state was weighted using FL utility scores (Pettengell et al. 2008) to account for quality of life and estimate the Quality Adjusted Life Years (QALYs). Costs associated with the average dose of R-maintenance, post-progression treatments and managing grade 3/4 adverse events observed in PRIMA were incorporated into the relevant health state. Drug administration, patient monitoring and pharmacy costs were informed by expert opinion and the NHS schedule of reference costs. RESULTS: The average overall survival in the 1st line R-maintenance cohort was projected to be 1.27 years longer on average than in the Obs cohort (10.31 vs 9.05); and associated with an additional 1.17 QALYs. This is largely due to patients treated with 1st line R-maintenance spending more time in progression-free in first line (1.17 years). Total costs were £14,129 higher in the 1st line R-maintenance than the Obs arm and were driven by the cost of the study drug and its administration. However, this was partially compensated by the lower costs of rituximab therapy in 2nd line (cost saving £198) and the lower costs of supportive care incurred at disease progression (cost saving £906). The incremental cost-effectiveness ratios (ICERs) for 1st line R maintenance was £14,712 Life Year Gained and £15,983 per QALY gained, well below an assumed willingness to pay threshold of £30,000. Although there is uncertainty associated with the progression of FL and relapse treatment costs, the ICER did not exceed £21,155 per QALY despite a wide variation in each parameter value used in both the probabilistic and deterministic sensitivity analysis. CONCLUSIONS: The cost-effectiveness of R-maintenance in FL patients after response to R-chemotherapy is well within the acceptable willingness to pay ceiling and remains valid under most plausible sensitivity scenarios. This provides adequate reassurance that the superior clinical benefits of 1st line R-maintenance are sufficient to justify the additional costs over observational practice. Disclosures: Papadakis: F. Hoffmann-La Roche Ltd: Employment. Boyer:F. Hoffmann-La Roche Ltd: Employment. Bashir:F. Hoffmann-La Roche Ltd: Employment. Ball:F. Hoffmann-La Roche Ltd: Employment. Aultman:F. Hoffmann-La Roche Ltd: Employment. Carr:F. Hoffmann-La Roche Ltd: Employment.

Final Results of a Randomized Phase 2 Multicenter Study of Two Bortezomib Schedules In Patients with Recurrent or Refractory Follicular Lymphoma. Groupe d'Etude Des Lymphomes De l'Adulte (GELA) Study FL-05

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 768-768 ◽  
Author(s):  
Vincent Ribrag ◽  
Herve Tilly ◽  
Olivier Casasnovas ◽  
Andre Bosly ◽  
Reda Bouabdallah ◽  
...  
Keyword(s):  
Clinical Study ◽  
Follicular Lymphoma ◽  
Interim Analysis ◽  
Research Funding ◽  
Optimal Schedule ◽  
Dose Schedule ◽  
Open Label ◽  
Qualitative Comparison ◽  
Duration Of Response ◽  
Indolent Lymphomas

Abstract Abstract 768 Background: Bortezomib has previously demonstrated activity in indolent lymphomas including follicular lymphoma (FL). However, the optimal schedule, dose and precise activity of bortezomib in FL remain to be investigated. Aims: To evaluate the efficacy and tolerability of bortezomib in the treatment of advanced FL, but also using a qualitative comparison of two different dose schedules, based on safety, efficacy and dosing convenience to recommend a dose schedule for further clinical studies. Methods: This prospective, randomized, sequential, international, multicenter, 2-arm, non-comparative, open-label, clinical study was conducted from 08–2005 to 09–2008. The eligible subjects (follicular lymphoma grade 1–3, no CNS involvement, in relapse or refractory to previous therapy, ECOG 0–2, Absolute neutrophil count > 1000 cells/mL; Platelets > 50,000 cells/mL, Aspartate transaminase < 3 × ULN; Alanine transaminase < 3 × ULN; Total bilirubin < 2 × ULN; Creatinin level < 150 μmol/L, without known previous HIV serology) were randomized to receive either treatment in a 1:1 ratio. Treatment arm A patients (pts) received 1.5 mg/m2 bortezomib administered biweekly on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles. Treatment arm B pts received 1.6 mg/m2 bortezomib administered weekly on days 1, 8, 15, and 22 of a 35-day cycle for 6 cycles. Treatment allocation was stratified according to number of prior therapies (1 or 2 versus > 2) and time to progression (TPP) for the last given anti-lymphoma therapy (≤ 12 months versus > 12 months). Responses were assessed using 1999 IWG criteria. An interim analysis was planned after 15 evaluable pts randomized in each treatment arm; if only 5 subjects or fewer respond, the treatment arm was concluded to be ineffective and the treatment arm closed to inclusion; otherwise this treatment arm proceeded to include 50 pts. Results: 87 pts (51 [59%] men and 36 [41%] women) with median age of 65 years (range:40 to 77) were treated with bortezomib. Prior therapies were >2 in 62% and progression <12 months from last therapy in 49%. 30% previously received HDT with ASCT, and all of them were previously treated with immunotherapy. Arm B was closed to inclusion after interim analysis. After this interim analysis, the 6 patients still on therapy in this arm completed therapy according to arm A. 15/50 pts (32%) in arm A (bortezomib 1.5 mg/m2) and 8/37 pts (23%) in arm B (bortezomib 1.6 mg/m2) achieved a complete, unconfirmed complete or partial response at the end of treatment. Median duration of response was 16 (range 1–45) and 15 (1-39) months and PFS was 6 and 7.5 months for arms A and B, respectively. Most drug-related AEs (all grades, all cycles) were mild. AEs > grade 3 observed in more than 5% of pts were lymphopenia (25% both arms), thrombocytopenia (19% and 25% in arms A and B, respectively) and neutropenia (8% both arms). One pt died of possibly drug-related cardiac failure associated with hyponatremia. Conclusions: This study demonstrates tolerability and durable clinical benefit of bortezomib when given at 1.5 mg/m2 biweekly on a 21 days cycle in pts with recurrent or refractory FL. These results suggest recommending this dose schedule for further clinical study. Disclosures: Ribrag: LFB: Honoraria, Research Funding; servier: Research Funding; celgene: Research Funding; pfizer: Honoraria; novartis: Honoraria. Tilly:Amgen: Honoraria. Feugier:roche: Consultancy, Honoraria.

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