scholarly journals Baseline SUVmax did not predict histological transformation in follicular lymphoma in the phase 3 GALLIUM study

Blood ◽  
2020 ◽  
Vol 135 (15) ◽  
pp. 1214-1218 ◽  
Author(s):  
Farheen Mir ◽  
Sally F. Barrington ◽  
Helen Brown ◽  
Tina Nielsen ◽  
Deniz Sahin ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Standardized Uptake Value ◽  
Tumor Burden ◽  
Phase 3 ◽  
High Tumor Burden ◽  
Positron Emission ◽  
Histological Transformation ◽  
The Difference ◽  
The Relationship ◽  
Pet Scans

Abstract A minority of patients with follicular lymphoma (FL) undergo histological transformation (HT). This retrospective analysis of 549 patients from the phase 3 GALLIUM study (NCT01332968) assessed the relationship between maximum standardized uptake value (SUVmax) at baseline on positron emission tomography (PET) and HT risk. Previously untreated patients with high tumor burden grade 1-3a FL received obinutuzumab- or rituximab-based chemotherapy induction. The relationship between baseline SUVmax (bSUVmax) and HT risk was assessed using cutoff values for SUVmax >10 and >20. Overall, 15 of 549 (2.7%) patients with baseline PET scans experienced biopsy-confirmed HT (median follow-up, 59 months). More than 65% of patients had bSUVmax > 10, with 3.3% of these experiencing HT. Only 1 of 74 (1.4%) patients with bSUVmax > 20 underwent HT. Median bSUVmax in patients with HT vs without HT was 12.4 (range, 8.1-28.0) vs 11.8 (range, 3.1-64.4), respectively; median bSUVrange (the difference between bSUVmax of the most and least 18F-fluorodeoxyglucose–avid lymphoma sites) was 8.0 (range, 1.1-23.9) vs 7.1 (range, 0.0-59.8), respectively. There was no temporal relationship between bSUVmax and HT. Neither bSUVmax nor bSUVrange predicted HT in GALLIUM, suggesting that there may be little benefit in rebiopsy of lesions to exclude HT based on SUVmax alone before initiating therapy in patients with high tumor burden FL.

Identification of Patient Subgroups Demonstrating Longer Progression-Free Survival (PFS) Benefit with Bortezomib-Rituximab Versus Rituximab in Patients with Relapsed or Refractory Follicular Lymphoma (FL): Biomarker Analyses of the Phase 3 LYM3001 Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 265-265 ◽  
Author(s):  
Bertrand Coiffier ◽  
Weimin Li ◽  
Erin D Henitz ◽  
J. D. Karkera ◽  
Reyna Favis ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Germ Line ◽  
Tumor Burden ◽  
Advisory Board ◽  
Multiple Comparison ◽  
Phase 3 ◽  
High Tumor Burden ◽  
Equity Ownership ◽  
Patient Subgroups

Abstract Abstract 265 Background: Treatment goals in patients with relapsed FL are to prolong PFS and improve overall survival (OS). To optimize treatment for individual patients, identification of subgroups most likely to benefit from a specific therapy is important. The international, randomized, phase 3 LYM3001 study in patients with relapsed or refractory FL demonstrated improved PFS with bortezomib-rituximab vs rituximab alone (median 12.8 vs 11.0 months, HR 0.822, p=0.039), plus increased overall response rate (ORR; 63% vs 49%, p=0.0004), complete response rate (CR/CRu; 25% vs 18%, p=0.035), and durable (≥6 months) response rate (50% vs 38%, p=0.002) in an unselected patient population. Here we present exploratory biomarker analyses aimed at identifying patient subgroups deriving a longer PFS benefit with bortezomib-rituximab and showing a trend for better OS. Methods: Patients received five 5-week cycles of bortezomib-rituximab (N=336) or rituximab (N=340). Response was assessed using modified International Working Group response criteria. Archived tumor tissue was collected at baseline from 502 (74%) patients; whole blood samples for germ-line DNA were collected on day 1 of cycle 1 from 619 (92%) patients. Protocol-specified candidate biomarkers were based on associations with bortezomib (NF-κB p65, PSMA5, p27, PSMB1/5/8/9) or rituximab (CD68, FCGR2A/3A) activity. Immunohistochemistry assays were used for protein analysis. Taqman SNP assays and PCR/LDR were used for genotyping. Statistical analyses included single-marker analyses, pair-wise combination analyses (n=1140 comparisons), and multiple comparison analyses of all evaluable patients in LYM3001. Clinical covariates included in the analysis were baseline FLIPI score, prior rituximab, time since last anti-lymphoma therapy, region, age, gender, race, Ann Arbor stage, high tumor burden, and number of prior lines of therapy. Results: Single markers and biomarker pairs (n=102) highlighted patient subsets that had significantly improved outcomes with bortezomib-rituximab vs rituximab. For 14 of the pairs, the PFS benefit was ≥6 months. Using false discovery rate (FDR) to control for multiple comparison corrections, one biomarker pair was significant. This pair (presence of the PSMB1 P11A C/G heterozygote, and low CD68 expression [0–50 CD68-positive macrophages in the follicular space]) was associated with significantly improved PFS in patients receiving bortezomib-rituximab vs rituximab (median 16.6 vs 9.1 months, HR 0.407, p<0.0001, FDR=0.051) and had a population frequency of 33% (n=118) in biomarker-evaluable patients (N=356). Patients with high-risk features were represented in the biomarker-selected population (54% high tumor burden, 41% high FLIPI, 30% >2 prior lines of therapy). There was also a trend towards an OS benefit (medians not reached, HR 0.426, p=0.0550), as well as a significantly higher ORR (73.7% vs 47.5%, p=0.0077), a higher CR rate (33.3% vs 23%, p=0.3044), and a significantly longer time to next therapy (median 33.1 vs 14.8 months, p=0.0013). In patients lacking this biomarker pair (N=238) no significant efficacy differences were seen. No other similar studies were available to confirm the reproducibility of these analyses. Therefore, we split the LYM3001 dataset into discovery and confirmation cohorts (7:3 ratio of biomarker-evaluable patients) to enable evaluation and confirmation in independent cohorts of patients The significant biomarker pair of PSMB1 P11A C/G heterozygote and low CD68 was identified in the discovery cohort (N=198) with a PFS advantage with bortezomib-rituximab vs rituximab of 5.7 months (median 14.2 vs 8.4 months, p=0.0003) and an indication of longer OS (HR 0.47, p=0.1291). This biomarker pair also showed a clear PFS advantage in the confirmation cohort (N=108, 8.7-month PFS benefit; median 18.2 vs 9.5 months, HR 0.44, p=0.0817). Other significant biomarker combinations, including combinations of molecular and clinical variables (e.g. high tumor burden) were identified and will be presented. Conclusions: Analyses of the phase 3 LYM3001 trial identified biomarker combinations present in a third of patients offering a significant PFS benefit with bortezomib-rituximab vs rituximab. Use of such biomarker assays in patients with relapsed or refractory FL may aid identification of subgroups deriving maximal benefit from the addition of bortezomib to rituximab therapy. Disclosures: Coiffier: Janssen-Cilag: Consultancy; Roche: Consultancy; Amgen: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Millennium Pharmaceuticals, Inc.: Consultancy; Celgene: Consultancy; Pharmacyclics: Consultancy; MedImmune: Consultancy; CTI: Consultancy. Off Label Use: Bortezomib used in combination with rituximab in patients with relapsed/refractory follicular lymphoma. Li:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Henitz:Janssen Research & Development: Employment. Karkera:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Favis:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Gaffney:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Shapiro:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Theocharous:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Elsayed:Janssen Research & Development: Employment; Johson & Johnson: Equity Ownership. de Velde:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Rule:Johnson & Johnson: Advisory Board, Institutional grant, meeting attendance expenses, Honoraria. Walewski:Janssen-Cilag: Institutional/personal grants, advisory board; Hoffman La Roche: Honoraria, Institutional/personal grants, travel/accommodation expenses; Mundipharma: Honoraria; Celgene: Honoraria. de Vos:Millennium Pharmaceuticals, Inc: Consultancy. Crump:Janssen/Ortho-Biotech: Consultancy. Shpilberg:Janssen-Cilag: Consultancy, Honoraria. Cakana:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership. Esseltine:Millennium Pharmaceuticals, Inc: Employment; Johnson & Johnson: Equity Ownership. Mulligan:Millennium Pharmaceuticals, Inc.: Employment. Ricci:Janssen Research & Development: Employment; Johnson & Johnson: Equity Ownership.

scholarly journals Evaluation of Skeletal Muscle Activity During Foot Training Exercises Using Positron Emission Tomography

2021 ◽  
Author(s):  
Tomoyuki Kanayama ◽  
Junsuke Nakase ◽  
Takafumi Mochizuki ◽  
Kazuki Asai ◽  
Rikuto Yoshimizu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Positron Emission Tomography ◽  
Muscle Activity ◽  
Skeletal Muscles ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
Abductor Hallucis ◽  
Continuous Training ◽  
Positron Emission ◽  
The Difference

Abstract The foot exercises “rock-paper-scissors” and “towel gathering” are widely used in patients with lower limb disorders; however, there are no detailed reports on muscle activity during such training. We quantitatively evaluated the difference in skeletal muscle activity between the two exercises using positron emission tomography. Eight university student athletes were included. Four participants each were assigned to the foot rock-paper-scissors and towel gathering groups. Participants in each group underwent continuous training for 15 min. They received an intravenous injection of 18F-fluorodeoxyglucose and retrained for 15 min, following which they rested for 45 min. Regions of interest were defined in 25 muscles. The standardized uptake value (SUV) in the trained limb was compared with that in the non-trained control limb. SUVs increased in four skeletal muscles (tibialis anterior, peroneus brevis, extensor hallucis brevis, and abductor hallucis) in the rock-paper-scissors group, and in four muscles (flexor digitorum longus, extensor hallucis brevis, extensor digitorum brevis, and quadratus plantae) in the towel gathering group. Thus, foot rock-paper-scissors and towel gathering affected skeletal muscles related to the medial longitudinal arch and toe grip strength, respectively. Given that the two exercises target different skeletal muscles, they should be taught and implemented according to their respective purposes.

scholarly journals Determination of receptor occupancy in the presence of mass dose: [11C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746

2016 ◽  
Vol 37 (3) ◽  
pp. 1095-1107 ◽  
Author(s):  
Jean-Dominique Gallezot ◽  
Beata Planeta ◽  
Nabeel Nabulsi ◽  
Donna Palumbo ◽  
Xiaoxi Li ◽  
...  
Keyword(s):  
Binding Sites ◽  
Human Subjects ◽  
Receptor Occupancy ◽  
Healthy Human ◽  
Positron Emission ◽  
Relationship Of ◽  
The Relationship ◽  
Pet Scans

Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds “tracer” levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant Kd of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo Kd. This method was applied in a study of healthy human subjects with the histamine H3 receptor radioligand [11C]GSK189254 to measure the PK-occupancy relationship of the H3 antagonist PF-03654746. From three test/retest studies, [11C]GSK189254 Kd was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%–97% and 30%–93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%–15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H3 binding sites ( ROmax = 100%), and its IC50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC50 was 26% higher.

Obinutuzumab plus lenalidomide (GALEN) in advanced, previously untreated follicular lymphoma in need of systemic therapy

Blood ◽  
2021 ◽  
Author(s):  
Emmanuel Bachy ◽  
Roch Houot ◽  
Pierre Feugier ◽  
Krimo Bouabdallah ◽  
Reda Bouabdallah ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Safety Profile ◽  
Response Rate ◽  
Metabolic Response ◽  
Complete Response ◽  
Tumor Burden ◽  
Common Adverse Event ◽  
Induction Treatment ◽  
High Tumor Burden ◽  
Grade 3

Obinutuzumab and lenalidomide (GALEN) is an active immunomodulatory combination with a manageable safety profile in multiple types of lymphoma. We report efficacy and safety results for the phase 2 GALEN study in previously-untreated patients with advanced follicular lymphoma (FL). Eligible patients aged ≥ 18 years had ECOG PS ≤ 2, high-tumor burden, grade 1-3a FL. Induction treatment was obinutuzumab (1000 mg IV, days 8/15/22, cycle 1; day 1, cycles 2-6) plus lenalidomide (20 mg/day, days 1-21, cycle 1; days 2-22, cycles 2-6) for 6 cycles. Maintenance included obinutuzumab (1000 mg every 2 cycles) plus lenalidomide (10 mg, days 2-22) for ≤ 12 cycles (year 1) followed by obinutuzumab (1000 mg every 56 days) for 6 cycles (year 2). The primary endpoint was complete response rate (CRR) after induction per IWG 1999 criteria. From October 2015 to February 2017, 100 patients were enrolled. CRR after induction was 47% and overall response rate (ORR) 92%. Post-hoc analyses per 2014 Lugano classification including patients with missing bone marrow assessments identified an additional 13 patients fulfilling CRR criteria, resulting in a complete metabolic response of 80% and ORR of 94%. At a median follow-up of 3.7 years, 3-year progression-free and overall survival were 82% and 94%, respectively. The most common adverse event was neutropenia (48% any-grade; 47% grade ≥ 3) but only 2% of patients presented febrile neutropenia; others were mainly grade ≤ 2. No other specific grade ≥3 toxicity occurred at a frequency higher than 3%. Overall, these results demonstrated promising clinical efficacy for the chemo-free backbone obinutuzumab and lenalidomide in previously untreated, high tumor burden FL patients. Except for neutropenia, the safety profile of the combination is remarkable. The study was registered with ClinicalTrials.gov, number NCT01582776

scholarly journals The Relationship Between IDH1 Mutation Status and Metabolic Imaging in Nonenhancing Supratentorial Diffuse Gliomas: A 11C-MET PET Study

2019 ◽  
Vol 18 ◽  
pp. 153601211989408
Author(s):  
Nijiati Kudulaiti ◽  
Huiwei Zhang ◽  
Tianming Qiu ◽  
Junfeng Lu ◽  
Abudumijiti Aibaidula ◽  
...  
Keyword(s):  
Standardized Uptake Value ◽  
Idh1 Mutation ◽  
Metabolic Imaging ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 1 ◽  
Mutation Status ◽  
Positron Emission ◽  
Diffuse Gliomas ◽  
The Relationship ◽  
Met Pet

Purpose: We evaluated the relationship between isocitrate dehydrogenase 1 (IDH1) mutation status and metabolic imaging in patients with nonenhancing supratentorial diffuse gliomas using 11C-methionine positron emission tomography (11C-MET PET). Materials and Methods: Between June 2012 and November 2017, we enrolled 86 (38 women and 48 men; mean age, 41.9 ± 13.1 years [range, 8-67 years]) patients with newly diagnosed supratentorial diffuse gliomas. All patients underwent preoperative 11C-MET PET. Tumor samples were obtained and immunohistochemically analyzed for IDH1 mutation status. Results: The mutant and wild-type IDH1 diffuse gliomas had significantly different mean maximum standardized uptake value values (2.73 [95% confidence interval, CI: 2.32-3.16] vs 3.85 [95% CI: 3.22-4.51], respectively; P = .004) and mean tumor-to-background ratio (1.90 [95% CI: 1.65-2.16] vs 2.59 [95% CI: 2.17-3.04], respectively; P = .007). Conclusions: 11C-methionine PET can noninvasively evaluate the IDH1 mutation status of patients with nonenhancing supratentorial diffuse gliomas.

scholarly journals Follicular lymphoma patients with a high FLIPI score and a high tumor burden: A risk stratification model

2015 ◽  
Vol 72 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Bosko Andjelic ◽  
Milena Todorovic-Balint ◽  
Darko Antic ◽  
Jelena Bila ◽  
Vladislava Djurasinovic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Follicular Lymphoma ◽  
Histological Grade ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Tumor Burden ◽  
Cox Regression Analysis ◽  
High Tumor Burden

Background/Aim. The widely accepted Follicular Lymphoma International Prognostic Index (FLIPI) divides patients into three risk groups based on the score of adverse prognostic factors. The estimated 5-year survival in patients with a high FLIPI score is around 50%. The aim of this study was to analyse the prognostic value of clinical and laboratory parameters that are not included in the FLIPI and the New Prognostic Index for Follicular Lymphoma developed by the International Follicular Lymphoma Prognostic Factor Project (FLIPI2) indices, in follicular lymphoma (FL) patients with a high FLIPI score and high tumor burden. Methods. The retrospective analysis included 57 newly diagnosed patients with FL, a high FLIPI score and a high tumor burden. All the patients were diagnosed and treated between April 2000 and June 2007 at the Clinic for Hematology, Clinical Center of Serbia, Belgrade. Results. The patients with a histological grade > 1, erythrocyte sedimentation rate (ESR) ? 45 mm/h and hypoalbuminemia had a significantly worse overall survival (p = 0.015; p = 0.001; p = 0.008, respectively), while there was a tendency toward worse overall survival in the patients with an Eastern Cooperative Oncology Group (ECOG) > 1 (p = 0.075). Multivariate Cox regression analysis identified a histological grade > 1, ESR ? 45 mm/h and hypoalbuminemia as independent risk factors for a poor outcome. Based on a cumulative score of unfavourable prognostic factors, patients who had 0 or 1 unfavourable factors had a significantly better 5-year overall survival compared to patients with 2 or 3 risk factors (75% vs 24.1%, p = 0.000). Conclusion. The obtained results suggest that from the examined prognostic parameters histological grade > 1, ESR ? 45 mm/h and hypoalbuminemia can contribute in defining patients who need more aggressive initial treatment approach, if two or three of these parameters are present on presentation.

scholarly journals Is interim 18F-fluoride PET/CT a predictor of outcomes after radium-223 therapy?

2019 ◽  
Vol 52 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Elba Etchebehere ◽  
Ana Emília Brito ◽  
Kalevi Kairemo ◽  
Eric Rohren ◽  
John Araujo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Standardized Uptake Value ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Free Survival ◽  
Radium 223 ◽  
Positron Emission ◽  
Pet Ct ◽  
Hormone Refractory ◽  
18F Fluoride

Abstract Objective: To determine whether an interim 18F-fluoride positron-emission tomography/computed tomography (PET/CT) study performed after the third cycle of radium-223 dichloride (223RaCl2) therapy is able to identify patients that will not respond to treatment. Materials and Methods: We retrospectively reviewed 34 histologically confirmed cases of hormone-refractory prostate cancer with bone metastasis in patients submitted to 223RaCl2 therapy. All of the patients underwent baseline and interim 18F-fluoride PET/CT studies. The interim study was performed immediately prior to the fourth cycle of 223RaCl2. The skeletal tumor burden-expressed as the total lesion fluoride uptake above a maximum standardized uptake value of 10 (TLF10)-was calculated for the baseline and the interim studies. The percent change in TLF10 between the baseline and interim studies (%TFL10) was calculated as follows: %TFL10 = interim TLF10 - baseline TLF10 / baseline TLF10. End points were overall survival, progression-free survival, and skeletal-related events. Results: The mean age of the patients was 72.4 ± 10.2 years (range, 43.3-88.8 years). The %TLF10 was not able to predict overall survival (p = 0.6320; hazard ratio [HR] = 0.753; 95% confidence interval [CI]: 0.236-2.401), progression-free survival (p = 0.5908; HR = 1.248; 95% CI: 0.557-2.797) nor time to a bone event (p = 0.5114; HR = 1.588; 95% CI: 0.399-6.312). Conclusion: The skeletal tumor burden on an interim 18F-fluoride PET/CT, performed after three cycles of 223RaCl2, is not able to predict overall survival, progression-free survival, or time to bone event, and should not be performed to monitor response at this time.

scholarly journals Characterization of 18F-PM-PBB3 (18F-APN-1607) Uptake in the rTg4510 Mouse Model of Tauopathy

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1750 ◽  
Author(s):  
Chi-Chang Weng ◽  
Ing-Tsung Hsiao ◽  
Qing-Fang Yang ◽  
Cheng-Hsiang Yao ◽  
Chin-Yin Tai ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ex Vivo ◽  
Standardized Uptake Value ◽  
Dynamic Imaging ◽  
Scanning Time ◽  
Positron Emission ◽  
Image Characteristics ◽  
Uptake Pattern ◽  
Pet Scans

Misfolding, aggregation, and cerebral accumulation of tau deposits are hallmark features of Alzheimer’s disease. Positron emission tomography study of tau can facilitate the development of anti-tau treatment. Here, we investigated a novel tau tracer 18F-PM-PBB3 (18F-APN-1607) in a mouse model of tauopathy. Dynamic PET scans were collected in groups of rTg4510 transgenic mice at 2–11 months of age. Associations between distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) with cerebellum reference were used to determine the optimal scanning time and uptake pattern for each age. Immunohistochemistry staining of neurofibrillary tangles and autoradiography study was performed for ex vivo validation. An SUVR 40–70 min was most consistently correlated with DVR and was used in further analyses. Significant increased 18F-PM-PBB3 uptake in the brain cortex was found in six-month-old mice (+28.9%, p < 0.05), and increased further in the nine-month-old group (+38.8%, p < 0.01). The trend of increased SUVR value remained evident in the hippocampus and striatum regions except for cortex where uptake becomes slightly reduced in 11-month-old animals (+37.3%, p < 0.05). Radioactivity distributions from autoradiography correlate well to the presence of human tau (HT7 antibody) and hyperphosphorylated tau (antibody AT8) from the immunohistochemistry study of the adjacent brain sections. These findings supported that the 40–70 min 18F-PM-PBB3 PET scan with SUVR measurement can detect significantly increased tau deposits in a living rTg4510 transgenic mouse models as early as six-months-old. The result exhibited promising dynamic imaging capability of this novel tau tracer, and the above image characteristics should be considered in the design of longitudinal preclinical tau image studies.

PET Evaluation Before Autografting Has a Strong Prognostic Impact in High-Risk, Relapsed Follicular Lymphoma Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1612-1612
Author(s):  
Loic Ysebaert ◽  
Jehan Dupuis ◽  
Michel Meignan ◽  
Anne Julian ◽  
Christian Recher ◽  
...  
Keyword(s):  
Stem Cell ◽  
Follicular Lymphoma ◽  
Conditioning Regimen ◽  
Tumor Burden ◽  
Prognostic Impact ◽  
High Tumor Burden ◽  
Richter Syndrome ◽  
The Impact ◽  
Cell Harvest

Abstract Abstract 1612 INTRODUCTION: in follicular lymphoma (FL) patients with high tumor burden (as defined by GELF criteria), R-CHOP is the standard upfront immunochemotherapy. Results from the PRIMA study suggest that a positive PET after induction therapy predicts for earlier relapses, even despite maintenance with rituximab (RTX) for two years [Trotman J, 2011]. For patients under 65y, who relapse after R-CHOP+/−RTX maintenance with high tumor burden, R-chemo+autografting is a recommended option. In a retrospective cohort of 43 relapsed FL pts in two French University Hospitals, we explored the role of such a strategy on outcome - in the era of new RTX based modalities - and also evaluated the impact of PET results before autografting. PATIENTS AND METHODS: Patients with relapsed FL after R-CHOP, with at least 1 GELF criteria at relapse (high tumor burden), and who received R-chemo before autografting were eligible. IWC+PETresponse criteria (Cheson 2007) were used, after R-CHOP frontline, and after salvage (before autografting). Patients with Richter transformation at relapse were excluded from this study. OS was calculated from date of salvage to date of death or last follow-up; progression-free survival (PFS) and time to next treatment (TTNT) were calculated from completion of salvage to date of FL relapse or next chemotherapy, respectively. RESULTS: 43 pts (60% males) younger than 65y were identified: they received either FCR-based (2 cycles of FCR, 1 cycle of R-DHAP then stem cell harvest, 2 last cycles of FCR, n=25) or R-DHAP-based (4 cycles of R-DHAP or DHAOx (oxaliplatin replacing cisplatin), and stem cell harvest, n=18). Characteristics at salvage: median age was 54 (range 28–62), with median GELF score of 1 (1–4). Thirty % had progression within 6 mo of R-CHOP (refractory);median PFS was 12mo (range 1–40mo) andmedian TTNT was 15mo. RTX maintenance in 12/43 pts did not significantly increased PFS (15 vs 9 mo, p=0.1). FLIPI1 was low in 39%, Int 36%, high 25% of pts, and FLIPI2 was low in 22%, Int 62.5%, high 15.5% of pts. 1/43 pt had CD20- relapse (who received RTX maintenance), and received FC without RTX. Results: response to FCR/R-DHAP included CR+CRu 68/72%, PR 24/28% respectively, PET evaluation was found negative in 23.5/36% respectively (p=ns). Median stem cell harvest (median 2 leukaphereses) was 4.37 vs 7.8.106 CD34+/kg in FCR vs R-DHAP pts (Mann-Whitney p=0.09), without failure (only one patient required plerixafor). Four patients did not receive the planned autologous transplant (2 failures after FCR (including one Richter transformation), 1 hepatitis before conditioning regimen, 1 withdrawal of consent). Conditioning regimen for the remaining 39 pts was BEAM in 16 (4 FCR+12 R-DHAP), Zevalin-BEAM in 23 pts (9 FCR+14 R-DHAP), including 9 pts who further received RTX maintenance post-autografting. At a median follow up of living pts of 18mo, 9 pts had relapsed, of which 8 needed additional therapy. At time of analysis (June 2011), 37 pts were alive. Causes for death included 1 pancytopenia and infection, 1 Richter syndrome, 1second cancer, 2 complications of allografting (received later on). Late complications were common: pancytopenia or prolonged grade III-IV neutropenia (>3mo) after procedure occurred in 5/43 pts (3 FCR, 2 R-DHAP, without evidence of MDS/AML in these cases), Richter syndrome occurred in 2 patients (1 death), second cancer in 3 pts (1 Hodgkin, 1 womb sarcoma, 1 lung cancer). On an intend-to-treat basis, 41 pts are evaluable. For FCR/R-DHAP pts, 2y PFS was 68/68%, 2y TTNT 80/70%, and 2y OS 73/100%, respectively (logrank p=ns). Two years TTNT tended to be higher in pts receiving Z-BEAM (55 vs 83%), or with PET negativity before autografting (70 vs 85%), both without reaching significance (logrank p=0.1). PET negativity before autografting was the only variable statistically associated with superior OS in our series (logrank p=0.0003). CONCLUSIONS: Our data suggest that PET negativity before consolidative autografting is an achievable and desirable goal in FL salvaged after R-CHOP. Disclosures: Ysebaert: Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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