Kooperativer Bibliotheksverbund

In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 57, No. 6 ( 2022-06), p. 966-974

Type of Medium: Online Resource

ISSN: 0268-3369 , 1476-5365

URL: Article

DOI: 10.1038/s41409-022-01648-z

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 2004030-1

In: Medical Mycology, Oxford University Press (OUP), Vol. 59, No. 5 ( 2021-05-04), p. 486-497

Abstract: Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain.

Type of Medium: Online Resource

ISSN: 1369-3786 , 1460-2709

URL: Article

DOI: 10.1093/mmy/myaa086

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2021

detail.hit.zdb_id: 2020733-5

SSG: 12

In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4576-4576

Abstract: Abstract 4576 Introduction Allo-HSCT procedure is associated with a frequent and potentially severe malnutrition which could highly participate to the transplant-related morbidity (TRM). Optimal nutritional management is still poorly known while both enteral nutrition (EN) and parenteral nutrition (PN) are effective. We proposed to retrospectively evaluate the impact of EN versus PN as nutritional support on early outcome of allo-HSCT. Patients and methods We retrospectively analyzed all the successive patients who needed a nutritional support during their first allo-HSCT in our center from January 2009 to October 2010, excepting whose who had a progressive disease at time of transplant. Datas were compared in an intent to treat analysis according the EN or PN initial nutritional support strategy. Results We analysed early outcome of 56 successive patients. Twenty of them received a myeloablative conditioning regimen and 36 a reduced intensity one. A total of 28 agreed to receive EN via a nasogastric feeding tube and the remaining 28 received PN. No significant difference in terms of age, diagnosis, disease status at transplant, conditioning regimens, stem cell source, GVHD nor antifungal secondary prophylaxis could be observed between the EN and PN groups. We found a lower median duration of fever in EN (2[0–8] vs. 5[0–17] (days); p=0.0026) and a lower need for antifungal therapy in EN group (7/28 vs. 17/28; p=0.0069), with a lower median duration of intravenous antifungal use (0 day [0–99] in EN vs. 7 days [0–93] in PN; p=0.00034) while incidence of bacteriemiae was not different. We observed a lower rate of replacement of central veinous catheter in EN group (3/28 in EN vs. 9/28 in PN; p=0.05) and a lower rate of transfer to ICU in the EN group (2/28 in EN vs. 8/28 in PN, p=0.036) but early death rate ( 〈 100 days) was the same in each group (4/28 vs. 4/28, p=NS). Median neutropenia and thrombopenia duration and median transfusion requirements were not significantly different. Fourteen patients in EN group and 18 in PN group presented a grade 3–4 oral mucositis (p=NS). Grade III-IV GVHD incidence was comparable in both groups (4/28 vs. 8/28; p=0.19). Conclusion Compared with PN, EN directly decreases the infectious risk, particularly the fungal risk, and its complications in allo-HSCT, without influencing hematopoietic toxicity nor GVHD incidence. Based on these encouraging results, we are now conducting a prospective, multicentric and randomized trial to confirm EN benefice in allo-HSCT. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V118.21.4576.4576

Language: English

Publisher: American Society of Hematology

Publication Date: 2011

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 6 ( 2021-06), p. 1597-1609

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-020-01009-z

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2008023-2

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4202-4202

Abstract: BACKGROUND: the combination of rituximab (RTX) and lenalidomide (LEN) has been shown to be synergistic in pre-clinical models and in patients (pts) with previously untreated and relapsed follicular lymphoma (FL). Furthermore, LEN demonstrated single agent efficacy in pts with mantle cell lymphoma (MCL) and diffuse large B cell lymphoma (DLBCL). We hypothesized that the combination of obinutuzumab (GA), a glycoengineered type II anti-CD20 antibody, with LEN (GALEN) might be even more efficient while retaining a similarly manageable safety profile. In 2012, we started a phase Ib/II study to assess the safety and efficacy of this combination (ClinicalTrials.gov: NCT01582776) in pts with relapsed/refractory lymphoma. Phase IB defined the recommended dose (RD) of LEN as being 20mg in combination with GA. Here, we report the results of the Phase II part assessing efficacy and safety of GALEN therapy during a 6 months induction followed, for responders, by a reduced LEN maintenance GALEN regimen (in a cohort of relapsed/refractory aggressive NHL (DLBCL or MCL) pts. METHODS: pts with a histologically confirmed DLBCL (de novo or transformed low-grade NHL) or MCL were eligible if they had a ECOG PS of ²2, a life expectancy 〉 3 months (mo) and had previously received ³1 prior therapy including at least one RTX-containing regimen. Induction treatment consisted of LEN 20 mg given orally once daily on days 1-21 of a 28-day cycle for the first cycle and on days 2-22 of a 28-day cycle from cycles 2 to 6. Intravenous infusions of GA were given at a flat dose of 1000mg on days 8, 15, and 22 of cycle 1 and at D1 of cycles 2 to 6 (total of 8 infusions). Responding pts then received 12 cycles of LEN at 10 mg daily on days 2-22 every 28 days for a total of 18 cycles and GA 1000mg every 8 weeks for 12 additional cycles until progression or unacceptable toxicity. All pts were required to take daily aspirin (100 mg) for deep vein thrombosis (DVT) prophylaxis during study period. Pts who were unable to tolerate aspirin and had a prior history of DVT or were at high risk for a DVT received low molecular weight heparin therapy or warfarin (coumadin) treatment. The primary study endpoint was overall response rate (ORR) by investigator assessment at the end of induction according to 1999 IWG criteria. Secondary endpoints included ORR and complete response (CR) according to IWG 2007, best ORR, duration of response, progression-free survival, overall survival (OS) and safety. RESULTS: ninety-one pts (DLBCL [n=77 including 18 transformed], MCL [n=13] , and other [n=1]) were enrolled between June 2014 and March 2015 at 22 LYSA centers in France and Belgium. At baseline, median age was 70 (range, 48-84) years with 64.7% men, ECOG PS of 1 (47.1%) or 2 (18.8%), 83.5% Ann Arbor stage III-IV and 66.3% with elevated LDH. Median number of prior systemic therapies was 2 (range, 1-9) including haematopoietic stem cell transplantation in 17pts (20%); 61% were refractory to a RTX-containing regimen and 53% refractory to last prior therapy. Three pts were withdrawn before receiving any treatment due to major protocol violation, concurrent illness or ulceration of the tumor in the stomach and 3 pts received one of both study drugs, leaving 85 pts assessable for efficacy. Cut-off date was March 25th 2016. With amedianfollow-up of 14.5 mo,39pts (45.8%) completed induction (32 DLBCL and 7 MCL) and 20 (23.5%) are still ongoing in maintenance (16 DLBCL, 4 MCL). At the time of the cut-off, 44pts (51.8%) h ad died mainly due to lymphoma (88.6%). Response at the end of induction, best ORR during induction and OS are summarized in the table. Table Analysis of other secondary endpoints and correlation with cell of origin is ongoing. The most common treatment emergent AEs during induction (all grades 〉 10%pts/ % grade 3/4) were neutropenia (51.1/31.8), infections (45.5/12.5), constipation (30.7/0.0), cough (21.6/1.1), diarrhea (17.0/3.4), nausea (17.0/0) anemia (15.9/10.2), thrombocytopenia (15.9/10.2), muscle spasms (13.6/0.0), fatigue (12.5/1.1) and dyspnea (11.4/4.5). Febrile neutropenia occurred in 4.5% pts. There was onlyone secondprimary malignancy (basal carcinoma). CONCLUSION: oral LEN plus GA infusion is effective in relapsed or refractory DLBCL and MCL pts with no unexpected toxicity. Longer follow-up and additional translational studies are needed to identify the subset of pts most benefiting of this regimen. Correlative studies will be presented at the meeting. Table Table. Disclosures Morschhauser: celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; servier: Consultancy, Honoraria; gilead: Consultancy, Honoraria; janssen: Honoraria. Cartron:Roche: Consultancy, Honoraria; Celgene: Honoraria; Gilead: Honoraria; Jansen: Honoraria. Salles:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Mundipharma: Honoraria; Novartis: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding. Maerevoet:ARGN-X: Membership on an entity's Board of Directors or advisory committees; roche: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Bonnet:ROCHE: Membership on an entity's Board of Directors or advisory committees; SERVIER: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; JANSSEN: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.4202.4202

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4206-4206

Abstract: Introduction: in large unselected series, the median age of Primary CNS Lymphoma (PCNSL) patients (pts) is about 70 years. In one USA cancer registry study for PCNSL patients (pts) older than 65 years, 14% of them are older than 80 years. Data on clinical characteristics, therapeutical management, toxicity of treatment and outcome of these very elderly pts are limited. Methods: We reviewed PCNSL pts aged of 80 years or older included in the database of the French Oculo-Cerebral lymphoma (LOC) network. From January 2011, this network prospectively recorded all newly diagnosed PCNSL from 22 regional expert centers in France. For this study, 110 PCNSL pts with a histological diagnosis of diffuse large B-cell lymphoma (DLBCL) aged of 80 years or older were analyzed. All medical records were reviewed for clinical and biological characteristics, modality of treatment and supportive care, toxicities and outcome. Results: 110 pts with a DLBCL PCNSL aged of 80 years or older were diagnosed between January 2011 and January 2018 representing 8% of pts available in the LOC database. The clinical characteristics were as follows: 63% of females; median age: 83y (80-92); performance status (PS) according to EORTC scale: 1, 24% of pts, 2, 21% of pts, 3-4, 55% of pts. 23.6% of pts had a CIRS-G grade 3 or 4 in at least one category and 40.9% had a cumulative CIRS-G score more than 6. Diagnosis procedure was biopsy (87%), tumor resection (5%), vitrectomy (4%), CSF cytology (4%). At diagnosis, 9/68 (13%) of evaluable pts had ocular involvement, 13/61 (21%) cerebrospinal (CSF) involvement, 79/110 (72%) involvement of the deep structures of the brain and 35/86 (41%) had elevated LDH level. Median creatinine clearance (CKD.EPI) was 70ml/min (min: 24, max: 102). Treatment was initiated either by a neuro-oncology or a hematology team in 35% and 65% of cases, respectively. Median delay between first symptoms and treatment was 60 days. First line treatment was high-dose (HD) methotrexate (MTX) based chemotherapy (CT) in 85 pts (77%), other chemotherapy regimen in 13 pts (12%) and palliative care in 12 pts (11%). Median number of CT cycles was 3 (1-11) with a median dose of MTX of 3g/m2 (0.5-5.0). Interestingly, no difference of distribution for the main clinical and biological characteristics (median age, PS, symptoms, tumor localization, albumin level, creatinine clearance) was observed between these three groups. Rituximab was used in combination with CT in 53/98 treated pts (54%). After first-line induction chemotherapy, response rate for evaluable patients (n=85) were as follows: 37% of complete response, 9% of partial response, 54% of stable or progressive disease. Finally, 27 pts (32%) received consolidation treatment with high-dose cytarabine after MTX-based CT. For toxicity, among the 351 infusions performed for the 85 pts who received MTX-based CT, grade 3-4 toxicities were: 46% of any events, 15% of infection, 13% of cytopenia, 10.5% of acute renal failure and 8% of elevated liver enzymes. 13% of pts presented toxic death. Median progression free survival (PFS) and overall survival (OS) were 3.9 months and 7 months, respectively. Pts treated with MTX-based CT had a significantly prolonged PFS and OS as compared to patients treated without MTX or with palliative care (Figure 1A, 1B). In the univariate analysis performed for the 85 pts treated with MTX-based CT, no initial clinical and biological characteristics (age, PS, type of symptoms, CIRS-G, tumor localization, LDH level, albumin level, hemoglobin level, lymphocyte count, creatinine clearance) influenced PFS or OS. The initial dose of MTX did not influence outcome but intravenous rituximab used in first line therapy significantly improved PFS and OS (Figure 1C, 1D). Conclusions: to the best of our knowledge, this is the largest series of consecutive PCNSL pts aged of 80y or over prospectively recorded in a national database. This study showed that the prognosis remains poor with major toxicity under conventional treatment. No clinical predictor of survival was highlighted in our series but patients initially treated with MTX-based CT in combination with rituximab had an improved outcome. The development of target and innovative therapies is needed for this category of patients representing 8% of all PCNSL in the database of the LOC network. Disclosures Houot: Celgene: Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Novartis: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-117331

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 113, No. 5 ( 2009-01-29), p. 995-1001

Abstract: Autologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%; P = .004). A PFS plateau was observed in the HDT group after 7 years. On multivariate analysis, OS and PFS were independently affected by the per-formance status score, the number of nodal areas involved, and the treatment group. Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs 1 acute myeloid leukemia, P = .01). The occurrence of a PFS plateau suggests that a subgroup of patients might have their FL cured by ASCT. However, the increased rate of secondary malignancies may discourage the use of purged ASCT in combination with TBI as first-line treatment for FL. This trial has been registered with ClinicalTrials.gov under identifier NCT00696735.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2008-05-160200

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 782-782

Abstract: Background Despite a significant improvement of therapeutic results with the current immuno-chemotherapies, a consolidation treatment is still required for decreasing the risk of relapse. WBRT has been the historical standard consolidation in PCNSL patients, but IC + HCR has shown encouraging results in non-controlled studies. However, each procedure exposes patients to specific side effects, such as cognitive dysfunctions and treatment-related mortality, respectively. In this trial, we addressed the efficacy and toxicity of a standard chemo-immunotherapy followed by either WBRT or IC+HCR in first-line treatment of PCNSL patients. Methods Immuno-competent patients (aged 18-60) with newly diagnosed PCNSL and measurable disease were enrolled from 23 French centers. All the patients received 2 cycles of R-MBVP (Rituximab 375 mg/m2 D1, Methotrexate 3 g/m2 D1 and D15, VP16 100 mg/m2 D2, BCNU 100 mg/m2 D3, Prednisone 60 mg/kg/D D1-D5) followed by 2 cycles of R-AraC (Rituximab 375 mg/m2 D1, Cytarabine 3g/m2 D1-D2) as induction chemotherapy. Participants were stratified upfront according to performance status (0-1 vs 2-4) and treating institution and randomly assigned (1:1)to receive either WBRT (Arm A) or IC + HCR (Arm B) as a consolidation treatment. IC consisted in thiotepa (250 mg/mg/m2/d days-9 through-7, busulfan 10 mg/kg (total dose) days-6 through -4, and cyclophosphamide 60 mg/kg/d days -3 and -2). Prospective neuro-cognitive evaluations were planned in both arms. Responses were assessed according to the IPCG criteria. A central review of MRIs was scheduled. The primary end-point was the 2-year progression free survival (PFS). Thirty-eight assessable patients who received the complete study treatment for each treatment were needed. Either of the two arms would be deemed effective if 〉 24/38 patients are free of disease at 2 year with no major side effects. Analysis was intent to treat, in a non-comparative phase 2 trial design.This study is registered with ClinicalTrials.gov, number NCT00863460. Results Between Oct 2008 and Feb 2014, 140 patients (male: 101; female: 39) were recruited (median age = 55 years, range 22-60) and randomized in Arm A (n=70) or Arm B (n = 70). Sixty-seven patients were assessable in each arm. Two patients withdrew their consent during the induction cycles (Arm A: n = 1; Arm B: n = 1). After two cycles of R-MBVP, overall response rates were 82% (CR + uCR = 24 %) and 77 % (CR + uCR = 23 %) in arm A and arm B respectively. At the end of the induction chemotherapy, ORR was 74 % (CR+ uCR = 44 %) and 67 % (CR+ uCR = 42 %) in arm A and B respectively. WBRT was given to 53 patients in arm A and IC+HCR was given to 44 patients in arm B. After consolidation treatment, ORR was 71 % (56 % CR+ Cru) and 67 % (60 % CR+ Cru) in arm A and B respectively. Five treatment-related deaths were reported, during induction chemotherapy in arm A (n = 2) and after IC+ HCT (n = 3). Median follow-up was 27.2 and 28.6 months in arm A and arm B respectively. Relapses occurred in 21 patients after the end of treatment (arm A: n = 16; Arm B: n = 5) with a median time to relapse of 15.1 and 8.5 months in arm A and B respectively. 2-y PFS in the experimental arm was 86.8% (95 CI, 76.6 to 98.3%). 2-y PFS in arm A will be given after the completion of the ongoing MRI review in this arm. The analysis of the prospective neuropsychological evaluations is pending. Conclusion:This study shows a favorable outcome of patients who received the IC+HCR arm. Improvement of the ORR after induction chemotherapy is still needed. The results of the 2-y PFS in arm A and of the neuropsychological evaluations are awaited to define the further standard of treatment in young patients with PCNSL. Fundings: French Government, Roche, Pierre Fabre Figure. Figure. Disclosures Choquet: Janssen: Consultancy; Celgene: Consultancy. Thyss:Takeda: Research Funding; Millennium: Research Funding. Soussain:Pharmacyclics: Research Funding; Roche: Research Funding; Celgene: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.782.782

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: mBio, American Society for Microbiology, Vol. 5, No. 6 ( 2014-12-31)

Abstract: Several cases of rapidly fatal infections due to the fungus Saprochaete clavata were reported in France within a short period of time in three health care facilities, suggesting a common source of contamination. A nationwide alert collected 30 cases over 1 year, including an outbreak of 18 cases over 8 weeks. Whole-genome sequencing (WGS) was used to analyze recent and historical isolates and to design a clade-specific genotyping method that uncovered a clone associated with the outbreak, thus allowing a case-case study to analyze the risk factors associated with infection by the clone. The possibility that S. clavata may transmit through contaminated medical devices or can be associated with dairy products as seen in previous European outbreaks is highly relevant for the management of future outbreaks due to this newly recognized pathogen.

Type of Medium: Online Resource

ISSN: 2161-2129 , 2150-7511

URL: Article

DOI: 10.1128/mBio.02309-14

Language: English

Publisher: American Society for Microbiology

Publication Date: 2014

detail.hit.zdb_id: 2557172-2

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 446-446

Abstract: BACKGROUND: Obinutuzumab is a type II anti-CD20 monoclonal antibody that induces antibody-dependent cellular cytotoxicity, antibody-dependent cell-mediated phagocytosis, and direct cell death better than rituximab. Given promising results with lenalidomide and rituximab (R2), we assessed the safety and efficacy of lenalidomide combined with obinutuzumab (GALEN)in a large phase Ib/II study in separate patient populations (NCT01582776). In relapsed/refractory follicular B-cell lymphoma (FL), we found the GALEN regimen might be even more efficient than R2 while retaining a similarly manageable safety profile. Here, we report the results for the phase II part assessing efficacy and safety of GALEN in advanced untreated FL patients (pts) in need of systemic therapy. METHODS: Eligible pts had grade 1-3a FL and required systemic therapy per GELF criteria. Induction treatment consisted of lenalidomide (LEN) 20 mg on day (d) 1-21 of a 28-d cycle for the first cycle and on d2-22 of a 28-d cycle from cycles 2 to 6. Obinutuzumab (GA) 1000 mg was given IV on d8, 15, and 22 of cycle 1 and d1 of cycles 2 to 6. Responding pts then received maintenance with LEN at 10 mg on d2-22 every 28d for 12 cycles and GA 1000 mg every 8 wk for 12 cycles until progression or unacceptable toxicity. The primary study endpoint was complete response (CR)/CR unconfirmed (CRu) rate by investigator assessment at the end of induction according to 1999 IWG criteria. Secondary endpoints included overall response rate (ORR) and CR according to IWG 2007, progression-free survival (PFS), duration of response (DOR), overall survival (OS) and safety. RESULTS: 100 pts with WHO FL gr 1-2 (91%) and 3a (9%) according to local pathology reports were enrolled between October 2015 and February 2017. Median age was 60.5 years (range, 32-89), 43% had FLIPI score ≥3, 89% stage III/IV, and 31% bulky disease ( 〉 7 cm). All 100 pts were evaluable for safety and efficacy. At a median follow-up of 2.1 years, 96 pts (96%) completed induction, 41 completed maintenance, 36 were ongoing in maintenance, and 23 prematurely discontinued treatment due to disease progression (n=12, including 2 during induction), toxicity (n=6, including 2 during induction), concurrent illness (n=3), consent withdrawal (n=1), or other cause (n=1). At the end of induction, 61 pts had regression by more than 75% of sum of the product of the greatest diameters (SPD) of target lesions and 83/97 (85.6%) with PET assessment were PET negative (Juweid criteria) including 79/93 (84.9%) with a 5PS (Deauville scale) score of 1-3. Sixteen pts with SPD regression 〉 75% and 25 pts with negative PET were conservatively downgraded to PR due to missing bone marrow evaluation, leading to 47% CR/CRu rate and 59% CR rate at the end of induction per IWG1999 and 2007 criteria, respectively. Response rates at the end of induction, PFS, DOR and OS are summarized in the Table and Figure. Most common AEs ( 〉 10% of pts) during induction (% all gr/% gr 3/4) were neutropenia (43/42), asthenia (35/2), constipation (32/0), infusion-related reactions (23/3), diarrhea (21/2), rash (21/2), cough (18/0), nausea (13/0), pruritus (12/1), weight decrease (12/0), bronchitis (11/0), muscle spasms (11/1), and pyrexia (11/0). Febrile neutropenia occurred in 2% of pts. Eight second primary malignancies were reported in 8 pts, including 2 deemed unrelated since they were misdiagnosed at baseline. Three (3%) pts had died, 1 each due to lymphoma, toxicity of additional treatment, and intestinal adenocarcinoma. CONCLUSION: The immunomodulatory GALEN regimen is highly effective with no unexpected toxicity in advanced, untreated FL pts in need of systemic therapy and has the potential to challenge immunochemotherapy in this setting. Disclosures Morschhauser: BMS: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy; Janssen: Other: Scientific Lectures. Salles:Celgene: Honoraria, Research Funding; AbbVie: Honoraria; Acerta: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Amgen: Honoraria; Epizyme: Honoraria; Merck: Honoraria; Morphosys: Honoraria; Takeda: Honoraria; Servier: Honoraria; Pfizer: Honoraria; Roche: Honoraria, Research Funding; Novartis: Consultancy, Honoraria. Feugier:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cartron:Celgene: Consultancy, Honoraria; Janssen: Honoraria; Roche: Consultancy, Honoraria; Sanofi: Honoraria; Gilead Sciences: Honoraria. Maerevoet:abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grant; roche: Other: travel grant; takeda: Membership on an entity's Board of Directors or advisory committees, Other: travel grant; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Tilly:Roche: Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria. Haioun:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sciences: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Houot:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-112805

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7