Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1641-1641

Abstract: Introduction: The role of minimal residual disease (MRD) in Multiple Myeloma (MM) as a surrogate biomarker of patients' outcome, as well as the prognostic information of functional imaging response after treatment have been established in recent years. Furthermore, the predictive relevance of sustained MRD negativity assessed by marrow and imaging techniques and its association with an excellent outcome is emerging in clinical trials. Diffusion-weighted whole-body MRI (DW-MRI) is increasingly used in the management of MM patients, but data regarding the predictive role of sustained DW-MRI response after treatment are lacking. The Myeloma Response Assessment and Diagnosis System (MY-RADS) recommendations have established criteria for Response Assessment Category (RAC) (Messiou C et al, Radiology 2019) with a 5 point scale defining the probability of complete imaging response (i.e. RAC 1) or progressive disease after treatment (i.e. RAC 5). We implemented the RAC criteria in our clinical practice and DW-MRI at 1-year in MM patients treated with autologous stem cell transplantation (ASCT) followed by maintenance therapy. Patients and methods: We retrospectively analyzed the outcome of 57 newly diagnosed MM patients (median age 61 years) diagnosed at our institution from January 2015 to December 2019 receiving maintenance therapy after ASCT. Patients underwent DW-MRI evaluation according to MY-RADS criteria at day +100 after ASCT, before maintenance, and after 1 year with the aim of monitoring imaging residual disease. Bone marrow samples were collected for MRD assessment by 8-color FCM (sensitivity 10-5) at day +100 after ASCT, before maintenance, and after 1 year. We focused on sustained 1-year DW-MRI negativity evaluated according to RAC response, and its potential predictive role at that timepoint on progression free survival (PFS) and overall survival (OS). In patients with available 1-year MRD evaluations, concordance between 1-year MRD and DW-MRI results was calculated and the level of agreement was expressed by Cohen's kappa statistics. Results: Out of 57 patients, 23 (40%) were ISS stage 3 and 14 (25%) showed high risk cytogenetics. Patients were treated with the following induction regimens: VTD 42, VRD 5, Dara-VRD 6, KRD 3, KCD 1. Single ASCT with MEL200 conditioning was performed in 33 patients (58%), whereas 24 patients (42%) received double ASCT. Subsequent maintenance was performed with lenalidomide (49 patients, 86%) or daratumumab-lenalidomide (8 patients, 14%). Response rates after ASCT were PR 9%, VGPR 23%, CR 51% and sCR 17%. According to MY-RADS, a complete imaging response (RAC1) at day +100 after ASCT was observed in 34 patients (60%). Sustained 1 year complete imaging response during maintenance therapy was observed in 43 patients (75%). Some residual disease was identified at that timepoint in 14 patients (25%) [RAC 2: 6 (11%), RAC & gt; 2: 8 (14%)]. After a median follow up of 36 months, PFS and OS were significantly longer in patients with sustained 1-year imaging negativity, compared to patients with imaging residual disease (RAC 1 vs RAC ≥2): median PFS 56 vs 24,1 months, p & lt;0,0001, HR 0,11 (95% CI: 0,030-0,382); median OS NR vs 40,5 months, p & lt; 0,0001, HR 0,05 (95% CI: 0,006-0,364). MRD at 1-year timepoint was available in 30 patients and was negative in 28 (93%) cases. Concordance between 1-year DW-MRI and MRD results was high (97%, kappa 0,783: 7% both positive, 90% both negative). Conclusion: Our real-life data analysis confirms the predictive value of imaging residual disease assessment with DW-MRI after ASCT and highlights the importance of achieving sustained imaging MRD negativity during maintenance therapy regardless of different treatment strategies. Moreover, given the high rates of CR seen in patients with MM with novel effective treatment combinations, the detection of residual disease with the combined evaluation of marrow and functional imaging techniques during maintenance therapy can help the physician to identify patients with increased risk of early relapse and particularly poor prognosis. Our preliminary data regarding the high concordance observed between DW-MRI and MRD results during maintenance therapy suggest that DW-MRI could represent a reliable non-invasive technique to monitor residual disease. Disclosures Belotti: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; GSK: Membership on an entity's Board of Directors or advisory committees. Ribolla: Janssen: Membership on an entity's Board of Directors or advisory committees. Cancelli: Amgen: Membership on an entity's Board of Directors or advisory committees. Roccaro: Amgen, Celgene, Janssen, Takeda: Membership on an entity's Board of Directors or advisory committees; AstraZeneca,: Research Funding; Associazione Italiana per la Ricerca sul Cancro (AIRC): Research Funding; European Hematology Association: Research Funding; Fondazione Regionale per la Ricerca Biomedica (FRRB), Transcan-2 ERA-NET: Research Funding. Rossi: Sanofi: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Tucci: janssen: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Takeda: 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-2021-147694

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Cancers, MDPI AG, Vol. 14, No. 19 ( 2022-09-28), p. 4716-

Abstract: The prognosis of acute myeloid leukemia depends on genetic aberrations, particularly NPM1 and FLT3-ITD mutations. The targeted drugs’ availability has renewed interest in FLT3 mutations, but the impact of these genetic alterations using these treatments is yet to be confirmed. Our objective was to evaluate the results obtained with the intensified NILG-AML 01/00 protocol (ClinicalTrials.gov Identifier: NCT 00400673) in 171 unselected patients (median age, 54.5 years, range 15–74) carrying the FLT3 (ITD or TKD) and/or NPM1 mutations. The CR rate and 5-y survival were 88.3% and 58% +/− 4, respectively, significantly higher in the NPM1-mutated (CR 93.9%, p: 0.0001; survival 71% +/− 6, p: 0.0017, respectively). In isolated ITD patients, the CR was lower (66.7%, p: 0.0009), and the 3 years-relapse-free survival worse (24%, p: 〈 0.0002). The presence of ITD, irrespective of the allelic ratio, or TKD mutation, did not significantly affect the survival or relapse-free survival among the NPM1-co-mutated patients. Our data indicate that a high dose of ARAC plus idarubicin consolidation exerts a strong anti-leukemic effect in NPM1-mutated patients both with the FLT3 wild-type and mutated AML, while in the NPM1 wild-type and FLT3-mutated, the therapeutic effect remains unsatisfactory. New strategies incorporating target therapy with second-generation inhibitors will improve these results and their addition to this aggressive chemotherapeutic program merits testing.

Type of Medium: Online Resource

ISSN: 2072-6694

URL: Article

DOI: 10.3390/cancers14194716

Language: English

Publisher: MDPI AG

Publication Date: 2022

detail.hit.zdb_id: 2527080-1

In: HemaSphere, Ovid Technologies (Wolters Kluwer Health), Vol. 7, No. S3 ( 2023-08), p. e624532e-

Type of Medium: Online Resource

ISSN: 2572-9241

URL: Article

DOI: 10.1097/01.HS9.0000973028.62453.2e

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 2023

detail.hit.zdb_id: 2922183-3

In: American Journal of Hematology, Wiley, Vol. 95, No. 7 ( 2020-07), p. 759-765

Abstract: Autologous stem cell transplantation (ASCT) is feasible and effective in selected older patients with Multiple Myeloma, but specific criteria for evaluating ASCT eligibility in elderly patients are lacking. We evaluated 131 patients aged 65‐75 considered for ASCT at our center: The Charlson Comorbidity Index (CCI), Hematopoietic cell transplantation comorbidity index (HCT‐CI) and IMWG frailty score were obtained at diagnosis, but the intensity of treatment was left to physician's choice. The scores and age's impact on outcome was analyzed: 85 patients were judged transplant eligible, whereas 46 patients received a less intensive treatment (median follow up 27 months). No patients classified as frail had been considered eligible to ASCT with a worse outcome compared to fit and unfit patients (median PFS (progression free survival): 7.9 vs 32.9 and 29.6 months; P 〈  .001). PFS was superior in the ASCT group (35.6 vs 19.9 months, P .013). In the ASCT group, PFS was better in patients aged 65‐69 years than in patients ≥70 (51.5 vs 27.7 months, P .004). Indeed, in unfit patients aged ≥70 the PFS of the ASCT group was comparable to NO ASCT group (18 vs 27 months, P = .33) whereas in unfit patients aged 65‐69 PFS was superior in the ASCT group: 43.3 vs 18.4 months, P .01. ISS III and impaired functional status independently affected PFS in a multivariate analysis ( P .011 and P .006). While CCI and HCT‐CI did not predict different outcome in ASCT patients, the IMWG frailty score would be of help in identifying unfit patients aged 70‐75, whose outcome with ASCT selected by clinical judgment was no better than with less intensive treatments.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v95.7

DOI: 10.1002/ajh.25797

Language: English

Publisher: Wiley

Publication Date: 2020

detail.hit.zdb_id: 1492749-4

In: American Journal of Hematology, Wiley, Vol. 90, No. 3 ( 2015-03), p. 230-234

Abstract: High‐dose chemotherapy with autologous stem cell transplantation (ASCT) has been shown effective in the control of relapsed/refractory follicular lymphoma. We evaluate the long‐term outcome of patients with relapsed or refractory follicular lymphoma treated with ASCT with in vivo purged progenitors cells. We report the long‐term results of a prospective multicenter phase 2 trial on 124 relapsed/refractory follicular lymphoma patients treated with a program of anthracycline‐based debulking chemotherapy, immunochemotherapy, mobilization of in vivo purged PBSC followed by ASCT. Median age was 52 years; 14% of patients had grade 3A histology. Debulking chemotherapy produced CR in 16% and PR in 71%, while 13% of patients progressed. After rituximab, cyclophosphamide, vincristine, prednisone (R‐COP), CR was obtained in 60% and PR in 35%; 118 patients successfully mobilized PBSC and 117 proceeded to ASCT. The harvest in all the 32 molecularly informative patients was bcl‐2 negative. TRM was 0%. The 5‐year PFS was 54% and the 5‐year OS was 83%. After a median f‐up of 6.7 years (range 1.5–13.6), 54% are still in CR. These data show that prolonged PFS is achievable in relapsed/refractory patients with high dose autologous transplantation of in vivo purged progenitor cells. Am. J. Hematol. 90:230–234, 2015. © 2014 Wiley Periodicals, Inc.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v90.3

DOI: 10.1002/ajh.23919

Language: English

Publisher: Wiley

Publication Date: 2015

detail.hit.zdb_id: 1492749-4

In: Cancer, Wiley, Vol. 125, No. 10 ( 2019-05-15), p. 1674-1682

Abstract: Among patients who have chronic myeloid leukemia and receive treatment with tyrosine kinase inhibitors, the likelihood of obtaining a sustained deep molecular response and a durable treatment‐free remission is lower in those who have the e13a2 BCR‐ABL transcript. After 5 years of treatment, the probability that patients with the e13a2 transcript will achieve a sustained deep molecular response is 17.4% with imatinib and 36.2% with second‐generation tyrosine kinase inhibitors.

Type of Medium: Online Resource

ISSN: 0008-543X , 1097-0142

URL: Article

DOI: 10.1002/cncr.31977

Language: English

Publisher: Wiley

Publication Date: 2019

detail.hit.zdb_id: 1479932-7

detail.hit.zdb_id: 2599218-1

detail.hit.zdb_id: 2594979-2

detail.hit.zdb_id: 1429-1

In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5273-5273

Abstract: Background Hemophagocytic Lymphohystiocytosis (HLH) is a rare disorder, characterized by uncontrolled hyperinflammation, fever, cytopenias, hepatosplenomegaly and hemophagocytosis caused by genetic defects, e.g. perforin 1, causing impaired natural killer (NK) and cytotoxic T-cell function. A disease characterized by hyperactive phagocytosis similar to familial HLH can occasionally develop in adult patients (pts) and is called acquired hemophagocytic syndrome (AHS). The diagnosis of AHS is often overlooked because of its rarity and heterogeneous clinical presentation. It is usually associated with virus infection (VAHS), autoimmune disorders or malignancies. AHS has been described in Asian pts with lymphoma particularly of T-cell or intravascular large B cell phenotype but has been only occasionally reported in pts of Western origin. Aims To evaluate the occurrence of AHS in adult lymphoma pts of Western origin, focusing on its biological and clinical features. Methods From 2/03 through 02/08 the revised diagnostic criteria of the Histiocyte Society were applied to lymphoma pts presenting with persistent FUO, unexplained cytopenia or clinical signs of AHS. Work-up included detection of HHV-8, EBV, CMV, Parvovirus viral DNA, evaluation of NK activity of PBMCs by 4-hour51Cr-release assay with K562 cells, perforin expression on NK cells by flow cytometry, and by immunohystochemistry on bone marrow biopsy and analysis of perforin gene mutations by PCR and sequencing. Results Fifteen pts fulfilling the criteria for HLH were identified. Their M/F ratio was 1,5 and median age was 66 (31–79). Lymphoma diagnoses clustered in three groups: 5 cases of indolent B cell lymphoma (4 SLL/CLL, 1 SMZL), 5 cases of diffuse large B cell lymphoma (DLBCL), two of which associated with Hodgkin lymphoma (HL),1 case of HL, and 4 cases of T cell lymphoma (1 anaplastic, 1 peripheral unspecified and 2 enteropathic). Among HLH diagnostic criteria, fever, cytopenia and high ferritin occurred in 100%, hypertriglyceridemia in 86%; hypofibrinogenemia and splenomegaly in 66%, and prominent bone marrow hemophagocytosis in 46% of cases. Median Hgb level was 9,1 g/L, ANC 0,7 × 109/L and platelets 23 × 109/L. Median trygliceride levels was 305 mg/dL, fibrinogen 122 mg/dL ferritin 6800 ng/mL. Moreover LDH was elevated in 13/15 cases (median 711 U/L). No significant differences were recorded between the different types of lymphoma except for a lower platelet count in pts with indolent B cell lymphoma (P=.008). No recurrent immunological abnormalities were identified except for direct antiglobulin test positivity in 5/8 pts with B cell lymphoma, without signs of overt hemolysis. Viral DNA was detected only in 3 pts (1 EBV, 1 CMV and 1 CMV+EBV). Biological investigations showed defective NK activity in 83% of pts. Among 9 evaluable pts, analysis of PRF1 gene identified G1070A mutation in 1 pt. and A91V heterozygous polymorphism in 2 pts showing defective PRF1 expression of NK cells by flow cytometry. Perforin expression on bone marrow biopsies was increased in 6 of 11 evaluable pts. Twelve pts died 1–120 days after diagnosis in spite of therapy with steroid, rituximab, high-dose IgG, antivirals and etoposide. Three are alive 22–34+ months after diagnosis. They had not distinctive clinicopathological features at presentation. Conclusions AHS is not unusual in Western adults with lymphoma of T-cell but also of B cell phenotype, being overrepresented in SLL/CLL and in DLBCL, particularly when associated with HL. Genetic abnormalities of PRF1 are predisposing factors in some cases. However further mechanisms of defective NK function likely account for the development of this very severe condition and should be actively explored in order to ameliorate its dismal prognosis.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V112.11.5273.5273

Language: English

Publisher: American Society of Hematology

Publication Date: 2008

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. 2151-2151

Abstract: Introduction: Autologous stem cell transplantation (ASCT) has proven effective in Multiple Myeloma (MM) patients (pts) aged 〈 65. However in several studies ASCT has proven safe and effective also in selected MM pts aged 〉 65. With the increase of treatment options, several geriatric assessment tools have been proposed to help physicians in selecting treatment of appropriate intensity. However specific criteria for evaluating ASCT eligibility in elderly MM pts have been seldom investigated.Patients and Methods: From January 2013 to December 2017 131 consecutive newly diagnosed symptomatic MM pts aged 65-75 (M/F: 66/65) were considered for ASCT at our center according to physician's clinical judgement. The variables included in Charlson Comorbidity Index (CCI), Hematopoietic cell transplantation comorbidity index (HCT-CI), and International Myeloma Working Group (IMWG) frailty score were not considered for selection but were retrieved for this study and pts were classified accordingly. Of note, ADL and IADL were referred to pts status prior the occurrence of MM related symptoms. The impact of age and the predictive role of the above mentioned scores on progression-free survival (PFS) of pts selected or not for ASCT was analyzed. Pts characteristics are shown in Table 1. Results: Of 131 pts, 85 (65%) were judged transplant eligible (ASCT ITT arm) by the clinician and received bortezomib-based induction (VTD 94%, VD 5%, VCD 1%); 72 of them (85%) actually underwent ASCT (70% single, 30% double) with melphalan conditioning 200 mg/sqm in 68% of cases. The 46 pts considered ineligible to ASCT received a less intensive first line treatment (89% VMP, 4% Daratumumab-VMP, 2% MP, 5% steroids/palliation). Complete remission (CR) after the first ASCT was higher in the ASCT (ITT) vs the NO ASCT group (43,5% vs 26%, respectively; p 0.048), whereas ORR and ³VGPR rates were comparable (83% vs 74% and 76,4% vs 61%, respectively). Transplant related mortality (TRM) was 0%. 2 year death rate was 13% in the ASCT (ITT) arm and was due to PD in 91% of cases (the latter 9% concerns a cardiac arrest secondary to aspiration pneumonia in a pt in VGPR 3 months after first ASCT). After a median follow-up of 27 months, PFS was 35,6 in the ASCT (ITT) group vs 19,9 months in NO ASCT pts, respectively; p 0,013, HR 0,42 (95% CI: 0,25-0,71). HCT-CI was ≥2 in 87% of pts overall. PFS was better in pts with HCT-CI 0-1 compared to HCT≥2 (NR vs 27,3 months; p 0,025, HR 0,45, 95% CI 0,23-0,91) and also in pts with HCT-CI ³2 undergoing ASCT (ITT) than in NO ASCT pts: median 34 vs 19,9 months, p 0,008 (HR 0,5, 95%CI 0,30-0,84). CCI was 0-3 in 78% of pts. Their outcome according was similar to pts with CCI 〉 3 but ASCT performed better than NO ASCT also in the few (median PFS 51,4 vs 16,9 months; p 0,04, HR 0,37, 95%CI 0,15-0,95). IMWG frailty score was more useful. No pts classified as FRAIL had been considered eligible to ASCT by clinical decision with a significantly worse outcome compared to FIT and UNFIT pts (median PFS: 7,9 months vs 32,9 and 29,6; FIT vs FRAIL: p 〈 0.0001, HR 0,02, 95%CI 0,004-0,008; UNFIT vs FRAIL: p 〈 0,001, HR 0,03 95%CI 0,007-0,12). Unlike HCT-CI and CCI, the distribution of patients according to IMWG score was more balanced both overall and between the ASCT (ITT) and NO ASCT groups, particularly for UNFIT pts. However on the whole no outcome differences were observed between FIT and UNFIT pts. PFS was better in FIT & UNFIT pts in the ASCT (ITT) group than in the NO ASCT group: median 35,6 months vs 25,8 months; p 0,04, HR 0,54, 95%CI 0,31-0,97. However, in the ASCT (ITT) group, the age group 65-69 years fared better than pts ³70 years (51,5 vs 27,7 months, p 0,0037; HR 0.34, 95% CI 0.17-0.7). Indeed, in IMWG UNFIT patients aged ³70, the PFS of the ASCT (ITT) group was comparable to NO ASCT group (18 vs 27 months, p 0,33) whereas in UNFIT pts aged 65-69, PFS was superior in pts treated more intensively by physician choice: 43,3 months in ASCT (ITT) arm vs 18,4 months in NO ASCT (p 0.01, HR 0.03; 95%CI 0.003-0.24). Conclusion: In an unselected series of elderly MM pts aged 65-75 and undergoing ASCT according to clinical judgement the outcome of ASCT pts was better than those of NO ASCT. CCI and HCT-CI score proved of little help for better identifying the best candidates to ASCT. Conversely the IMWG frailty score would be of help in identifying the category of UNFIT pts aged 70-75 whose outcome with ASCT selected by clinical judgement was no better than with less intensive treatments. Table 1: Disclosures Belotti: Amgen: Other: Advisory Board; Celgene: Other: Advisory Board. Cattaneo:GILEAD: Other: Advisory Board. Rossi:TEVA: Other: ADVISORY BOARD; CELGENE: Other: ADVISORY BOARD; SANOFI: Other: ADVISORY BOARD; MUNDIPHARMA: Honoraria; ABBVIE: Other: ADVISORY BOARD; JANNSEN: Other; PFIZER: Other: ADVISORY BOARD; ROCHE: Other: Advisory Board; NOVARTIS: Honoraria; SANDOZ: Honoraria; GILEAD: Other: ADVISORY BOARD; BMS: Honoraria; JAZZ: Other: ADVISORY BOARD; AMGEN: Other: ADVISORY BOARD.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-113022

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. 126, No. 23 ( 2015-12-03), p. 3985-3985

Abstract: Introduction: we previously reported (Vitolo U, JCO 2013) the results of a randomized study with brief first-line chemoimmunotherapy followed by rituximab maintenance vs observation. With a median follow-up of 42 months, 3-year Progression Free Survival (PFS) and Overall Survival (OS) were 66% and 89%, respectively. The addition of Rituximab maintenance gave a benefit to the patients: 2-year PFS was 81% for rituximab maintenance versus 69% for observation with a HR of 0.63 (95% CI: 0.38-1.05, p=0.079), although not statistically significant. Moreover we also found that achievement of Minimal Residual Disease (MRD) negativity predicted a better PFS: 3-year PFS 72% vs 39%, HR 3.1 (Ladetto M, Blood 2013). Overall these data showed the good efficacy of this brief chemoimmunotherapy regimen in elderly FL patients. Aim of this analysis was to report long-term outcome and long-term toxicities of this regimen. Methods: From January 2004 to December 2007, 242 treatment-naive patients aged 60-75 years with FL Grade I, II and IIIa were enrolled by 33 FIL centres. Patients had to have advanced (high tumor burden stage II or stage III-IV) disease requiring treatment: 4 monthly courses of R-FND (standard doses of Rituximab, Fludarabine, Mitoxantrone, Dexamethasone) every 28 days followed by 4 weekly Rituximab infusions as consolidation. Responders patients [complete remission (CR) + unconfirmed CR + partial remission (PR)] were randomized to brief rituximab maintenance (Arm A), once every 2 months for a total of 4 doses, or observation (Arm B). MRD for the bcl-2/IgH translocation was determined on bone marrow cells in a centralized laboratory belonging to Euro-MRD consortium, using qualitative and quantitative PCR. Results: a total of 234 patients began chemoimmunotherapy: after induction and consolidation treatment overall response rate was 86%, with 69% CR. Of these, 210 completed the planned treatment and 202 responders were randomized. Up to date, median follow-up were 96 months from enrollment and 87 months from randomization; additional follow-up data were available for 127/146 (87%) not relapsed/progressed patients. Five- and 7-year PFS for the whole population were 57% and 51%, respectively; 5- and 7-year OS for the whole population were 85% and 80%, respectively. From enrollment, an advantage in term of PFS and also OS was observed in FLIPI low risk patients: 7-year PFS was 67% for low risk versus 38% for intermediate-high risk patients (p 〈 0.001) and 7-year OS was 86% versus 75%, respectively (p=0.03). After randomization, no differences between the two arms were detected for both PFS and for OS at 5 (data not showed) and 7 years: 7-year PFS was 55% for rituximab maintenance arm versus 52% for observation arm (p=0.331; HR 0.8); 7-year OS was 83% for both arms (p=0.208; HR 0.67). Moreover, after randomization no differences between the two arms were detected for both FLIPI low risk and intermediate-high risk patients: 7-year PFS was 67% for Rituximab maintenance arm versus 68% for observation arm (p=0.808) in low risk patients; in intermediate-high risk patients 7-year PFS was 46% vs 35% (p=0.301), respectively in Arm A vs B. Conversion to PCR negativity at the end of treatment maintains predictive value for better PFS: 7-year PFS were 58% and 36% (p=0.084), respectively for MRD negative vs positive patients. The same risk of late toxicity (infections or cardiac events) or secondary cancers was observed in both arms: in particular, 13 secondary neoplasms in maintenance arm vs 16 in observation arm were recorded. Conclusions: the present long-term results of this trial with a prolonged follow-up of 7 years confirm that a good outcome is achievable in elderly FL patients with a short-term chemoimmunotherapy (R-FND + Rituximab consolidation) with a 7-year PFS of 51% and low toxicity. In addition these results did not show clear evidence in favor of a shortened Rituximab maintenance after R-fludarabine containing chemotherapy. Conversely, the achievement of PCR negativity maintains predictive value for a better outcome. Figure 1. Figure 1. Disclosures Off Label Use: Rituximab maintenance was not licensed in first-line treatment for follicular lymphoma at that time in Italy; Rituximab was provided free by Roche.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.3985.3985

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 21 ( 2021-10), p. S36-S37

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/S2152-2650(21)02130-3

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3