Kooperativer Bibliotheksverbund

In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-12-6)

Abstract: Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor venetoclax was investigated in a prospective phase II trial in patients with BCL2-positive R/R PTCL after at least one previous standard line of treatment (NCT03552692). Venetoclax given alone at a dosage of 800 mg/day resulted in one complete response (CR) and two stable diseases (SDs) among 17 enrolled patients. The majority of patients (88.2%) interrupted the treatment due to disease progression. No relationship with BCL2 expression was documented. At a median follow-up of 8 months, two patients are currently still on treatment (one CR and one SD). No case of tumor lysis syndrome was registered. Therefore, venetoclax monotherapy shows activity in a minority of patients whose biological characteristics have not yet been identified. Clinical Trial Registration www.clinicaltrials.gov (NCT03552692, EudraCT number 2017-004630-29).

Type of Medium: Online Resource

ISSN: 2234-943X

URL: Article

URL: Article

DOI: 10.3389/fonc.2021.789891

DOI: 10.3389/fonc.2021.789891.s001

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2021

detail.hit.zdb_id: 2649216-7

In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1713-1713

Abstract: Abstract 1713 Poster Board I-739 Introduction: Previous reports have highlighted the activity of Lenalidomide (Len) in patients with relapsed or refractory mantle cell lymphoma (MCL), achieving a 53% overall response rate (ORR), which included 20% complete responses (CR) (Haberman et al. Br J Haematol. 2009). In vitro studies on Burkitt's Lymphoma and MCL cell lines showed that combining Dexamethasone (Dex) with Len results in potent and synergistic anti-proliferative effects. To assess whether this effect translates to a clinical setting, and on the basis of data coming from multiple myeloma, we initiated a prospective, multicenter, phase II study, to evaluate safety and efficacy of Len administered in combination with Dex for adult patients with relapsed or refractory MCL. Methods: Patients had to have ≥1 prior treatment regimen, and were either not eligible for, or had relapsed after, more intensive treatments including stem cell transplantation (SCT). During the induction phase (month 1 to 3), patients received Len 25 mg/day on days 1 to 21 and Dex 40 mg/day on days 1, 8, 15, 22 of a 28-day cycle (Len Dex). Enoxiparin 4.000 U/day was administered as anti-thrombotic prophylaxis. Patients who achieved a partial response (PR) or stable disease (SD) at the end of the induction phase continued to the consolidation phase, which consisted of treatment with Len Dex until disease progression, unacceptable toxicity, or a CR, for a maximum of 12 months. Patients with a CR at the end of the induction phase, or those who achieved a CR during consolidation, received an additional 3 courses of Len Dex. The primary objective is to evaluate the ORR and CRR (IWG criteria Cheson et al 2007). Secondary objectives include safety, response duration (RD), overall survival (OS), and to explore changes in tumour biomarkers relative to response to treatment with Len Dex. Severity of adverse events (AE) is graded on a scale of 1 to 5 (NCI CTCAE v.3). Results: Between July 2008 and July 2009, 33 patients were enrolled on this study, representing the intent to treat population. Patients' median age is 68 years (range 51-80); 30 have the classic histology while 3 patients have the blastoid variant; 9 patients previously received two lines of therapy, 9 patients had three lines and 12 patients had 〉 3 prior lines (median 3; range 1-7). Twelve patients previously underwent an autologous SCT and 7 received prior therapy with Bortezomib. At present, 21 out 33 enrolled patients are evaluable for response to the induction phase of the study: 11 patients responded to Len Dex (52% OR), including 3 CRs (14%); 1 patient (5%) has SD and 9 patients (43%) either had not responded or had progressed while on study. Nine patients discontinued treatment for the following reasons: skin reaction in 1 patient, progression in 7 patients, 1 patient died while on study. So far, 28 patients are valuable for safety during the induction phase. Most common Grade 3-4 adverse events were hematologic and included leucopenia (n=6; 21%), neutropenia (n=10; 36%), thrombocytopenia (n=4; 14%) and anemia (n=1; 3%). Other events included 3 patients (10%) with grade 3-4 neutropenic fever and 2 patients (7%) with grade 3 bacterial pneumonia. Grade 3-4 hypotension and dyspnea developed in 1 patient each, and none of the patients developed thromboembolic or neuropathic complications. Initial results from this study confirm the high therapeutic activity of Len in patients with relapsed and refractory MCL. Conclusions: Preliminary evaluation of the safety and efficacy of the Len Dex regimen indicates that the combination has a favourable safety profile, but the addition of Dex does not appear to substantially improve the activity of Len in the treatment of patients with relapsed or refractory MCL. Disclosures: Off Label Use: Lenalidomide is off label for treatment of Non Hodgkin Lymphoma.. Vitolo:Celgene: Lecture fees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.1713.1713

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 966-966

Abstract: Abstract 966 Backgrounds Previous in vivo and in vitro studies have highlighted the activity of Lenalidomide (Len) in patients with relapsed or refractory mantle cell lymphoma (MCL), achieving a 53% overall response rate (ORR), which included 20% complete responses (CR) (Habermann et al. Br J Haematol. 2009) and the possible synergistic anti-proliferative effect of Dexamethasone (Dex). Purpose: On this basis we performed a prospective, multicenter, phase II study, to evaluate safety and efficacy of Len Dex combination for adult patients with MCL. Patients and Methods Patients had to have ≥1 prior treatment regimen, and were either not eligible for, or had relapsed after, more intensive treatments including stem cell transplantation (SCT). During the induction phase (month 1 to 3), patients received Len 25 mg/day on days 1 to 21 and Dex 40 mg/day on days 1, 8, 15, 22 of a 28-day cycle (Len Dex). Enoxaparin 4000 U/day was administered as anti-thrombotic prophylaxis. Patients who achieved a partial response (PR) or stable disease (SD) at the end of the induction phase continued to the consolidation phase, which consisted of treatment with Len Dex until disease progression or unacceptable toxicity, for a maximum of 12 months. Patients with a CR at the end of the induction phase, or those who achieved a CR during consolidation, received an additional 3 courses of Len Dex. The primary objective was to evaluate the ORR and CRR. Response data were correlated with the modification of angiogenic biomarkers by analyzing immunohistochemistry macrophage infiltration and the bone marrow (BM) microvessel counts, and by measuring plasma levels of VEGF, bFGF and HGF before and after therapy. Results Between July 2008 and July 2009, 33 patients were enrolled on this study. Patients' median age is 68 years (range 51–80); 30 have the classic histology while 3 patients have the blastoid variant; 10 patients previously received two lines of therapy, 10 patients had three lines and 13 patients had 〉 3 prior lines (median 3; range 1–7). Twelve patients previously underwent an autologous SCT and 8 received prior therapy with Bortezomib. The number of patients who responded to induction phase was: OR= 22 (67%) including 5 CR (15%), SD= 1 (3%), no response (NR) or progression (PD)= 10 (30%); OR in patients previously treated with Bortezomib or an autologous SCT was 50% each. At present, 13 patients completed the therapeutic program, 15 discontinued therapy prematurely (14 NR or PD, 1 poor compliance) and 5 remain on therapy. The final response status at the end of the therapeutic program is: OR= 18 patients (55%) including 8 CR (24%), NR/PD= 15 (45%). After a median follow-up of 6 months (range 3–13 months) from the end of therapy, none of the CR patients had subsequent progression while 2 PR patients had progression 7 and 10 months after the end of therapy. The macrophage counts increased significantly in the BM after the first three months of therapy (P 〈 0.01; r2=0,8927). This was parallel to a significant increase in the microvessel counts (P 〈 0.05, r2= 0,1547). The within-group comparisons showed that both counts were always significantly correlated (P 〈 0.001). Regarding angiogenic plasma biomarkers, preliminary data of bFGF, VEGF and HGF concentrations showed a trend, albeit not significant, to decrease after the first three cycles of therapy. Most common Grade 3–4 adverse events were hematologic and included neutropenia (48%), thrombocytopenia (18%) and anemia (6%). Other events included 4 patients (12%) with Grade 3–4 neutropenic fever and 3 patients (9%) with Grade 3 bacterial pneumonia. Grade 3–4 hypotension and dyspnea developed in 1 and 3 patients respectively; no patient developed thrombo-embolic or neuropathic complications. Conclusions Results from this study confirm the high therapeutic activity of Len in association with Dex in patients with relapsed and refractory MCL with a favourable safety profile. The significant increase of the macrophage infiltration in the BM seems to be a possible immunomodulatory effect of Len. Perhaps, the increase in microvessel counts may be induced by the activated macrophages and be an example of “indirect angiogenesis”. On the other hand, angiogenic plasma biomarkers tend to be lower, suggesting only a limited effect of Len on the neovascularization. Disclosures: Off Label Use: Lenalidomide in Mantle Cell Lymphoma. Vitolo:Celgene: 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.V116.21.966.966

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2427-2427

Abstract: The R-BAC regimen is considered among standard first-line treatment for elderly fit patients with mantle cell lymphoma (MCL). In the previous R-BAC500 FIL trial, patients with the blastoid variant and/or high Ki67 proliferative index (High Risk - HR-) had a significantly higher risk of progression (2-years PFS of 40%), as compared to classical histologies and low proliferative index (Low Risk -LR-). When treated with R-BAC, LR patients had excellent outcome (median PFS not reached after 7 years), although no maintenance therapy was delivered. For this reason we designed a phase 2 trial that enrolled patients from 35 centers of the Fondazione Italiana Linfomi (FIL). At study entry, patients were centrally reviewed and stratified as "low risk (LR)", or "high risk (HR)", depending on morphology (blastoid versus others), Ki67 expression (≥30% versus others), TP53 mutation/TP53 deletions (present versus not). Patients with any of the three risk factors were classified as HR. The primary endpoint was 2-years progression-free survival (PFS) for the HR patients. Patients had to be aged ≥65 years and fit according to the geriatric CGA assessment, or age ≤64 years if not eliglible to high-dose chemotherapy plus transplantation. Asymptomatic patients with non-nodal disease were excluded. Treatment consisted of 6 cycles of R-BAC (rituximab 375 mg/m2 d 1; bendamustine 70 mg/m2 d 1,2; cytarabine 500 mg/m2 d 1,2,3) for LR patients. HR patients received abbreviated induction with a maximum of 4 R-BAC followed by consolidation (4 months, 800 mg/d), and maintenance (20 months, 400 mg/d) with venetoclax. First patient was included on the 3rd of september, 2018, and last patient on the 20th of july, 2021. Overall, 140 patients were enrolled, of whom 52 were HR (37%). Median age was 72 (range 57-79), and 75% were males. The prevalence of TP53 mutations and deletions in the whole series was 21%, and 13%, respectively; Ki67 was ≥30% in 24%, and the blastoid variant was diagnosed in 9%. Demographic characteristics of HR versus LR patients (127 patients with available data at the present time) are reported in Table 1A. Median follow-up was 9 months (range 0-34). The two groups (HR and LR) had similar age, gender, and MIPI, but differed for LDH, and SUVmax at diagnosis, both being significantly more elevated in the HR group. The VR-BAC trial represents the first prospective study that stratified patients with MCL to different frontline treatments according to centralized on-time evaluation of the risk profile. We have shown that almost 40% of elderly patients with MCL in need of treatment have HR features. Data on tolerance, and tumor response will be presented at the meeting. Figure 1 Figure 1. Disclosures Tisi: GILEAD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BWS: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Takeda: Other: travel expenses, accommodation; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau. Corradini: AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Honoraria; BMS: Other: Travel and accommodation; Novartis; Gilead; Celgene: Consultancy, Other: Travel and accommodations; Amgen; Takeda; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations; KiowaKirin; Incyte; Daiichi Sankyo; Janssen; F. Hoffman-La Roche; Kite; Servier: Consultancy; Sanofi: Consultancy, Honoraria; Incyte: Consultancy; AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Consultancy; Novartis, Janssen, Celgene, BMS, Takeda, Gilead/Kite, Amgen, AbbVie: Other: travel and accomodations. Musuraca: janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Puccini: Takeda: Membership on an entity's Board of Directors or advisory committees. Cavallo: Servier: Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees; Gilead: Speakers Bureau. Merli: EUSA Pharma: Other: Travel, Accomodations, Expenses; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; MSD: Membership on an entity's Board of Directors or advisory committees; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Celgene: Other: Travel, Accomodations, Expenses. Ferreri: PletixaPharm: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Beigene: Research Funding; Hutchison Medipharma: Research Funding; ADC Therapeutics: Research Funding; Adienne: Membership on an entity's Board of Directors or advisory committees; Genmab: Research Funding; Amgen: Research Funding; x Incyte: Membership on an entity's Board of Directors or advisory committees; Ospedale San Raffaele srl: Patents & Royalties; Pfizer: Research Funding. Santoro: AstraZeneca: Speakers Bureau; AbbVie: Speakers Bureau; Amgen: Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Speakers Bureau; Sandoz: Speakers Bureau; Eli-Lilly: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eisai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; Sanofi: Consultancy; Arqule: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zinzani: KYOWA KIRIN: Other, Speakers Bureau; SERVIER: Other: Advisory board, Speakers Bureau; SANDOZ: Other: Advisory board; TG Therapeutics: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; BMS: Other: Advisory board, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; MSD: Consultancy, Other: Advisory board, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; Beigene: Other, Speakers Bureau; ADC Therap.: Other; Incyte: Other, Speakers Bureau; JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; GILEAD: Other: Advisory board, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. OffLabel Disclosure: Venetoclax is off-label in Italy in mantle cell lymphoma

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-145421

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

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detail.hit.zdb_id: 80069-7

In: Leukemia & Lymphoma, Informa UK Limited, Vol. 60, No. 12 ( 2019-10-15), p. 2890-2898

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.1080/10428194.2019.1608529

Language: English

Publisher: Informa UK Limited

Publication Date: 2019

detail.hit.zdb_id: 2030637-4

In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 11 ( 2021-11), p. 3314-3318

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-021-01210-8

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. 122, No. 21 ( 2013-11-15), p. 3047-3047

Abstract: Histone deacetylases (DACs) are involved in chromatin structure regulation and function. Treatment with DACs inhibitors leads to the activation or repression of genes regulating apoptosis, proliferation, differentiation, angiogenesis, immune responses. These agents resulted to be active for the treatment of T and B-cell lymphoma and other haematological malignancies. Previous in vitro studies underlined the possible pathophysiological role of DACs in diffuse large B-cell lymphoma (DLBCL). In FIL-PanAL10 we evaluate the therapeutic activity and safety of Panobinostat, a potent pan-DACs inhibitor, in patients with relapsed or refractory (R/R) DLBCL. Methods FIL-PanAL10 (NCT01523834) is a phase II, prospective multicenter trial of the Fondazione Italiana Linfomi (FIL). Enrolled patients are ≥ 18 years old with R/R DLBCL, following ≥ 1 line of chemo-immunotherapy (R-CHOP) including high dose therapy with autologous stem cell support (ASCT) in eligible patients. Patients with 〉 5 prior systemic lines of treatment, CNS involvement, HIV positivity, impaired cardiac function (according to the protocol) are excluded. Patients are scheduled to receive Panobinostat po 40 mg three-times every week as part of a 4-weeks treatment cycle up to disease progression, unacceptable toxicity, or patient’s refusal. The primary endpoint of the study is to explore the antitumor activity of Panobinostat in terms of overall response (ORR) according to the Cheson criteria 1999. Secondary objectives are the evaluation of complete response (CR), time to response (TTR), progression free survival (PFS), overall survival (OS) and safety. Exploratory objectives evaluate the predictive role of pharmacogenetics, immunohistochemical and specific gene expression in relation to the response to Panobinostat; for this aim a new lymph node or other pathologic tissue biopsy is requested before starting treatment. With the null (P0) and P1 hypothesis of overall response (ORR) corresponding to 〈 10% and ≥ 30%, 35 patients will be needed (α: 0.5; β: 0.10) and at the end of the trial treatment with Panobinostat will be considered active if ≥ 7 responses will be occurred. Results Between February 2011 and May 2013, 23 patients were enrolled on this study. Patients’ median age is 73 years (range 44-83 years); 7 (30%) patients received ≥ 3 previous lines of chemotherapy. Five patients responded to Panobinostat (ORR= 22%) including 3 CR (13%) and 2 (9%) partial response (PR): 1 patient had (4%) stable disease (SD). TTR was 2.5 months (range 2-3 months ). All 6 patients with ORR or SD are still in treatment with Panobinostat after 4, 5, 12, 12, 15, 24, months; 17 patients discontinued therapy because of progression (15) or side effects (2). After a median period of observation of 11 months from the beginning of treatment, 1-year PFS and OS are 22% and 28%, respectively. Most common observed grade 3-4 adverse events were hematological and included thrombocytopenia (88%) and neutropenia (34%); grade 3-4 diarrhoea was present in 3 (13%). The therapeutic schedule was modified from the three times week to three times every other week in 15 patients; a further dose reduction from 40 mg to 30 mg resulted to be necessary in 8 patients. The analysis of exploratory biologic objectives and of their relationship with outcome is still under investigation and will be ready for December 2013. Conclusions The preliminary results of this study indicates that Panobinostat is an active salvage therapy in nearly 20% of heavily pretreated R/R DLBCL patients; the relatively short TTR observed allows a prompt shift to other rescue treatments in non responders. The analysis of biologic biomarkers will hopefully better address Panobinostat therapy to a specific biologic subgroup. Disclosures: Zaja: Mundipharma: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Celgene: Consultancy; GSK: Consultancy, Honoraria; Amgen: Consultancy. Off Label Use: Panobinostat in DLBCL.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.3047.3047

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4860-4860

Abstract: Abstract 4860 Background At present, the standard salvage treatment for relapsed/refractory (R/R) T-cell non Hodgkin lymphoma (NHL) has not been defined yet. Several studies indicated the high therapeutic activity and good safety profile of Bendamustine in B-cell NHL while, on the contrary, only few data are available in T-cell NHL. Recently, a multicenter phase II study showed that Bendamustine is active in angioimmunoblastic lymphoma and other T-cell NHL with 50% overall response rates (OR) and 28% complete responses (CR) (Gressin et al. J Clin Oncol, 2012 ASCO Annual Meeting Proceedings, 30, 15 suppl: 8026). Purpose On this basis we evaluated in the contest of everyday clinical practice the efficacy and safety of Bendamustine salvage monotherapy in unselected adult patients with T-cell NHL. Patients and Methods Hematological and Oncological Italian centers involved in the treatment of patients with lymphomas were asked to report retrospectively the results of their experience regarding the use of Bendamustine in T-cell NHL. Response status and toxicity were evaluated according to Cheson 2007 and to the Common Terminology Criteria For Adverse Events V 4.0. Results Clinical data of 20 patients with R/R T-cell NHL (median age 73 years, range 31–83; 14 males) treated with Bendamustine in seven Italian centers between March 2009 and June 2012 were analyzed. Investigated series included 6 peripheral T-NHL-NOS, 4 angioimmunoblastic (AILT), 3 prolymphocytic T-cell leukemia (PLL), 3 advanced- stage Mycosis Fungoides (MF)/Sezary Syndrome (SS), 2 large granular lymphocyte (LGL) NHL and 2 ATLL- like HLTV-1 negative NHL. The median interval from diagnosis to Bendamustine treatment was 18 months (range 1–74). Eleven patients received up to 2 previous lines of therapy, while 9 received more than 2, including CHOP or CHOP-like therapy (14 patients), Fludarabine or Pentostatine (5), Gemcitabine based therapy (7), Alemtuzumab (4), Romidepsin (1), allogeneic stem cell transplant (1). Nearly 70% of patients were refractory to the last previous chemotherapy. Bendamustine was given as monotherapy at a dosage of 60 and 70 mg/m2 (7 patients) or 90–100 mg/m2(13) for a median number of 2.5 cycles (range 1–8) and a total number of 67 cycles. Response to Bendamustine was CR in 2 (10%) and PR in 8 (40%), with an ORR of 50%, including 3 PR in T-cell NHL/NOS, 1 CR in AILT, 3 PR in PLL, 1 PR in MF/SS, 1 CR and 1 PR in LGL NHL. The median period of observation was 6 months (range 1–18 months); 6- months estimated PFS, OS and response duration are 63%, 70% and 60%, respectively. Three patients in PR (2 PLL and 1 MF) progressed after 3, 4 and 7 months. Grade 3–4 neutropenia, thrombocytopenia and anemia were registered in 44%, 25% and 19% of cases. Three patients developed pneumonia (1 invasive aspergillosis) and 1 had septic shock; no grade 3–4 extra hematological toxicity was reported. Conclusions Bendamustine is a safe and active agent that desertes further investigation in patients with T-cell NHL. Combinations with other cytostatics or target therapy with potential synergistic effect should be assessed in future prospective trials. Disclosures: Zaja: Mundipharma: Honoraria. Off Label Use: Bendamustine In T-NHL. Fanin:Mundipharma: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V120.21.4860.4860

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 2985-2985

Abstract: Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin Lymphoma. Although a typical presentation as an indolent lymphoma, without systemic symptoms and with a good performance status, the mantle cell lymphoma is an aggressive one, hardly curable with standard chemo-immunotherapy. Although current approaches to mantle cell lymphoma, including newer agents (such as bortezomib, lenalidomide, temsirolimus and ibrutinib) and autologous stem cell transplantation, have greatly improved the outcomes of affected patients, this disease is still characterized by high relapse rates, with most patients eventually dying of lymphoma progression. Before official approval by EMA, patients with relapsed/refractory mantle cell lymphoma with unsatisfied critical medical urgency were granted ibrutinib early access through a Named Patient Program in Italy (NPP, DM 8 May 2003). This observational, non-interventional, retrospective, multicenter study focuses on collecting information about the effectiveness and safety of ibrutinib as single-agent in patients who received at least one dose of ibrutinib under the NPP in the period between 29/Jul/2014 and 25/Jan/2015 in Italy. Data from patients treated with ibrutinib outside a controlled clinical trial within a NPP could give additional information about the clinical use, treatment duration, efficacy and toxicity of ibrutinib given to relapsed or refractory MCL patients in a real life context. Fifty-three heavily pretreated patients were enrolled. They had received a median of previous therapies of 3, comprising lenalidomide, bortezomib, temsirolimus and autologous stem transplant. Ninety-one percent had measurable disease and 83.0% had and ECOG performance status ≤2. At the end of therapy there were 11 complete responses (20.8%), 7 partial responses, 5 stable diseases and 30 progressions with an overall response rate of 33.9%. Twenty-six patients received ≥3 concomitant medications during ibrutinib therapy. At 20 months overall survival (OS) was 26.8% (median reached at 9 months) and disease free survival (DFS) 75% at 15 months: 10/11 patients are in continuous complete response with a median of 10.5 months. Hematological toxicities were manageable, 6 thrombocytopenia occurred, of which only 2 grade 4 (due to disease bone marrow infiltration) and the other 4 related to ibrutinib. Main extra-hematological toxicities were diarrhea (9.4%) and lung infections (7.5%) which all lead to early drug discontinuation. The observed occurrence of diarrhea by severity was 0 for CTCAE Grade 1, 4 for Grade 2, 2 for Grade 3 and 0 for Grade 4. Lung infection had a lower occurrence: 0, 2, 2 and 0 split by CTCAE Grade 1, 2, 3 and 4 respectively. There is a boundary zone in the passage from phase III to phase IV trials, i.e. from experimental to marketing and free use phases: in this zone we can find NPP and compassionate and off-label use. Despite the known potential bias of all the observational retrospective studies, reports on the real life experience make an important contribution to medical knowledge prior to widespread utilization: ibrutinib therapy is effective and tolerable also in a clinical setting mimicking the real world. Our results, in fact, are superimposable to those obtained in clinical trials: for safety, thrombocytopenia, diarrhea and lung infections are the relevant adverse events to be clinically focused on; for effectiveness, ibrutinib is confirmed to be a valid option for refractory/relapsed MCL. Disclosures Cascavilla: Janssen-Cilag: Honoraria. Zinzani:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celegene: Membership on an entity's Board of Directors or advisory committees; Roche: 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.V128.22.2985.2985

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

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detail.hit.zdb_id: 80069-7

In: European Journal of Haematology, Wiley, Vol. 85, No. 4 ( 2010-07-28), p. 329-334

Type of Medium: Online Resource

ISSN: 0902-4441

URL: Issue

URL: Article

DOI: 10.1111/ejh.2010.85.issue-4

DOI: 10.1111/j.1600-0609.2010.01486.x

Language: English

Publisher: Wiley

Publication Date: 2010

detail.hit.zdb_id: 2027114-1