Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3608-3608

Abstract: Primary cutaneous B-cell lymphomas (PCBCL) are a distinct group of primary cutaneous lymphomas with few and controversial reports on their treatment and prognostic factors. The aim of this retrospective study of a large international series of PCBCL patients was to analyze the patient and lymphoma characteristics as well as treatment-related variables associated with clinical outcome. From 1980 to 2006, 507 patients were referred to 19 cancer centers of 6 countries all over the world. The median age was 55 years (range,16–92 years) and the M/F ratio was 1.4. According to the WHO-EORTC classification indolent lymphomas included 341 FCL and 122 MZL, while aggressive NHL were represented by DLBCL, leg type (n=44). Sixty patients (12%) had stage II. The majority of cases was diagnosed in trunk/arms (52%), while in 29% in head/neck and in 13% in the legs; 7% of patients had a generalized disease ( 〉 1 site). The maximal lesion diameter was 〉 4 cm in 21% of cases and ≥2 lesions were recorded in 39%. The prevailing type of lesions were nodules (74%), while only a minority of patients (6%) were affected by tumors. Few patients had B symptoms (5%), poor ECOG-PS (9%) or elevated LDH (7%). Two hundred eighty-four out of 446 patients (64%) were treated only with surgery (n=86) or chemotherapy (n=95), mostly consisting of a short course of anthracyclin containing regimens, or radiotherapy (30–50 Gy) (n=103). One hundred sixty two cases (36%) received combined therapy, mostly including surgery or chemotherapy, followed by radiotherapy. A small subgroup of 35 patients were given rituximab alone (n=19) or in combination with other treatments. The remaining 26 patients did not receive any therapy. The response rate of 446 patients was the following: 402 achieved CR (86%), 38 PR and 6 were in SD. Neither histology nor treatment significantly influenced CR rate. Among 402 responders, 128 (32%) eventually relapsed, 86% in the skin, 10% in extracutaneous sites and 4% in both. The relapse rate varied according to histology, ranging from 52% in DLBCL leg-type to 29% in MZL and 28% in FL. Moreover, combined treatments significantly reduced relapse rate (24% vs. 37%; p=0.008). The achievement and maintenance of CR significantly influenced the long-term disease specific survival (at 20 year 99 % vs. 45%; p=0.0001). The CR rate of subgroup of 35 patients treated with rituximab, was 74%, while the relapse rate was 35%. These results were not influenced by the addition of other therapies to rituximab. After a median follow-up of 53 months (range, 2–333 months), 5 and 10-year estimate of OS, disease-specific survival, PFS and DFS were 91%, 92%, 61%, 65% and 82%, 88%, 49% and 56%, respectively. Cox multivariate analysis, stratified for age with a stepwise selection of the significant variables, identified DLBCL, leg-type histology, elevated LDH, type of lesion (nodules and tumors), B symptoms and female gender, as significant predictors of a poor OS. In conclusion this retrospective analysis confirms, on a large series of cases, that patients with PCBCL belong to different risk categories requiring a tailored treatment approach. These data can be usefully taken into account for an adequate management strategy of PCBCL patients.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V112.11.3608.3608

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. 116, No. 21 ( 2010-11-19), p. 3965-3965

Abstract: Abstract 3965 Introduction. Gene-profiling studies demonstrated a constitutive activation of the NFκB signalling pathway in Mantle Cell Lymphoma (MCL) and Marginal Zone Lymphoma (MZL). Bortezomib, a potent inhibitor of the 26S proteasome, is a good candidate to block this pathway and was tested in relapsed or refractory MCL with encouraging results (objective response up to 45%, with a median PFS of 5–7 months). In vitro, the combination of Bortezomib and Rituximab has been shown synergistic apoptosis and enhanced NFkB depletion in MCL and MZL cells. Aim. On these bases, the IIL conducted a phase II multicenter study to evaluate safety and efficacy of Rituximab and Bortezomib combination in relapsed/refractory indolent non-follicular lymphoma (Linfocytic Lymphoma, LL, or MZL) and MCL not eligible for high-dose chemotherapy. Patients and methods. Inclusion criteria were: age 18–75 years, histological proven relapsed or refractory LL, MZL and MCL after 1–4 lines of therapies. Treatment plan was: one course of four weekly intravenous bolus of 1.6 mg/sqm Bortezomib in combination with four infusion of 375 mg/sqm Rituximab followed by two courses of four weekly bolus of 1.6 mg/sqm Bortezomib. Patients with complete (CR), partial remission (PR) and stable disease at the intermediate evaluation were planned to be given three further courses with the same schedule. Results. From September 2006 to March 2008, 55 patients entered into the study. Central histology revision was performed. Forty-nine patients fulfilled inclusion criteria and were evaluable. Clinical characteristics were: median age 68 (50-74) years; 16 LL, eight MZL, 25 MCL; 42 stage III/IV; 33 bone marrow involvement; 20 at intermediate-high/high International Prognostic Index (IPI) risk. Thirty-eigh patients performed more than two prior lines of chemotherapy; 34 were Rituximab-pretreated; 21 refractory and 28 relapsed disease. Overall Response Rate (ORR) was 53% (CR 26.5%, PR 26.5%); no response 43% and 4% off therapy for other causes. ORR by histology was: 37% in LL, 50% in MZL and 64% in MCL. ORR was not adversely affected by Rituximab pretreatment: Rituximab-pretreated 62% and Rituximab-naïve 33%. ORR was higher in relapsed patients compared with refractory ones: 64% and 38% (p .06). (Table 1). With a median follow-up of 25 months, 2-year Overall Survival (OS) was 80% (95%CI: 66–89) and 2-year PFS was 25% (95%CI: 14–38) (Figure 1A, 1B). Two-year PFS by histology was shown in Figure 1C. A total of 233 courses were delivered with a median of 4.7 courses/patient. Thirty patients completed the treatment plan; 19 did not due to progression disease in 13, adverse events in five (concomitant gastric neoplasia, neurotoxicity grade II, sepsis, pleural effusion and toxic death due to interstitial pneumonia). Grade 3–4 CTC haematological toxicity was rare: neutropenia in 5% of the courses and thrombocytopenia in 〈 2%. Grade 3–4 CTC cumulative non-hematological toxicity was observed in 4.7% of all courses. The most frequent non-hematological toxicities were: neurotoxicity grade III in four patients, with complete recover or return to grade I in all of them. Infections were observed in eight patient with ten events: viral reactivation in four, pneumonia in three, sepsis in one and micosis in two. Conclusions. The combination of Rituximab and Bortezomib in weekly schedule was effective and safe in treatment of relapsed/refractory indolent and MCL. PFS was promising also in Rituximab-pretreated patients and mainly in MZL and MCL. Table 1. ORR (%) MCL/MZL/LL 64/50/37 Rituximab-pretreated/Rituximab-naive 62/33 N of prior therapies 〈 2/≥2 75/46 Relapsed/Refractory 64/38 Disclosures: Off Label Use: The use of Bortezomib is off-label in Relapsed/Refractory Indolent Non-Follicular and Mantle Cell Lymphoma. Vitolo:Roche-Italy: Advisory committee; Celgene-Italy: Advisory committee; Janssen-Cilag: Lecture Fee.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.3965.3965

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 3062-3062

Abstract: Background: The antibiotic clarithromycin displays immunomodulatory properties, partially mediated by the suppression of IL-6 and other inflammatory cytokines. This macrolide can directly induce TNF-mediated apoptosis in mouse lymphoma cells, with a DNA fragmentation degree similar to that seen in cells treated with chemotherapeutic agents. In recent trials on multiple myeloma and Waldenstrom’s macroglobulinemia, the combination of clarithromycin with other immunomodulatory agents exhibited high tumour regression rates, and some case reports suggested an antineoplastic effect of clarithromycin in marginal zone B-cell lymphoma of MALT-type (EMZL) of the colon and the lung. Method: This is a phase II trial aimed to assess tolerability and activity of a 6-month regimen of oral clarithromycin in patients (pts) with relapsed/refractory EMZL. Clarithromycin (500 mg) was given orally twice daily for 6 months to 14 HIV-negative pts (age 318 ys; ECOG-PS ≤3) with relapsed/refractory EMZL and at least one measurable/parametrable lesion. Pre-registration assessments included physical examination, hemogram and biochemical profile, HIV, HBV and HCV serology, gastroscopy, gastric Helicobacter pylori (Hp) infection assessment (3 methods: histology, breath test, serology, and/or cagA in faeces), Chlamydia psittaci (Cp) infection assessment (PCR on tissue and PBMC, only in pts with ocular adnexal MALT lymphoma), total body CT scan, and bone marrow biopsy. Tolerability (physical examination and blood exams) was assessed every 8 weeks and objective response was assessed every 3 months. Results: Median age of eligible pts was 59 ys. (range 36–81; 7 females). Clarithromycin was the salvage therapy at first relapse in 8 pts, and the 3rd–6th line of treatment in the others. All pts had local disease at the time of treatment, two pts had also systemic dissemination. Extranodal sites were stomach (n=2), conjunctiva (n=4), orbit (n=7), and breast (n=1). No pt had increased LDH serum levels; only one pt had B symptoms. Chronic infections were caused by HCV in 2 pts, Hp in 2 and Cp in 5. Hp and Cp infections were successfully eradicated with specific antibiotics as part of upfront treatment, that is with a median time from bacterial eradication to clarithomycin treatment of 14 (7–40) months. This excludes that a potential clarithomycin antitumor activity could be due to antimicrobial effect. The treatment was completed in 13 pts and is ongoing in the remaining one. Two pts achieved a complete remission (22+, 24+) and 2 pts achieved a partial response (11+, 14), with an ORR of 31%; 1 pt had a minimal response (11+), 5 pts had stable disease (15+, 15+, 16+, 22, 24), 3 pts experienced disease progression (10, 10, 16). The median time to the best response was 10 months. Three of the major responses were observed among the 4 pts with conjunctival lymphoma, treatment is ongoing in the remaining one. The number of previous lines of treatment did not influence response. Tolerability was excellent-good in all pts but two (episodic nausea). No biochemical abnormalities were detected after 6 months of treatment. After a median follow-up of 15 months, 6 pts experienced disease progression, with a median time to progression of 11+ months. The pt with B symptoms experienced a high-grade transformation and was not responsive to clarithromycin. All pts but one (HCV-related cirrhosis) are alive with a median OS of 42 months. Conclusions: This 6-month regimen of oral clarithromycin seems to be safe and active in EMZL, mostly in pts with conjunctival MALT lymphoma. Response to clarithromycin does not seem to be mediated by eradication of common MALT-related bacterial infections. Clarithromycin deserves to be further investigated in EMZL.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V112.11.3062.3062

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. 134, No. Supplement_1 ( 2019-11-13), p. 2879-2879

Abstract: BACKGROUND Outcomes for patients (pts) with primary CNS diffuse large B cell lymphoma (PCNSL) have improved over recent years, largely through optimisation of first-line methotrexate (MTX)-containing protocols and dose-intensive chemotherapy consolidation. However, 30-50% of pts experience refractory or relapsed (r/r) disease, which confers very poor outcomes and short survival. By contrast to systemic DLCBL, there is no accepted standard approach for r/r PCNSL. Thiotepa is an alkylating agent highly efficient at crossing the BBB and widely incorporated within high-dose therapy and autologous stem cell transplantation (HDT-ASCT) protocols for PCNSL, but has not undergone dose-finding studies nor been incorporated within salvage regimens for PCNSL. The TIER study investigates the safety and efficacy of adding thiotepa, in a dose-escalation design, to the Rituximab, Ifosphamide and Etoposide (R-IE) salvage regimen1. METHODS TIER is an open label, phase I/II UK NCRI TAP study for pts with r/r PCNSL, previously treated with a high-dose MTX-based regimen. In phase I, the RP2D of thiotepa within the TIER combination was established using a 3+3 design, with dose escalations of 30, 40 and 50mg/m2 (dose level 2 (n=4), 3 (n=5) and 4 (n=27) respectively), given on day 5 of R-IE cycle1. The Phase II primary endpoint was overall response rate (ORR) after cycle 2 of TIER (C2) by centrally reviewed contrast-enhanced MRI2, on an intention-to-treat (ITT) basis. Further treatment and consolidation after the primary endpoint MRI was at the discretion of investigators. Key secondary end-points were 2-year PFS, EFS and OS. RESULTS Thirty-six pts were recruited from Jun 2015-Apr 2019 at 13 centres (characteristics: Table 1). The median number of prior lines was 2 (range 1-4) with 44% of patients deemed refractory to their previous line of therapy. During phase I (n=10) no dose limiting toxicities (DLTs) were observed up to and including 50mg/m2 thiotepa, constituting the RP2D (n=27). 56 cycles of TIER were administered across both phases; 5 pts had 〉 1 dose reductions. Median time between C1D1 and C2D1 was 24.7 days (range 22-38). Relative mean dose intensity of thiotepa, ifosphamide and etoposide was 71.8 (SD 44.9), 76.4 (SD 41.6), and 76.8 (SD 41.8) respectively. Further therapy after 2 cycles of TIER was delivered to 41.7% of pts (16.7% ASCT, 22.2% TIE, and 2.8% WBRT). The most common grade 3 / 4 adverse events were thrombocytopenia and neutropenia (47.2 and 55.6% occurring in 15 and 18 pts respectively). 17 serious adverse events (SAEs) were reported in 12 pts, of which 4 were haematological. Of these, 13 were considered related to TIER. Commonly occurring non-haematological SAEs were respiratory tract infections (23.5%) and seizures (11.8%). At data lock, 10/27 pts had responded to treatment as assessed by local investigators (ORR 37%, CR rate 15%). 13 pts were non-evaluable (7 progressed prior to C2 scan, 2 withdrew consent, and 4 awaiting scans) and classed as non-responders. Following data lock, responses were reported for 3 further pts (2 by local investigators and 1 by central review), resulting in a provisional ORR of 13/27 (48%). For the ITT population, median OS time was 3.52 months (95% CI 2.50, 14.17), and median PFS 2.86 months (95%CI 2.34, 6.05) (Figure 1). 6 pts underwent ASCT consolidation after TIER, of whom 2 have relapsed. CONCLUSIONS This is an early analysis of data from the phase I/II TIER study for a heavily pre-treated group of r/r PCNSL; the first such dose-escalation study for this patient group. Phase I determined a RP2D of 50mg/m2 of thiotepa incorporated in the R-IE regimen. There were no DLTs and toxicities, consistent with an intensive ifosphamide-based regimen. ORR was 10 pts (37%) with 3 further responses reported after data lock. If confirmed by central review, the primary endpoint of activity (ORR 40%) will have been reached. However, notwithstanding the response endpoint, most pts experienced very poor survival outcomes. These data describe the feasibility of TIER as a salvage regimen for r/r PCNSL but question the utility of this approach as a standard option, given the short PFS and OS times, except for the minority of pts who received ASCT. Biological and imaging sub studies are underway to identify predictors of outcome. In the modern era of effective first line immunochemotherapy approaches, pts with r/r PCNSL remain a major area of unmet need for whom novel experimental approaches are urgently required. Disclosures Fox: Gilead: Consultancy; AbbVie: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Sunesis: Consultancy; Takeda Pharmaceuticals: Consultancy; Atara Biotherapeutics: Consultancy; Adienne: Other: Travel Support. Martinez-Calle:ABBVIE: Other: Travel support. Collins:Gilead: Consultancy, Honoraria. Ferreri:Novartis: Consultancy; Celgene: Consultancy, Research Funding; Roche: Research Funding; Kite: Consultancy. Davies:BioInvent: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Research Funding; Bayer: Research Funding; ADCT Therapeutics: Honoraria, Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; MorphoSys AG: Honoraria, Membership on an entity's Board of Directors or advisory committees. Johnson:Roche: Consultancy, Honoraria, Speakers Bureau; Takeda: Other: Travel, accomodations, expenses. Cwynarski:Adienne: Consultancy; Takeda: Consultancy, Other: conference and travel support , Speakers Bureau; Roche,: Consultancy, Other: conference and travel support, Speakers Bureau; Autolus: Consultancy; KITE: Consultancy; Gilead: Consultancy, Other: conference and travel support, Speakers Bureau; Celgene: Consultancy; Atara: Consultancy; Janssen: Other: conference and travel support, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-122830

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2636-2636

Abstract: Abstract 2636 Background and objectives: Quality of response assessed with [18F]fluorodeoxyglucose - Positron Emission Tomography (FDG-PET) is confirmed as a strong independent prognostic factor in patients with Hodgkin lymphoma and Diffuse Large B-Cell Lymphoma. Recently the prognostic role of response assessment with PET was also shown in patients with Follicular Lymphoma (FL) (Trotman et al JCO 2011). We conducted a retrospective analysis to investigate the role of FDG-PET after immunochemotherapy in FL. Patients and methods: The study was designed as a retrospective unplanned analysis of newly diagnosed FL patients randomized among R-CVP, R-CHOP, R-FM in the FOLL05 clinical trial (NCT00774826). To be included in the study patients should have confirmed eligibility for the FOLL05 trial, have available data on clinical presentation, treatment details and results, and on follow-up. As mandatory patients should have undergone staging and restaging at the end of treatment with FDG-PET. Local PET interpretation was used to identify clearly positive and clearly negative cases. For this phase of the study uncertain cases were not analyzed for study endpoints: centralized review is ongoing. Contrast enhanced computed tomography (CECT) scans were also collected to confirm quality of response: in particular a cut off of 1.5 cm for the maximum transverse diameter of residual lymph nodes was considered to separate Complete vs. Partial remissions according to International Workshop Criteria (IWC) (Cheson et al JCO 1999). The primary study endpoint was Progression Free Survival. Results: Among 534 patients enrolled in the FOLL05 trial, 114 cases fulfilled eligibility criteria for this study. Baseline patients characteristics did not differ from the overall FOLL05 patient population. In particular FLIPI was 0–1 in 23%, 2 in 42% and 3–5 in 35%. First-line immunochemotherapy, included R-CHOP (36 pts.), R-CVP (33), and R-FM (45). No maintenance therapy with Rituximab was given. Overall response rate at the end of therapy, defined according to IWC, was 97% including a 78% complete remissions (CR) rate. Baseline PET scan was positive in all patients. In 16 cases an interim PET was also available and resulted clearly positive in 6 patients (38%). At the end of treatment 10 cases had inconclusive final PET results and were excluded from subsequent analyses; a clearly positive PET scan was recorded in 26 out of the remaining 104 (25%). In univariate logistic analysis number of nodal sites ( 〉 4) was predictive of final positive PET. Although a trend towards a higher rate of PET positive scans was observed with increasing FLIPI and FLIPI2 this difference was not statistically significant. The rate of patients with negative final PET was 81%, 57%, and 60% for those in CR, PR, and less than PR (Fisher exact test: P=0.021). Assessing response with International Harmonization Project (IHP) criteria (Cheson et al JCO 2007), that also consider PET, 14/74 (19%) of patients previously defined in CR according to IWC were changed to PR and 13/23 (57%) of those in PR were switched to CR. The CR rate changed from 78% to 75% with an agreement rate of 70% between IWC and IHP. With a median follow up of 28 months (range 9–56), 3 year PFS was 68% (95% IC 54%–79%). In univariate analysis a shorter 3yr PFS was observed in post-treatment PET+ vs. PET- patients: 48% vs 84% (log rank p=0.036, HR 2.34, 95% CI 1.03–5.3). A positive final PET was confirmed as a poor prognostic factor when adjusted by FLIPI and FLIPI2 (HR 2.33 P=0.048, and HR 2.41 P=0.039, respectively). Prognostic role of final PET was not affected by treatment arm or by any of analyzed prognostic factors. Finally a trend toward a prolonged duration of remission was observed for patients who achieved a PET negative CR, compared with PET+ CRs and and both PET+/− PRs. Conclusions: This FOLL05 ancillary study confirms that post-treatment PET-CT can modify response allocation and is a predictor of PFS after first line immunochemotherapy in patients with FL. If the prognostic role of PET assessment of response will be confirmed in a larger series and in prospective studies a response adapted treatment strategy could be tested also in FL. Disclosures: Di Raimondo: Celgene: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V118.21.2636.2636

Language: English

Publisher: American Society of Hematology

Publication Date: 2011

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 452-452

Abstract: Introduction: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is uncommon but is associated with poor outcomes. In selected high risk patients (pts), high dose methotrexate (HDMTX) is often used as CNS prophylaxis with frontline (1L) DLBCL therapy despite uncertain efficacy, optimum dose and timing of delivery. A recent UK study (Wilson et al 2020) showed that intercalated HDMTX (i-HDMTX) was associated with increased toxicity and R-CHOP delays compared to end of treatment (EOT) delivery. Although hypothesis generating, the study size was insufficient to determine whether EOT was non-inferior in terms of CNS relapse risk. Methods: We conducted an international, multicentre retrospective analysis of consecutive DLBCL or high grade BCL pts between 2007-20 from 47 centers in Europe, Australia and N. America. Pts were included if they received R-CHOP or R-CHOP-like 1L therapy with curative intent as well as HDMTX CNS prophylaxis (≥1 cycle). Concurrent intrathecal (IT) prophylaxis was permitted. Pts with known CNS involvement at baseline and those treated with more intensive protocols (e.g. R-DA-EPOCH) were excluded. i-HDMTX was defined as any pt receiving a HD-MTX cycle before the final R-CHOP cycle. CNS relapse events were excluded if occurring after first systemic lymphoma relapse/progression. Time to event endpoints were measured from diagnosis to first event or censor and analysed using Kaplan-Meier and Cox regression methods. Time to CNS relapse was analysed using competing risk Fine and Gray method (for death and non-synchronous systemic relapse). To mitigate for possible immortality bias in the EOT arm, a landmark analysis for pts alive and free from progression at 6 months was conducted. We aimed to exclude a 5% difference in 2-year (y) CNS relapse rates. Results: 1,384 pts were analysed. 750 received i-HDMTX and 634 received EOT HDMTX. Key baseline characteristics are summarised in Table 1. Median follow up was 37.9 months. 44.2% had high CNS IPI (4-6) with no significant difference between i-HDMTX and EOT groups (45.1% vs 43.1%, p=0.087). ≥2 cycles of HDMTX were used in 86.6% with no difference between groups (85.6% vs 87.9%, p=0.22). Concurrent IT prophylaxis use was higher for EOT pts (55.6% vs 38.1% p & lt;0.0001). 78 CNS relapses (42 i-HDMTX, 36 EOT) were observed: parenchymal in 41 (53%), parenchymal and leptomeningeal in 16 (21%) and isolated leptomeningeal in 21 (27%). There was no significant difference in 2y CNS relapse rates between i-HDMTX and EOT in all pts: 5.2% vs 3.9%, adjusted hazard ratio (HR) 0.92 (95% CI 0.58-1.47), p=0.74, 2y difference -0.2% (-2.0-2.5) or landmark analysis: 2.8% vs 4.1%, HR: 0.93 (0.56-1.55), p=0.79, 2y difference: -0.3% (-1.8-2.2%) (Fig 1a/b). Exploratory analyses focusing on pts with isolated CNS relapse (n=57) demonstrated similar results (2y rates 3.6% vs 3.0%, p=0.99). On multivariable analysis (MVA) of risk factors for CNS relapse, renal/adrenal involvement was the only variable associated with increased CNS relapse risk (adjusted HR 1.74 (1.03-2.92), p=0.038). Notably, IT prophylaxis was not associated with reduction in CNS relapse. In 600 high CNS IPI (4-6) pts, there was no difference in CNS relapse risk between i-HD-MTX and EOT (3y rates 9.4% vs 8.6%, HR 0.92 (95% CI 0.52-1.62)). In a composite high risk group including CNS IPI 4-6 and/or any of the following: ≥3 extranodal sites, renal, adrenal, testicular or breast involvement (n=885) there was no difference in 3y CNS relapse rates between groups (i-HDMTX 7.6% vs EOT 7.4%, HR 0.94 (0.58-1.53)). Progression-free survival (PFS) and overall survival (OS) in the i-HDMTX and EOT groups were as follows: 3y PFS 70.7% vs 76.7% (p=0.098), 3y OS 79.9% vs 87.0% (p=0.0016). However, there were no PFS/OS differences between groups on landmark analysis (n=1259) (Fig 1c). On analysis of pts experiencing ≥1 R-CHOP delay of ≥7 days, use of i-HDMTX was the only factor on MVA associated with increased delays (p & lt;0.0001). Discussion: We found no evidence that EOT delivery increases CNS relapse risk when compared to i-HDMTX in this large analysis of pts treated with 1L R-CHOP. Delays to R-CHOP cycles were increased with i-HDMTX. Findings in a high risk subgroup were unchanged and rates of CNS relapse in this HDMTX treated group were similar to published comparable high risk cohorts receiving infrequent CNS prophylaxis. Where HDMTX prophylaxis is used, delivery could be deferred until R-CHOP completion. Figure 1 Figure 1. Disclosures Wilson: Takeda: Other: Conference fees; Janssen: Other: Conference fees; Abbvie: Honoraria. Eyre: Janssen: Honoraria; Secura Bio: Consultancy, Honoraria; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel to conferences; AstraZeneca: Honoraria, Research Funding; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Beigene: Honoraria, Research Funding. Ahearne: Pfizer: Research Funding; Takeda: Honoraria; Roche: Honoraria. Schorb: Roche: Research Funding; Riemser Pharma GmbH: Honoraria, Research Funding; AbbVie: Research Funding. Ku: Antegene: Consultancy; Roche: Consultancy; Genor Biopharma: Consultancy. Narkhede: Genentech/Roche: Research Funding; Gilead: Research Funding; Genmab: Other: Medical writing support, Research Funding; TG Therapeautics: Research Funding. Lewis: AstraZeneca: Consultancy, Honoraria; Janssen: Honoraria, Patents & Royalties; Novartis: Patents & Royalties; Roche: Consultancy, Honoraria. Øvlisen: Abbvie: Other: Travel expenses. Santarsiere: Janssen: Honoraria. Shah: Abbvie, Janssen and Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Roulin: Janssen: Other: Travel and meetings. Manos: Bristol-Myers Squibb: Other: Travel and meetings. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lopez-Garcia: Roche: Other: Speaker Honoraria, Travel and accommodation grants; Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding; Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants; Celgene: Other: Speaker Honoraria; Fresenius: Other: Speaker Honoraria; Novonordisk: Other: Speaker Honoraria. El-Galaly: ROCHE Ltd: Ended employment in the past 24 months; Abbvie: Other: Speakers fee. Cheah: Beigene: Consultancy, Honoraria, Other: advisory; AbbVie: Research Funding; Celgene: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: advisory; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory; Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Gilead: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory. Ferreri: Gilead, Novartis, Juno, PletixaPharm, Roche, Incyte: Membership on an entity's Board of Directors or advisory committees; BMS, Beigene, Pharmacyclics, Hutchison Medipharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, Pfizer: Research Funding. Fox: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Other: speaker fees. Cwynarski: Gilead: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Atara: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Kite, a Gilead Company: Consultancy, Other: travel to scientific conferences, Speakers Bureau; Janssen: Consultancy, Other: travel to scientific conferences; Roche: Consultancy, Other: travel to scientific conferences, Speakers Bureau; BMS/Celgene: Other: travel to scientific conferences. McKay: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Other: Travel Support; KITE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Janssen: Honoraria, Other: Travel Support; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Honoraria, 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-2021-144820

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Nature Clinical Practice Oncology, Springer Science and Business Media LLC, Vol. 5, No. 10 ( 2008-10), p. 619-622

Type of Medium: Online Resource

ISSN: 1743-4254 , 1743-4262

URL: Article

DOI: 10.1038/ncponc1218

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2008

detail.hit.zdb_id: 2166911-9

detail.hit.zdb_id: 2491410-1

detail.hit.zdb_id: 2491414-9

detail.hit.zdb_id: 2173301-6

In: Leukemia Research Reports, Elsevier BV, Vol. 16 ( 2021), p. 100263-

Type of Medium: Online Resource

ISSN: 2213-0489

URL: Article

DOI: 10.1016/j.lrr.2021.100263

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 2706248-X

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 131-131

Abstract: Background: Follicular lymphoma is an indolent disease with a continuous relapsing pattern and typically requires multiple lines of therapy. Novel therapies such as tisagenlecleucel are being investigated to improve outcomes. Primary analysis of the single-arm, multicenter, Phase II ELARA trial in r/r FL demonstrated that tisagenlecleucel resulted in high overall (ORR) and complete response rates (CRR), and prolonged progression-free survival (PFS) at a median follow-up of 11 months (mo). Here, we report updated efficacy results from the overall population at a median follow-up of 17 mo, and a subgroup analysis of pts with high-risk disease from the ELARA trial (NCT03568461). Methods: Eligible adult pts had histologically confirmed r/r FL (grades 1-3A) after ≥2 lines of therapy or had relapsed after autologous stem cell transplant. Bridging therapy was allowed and was followed by disease evaluation before tisagenlecleucel infusion. Pts received tisagenlecleucel (0.6-6×10 8 CAR+ viable T cells) after lymphodepleting chemotherapy (fludarabine [25 mg/m 2] + cyclophosphamide [250 mg/m 2] QD for 3 d or bendamustine [90 mg/m 2] QD for 2 d). Endpoints included ORR, CRR, PFS, and duration of response (DOR). Descriptiv e efficacy subanalyses were performed for 9 high-risk subgroups, including prior hematopoietic stem cell transplant (HSCT), ≥5 prior lines of therapy, progression of disease within 24 mo from first immunochemotherapy (POD24), double-refractory disease, high Follicular Lymphoma International Prognostic Index (FLIPI) at study entry, high lactate dehydrogenase at baseline, high C-reactive protein (CRP) prior to infusion, radiological bulky disease (by GELF criteria), and high total metabolic tumor volume (TMTV; & gt;510 cm 3) at baseline (median 155.32 cm 3; range 0.1-2470.4 cm 3). Descriptive subgroup analysis was supported by multivariate analysis to identify factors predictive of worse outcomes. Results: As of March 29, 2021, 97 pts received tisagenlecleucel and 94 were evaluable for primary efficacy analysis (median follow-up 17 mo). High and durable responses were seen in the overall ELARA population (ORR 86.2%, CRR 69.1%, 9-mo DOR 76.0%, and 12-mo PFS 67.0%). In CR pts at 9 mo, PFS was 85.5% and estimated probability of remaining in response was 86.5%. Safety reflected known tisagenlecleucel profile; 48% of pts had CRS (majority were grade 1/2) and 11.3% had neurological events (3% grade ≥3). In the subgroup analysis, pts were stratified into risk groups. Efficacy (ORR, CRR) and durability of response were well maintained in all high-risk subgroups, except for POD24 (n=35), high TMTV (n=20), and ≥5 prior lines of therapy (n=27). Compared with corresponding low-risk subgroups, there was a numerical reduction in CRR for high-risk subgroups (POD24 59.0% vs 87.9%; high TMTV 40.0% vs 76.4%; ≥5 prior lines of therapy 59.3% vs 73.1%) (Figure). A reduction in 12-mo PFS was also identified for pts in these subgroups: POD24 (60.8% vs 77.9%), high baseline TMTV (54.5% vs 68.5%), and ≥5 prior lines of therapy (59.6% vs 69.7%). Evaluating the disease characteristics of the high TMTV subgroup compared with low TMTV, high TMTV was associated with a higher incidence of bulky disease (58.3% vs 90.0%), high FLIPI (54.2% vs 85.0%), and high CRP (45.8% vs 70.0%). In the multivariate analysis of high-risk factors, only POD24 (hazard ratio [HR] 2.34; 95% CI, 1.02- 5.34) and high TMTV (HR 2.53; 95% CI, 1.14-5.65) were associated with shorter PFS. For pts with both POD24 and high TMTV (n=12), the CRR was 16.7% with a 12-mo PFS of 36.0%. These analyses of high-risk subgroups are exploratory in nature and should be validated in a larger study cohort. Conclusions : With 17-mo median follow-up, tisagenlecleucel produced high ORR and CRR and was associated with durable response and promising 12-mo PFS in pts with r/r FL and 2+ prior lines of therapy. Safety was consistent with known tisagenlecleucel profile. POD24 and high TMTV were independently associated with PFS. These results suggest that tisagenlecleucel can induce high rates of durable response, including most pts in the high-risk disease subgroups, who have poor prognosis with current non-CAR-T cell therapies. Figure 1 Figure 1. Disclosures Thieblemont: Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: 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, Other: Travel, Accommodations, Expenses , Research Funding; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Dickinson: Amgen: Honoraria; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Research Funding; Celgene: Research Funding; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Martinez-Lopez: Incyte: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Astellas: Research Funding, Speakers Bureau. Kolstad: Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees, Research Funding. Popplewell: Pfizer: Other: Travel; Novartis: Other: Travel; Hoffman La Roche: Other: Food. Chavez: AstraZeneca: Research Funding; Novartis: Consultancy; MorphoSys: Speakers Bureau; Karyopharm Therapeutics: Consultancy; Adaptive: Research Funding; Kite/Gilead: Consultancy; Abbvie: Consultancy; Merck: Research Funding; BeiGene: Speakers Bureau; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Speakers Bureau; Epizyme: Speakers Bureau. Bachy: Roche: Consultancy; Takeda: Consultancy; Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Incyte: Consultancy. Kato: Kyowa Kirin: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Research Funding; Dainippon-Sumitomo: Honoraria; Daiichi Sankyo: Consultancy, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; AstraZeneca: Consultancy; Abbvie: Consultancy, Research Funding; MSD: Honoraria; Mundi: Honoraria; Novartis: Consultancy, Research Funding; Ono: Honoraria, Research Funding. Harigae: Novartis Pharma: Honoraria, Research Funding; Chugai Pharma: Honoraria; Janssen Pharma: Honoraria; Ono pharma: Honoraria, Other: Subsidies or Donations; Astellas Pharma: Other: Subsidies or Donations; Kyowakirin: Other: Subsidies or Donations; Bristol Myers Squibb: Honoraria. Kersten: Kite/Gilead: Honoraria, Research Funding; Novartis: Honoraria; Miltenyi Biotech: Honoraria; BMS/Celgene: Honoraria, Research Funding; Roche: Honoraria; Takeda: Honoraria. Andreadis: GenMAB: Research Funding; Karyopharm: Honoraria; Incyte: Honoraria; BMS/Celgene: Research Funding; Epizyme: Honoraria; Crispr Therapeutics: Research Funding; Atara: Consultancy, Honoraria; Novartis: Research Funding; Kite: Honoraria; Merck: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; TG Therapeutics: Honoraria. Riedell: Kite/Gilead: Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding; BeiGene: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Tessa Therapeutics: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Xencor: Research Funding; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Calibr: Research Funding. Pérez-Simón: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Chen: Mesolbast: Honoraria; Morphosys: Honoraria. Nastoupil: MorphoSys: Honoraria; Bayer: Honoraria; Genentech: Honoraria, Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; IGM Biosciences: Research Funding; Denovo Pharma: Other: DSMC; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Novartis: Honoraria, Research Funding; Gilead/Kite: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Epizyme: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Von Tresckow: Pentixafarm: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Congress and travel support, Research Funding; MSD: Consultancy, Honoraria, Other: Congress and travel support, Research Funding; Kite-Gilead: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: Congress and travel support; AstraZeneca: Honoraria, Other: Congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: Congress and travel support; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding. Ferreri: Gilead, Novartis, Juno, PletixaPharm, Roche, Incyte: Membership on an entity's Board of Directors or advisory committees; BMS, Beigene, Pharmacyclics, Hutchison Medipharma, Amgen, Genmab, ADC Therapeutics, Gilead, Novartis, Pfizer: Research Funding. Teshima: Fuji pharma CO.,Ltd: Research Funding; Astellas Pharma Inc.: Research Funding; TEIJIN PHARMA Limited: Research Funding; CHUGAI PHARMACEUTICAL CO., LTD.: Research Funding; Pfizer Inc.: Honoraria; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Co.,Ltd.: Honoraria, Research Funding; Takeda Pharmaceutical Company: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis International AG: Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Janssen Pharmaceutical K.K.: Other; Nippon Shinyaku Co., Ltd.: Research Funding; Bristol Myers Squibb: Honoraria; Sanofi S.A.: Research Funding; Gentium/Jazz Pharmaceuticals: Consultancy. Patten: ASTRA ZENECA: Honoraria; ABBVIE: Honoraria; NOVARTIS: Honoraria; GILEAD SCIENCES: Honoraria, Research Funding; ROCHE: Research Funding; JANSSEN: Honoraria. McGuirk: Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Novartis: Research Funding; Gamida Cell: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; EcoR1 Capital: Consultancy; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Astelllas Pharma: Research Funding; Bellicum Pharmaceuticals: Research Funding; Pluristem Therapeutics: Research Funding. Petzer: AppVie: Honoraria; Astra Zeneca: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Sandoz: Honoraria. Viardot: University Hospital of Ulm: Current Employment; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zinzani: JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; SANDOZ: Other: Advisory board; MSD: Consultancy, Other: Advisory board, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; BMS: Other: Advisory board, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; SERVIER: Other: Advisory board, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; Incyte: Other, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; ADC Therap.: Other; GILEAD: Other: Advisory board, Speakers Bureau; Beigene: Other, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. Malladi: Gilead Science: Consultancy; Gilead: Honoraria, Other: Travel support. Lobetti Bodoni: Spouse: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Spouse: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Spouse: Celgene: Honoraria; Spouse: Harlcok Healthcare: Current holder of individual stocks in a privately-held company; Spouse: Takeda: Consultancy, Honoraria, Speakers Bureau; Spouse: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spouse: NHS: Ended employment in the past 24 months; Spouse: F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company; Gilead: Other: Travel sponsorship in June 2019; Novartis: Current Employment, Current equity holder in publicly-traded company. Masood: Novartis: Current Employment, Current holder of stock options in a privately-held company. Schuster: Genentech/Roche: Consultancy, Research Funding; Tessa Theraputics: Consultancy; Loxo Oncology: Consultancy; BeiGene: Consultancy; Juno Theraputics: Consultancy, Research Funding; Alimera Sciences: Consultancy; Merck: Research Funding; Incyte: Research Funding; Acerta Pharma/AstraZeneca: Consultancy; Abbvie: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; TG Theraputics: Research Funding; Pharmacyclics: Research Funding; Adaptive Biotechnologies: Research Funding; Nordic Nanovector: Consultancy; Celgene: Consultancy, Honoraria, Research Funding. Fowler: Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company. Dreyling: Bayer HealthCare Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau; Astra Zeneca: Consultancy, Speakers Bureau; BeiGene: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; Genmab: Consultancy; Amgen: Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Abbvie: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-145025

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3758-3758

Abstract: Abstract 3758 Poster Board III-694 Introduction The combination of Bortezomib (B) and Rituximab (R) has been shown in vitro synergistic apoptosis and enhanced NFkB depletion in Mantle Cell Lymphoma (MCL) and Marginal Zone Lymphoma (MZL) cells. Rituximab in combination with Bortezomib is well tolerated without overlapping toxicities. Our study was aimed to evaluate safety and efficacy of the association of Rituximab and Bortezomib in relapsed/refractory indolent non follicular and mantle cell lymphoma patients not eligible to high dose chemotherapy and ASCT. The study was designed according to Simon's two stage Optimal Design and the primary endpoint was the achievement of an Overall Response Rate (ORR) 〉 40%. Patients and methods From September 2006 to March 2008, 54 patients were enrolled into the study. Histology was centrally reviewed in all cases: 49 diagnosis fulfilled the inclusion criteria and were evaluable for the analysis. Clinical characteristics were as follows: 28 males and 21 females; median age 68 years (range 50-74); 16 lymphocytic/lymphoplasmacytic (LL), 8 MZL and 25 MCL; seven stage I-II disease, nine III and 33 IV; 33 were BM positive; according to IPI 36 patients were at low-intermediate risk and 18 at intermediate-high/high risk; 11 patients had 1 and 38 〉 2 prior lines of chemotherapy; 15 were R-naïve patients and 34 R-pretreated, 21 patients had refractory disease ( 〈 1 yr from the last therapy) and 28 were in relapse ( 〉 1 yr). The treatment plan was: one course of 4 weekly doses of Rituximab (375 mg/sqm) and Bortezomib (1.6 mg/sqm IV bolus) followed by 2 courses of 4 weekly IV bolus of B (1.6 mg/sqm) as single agent. Responding (CR+ PR) and stable disease patients were planned to be given three further courses with the same schedule. Results ORR was 26/49 (53%). Responses were as follows: 13 CR (26.5%) and 13 PR (26.5%). ORR by histology was: 6/16 (37.5%) in LL, 4/8 (50%) in MZL and 16/25 (64%) in MCL respectively. Pretreatment with Rituximab did not adversely affect the ORR: 21/34 (62%) in R-pretreated patients and 5/15 (33%) in R-naïve patients (p .06). ORR was higher in relapsed patients compared with refractory ones: 18/28 (64%) and 8/21 (38%) (p .06). With a median follow-up of one year, Overall Survival (OS) was 93% (95%CI: 79.7-97.9) and 1-year Progression free survival (PFS) was 45% (95%CI: 30-59) (Figure 1). A total of 233 courses were delivered with a median of 4.7 courses per patient. Twenty-eight patients completed the treatment plan and 21 were withdrawn from the study because of: 17 PD during treatment and 4 AE (1 concomitant gastric neoplasia, 1 neurotoxicity grade II, 1 pleural effusion and 1 toxic death due to interstitial pneumonia). Grade 3-4 CTC haematological toxicity was rare with neutropenia in 5% of the courses and thrombocytopenia in 〈 2%. Grade 3-4 CTC cumulative non hematological toxicity was observed in 4.7% of all courses delivered. The most frequent of these were: neurotoxicity grade II in 13 patients and grade III in 5, with complete recover or return to grade I in all of them but one; infections were detected in 3 patients (pneumonia), constipation grade III in 2 and diarrhoea grade 〉 III in 5. Conclusions This study suggests that the combination of Rituximab and Bortezomib is feasible and effective in relapsed/refractory indolent non follicular lymphoma and MCL. This treatment combination is a good therapeutic option without chemotherapy mainly in MCL and MZL also in Rituximab pretreated patients. Our data suggest a promising PFS in this subset of heavily pretreated patients. The combination of Rituximab plus Bortezomib should be explored in further and larger studies. Disclosures: Vitolo: Roche: lecture fees. Off Label Use: Bortezomib was provided free by Jansen-Cilag who gave a research grant to support the study.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.3758.3758

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7