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  • 1
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    Positron Emission Tomography (PET) Guided Therapy of Aggressive Lymphomas - Interim PET-Based Outcome Prediction and Treatment Changes in Patients with B Cell Lymphomas Participating in the PETAL Trial
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 1857-1857
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    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1857-1857
    Abstract: Introduction: The PETAL trial is a multicenter randomized controlled study for patients with aggressive lymphomas of diverse histologies (EudraCT 2006-001641-33, NCT00554164). In the study population as a whole interim PET (iPET) reliably predicted time to treatment failure (TTTF) and overall survival (OS). Interim PET-based treatment changes, however, had no impact on outcome (ASH 2014, abstract 391). Here we report the exploratory analysis for aggressive B cell lymphomas. Methods: Pts. aged 18 to 80 yrs. with newly diagnosed aggressive lymphomas and a positive baseline PET received 2 cycles of rituximab (R), cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) followed by iPET. The conditions of iPET were strictly defined: 3-week interval between the 2nd R-CHOP cycle and iPET to avoid inflammatory reactions (Eur J Nucl Med Mol Imaging 30:682, 2003), no G-CSF after the 2nd cycle to avoid altered glucose biodistribution (J Nucl Med 47:950, 2006), standardized uptake value (SUV)-based PET interpretation to improve reproducibility (favorable iPET response: reduction of maximum SUV by 〉 66 % compared to baseline; J Nucl Med 48:1626, 2007). Pts. with CD20+ lymphomas and a favorable iPET were randomized to receive 4 more cycles of R-CHOP or the same treatment plus 2 extra doses of R (part A of the trial). Pts. with an unfavorable iPET were randomized to continue R-CHOP for 6 additional cycles or receive 6 blocks of a more complex methotrexate-, cytarabine- and etoposide-based regimen originally designed for Burkitt lymphoma (Blood 124: 3870, 2014; part B). R was omitted in pts. with CD20- lymphomas. Sample size of the entire study population was based on the empirically derived assumption that treatment failure after 2 yrs. (TF: progression, relapse, treatment discontinuation due to toxicity, start of alternative therapy, death of any cause) could be improved from 80 % to 90 % in part A and from 30 % to 45 % in part B (alpha=0.05, power=0.8). Secondary endpoints included OS and toxicity. Results: Fifty-seven oncological centers and 23 nuclear medicine institutions participated in the trial. Between 2007 and 2012 1072 pts. were registered, and 862 (80.4 %) had a positive baseline PET, received 2 cycles R-CHOP, underwent iPET and were allocated to one of the post-iPET treatment arms detailed above. Reference pathology was available in 98 %, and median follow-up is 52 months. All in all, there were 779 patients with CD20+ aggressive B-cell lymphomas (90.4 % of all treated pts.) of whom 606 had diffuse large B-cell lymphoma (DLBCL), 42 primary mediastinal B-cell lymphoma (PMBCL) and 42 follicular lymphoma grade 3 (FL3). Interim PET was favorable in 691 pts. (88.7 %) and unfavorable in 88 pts. with CD20+ lymphomas (11.3 %). It was highly predictive of TTTF for CD20+ lymphomas in general and for each of the DLBCL, PMBCL and FL3 subgroups (Table). In CD20+ lymphomas and DLBCL, the iPET response predicted TF independently of the International Prognostic Index, and it was also predictive of OS. The groups of PMBCL and FL3 were too small for multivariate analyses. In part A, adding 2 extra doses of R failed to improve TTTF and OS in all histological entities. Separate analyses for subgroups defined by sex, age ( 〈 vs. 〉 60 yrs.) or a combination of the two showed no statistically significant benefit of extra doses of R in any of the subgroups. In pts. with an unfavorable iPET response, a switch from R-CHOP to the Burkitt regimen failed to improve TTTF or OS in CD20+ lymphomas in general (Figure) and in the DLBCL, PMBCL and FL3 subgroups. In part B, the Burkitt protocol was associated with more grade 3/4 leukopenia (82 % vs. 57 %, p=0.02), thrombocytopenia (59 % vs. 18 %, p=0.0001), infection (41 % vs. 16 %, p=0.017) and mucositis (39 % vs. 7 %, p=0.0007) than R-CHOP, but treatment-related mortality was similar in both arms (1 death each). Conclusion: In this large multicenter trial iPET proved highly predictive of outcome in pts. with CD20+ aggressive B-cell lymphomas, DLBCL, PMBCL or FL3 treated with R-CHOP. In pts. with a favorable iPET response, addition of 2 extra doses of R to 6 cycles R-CHOP failed to improve outcome in CD20+ lymphomas in general and in subgroups defined by histology, sex or age. In pts. with an unfavorable iPET response, switching to a more aggressive protocol also failed to improve outcome in any of the entities. Novel strategies are required for aggressive B-cell lymphomas failing to respond to the first 2 cycles of R-CHOP. Table Table. Figure Figure. Disclosures Duehrsen: Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Alexion Pharmaceuticals: Honoraria, Research Funding. Giagounidis:Celgene Corporation: Consultancy. Grube:BMS, Sanofi: Consultancy. Klapper:Roche, Novartis, Amgen, Takeda: Research Funding. Hüttmann:Bristol-Myers Squibb, Takeda, Celgene, Roche: Honoraria; Gilead, Amgen: Other: Travel cost.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.1857.1857
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 2
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    Six versus eight doses of rituximab in patients with aggressive B cell lymphoma receiving six cycles of CHOP: results from the “Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas” (PETAL) trial
    Springer Science and Business Media LLC ; 2019
    In:  Annals of Hematology Vol. 98, No. 4 ( 2019-4), p. 897-907
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    In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 98, No. 4 ( 2019-4), p. 897-907
    Type of Medium: Online Resource
    ISSN: 0939-5555 , 1432-0584
    URL: Article
    DOI: 10.1007/s00277-018-3578-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
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  • 3
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    Baseline and interim PET‐based outcome prediction in peripheral T‐cell lymphoma: A subgroup analysis of the PETAL trial
    Wiley ; 2020
    In:  Hematological Oncology Vol. 38, No. 3 ( 2020-08), p. 244-256
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    In: Hematological Oncology, Wiley, Vol. 38, No. 3 ( 2020-08), p. 244-256
    Abstract: The prospective randomized Positron Emission Tomography (PET)‐Guided Therapy of Aggressive Non‐Hodgkin Lymphomas (PETAL) trial was designed to test the ability of interim PET (iPET) to direct therapy. As reported previously, outcome remained unaffected by iPET‐based treatment changes. In this subgroup analysis, we studied the prognostic value of baseline total metabolic tumor volume (TMTV) and iPET response in 76 patients with T‐cell lymphoma. TMTV was measured using the 41% maximum standardized uptake value (SUV 41max ) and SUV 4 thresholding methods. Interim PET was performed after two treatment cycles and evaluated using the ΔSUV max approach and the Deauville scale. Because of significant differences in outcome, patients with anaplastic lymphoma kinase (ALK)‐positive lymphoma were analyzed separately from patients with ALK‐negative lymphoma. In the latter, TMTV was statistically significantly correlated with progression‐free survival, with thresholds best dichotomizing the population, of 232 cm 3 using SUV 41max and 460 cm 3 using SUV 4 . For iPET response, the respective thresholds were 46.9% SUV max reduction and Deauville score 1‐4 vs 5. The proportion of poor prognosis patients was 46% and 29% for TMTV by SUV 41max and SUV 4 , and 29% and 25% for iPET response by ΔSUV max and Deauville, respectively. At diagnosis, the hazard ratio (95% confidence interval) for poor prognosis vs good prognosis patients according to TMTV was 2.291 (1.135‐4.624) for SUV 41max and 3.206 (1.524‐6.743) for SUV 4 . At iPET, it was 3.910 (1.891‐8.087) for ΔSUV max and 4.371 (2.079‐9.187) for Deauville. On multivariable analysis, only TMTV and iPET response independently predicted survival. Patients with high baseline TMTV and poor iPET response (22% of the population) invariably progressed or died within the first year (hazard ratio, 9.031 [3.651‐22.336]). Due to small numbers and events, PET did not predict survival in ALK‐positive lymphoma. Baseline TMTV and iPET response are promising tools to select patients with ALK‐negative T‐cell lymphoma for early allogeneic transplantation or innovative therapies.
    Type of Medium: Online Resource
    ISSN: 0278-0232 , 1099-1069
    URL: Issue
    URL: Article
    DOI: 10.1002/hon.v38.3
    DOI: 10.1002/hon.2697
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 4
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    Abstract P1-19-33: Real-world efficacy of ribociclib + aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Second interim analysis from the RIBANNA study
    American Association for Cancer Research (AACR) ; 2020
    In:  Cancer Research Vol. 80, No. 4_Supplement ( 2020-02-15), p. P1-19-33-P1-19-33
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 4_Supplement ( 2020-02-15), p. P1-19-33-P1-19-33
    Abstract: Background: Ribociclib (RIB, a selective CDK4/6 inhibitor) plus an aromatase inhibitor (AI) or fulvestrant (FUL) is approved for the treatment of premenopausal and postmenopausal women with HR+/HER2- advanced breast cancer (aBC). Real-world evidence for the effectiveness, safety and tolerability of RIB + AI/FUL in routine clinical practice is needed to support the use of this combination. Methods: RIBANNA is a noninterventional study ongoing in Germany since October 2017. Premenopausal and postmenopausal patients (N=3020) treated with RIB + AI/FUL, or endocrine monotherapy (ET), or chemotherapy (CT) as first-line treatment for HR+/HER2- aBC in accordance with German guidelines were included. Data are being collected from clinical practice in all 3 cohorts. Further lines of treatment are noted to examine outcomes of sequential therapy. Results: For the first interim analysis, 461 patients were enrolled until October 9, 2018, while full analysis set comprised 282 patients (Table 1). The first-line mean daily dose of RIB was 382 mg including and 540 mg excluding dose interruptions, respectively. RIB was prescribed mainly in combination with letrozole (83%), anastrozole (8%), and exemestane (7%); ET included nonsteroidal AI (64%), selective estrogen receptor degrader (25%), selective estrogen receptor modulator (7%), and steroidal AI (5%); CT included taxane-based monotherapy (30%) or combination therapy (27%), other monotherapy (23%) or other combination therapy (13%), and anthracycline-based combination therapy (5%). Conclusion: RIBANNA study showed diverse population characteristics among patients who received RIB treatment in a real-world setting. Based on the baseline demographics data, RIB (CDK4/6 inhibitor) treatment was found to be very well adopted among premenopausal and postmenopausal patients with HR+/HER2- aBC. The second interim analysis is planned for October 2019. Updated baseline data of approximately 1200 to 1300 patients and information on safety and dose modification for first-line patients from all cohorts will be presented. Table 1. Baseline demographic characteristicsTotal (N = 282)RIB + AI (n = 216)Endocrine therapy (n = 26)Chemotherapy (n = 40)Mean age, years (SD)67 (11)67 (10)71 (12)62 (10)Mean time since initial diagnosis, years5.45.56.53.9T stage at initial diagnosis, n (%)T0+T161 (100)48 (79)6 (10)7 (11)T2-T4198 (100)149 (75)17 (9)32 (16)N stage at initial diagnosis, n (%)N0+N1186 (100)144 (77)16 (9)26 (14)N2+N364 (100)48 (75)5 (8)11 (17)M stage at initial diagnosis, n (%)M0156 (100)121 (78)14 (9)21 (13)M1101 (100)75 (74)9 (9)17 (17)Locally advanced, n (%)101 (100)73 (72)9 (9)19 (19)Metastatic, n (%)101 (100)75 (74)9 (9)17 (17)Metastatic location, n (%)CNS, liver, lungs119 (100)96 (81)1 (1)22 (18)Bone only84 (100)62 (74)17 (20)5 (6)Skin, lymph nodes, other52 (100)37 (71)6 (11)9 (17) Citation Format: Achim Wöckel, Pawel Basiora, Michael Bohlmann, Thomas Decker, Jörg Falbrede, Peter Fasching, Helmut Forstbauer, Tobias Hesse, Oliver Hoffmann, Christian Jackisch, Anna Kaczerowsky, Ralf Lorenz, Kerstin Lüdtke-Heckenkamp, Diana Lüftner, Frederik Marmé, Thomas Mueller, Christoph Mundhenke, Arnd Nusch, Volker Petersen, Gabriele Prange-Krex, Toralf Reimer, Thomas Resch, Christian Roos, Oliver Tomé, Anja Weishap. Real-world efficacy of ribociclib + aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Second interim analysis from the RIBANNA study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-33.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS19-P1-19-33
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 5
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    Spleen enlargement in healthy donors during G-CSF mobilization of PBPCs
    Wiley ; 2001
    In:  Transfusion Vol. 41, No. 2 ( 2001-02), p. 184-189
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    In: Transfusion, Wiley, Vol. 41, No. 2 ( 2001-02), p. 184-189
    Type of Medium: Online Resource
    ISSN: 0041-1132 , 1537-2995
    URL: Article
    DOI: 10.1046/j.1537-2995.2001.41020184.x
    Language: English
    Publisher: Wiley
    Publication Date: 2001
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  • 6
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    Effect of ABCG2 , OCT1 , and ABCB1 ( MDR1 ) Gene Expression on Treatment-Free Remission in a EURO-SKI Subtrial
    Elsevier BV ; 2018
    In:  Clinical Lymphoma Myeloma and Leukemia Vol. 18, No. 4 ( 2018-04), p. 266-271
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    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 18, No. 4 ( 2018-04), p. 266-271
    Type of Medium: Online Resource
    ISSN: 2152-2650
    URL: Article
    DOI: 10.1016/j.clml.2018.02.004
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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    detail.hit.zdb_id: 2193618-3
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  • 7
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    Response-guided first-line therapy and treatment of relapse in aggressive lymphoma: 10-year follow-up of the PETAL trial
    Elsevier BV ; 2024
    In:  Blood Neoplasia ( 2024-5), p. 100018-
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    In: Blood Neoplasia, Elsevier BV, ( 2024-5), p. 100018-
    Type of Medium: Online Resource
    ISSN: 2950-3280
    URL: Article
    DOI: 10.1016/j.bneo.2024.100018
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
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  • 8
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    Positron Emission Tomography (PET) Guided Therapy of Aggressive Lymphomas – a Randomized Controlled Trial Comparing Different Treatment Approaches Based on Interim PET Results (PETAL Trial)
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 391-391
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    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 391-391
    Abstract: Introduction: The predictive value of 18-fluorodeoxyglucose PET performed after a few cycles of chemotherapy has been questioned in aggressive lymphomas. Inconsistent study results, however, may be due to procedural differences rather than an inability of the method to predict outcome. Whether changing treatment in pts. with an unfavorable interim PET (iPET) improves outcome, has not been determined in a randomized study. The PETAL trial (EudraCT 2006-001641-33, NCT00554164) was initiated to resolve these issues. Methods: Pts. aged 18 to 80 yrs. with newly diagnosed aggressive lymphomas and a positive baseline PET received 2 cycles of rituximab (R), cyclophosphamide (C), doxorubicin (H), vincristine (O) and prednisone (CHOP) followed by iPET. The conditions of iPET were strictly defined: 3-week interval between the 2nd R-CHOP cycle and iPET to avoid inflammatory reactions (Eur J Nucl Med Mol Imaging 30:682, 2003), no G-CSF after the 2nd R-CHOP cycle to avoid altered glucose biodistribution (J Nucl Med 47:950, 2006), standardized uptake value (SUV)-based PET interpretation to improve objectivity of evaluation (favorable iPET response: reduction of maximum SUV by 〉 66 % compared to baseline; J Nucl Med 48:1626, 2007). Pts. with CD20-positive lymphomas and a favorable iPET were randomized to receive 4 additional cycles of R-CHOP or the same treatment plus 2 extra doses of R (Part A of the trial). Pts. with an unfavorable iPET were randomized to continue standard R-CHOP for 6 additional cycles or receive 6 blocks of a more complex and more intensive protocol yielding excellent results in Burkitt and other aggressive lymphomas (Part B). Its main components were hyperfractionated alkylating agents (C, ifosfamide) and high doses of methotrexate and cytarabine, with dose reductions in pts. 〉 60 yrs. Other constituents were R, H, O, vindesine, etoposide and dexamethasone (Blood 120: abstr 667, 2012). R was omitted in pts. with CD20-negative lymphomas. Sample size was based on the empirically derived assumption that treatment failure after 2 yrs. (TF: progression, relapse, treatment discontinuation due to toxicity, start of alternative therapy, death of any cause) could be improved from 80 % to 90 % in Part A and from 30 % to 45 % in Part B (alpha=0.05, power=0.8). Complete remission (CR), overall survival (OS) and toxicity were secondary endpoints. Results: From 2007 to 2012 926 pts. were recruited by 57 participating oncological centers and analyzed by PET in 23 nuclear medicine institutions. With a median follow-up of 33 months 853 pts. are currently evaluable in the intent-to-treat population. 757 pts. had CD20-positive B cell lymphomas (80 % diffuse large B cell [DLBCL], 3 % primary mediastinal B cell, 8 % follicular lymphoma grade 3), 13 had CD20-negative B cell lymphomas and 83 had peripheral T cell lymphomas. Interim PET was favorable in 746 pts. (87 %) and unfavorable in 107 (13 %). It was highly predictive of outcome, time to TF being significantly higher in Part A than Part B (2-year probability: 79 % vs. 47 %; hazard ratio (HR) for B 3.4, 95 % confidence interval (CI) 2.6 – 4.6, p 〈 0.0001; Figure). On multivariate analysis iPET response, International Prognostic Index and B vs. T cell lineage independently predicted TF. Interim PET was also predictive of OS (HR 3.9, CI 2.7 – 5.7, p 〈 0.0001). In pts. with CD20-positive lymphomas and a favorable iPET, addition of 2 extra doses of R failed to improve TF (HR for 2 extra doses 1.2, CI 0.8 – 2.1) and all secondary endpoints. Likewise, in pts. with an unfavorable iPET response, a switch from R-CHOP to the Burkitt-type regimen showed no beneficial effect on TF (HR for Burkitt 1.6, CI 0.9 – 2.7), CR rate (50 % vs. 31 %, p=0.10) or OS (HR 1.0, CI 0.5 – 2.1). Similar results were obtained, when the analysis was restricted to DLBCL, and for covariate adjusted Cox regression of all survival endpoints. Although treatment related deaths (3 vs. 2 pts.) were comparable in both treatment arms, the Burkitt protocol was associated with more severe grade 3/4 leukopenia (84 % vs. 67 %, p=0.043), thrombocytopenia (63 % vs. 35 %, p=0.007) and mucositis (41 % vs. 12 %, p=0.002). Conclusion: Applying strict rules to the procedure and its interpretation iPET proved highly predictive of outcome in pts. with aggressive lymphomas in this large multicenter trial. Because switching to a more aggressive protocol failed to improve outcome, our results do not support a change in cytotoxic regimen in poor iPET responders. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Duehrsen: Amgen: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Klapper:Roche: Research Funding. Hoelzer:Amgen: Speakers Bureau; Medac: 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.V124.21.391.391
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 9
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    Positron Emission Tomography Guided Therapy of Aggressive Non-Hodgkin's Lymphomas (PETAL trial): Correlation between Clinical Variables and PET Parameters.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 2695-2695
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    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2695-2695
    Abstract: Abstract 2695 Poster Board II-671 Introduction: Positron emission tomography (PET) performed after a few cycles of chemotherapy (interim-PET) in aggressive lymphomas correlates with long-term outcome: While the majority of patients with a negative interim-PET scan enjoy long-lasting remissions, patients with persistent pathological glucose uptake almost invariably relapse. The multicenter PETAL trial was initiated in Germany in 2008 to resolve the question whether a change in treatment protocol may improve the outcome of patients with a positive interim-PET scan (ClinicalTrials.gov Identifier: NCT00554164). Patients and Methods: The PETAL trial is open for patients with newly diagnosed aggressive B cell or T cell non-Hodgkin's lymphomas between 18 and 80 years of age with a performance status of 0 to 3 according to the Eastern Cooperative Oncology Group scale and a positive PET scan before starting any lymphoma-directed therapy. Interim-PET is done after 2 cycles of the CHOP protocol (cyclophosphamide, doxorubicine, vincristine, prednisone; plus rituximab (R) in CD20-positive lymphomas) administered at a 14-day interval. Precautions were taken to minimize the risk of false-positive interim-PET results. First, the interval between the second (R-)CHOP cycle and the interim-PET scan is three weeks. Second, hematopoietic growth factors accelerating blood cell recovery are not allowed after the second cycle of chemotherapy. Third, quantitative standard uptake value (SUV)-based assessment rather than exclusive visual interpretation is used for interim-PET evaluation as described by Lin et al (J Nucl Med 48: 1626, 2007). Results: So far, a total of 266 patients have been recruited into the trial. A negative pre-treatment scan was observed in 18 patients, the majority of whom had complete lymphoma resection. 196 patients have reached interim-PET scanning, 168 with diffuse large B cell lymphoma (86%), 11 with grade 3a/b follicular lymphoma (6%), and 17 with peripheral T cell lymphoma (8%). Median SUVmax at staging did not differ across these three lymphoma subgroups. However, the SUVmax reduction at interim-PET was significantly lower in T-cell lymphomas as compared to B-cell lymphomas. Six patients (3%) with a low SUV at staging ( 〈 10) were rated as non-responders by quantitative, but as responders by visual assessment. Maximum SUV at staging and SUV reduction after two cycles of (R-)CHOP were independent of the International Prognostic Index (IPI). In contrast to lymphoma patients with baseline SUV values below 30, patients with higher SUV values almost invariably met the predefined criteria for therapy response (p = 0,033, Fisher's exact test). With a median follow up of less than six months, lymphoma relapses across all IPI risk groups have occurred more frequently in patients with a positive interim-PET scan than in patients with a negative scan. Neither absolute baseline SUVmax levels nor magnitude of SUVmax reduction at interim-PET were predictive of relapse. Conclusion: A combined strategy of SUV-based quantitative and visual qualitative interim-PET assessment is feasible in a multicenter randomized trial designed to guide treatment in lymphoma patients. In this largest series of interim-PET scanning in aggressive lymphoma reported so far, interim-PET response and the IPI risk score proved to be independent. With an as yet short follow-up period relapses were unevenly distributed between PET responders and non-responders. The PETAL trial will help define criteria for interim-PET scanning and response prediction. Recruitment into the trial continues. Disclosures: Hüttmann: Roche: Research Funding; Amgen: Research Funding. Duehrsen:Amgen: Research Funding; Roche: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.2695.2695
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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    Positron Emission Tomography (PET) Guided Therapy of Aggressive Lymphomas - Interim PET-Based Outcome Prediction and Treatment Changes in Patients with T Cell Lymphomas Participating in the PETAL Trial
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 185-185
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    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 185-185
    Abstract: Introduction: The PETAL trial is a multicenter randomized controlled study for patients with aggressive lymphomas of diverse histologies (EudraCT 2006-001641-33, NCT00554164). In the study population as a whole interim PET (iPET) reliably predicted time to treatment failure (TTTF) and overall survival (OS). Interim PET-based treatment changes, however, had no impact on outcome (ASH 2014, abstract 391). Here we report the exploratory analysis for peripheral T cell lymphomas (PTCL). Methods: Pts. aged 18 to 80 yrs. with newly diagnosed aggressive lymphomas and a positive baseline PET received 2 cycles of rituximab (R), cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) followed by iPET. R was omitted in pts. with CD20-negative lymphomas. The conditions of iPET were strictly defined: 3-week interval between the 2nd (R-)CHOP cycle and iPET to avoid inflammatory reactions (Eur J Nucl Med Mol Imaging 30:682, 2003), no G-CSF after the 2nd cycle to avoid altered glucose biodistribution (J Nucl Med 47:950, 2006), standardized uptake value (SUV)-based PET interpretation to improve reproducibility (favorable iPET response: reduction of maximum SUV by 〉 66 % compared to baseline; J Nucl Med 48:1626, 2007). PTCL pts. with CD20-negative lymphomas and a favorable iPET uniformly received 4 additional cycles of CHOP (part A of the trial). Pts. with an unfavorable iPET were randomized to continue CHOP for 6 additional cycles or receive 6 blocks of a more complex methotrexate-, cytarabine- and etoposide-based regimen originally designed for Burkitt lymphoma (Blood 124: 3870, 2014; part B). Sample size of the entire study population was based on the empirically derived assumption that treatment failure after 2 yrs. (progression, relapse, treatment discontinuation due to toxicity, start of alternative therapy, death of any cause) could be improved from 30 % to 45 % in part B (alpha=0.05, power=0.8). Secondary endpoints included OS and toxicity. Results: Fifty-seven oncological centers and 23 nuclear medicine institutions participated in the trial. Between 2007 and 2012 1072 pts. were registered, and 862 (80.4 %) had a positive baseline PET, received 2 cycles (R-)CHOP, underwent iPET and were allocated to one of the post-iPET treatment arms detailed above. Reference pathology was available in 98 %, and median follow-up is 52 months. All in all, there were 76 pts. (8.8 % of all treated pts.) with T-cell lymphomas of whom 21 had ALK+ anaplastic large cell lymphoma (ALCL), 13 ALK- ALCL, 18 angioimmunoblastic T-cell lymphoma (AITL) and 20 PTCL not otherwise specified (NOS). Interim PET was favorable in 57 pts. (75 %) and unfavorable in 19 pts. with T-cell lymphomas (25 %). It was highly predictive of outcome, TTTF and OS being significantly higher in part A than B (2-year probability for TTTF: 63 % vs. 21 %; univariate hazard ratio (HR) for B 3.4, 95 % confidence interval (CI) 1.8 - 6.4, p 〈 0.0001; OS: 79 % vs. 25 %; univariate hazard ratio (HR) for B 5.0, 95 % CI 2.4 - 10.3, p 〈 0.0001; Figure). Interestingly, the proportion of T-cell lymphoma pts. with an unfavorable iPET response was more than twice as high as the corresponding proportion of B-cell lymphoma pts., and the difference in survival between pts. with a favorable vs. unfavorable iPET response was more pronounced in T-cell lymphomas than in B-cell lymphomas. TTTF (2-year probability: 81 % vs. 46 % vs. 49 % vs. 35 %; p=0.0110) and OS (90 % vs. 69 % vs. 52 % vs. 50 %; p=0.0026) were better in ALK+ ALCL than in ALK- ALCL, AITL or PTCL NOS. In pts. with an unfavorable iPET response, a switch from CHOP to the alternative regimen failed to improve TTTF or OS. The latter was associated with more frequent grade 3/4 neutropenia (40 % vs. 0 % vs. 11 %, p=0.0279), thrombocytopenia (70 % vs. 33 % vs. 23 %; p=0.0106), infection (60 % vs. 44 % vs. 18 %, p=0.0057) and mucositis (40 % vs. 33 % vs. 4 %, p=0.0025) as compared to 6 or 4 post-iPET cycles of CHOP, respectively, but treatment-related mortality was similar in all treatment arms (2 vs. 1 vs. 2 deaths). Conclusion: In this large multicenter trial iPET proved highly predictive of outcome in PTCL. A favorable iPET was found in 75 % of pts., and this was associated with long-term survival in about 70 %. In pts. with an unfavorable iPET response, outcome was dismal and could not be improved by switching to a more aggressive regimen. Novel strategies are required for PTCL pts. failing to respond to the first 2 cycles of CHOP. Disclosures Hüttmann: Gilead, Amgen: Other: Travel cost; Bristol-Myers Squibb, Takeda, Celgene, Roche: Honoraria. Giagounidis:Celgene Corporation: Consultancy. Klapper:Roche, Novartis, Amgen, Takeda: Research Funding. Duehrsen:Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Alexion Pharmaceuticals: Honoraria, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.185.185
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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