Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 115, No. 6 ( 2010-02-11), p. 1113-1120

Abstract: The phase 3 trial HOVON-50 was designed to evaluate the effect of thalidomide during induction treatment and as maintenance in patients with multiple myeloma who were transplant candidates. A total of 556 patients was randomly assigned to arm A: 3 cycles of vincristine, adriamycin, and dexamethasone, or to arm B: thalidomide 200 mg orally, days 1 to 28 plus adriamycin and dexamethasone. After induction therapy and stem cell mobilization, patients were to receive high-dose melphalan, 200 mg/m2, followed by maintenance with α-interferon (arm A) or thalidomide 50 mg daily (arm B). Thalidomide significantly improved overall response rate as well as quality of the response before and after high dose melphalan. Best overall response rate on protocol was 88% and 79% (P = .005), at least very good partial remission 66% and 54% (P = .005), and complete remission 31% and 23% (P = .04), respectively, in favor of the thalidomide arm. Thalidomide also significantly improved event-free survival from median 22 months to 34 months (P 〈 .001), and prolonged progression free from median 25 months to 34 months (P 〈 .001). Median survival was longer in the thalidomide arm, 73 versus 60 months; however, this difference was not significant (P = .77). Patients randomized to thalidomide had strongly reduced survival after relapse. This trial was registered on www.controlled-trials.com as ISRCTN06413384.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2009-05-222539

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

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In: Blood, American Society of Hematology, Vol. 113, No. 6 ( 2009-02-05), p. 1375-1382

Abstract: While commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible to receive consolidation by either an autologous SCT or an allo-SCT. Allo-SCT was performed in 91 of 96 patients with a compatible sibling donor. Cumulative incidences of relapse at 5 years were, respectively, 24 and 55% for patients with a donor versus those without a donor (hazard ratio [HR], 0.37; 0.23-0.60; P 〈 .001). Nonrelapse mortality estimated 16% (± 4) at 5 years after allo-SCT. As a result, disease-free survival (DFS) at 5 years was significantly better in the donor group: 60 versus 42% in the no-donor group (HR: 0.60; 0.41-0.89; P = .01). After risk-group analysis, improved outcome was more pronounced in standard-risk patients with a donor, who experienced an overall survival of 69% at 5 years (P = .05). In conclusion, standard-risk ALL patients with a sibling donor may show favorable survival following SCT, due to both a strong reduction of relapse and a modest nonrelapse mortality. This trial is registered with http://www.trialregister.nl under trial ID NTR228.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2008-07-168625

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. 112, No. 11 ( 2008-11-16), p. 157-157

Abstract: The randomised, open-label, phase III trial HOVON-50 was designed to evaluate whether the addition of Thalidomide to AD and HDM would prolong event-free survival (EFS) in patients with newly diagnosed MM. Patients with Salmon & Durie stage II or III, age 18–65 years inclusive were randomly assigned to arm A: 3 cycles of VAD or to arm B, the same regimen but with Thalidomide 200 orally, days 1–28 instead of Vincristine (TAD). Thalidomide was started at day 1 of the first TAD cycle and was stopped 2 weeks before stem cell mobilization was started. Patients in arm B received thrombosis prophylaxis consisting of subcutaneously Low Molecular Weight Heparin (LMWH). Stem cells were mobilized using the CAD regimen, including cyclophosphamide 1000 mg/m2 iv day 1, and G-CSF. After induction therapy all patients were to receive 1 or 2 courses of high dose Melphalan (HDM) 200 mg/m2 with autologous stem cell rescue followed by maintenance therapy with ƒÑ-Interferon (3 „e 106 IU, thrice weekly, arm A) or Thalidomide 50 mg daily (arm B). Between November 27, 2001 and May 31, 2005, 556 patients were randomised of which 18 patients were not eligible, while from 2 patients data were incomplete. EFS was defined as time from randomisation to induction failure, progression, or death from any cause. Patients (n=109) who received a non-myeloablative allogeneic transplant after HDM 1 before progression, were censored at the date of allo-SCT; those patients were usually entered into the HOVON-54 trial. Both arms were comparable with regard to age, myeloma stage and prognostic factors. Best responses achieved on protocol were significantly higher in the patients randomized to thalidomide: Minimal PR rates were 87% and 79 % (p & lt;0.01), VGPR 65 % and 54% (p & lt;0.01), CR% 30% and 21 % (p=0.03), respectively. Thalidomide also significantly improved EFS from median 22 months to 33 months (p & lt;0.001) and PFS from median 25 to 33 months (p & lt;0.001). Overall survival however in both arms was comparable, 62 months in arm A and 59 months in arm B (P=0.96). LDH & gt;ULN at diagnosis and higher ISS were identified as adverse prognostic factors for response and survival endpoints. Abnormalities of chromosome 13 as determined by FISH or conventional karyotyping had no prognostic impact. 96 patients (18%) went off protocol treatment without receiving HDM, mainly due to excessive toxicity (5 %), intercurrent death (4%) or ineligibility for further treatment (3%) comparable in both arms. IFN maintenance in 34% of patients of which 23 % stopped due to toxicity. Thalidomide maintenance started in 57% of patients in arm B of which 63% stopped due to toxicity Thalidomide resulted in significantly higher response rates and improved EFS and PFS. However, this did not translate into better overall survival

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V112.11.157.157

Language: English

Publisher: American Society of Hematology

Publication Date: 2008

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In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 27-27

Abstract: Background: We reported better PFS and OS in transplant eligible patients with newly diagnosed Multiple Myeloma (MM) who were treated with bortezomib during induction and maintenance, when compared with standard treatment in the HOVON-65/GMMG-HD4 trial. (P. Sonneveld et al., J Clin Oncol 30:2946-2955, 2012). Here the long-term follow up data are presented. Methods: 827 eligible patients were randomized to induction therapy with VAD (vincristine, doxorubicin, dexamethasone) or PAD (bortezomib, doxorubicin, dexamethasone) followed by high-dose melphalan (once or twice) and autologous stem cell transplant. Maintenance consisted of daily thalidomide (T) 50 mg (VAD arm) or 2-weekly bortezomib (B) 1.3 mg/m2 (PAD arm) for 2 years. The primary endpoint was progression-free survival (PFS) adjusted for ISS stage. Results: After a median follow up of 91.4 months (maximum 119) 410 patients are alive. Response rates were VAD/HDM/T: CR 25%, ≥VGPR 56%, ≥PR 83%; PAD/HDM/B: CR 37%, ≥VGPR 76%%, ≥PR 91%, The median duration of maintenance therapy was 14 months (thalidomide) and 23 months (bortezomib), respectively. Main reasons for discontinuation were toxicity (T: 31%; B: 11%), disease progression (T: 33%; B: 36%) or normal completion (T: 28%; B: 48%). Of 827 patients in the analysis, 206 are alive without progression/relapse. PFS was significantly better in the bortezomib arm, i.e. median 34 versus 28 months (HR=0.77, 95% CI=0.65-0.90, p=0.001). Median overall survival (OS) was 90 months in the bortezomib arm vs 83 months in the control arm, but 42% at 9 years in both arms. We used the restricted mean survival time (RMST) method to compare OS between the two treatment arms In univariate analysis. The difference in RMST8y was 4.8 months (95% CI 0.2-9.5, p=0.04) in favor of the bortezomib arm. A landmark analysis in patients who had received HDM starting at 12 months showed a significant PFS advantage of bortezomib in all patients (p=0.02), in patients in VGPR/PR (p=0.02) but not in CR (p=0.19). For OS there was no advantage for bortezomib in either group. PFS at 60 months in bortezomib treated patients was not different when single vs double HDM/ASCT was administered, i.e. 28% vs 27%. However, OS at 60 months was 71% vs 60% in favor of double HDM/ASCT (p=0.04). Subgroup analysis was performed based on presence/absence of adverse FISH (CA) in 395 patients treated with double HDM/ASCT. PFS at 60 months for each abnormality (CA or no CA) in bortezomib vs standard arm is given in Table 1 Table 1.PFS at 60 months, %OS at 60 months, %FISHnBortezomib armpStandard armBortezomib armpStandard Armt(4;14) yes/no50/29516% vs 27%0.048% vs 24%52% vs 75%0.0133% vs 64%add(1q) yes/no113/23116% vs 32%0.00510% vs 28%57% vs 79%0.00143% vs 70%del(17p) yes/no39/31222% vs 27%0.475% vs 24%65% vs 72%0.4818% vs 66% These data show that bortezomib treatment combined with double HDM/ASCT significantly improves PFS and OS in patients with del(17p) and almost abrogates the negative impact of this CA. In t(4;14) and add(1q) some improvement is observed, however the negative impact remains significant. In high-risk patients presenting with elevated creatinine 〉 2 mg/dL bortezomib significantly improved PFS at 60 months (32% vs 5%) (p=0.001) and OS at 60 months (66% vs 21% months (p 〈 0.001)). OS at 8 years was 46% vs 12%. Finally, OS from progression/relapse was not different between patients treated in the bortezomib vs standard arm (OS at 72 months: 33% vs 35%, p=0.73) Conclusions: We conclude that bortezomib leads to a significant and lasting improvement of PFS and OS. Bortezomib significantly reduces the high-risk impact of del(17p) and renal impairment on survival. This trial was registered as NTR213; EudraCT no. 2004-000944-26.and supported by the Dutch Cancer Foundation, the German Federal Ministry of Education and Research and an unrestricted grant from Janssen. The GMMG group received grants for this trial by Novartis, AMGEN, Chugai and Roche. Disclosures Sonneveld: SkylineDx: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Salwender:Celgene: Honoraria; Janssen Cilag: Honoraria; Bristol Meyer Sqibb: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Blau:MSD: Honoraria; Celgene: Honoraria, Research Funding; AMGEN: Honoraria; JAZZ pharm: Honoraria; BMS: Honoraria; Shire: Honoraria; Baxalta: Honoraria; Janssen: Honoraria, Research Funding. Zweegman:celgene: Honoraria, Research Funding; takeda millennium: Honoraria, Research Funding; onyx: Honoraria. Weisel:Noxxon: Consultancy; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Novartis: Other: Travel Support; Onyx: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel Support; BMS: Consultancy, Honoraria, Other: Travel Support; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding. Broijl:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Scheid:Janssen: Honoraria; Celgene: Honoraria. Potamianou:Janssen: Employment. Hose:Takeda: Other: Travel grant; EngMab AG: Research Funding. Kersten:takeda millennium: Research Funding; janssen: Honoraria, Research Funding; roche: Honoraria, Research Funding. Duehrsen:Alexion: Honoraria; janssen: Honoraria. Lokhorst:Janssen: Honoraria, Research Funding; Genmab: Honoraria, Research Funding; Amgen: Honoraria. Goldschmidt:celgene: Honoraria, Research Funding; janssen: Honoraria, Research Funding; novartis: Honoraria, Research Funding; chugai: Honoraria, Research Funding; onyx: Honoraria, Research Funding; millennium: Honoraria, Research Funding; BMS: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.27.27

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

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In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 29 ( 2020-10-10), p. 3377-3387

Abstract: Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.19.03418

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2020

detail.hit.zdb_id: 2005181-5

In: Blood Advances, American Society of Hematology, Vol. 5, No. 4 ( 2021-02-23), p. 1110-1121

Abstract: Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)–adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2020003855

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

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In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3841-3841

Abstract: Abstract 3841 The efficacy of azacitidine in the treatment of high risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20–30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analyzed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate patient named program. Patients received azacitidine for a median of 5 cycles (range 1–19). The overall response rate (CR/PR/HI) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13.0 (9.8–16.2) months. In multivariate analysis we confirmed that circulating blasts (HR 0.48, 95% CI 0.24–0.99; p=.05) and poor risk cytogenetics (HR 0.45, 95% CI 0.22–0.91; p=.03) are independent predictors for OS. Interestingly, in this analysis we also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5.4, 95% CI 0.73–39.9; p=.10). Of the 90 treated patients, 14 (16%) had an at least two-fold increase in platelet count after the first cycle of azacitidine, which was associated with significant better OS (p=.01, according to logrank test) (figure). Of these 14 patients 13 could be classified according the azacitidine prognostic scoring system for OS as recently proposed by Itzykson et al. (Blood:2011;117:403); 6 patients belonged to the low risk and 7 to the intermediate risk group. Median baseline platelet count of these patients was 35 x109/L (range 2–290 x109/L). Characteristics of this subgroup of patients were not significantly different from the patients without platelet doubling. Interestingly, platelet doubling was observed in all cytogenetic risk groups, in patients with and without circulating blasts, and in patients who are transfusion dependent and independent. In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible and subgroups with distinct efficacy of azacitidine treatment can be identified. Disclosures: Wijermans: Centocor Ortho Biotech Research & Development: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V118.21.3841.3841

Language: English

Publisher: American Society of Hematology

Publication Date: 2011

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In: British Journal of Haematology, Wiley, Vol. 155, No. 5 ( 2011-12), p. 599-606

Type of Medium: Online Resource

ISSN: 0007-1048

URL: Issue

URL: Article

DOI: 10.1111/bjh.2011.155.issue-5

DOI: 10.1111/j.1365-2141.2011.08893.x

Language: English

Publisher: Wiley

Publication Date: 2011

detail.hit.zdb_id: 1475751-5

In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4110-4110

Abstract: Abstract 4110 Background: The ACT trial (ACT-1 and −2) tests the addition of alemtuzumab (ALZ) to 6 courses of bi-weekly CHOP (A-CHOP-14) followed, in younger patients (ACT-1), by high-dose therapy with autologous stem cell transplant (HDT/ASCT) in newly diagnosed primary systemic peripheral T-cell lymphoma (PTCL). To date, the trial has accrued a total of 131 patients (ACT-1 n=72; ACT-2 n=59). Here, we present the first planned interim safety analysis of the ACT-1 trial based on the first 51 randomized patients. Aims: The aim of the present analysis is to report on the feasibility of a dose-dense chemo-immunotherapy schedule combining ALZ and bi-weekly CHOP followed by HDT/ASCT in ‘de novo' PTCL patients. Results: Results contain two data subsets corresponding to ALZ dose levels prior and subsequent to a dose-reduction amendment tapering ALZ dose from 360 mg (30 mg on days 1 and 2 of each CHOP course) to 120 mg (30 mg on day 1 of CHOP courses 1–4), respectively. Of the 51 randomized patients, 43 had a complete set of evaluable data and represent the background for the present set of results. Of these, 5 received the higher ALZ dose, 17 the lower and 21 belonged to the antibody-void control arm. Treatment arms were well balanced with regard to histological subtypes, IPI sub-groups, and single prognostic factors. Neither of the two treatment cohorts, and for the experimental one irrespective of ALZ dose level, showed significant treatment delay. The median duration of chemotherapy (calculated for 5 bi-weekly cycles of an expected cumulative duration of 70 days) for non-ALZ vs. ALZ-treated patients was 73 vs. 81 days, respectively. No suspected unexpected serious adverse reactions (SUSARs) were reported. Grade 3–4 leucopenia and anemia were more frequent in ALZ-treated patients (71% vs 29% and 47% vs 14%, respectively), whereas no difference was seen in terms of thrombocytopenia (17% vs 18%). Non-hematological toxicity unrelated to infectious complications was similar in the two groups. At the higher ALZ dose level, two cases of systemic fungal infection were reported, of which one (verified as being aspergillosis) with fatal outcome in a patient with pre-existing type II diabetes and steroid-requiring chronic obstructive pulmonary disease. These two events prompted the ALZ dose-reduction amendment, which led to a significant drop in the number of serious adverse events (SAEs) for ALZ-treated patients (SAE/patient pre-amendment: 2.6, post-amendment: 0.76) to a level comparable with the control arm (SAE/patient pre-amendment: 0.67, post-amendment: 0.44). With regard to the types of infection (≥grade 2), there was a similar frequency in reported fungal infections between the two treatment cohorts, bacterial infections were more often reported in the standard treatment arm (55% vs 46%), while the opposite was observed for viral infections (29% vs. 35%). Among the latter, there were 8 cases of cytomegalovirus reactivation among ALZ-treated patients, of which only two were clinically symptomatic and regressed upon specific treatment. Conclusion: In conclusion, the early-on impression of a SAE decrease subsequent to the ALZ dose-reduction amendment (applied on both ACT-1 and ACT-2) has been further confirmed by a larger cohort of patients treated at the lower ALZ dose level. The number of adverse events in the two study arms is now fairly comparable and adds further useful information to the previous reports on feasibility of stem cell harvest (Blood 2010;116: 2395) and hematopoietic recovery (Ann Oncol 2011;22(s4): 476) in ‘de novo' PTCL patients treated with a dose-dense ALZ-CHOP regimen followed by HDT/ASCT. Disclosures: Walewski: 4SC AG: Consultancy. Jantunen:Genzyme: 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.V118.21.4110.4110

Language: English

Publisher: American Society of Hematology

Publication Date: 2011

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In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 57-57

Abstract: Abstract 57 Background The ACT trial (ACT-1, younger patients aged 18–60 yrs and ACT-2, elderly patients aged 〉 60 yrs) is the first international randomized phase III trial in newly diagnosed primary systemic peripheral T-cell lymphoma (PTCL). It tests, in both younger and elderly patients, the efficacy of the addition of alemtuzumab (ALZ) to 6 courses of bi-weekly CHOP followed, only in younger patients (ACT-1), by high-dose therapy with autologous stem cell rescue. A dose reduction amendment tapering the cumulative ALZ dose from 360 mg (30 mg on days 1 and 2 of CHOP courses 1–6) to 120 mg (30 mg on day 1 of CHOP courses 1–4), respectively, was introduced early on due to two cases of systemic fungal infection (Blood 2011,118;4110). To date, the trial has accrued a total of 186 patients (ACT-1 n=98; ACT-2 n=88). Aim Here, we present the results from the first interim efficacy and safety analysis of the ACT-1 trial based on the first 68 randomized patients. Results Of the 68 patients, 63 had a complete set of treatment data. The median follow-up was 15 months (range 0.5–42 months). Thirty-two patients belonged to the experimental arm (exp) and 31 to the standard arm (std). Of the 32 patients treated according to exp, 4 received the higher dose of ALZ and 28 the lower. Treatment arms were well balanced with regard to main prognostic features such as age (std: median 53 yrs, range 21–60 yrs; exp: median 50 yrs, range 22–64 yrs; p=0.705), IPI subgroups (std: low 10%, low-intermediate 51%, intermediate-high 29%, high 10%; exp: low 12%, low-intermediate 44%, intermediate-high 19%, high 25%; p=0.392), advanced clinical stage (std: stage III-IV 94%; exp: 97%; p=0.613), performance status ECOG 〉 1 (std: 23%; exp: 28%; p=0.613), elevated LDH (std: 68%; exp: 69%; p=0.932), presence of B-symptoms (std: 68%; exp: 75%; p=0.524), bulky disease (std: 13%; exp: 13%; p=1.0) and bone marrow involvement (std: 39%; exp: 31%; p=0.535). Histological subtypes were also similarly distributed among both treatment arms (std: PTCL-NOS 55%, AILT 23%, other 22%; exp: PTCL-NOS 56%, AILT 28%, other 16%). No cases of anaplastic large cell PTCL (regardless of ALK-protein status) were included. Neither of the treatment cohorts showed significant treatment delay. The median duration of chemotherapy (calculated for 5 bi-weekly cycles of an expected cumulative duration of 70 days) for non-ALZ vs. ALZ-treated patients was 73 vs. 81 days, respectively. No suspected unexpected serious adverse reactions (SUSARs) were reported. Grade 4 leucopenia was more frequent in ALZ-treated patients (std: 24%, exp: 69%; p=0,001), whereas grade 3–4 anemia and grade 3–4 thrombocytopenia were not significantly different between treatment arms (anemia, std: 19%, exp: 31%; p=0,278; thrombocytopenia, std: 20%, exp: 12%, p=0,682). Non-hematological toxicity unrelated to infectious complications was mild and had a similar frequency in both arms. The number of serious adverse events (SAEs) per patient was 0.86 for patients treated at post-amendment ALZ dose levels, representing a significant reduction compared to the pre-amendment value (3.25), and 0.46 for patients treated in the control arm (p=0.002). The frequency of bacterial and fungal infections (grade ≥3) was similar in both treatment arms. ALZ treated patients had more viral events (9/32; 28% vs. 3/31; 10%), mainly (6 out of 9) consisting of asymptomatic cytomegalovirus reactivations. The overall (non-arm specific) 1-year event-free survival (primary end-point), progression-free survival and overall survival were 55% (95% CI: 42%-67%), 54% (95% CI: 42%-67%) and 78% (95% CI: 67%-88%), respectively. Conclusion The safety profile of the current standard and experimental treatment schedules, as well as the interim outcome results, support a continuation of the trial. A final analysis will be performed in Q2 2015. Disclosures: Jantunen: Genzyme: Has participated in EU Leadership meeting organized by Genzyme as well as Medical Advisory Board meeting organized by Genzyme Other, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V120.21.57.57

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

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