Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 3338-3340

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-166748

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 130, No. Suppl_1 ( 2017-12-07), p. 721-721

Abstract: Background: The addition of sorafenib to standard induction and consolidation therapy in newly diagnosed patients (pts) ≤60 years (yrs) with acute myeloid leukemia (AML) led to significant prolongation of event-free survival (EFS) and relapse-free survival (RFS) in the randomized placebo-controlled SORAML trial (NCT00893373). After a median follow-up of 3 yrs, a benefit for sorafenib treated pts was observed also in overall survival (OS), but this difference was not significant. Here, we present updated survival data and information on relapse treatment and outcome. Methods: In the SORAML trial, 267 newly diagnosed untreated fit AML pts up to 60 yrs of age and irrespective of FLT3 mutation status received two cycles of induction chemotherapy with DA (daunorubicin 60 mg/m2 days 3-5 plus cytarabine 100 mg/m2 cont. inf. days 1-7), followed by three cycles of high-dose cytarabine consolidation (3 g/m2 b.i.d. days 1, 3, 5). Allogeneic stem cell transplantation (SCT) was scheduled for all intermediate-risk pts in first complete remission (CR) with a sibling donor and for all high-risk pts with a matched related or unrelated donor. At study inclusion, pts were randomized to receive either sorafenib (2x400 mg/day) or placebo as add-on to standard treatment in a double blinded fashion. Study medication was given on days 10-19 of DA I+II, from day 8 of each consolidation until 3 days before the start of the next consolidation and as maintenance for 12 months (mos) after the end of consolidation. The primary endpoint of the trial was EFS. The results after follow-up of 3 yrs were presented at ASH 2014 (Röllig et al., Blood 2014; 124: 6) and fully published (Röllig et al., Lancet Oncol 2015; 16: 1691-9). Here, we present the results after prolonged follow-up. For this analysis, information on remission and survival status, mode and outcome of relapse treatment including SCT were collected for all randomized pts and analyzed by standard statistical methods. Results: Of 267 treated pts, 134 were randomized in the sorafenib arm and 133 in the placebo arm with a resulting CR rate of 60% and 59%, respectively. After a median observation time of 78 mos, the primary study endpoint EFS in the placebo vs sorafenib arm was 9 mos vs 26 mos (HR 0.68, p=0.01) in univariate Kaplan Meier analysis. The beneficial effect of sorafenib on EFS was confirmed in multivariate Cox regression analysis with a HR of 0.61 (p=0.005). Median RFS in the placebo vs sorafenib arms was 22 vs 63 mos, corresponding to a HR of 0.64 (p=0.033). Exploratory analyses were performed in the 70 relapsing pts (40 after placebo vs 30 after sorafenib treatment). Among relapsing pts, 82% vs 73% achieved a second CR. In these two groups, 88% and 87% of pts received a SCT as part of salvage treatment. A lower proportion of pts in the placebo arm received a second SCT as salvage treatment (5% vs 13%). In the context of salvage SCT, the proportion of haploident donors in the placebo and sorafenib group was 3% vs 15% and the incidence of Grade 3/4 GVDH was 17% vs 0%. SCT-related non-relapse mortality (NRM) was similar in both groups, but the cumulative incidence of second relapse (CIR) was higher in the sorafenib group (35% vs 54% after 48 mos). Therefore, median OS from relapse in the placebo vs sorafenib groups were 27 mos vs 10 mos, corresponding to a HR of 1.68 (p=0.098). The projected median OS from randomization is 83 mos in the placebo arm and was not reached for the sorafenib arm, corresponding to a 5-year OS of 52% vs 61% (HR 0.81, p=0.263). Conclusion: Mature follow-up data confirms the antileukemic efficacy of sorafenib in younger AML pts with and without FLT3 mutation. The addition of sorafenib to standard chemotherapy resulted in a significantly longer EFS and clinically relevant 36% risk reduction for relapse or death. Five pts need to be treated (NNT) to prevent one relapse or death at 3 years and six pts at 5 yrs. Exploratory analyses in relapsing pts show that survival after relapse is shorter after sorafenib which might be due to i) a higher rate of second SCTs and a higher incidence of haploidentical SCT despite the lower frequency of severe GVHD, most likely by chance and not explainable by systematic reasons and ii) a lower response to salvage treatment after sorafenib therapy. Despite these observations, primary sorafenib treatment led to an OS benefit with a 19% risk reduction for death which was not statistically significant since this phase II trial was not adequately powered to detect OS differences. Figure Figure. Disclosures Rollig: Bayer: Research Funding; Janssen: Research Funding. Hüttmann: Gilead, Amgen: Other: Travel cost; Bristol-Myers Squibb, Takeda, Celgene, Roche: Honoraria. Giagounidis: Acceleron: Consultancy; Celgene: Consultancy. Mackensen: AMGEN: Research Funding. Hänel: Roche: Honoraria; Novartis: Honoraria. Thiede: Roche: Consultancy; Novartis: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Agendix: Employment. Schetelig: Sanofi Aventis: Consultancy, Research Funding; Roche: Honoraria; Abbvie: Honoraria; Janssen: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V130.Suppl_1.721.721

Language: English

Publisher: American Society of Hematology

Publication Date: 2017

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 116, No. 18 ( 2010-11-04), p. 3564-3571

Abstract: Acute myeloid leukemia (AML) is commonly associated with alterations in transcription factors because of altered expression or gene mutations. These changes might induce leukemia-specific patterns of histone modifications. We used chromatin-immunoprecipitation on microarray to analyze histone 3 lysine 9 trimethylation (H3K9me3) patterns in primary AML (n = 108), acute lymphoid leukemia (n = 28), CD34+ cells (n = 21) and white blood cells (n = 15) specimens. Hundreds of promoter regions in AML showed significant alterations in H3K9me3 levels. H3K9me3 deregulation in AML occurred preferentially as a decrease in H3K9me3 levels at core promoter regions. The altered genomic regions showed an overrepresentation of cis-binding sites for ETS and cyclic adenosine monophosphate response elements (CREs) for transcription factors of the CREB/CREM/ATF1 family. The decrease in H3K9me3 levels at CREs was associated with increased CRE-driven promoter activity in AML blasts in vivo. AML-specific H3K9me3 patterns were not associated with known cytogenetic abnormalities. But a signature derived from H3K9me3 patterns predicted event-free survival in AML patients. When the H3K9me3 signature was combined with established clinical prognostic markers, it outperformed prognosis prediction based on clinical parameters alone. These findings demonstrate widespread changes of H3K9me3 levels at gene promoters in AML. Signatures of histone modification patterns are associated with patient prognosis in AML.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2009-09-240978

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. 135, No. 23 ( 2020-06-4), p. 2059-2070

Abstract: Noncoding RNAs, including small nucleolar RNAs (snoRNAs), play important roles in leukemogenesis, but the relevant mechanisms remain incompletely understood. We performed snoRNA-focused CRISPR-Cas9 knockout library screenings that targeted the entire snoRNAnome and corresponding host genes. The C/D box containing SNORD42A was identified as an essential modulator for acute myeloid leukemia (AML) cell survival and proliferation in multiple human leukemia cell lines. In line, SNORD42A was consistently expressed at higher levels in primary AML patient samples than in CD34+ progenitors, monocytes, and granulocytes. Functionally, knockout of SNORD42A reduced colony formation capability and inhibited proliferation. The SNORD42A acts as a C/D box snoRNA and directs 2′-O-methylation at uridine 116 of 18S ribosomal RNA (rRNA). Deletion of SNORD42A decreased 18S-U116 2′-O-methylation, which was associated with a specific decrease in the translation of ribosomal proteins. In line, the cell size of SNORD42A deletion carrying leukemia cells was decreased. Taken together, these findings establish that high-level expression of SNORD42A with concomitant U116 18S rRNA 2′-O-methylation is essential for leukemia cell growth and survival.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.2019004121

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

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detail.hit.zdb_id: 80069-7

In: Blood Advances, American Society of Hematology, Vol. 7, No. 12 ( 2023-06-27), p. 2811-2824

Abstract: Engraftment and differentiation of donor hematopoietic stem cells is decisive for the clinical success of allogeneic stem cell transplantation (alloSCT) and depends on the recipient’s bone marrow (BM) niche. A damaged niche contributes to poor graft function after alloSCT; however, the underlying mechanisms and the role of BM multipotent mesenchymal stromal cells (MSC) are ill-defined. Upon multivariate analysis in 732 individuals, we observed a reduced presence of proliferation-capable MSC in BM aspirates from patients (N = 196) who had undergone alloSCT. This was confirmed by paired analysis in 30 patients showing a higher frequency of samples with a lack of MSC presence post-alloSCT compared with pre-alloSCT. This reduced MSC presence was associated with reduced survival of patients after alloSCT and specifically with impaired graft function. Post-alloSCT MSC showed diminished in vitro proliferation along with a transcriptional antiproliferative signature, upregulation of epithelial-mesenchymal transition and extracellular matrix pathways, and altered impact on cytokine release upon contact with hematopoietic cells. To avoid in vitro culture bias, we isolated the CD146+/CD45–/HLA-DR– BM cell fraction, which comprised the entire MSC population. The post-alloSCT isolated native CD146+MSC showed a similar reduction in proliferation capacity and shared the same antiproliferative transcriptomic signature as for post-alloSCT colony-forming unit fibroblast–derived MSC. Taken together, our data show that alloSCT confers damage to the proliferative capacity of native MSC, which is associated with reduced patient survival after alloSCT and impaired engraftment of allogeneic hematopoiesis. These data represent the basis to elucidate mechanisms of BM niche reconstitution after alloSCT and its therapeutic manipulation.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2022008510

Language: English

Publisher: American Society of Hematology

Publication Date: 2023

detail.hit.zdb_id: 2876449-3

In: Blood Advances, American Society of Hematology, Vol. 7, No. 11 ( 2023-06-13), p. 2436-2448

Abstract: Patients with precursor B-cell acute lymphoblastic leukemia (pB-ALL) who have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), have relapsed more than once, or are resistant upfront have a dismal prognosis. CD19-targeted chimeric antigen receptor (CAR) T cells have evolved as potent immune therapies. Tisagenlecleucel (Tisa-cel) is a commercially available autologous CD19-directed CAR T-cell product. We performed a retrospective study inviting all CAR T-cell centers in Germany to participate. Eighty-one patients with pB-ALL were included. Twenty-eight days after CAR T-cell infusion, 71 patients (87.7%) were in complete response, and 8 (9.9%) were in nonremission. At 2 years, the probabilities of event-free survival (pEFS), relapse-free survival (pRFS), and overall survival (pOS) were 45.3%, 51.7%, and 53.2%, respectively. pEFS was not different in patients without (n = 16, 55.0%) vs with prior allo-HSCT (n = 65, 43.4%). In patients treated after allo-HSCT, the time to relapse after allo-HSCT was a strong predictor of outcome. Patients relapsing within 6 months of allo-HSCT had a disappointing pEFS of 18.4% (pOS = 16.0%); the pEFS for those relapsing later was 55.5% (pOS = 74.8%). Our study provides real-world experience in pediatric, adolescent, and young adult patients with ALL treated with Tisa-cel, where most patients were treated after having relapsed after allo-HSCT. A total of 45.3% were rescued with a single dose of Tisa-cel. Our novel finding that patients with ALL after allo-HSCT had by far a better pEFS if relapse occurred beyond 6 months might be helpful in clinical decision-making and motivates studies to uncover the reasons.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2022008981

Language: English

Publisher: American Society of Hematology

Publication Date: 2023

detail.hit.zdb_id: 2876449-3

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 10407-10409

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-156775

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

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. 1307-1307

Abstract: Background: Trisomy 4 is a recurrent but rare cytogenetic abnormality reported in patients with acute myeloid leukemia (AML). The prognostic significance of this abnormality in AML patients is not clear. Prognosis of AML patients with trisomy 4 seems to be poor as compared to that of patients with intermediate-risk cytogenetics. Allogeneic hematopoietic stem cell transplantation (allo-HCT) may improve survival if applied early in first complete remission (CR). However, neither prospective clinical nor larger retrospective cohort studies are available to support these results from small series. Aims: To characterize AML patients with trisomy 4 and compare outcomes according to different treatment strategies. Methods: We retrospectively studied 123 AML patients with trisomy 4 (median age at diagnosis, 58 years; range, 16-76 years) treated between 2000 and 2019 within 2 large study groups. Standard statistical methods were applied. Results: Median white blood cell count at diagnosis was 4.8/nl (range, 0.4-255/nl) and platelets 46/nl (range, 2-330/nl). Type of AML was de novo in 97 (79%), secondary after myelodysplastic syndrome/myeloproliferative neoplasm in 18 (15%), and therapy-related in 8 (6%) patients. Sixty-two (50%) patients were female. Cytogenetic analysis revealed trisomy 4 as the sole abnormality in 28 (23%), additional abnormalities in 95 (77%) patients, most frequently ≥3 (n=66) abnormalities, trisomy 8 (n=41), karyotypes characterized by trisomies only (n=21) and t(8;21) or inv(16) (CBF; n=10). A total of 98 patients (80%) had NPM1 and FLT3-ITD mutation testing. Of those, 21 (21%) and 15 (15%) harbored NPM1 and FLT3-ITD mutations. Only 2 (3%) of 72 patients were CEBPA double mutated. Data on response to intensive anthracycline-based induction therapy were available in 117 patients. Early death rate was 5% (n=6). CR was achieved in 68% (n=79) with 22 (19%) requiring an intensive salvage treatment cycle. Notably, patients with trisomy 4 as sole abnormality had a CR rate of 89% (n=25/28). There was no difference in the CR rate in FLT3-ITD positive (n=10/15) as compared to FLT3 wild type (n=56/83) patients (67% each, P=0.99). Univariable analysis revealed trisomy 4 as sole abnormality (OR, 5.76; P=0.007) and NPM1 (OR, 12.08; P=0.02) as favorable factors. An allo-HCT was performed in 40 (34%) patients, of whom 19 patients were transplanted in first CR after induction therapy. Nine patients achieved CR after salvage chemotherapy and went on to allo-HCT; another 12 patients received allo-HCT with active disease. Type of donor was matched-related in 8, matched-unrelated in 30, and unknown in 2 of the 40 patients, respectively. Median follow-up of the intensively treated cohort was 73 months (95%-CI, 36-91 months). Five-year overall survival (OS) and relapse-free survival (RFS) were 31% (95%-CI, 23-42%) and 27% (95%-CI, 18-42%). OS rates were significantly higher in patients with CBF leukemia or patients with trisomy 4 as compared to all other abnormalities (Figure 1; P & lt;0.001). Cox regression analysis on OS revealed CBF/CEBPA (HR, 0.75; P=0.02) and trisomy 4 as sole abnormality (HR, 0.63; P=0.04) as favorable factors; age with a difference of ten years was an in trend adverse factor (HR, 1.15; P=0.06; not significant: NPM1, FLT3-ITD, complex karyotype with ≥3 abnormalities). There was no difference on OS if patients proceeded to allo-HCT in CR1 or with active disease (P=0.8). Five-year RFS was 26% (95%-CI, 14-50%) in patients proceeding to allo-HCT after induction therapy (n=40), as compared to 28% (95%-CI, 17-46%; P=0.99) in those who received consolidation chemotherapy (n=49). Conclusions: Clinically, patients with trisomy 4 are very heterogeneous in particular with respect to cytogenetic and molecular abnormalities. In our cohort, patients with trisomy 4 as a sole abnormality had a high CR rate and favorable clinical outcome. In the total cohort, allo-HCT did not improve RFS. Figure 1 Figure 1. Disclosures Krause: Siemens: Research Funding; Takeda: Honoraria; Pfizer: Honoraria; art-tempi: Honoraria; Kosmas: Honoraria; Gilead: Other: travel support; Abbvie: Other: travel support. Schliemann: Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Other: travel grants; Astellas: Consultancy; AstraZeneca: Consultancy; Boehringer-Ingelheim: Research Funding; BMS: Consultancy, Other: travel grants; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Haenel: Takeda: Consultancy, Honoraria; Bayer Vital: Honoraria; Jazz: Consultancy, Honoraria; GSK: Consultancy; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy; Celgene: Consultancy, Honoraria. Crysandt: Incyte: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees. Fransecky: Medac: Honoraria; Amgen: Honoraria; Abbvie: Honoraria, Research Funding; Novartis: Honoraria; Takeda: Honoraria. Martinez-Lopez: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, 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; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: 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; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: 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. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding. Platzbecker: AbbVie: Honoraria; Celgene/BMS: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Geron: Honoraria; Takeda: Honoraria. Baldus: Novartis: Honoraria; Amgen: Honoraria; Celgene/BMS: Honoraria; Jazz: Honoraria. Müller-Tidow: Pfizer: Research Funding; Janssen: Consultancy, Research Funding; Bioline: Research Funding. Levis: Astellas and FujiFilm: Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Honoraria; Amgen, Astellas Pharma, Daiichi-Sankyo, FujiFilm, and Menarini: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Takeda: Honoraria. Montesinos: Stemline/Menarini: Consultancy; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: 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, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Forma Therapeutics: Consultancy; Glycomimetics: Consultancy; Tolero Pharmaceutical: Consultancy; Agios: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board, Research Funding, Speakers Bureau. Röllig: Roche: Honoraria, Research Funding; Bristol-Meyer-Squibb: Honoraria, Research Funding; Janssen: Honoraria; Jazz: Honoraria; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Honoraria; AbbVie: Honoraria, Research Funding. Schlenk: Novartis: Honoraria; Pfizer: Honoraria, Research Funding, Speakers Bureau; Hexal: Honoraria; Neovio Biotech: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; Celgene: Honoraria; Astellas: Honoraria, Research Funding, Speakers Bureau; Abbvie: Honoraria; Agios: Honoraria; Roche: Honoraria, Research Funding; AstraZeneca: Research Funding; Boehringer Ingelheim: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-150281

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. 128, No. 22 ( 2016-12-02), p. 516-516

Abstract: Background High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the established standard-of-care for patients with newly diagnosed multiple myeloma (NDMM) who are young and/or fit. The number of older patients receiving HDT-ASCT is increasing, although they often receive lower-intensity treatment. Novel agent-based consolidation therapy can be used to improve responses following ASCT and prolong progression-free survival (PFS). The proteasome inhibitor bortezomib, given as post-ASCT consolidation therapy, resulted in an improved PFS compared with observation alone (median 33.6 vs 27.8 months, adjusted hazard ratio [HR] 0.70, p=0.0058) in a combined analysis of two phase 3 trials (MMY3012 [DSMM XIb; NCT00416273] and MMY3013 [DSMM X; NCT00416208]; JCO 2015;33:8511). These studies enrolled 222 patients aged ≤60 years and 158 aged 〉 60 years. In this post-hoc analysis we investigated the effect of age and related treatment factors on PFS in more detail. Methods In both trials, 371 patients were randomized 1:1 following ASCT to receive four 35-day cycles of bortezomib consolidation (n=186; bortezomib 1.6 mg/m2 IV administered on days 1, 8, 15, and 22) or observation (n=185; no treatment). The primary endpoint was PFS from the start of induction chemotherapy. Response and progression were assessed at the start of each bortezomib cycle and at the end-of-treatment/observation visit (week 25), as well as during the follow-up period of 30-60 months. Patient characteristics and treatments were compared between trials; PFS following randomization was assessed separately for each study. Univariate, bivariate, and multivariate Cox regressions were conducted to evaluate the impact of treatment group, age (≤60 vs 〉 60 years), single vs tandem ASCT, melphalan conditioning dose (MEL 〈 200 vs 200 mg/m2), bortezomib exposure during induction (exposed vs naïve), post-ASCT response (partial response vs ≥very good partial response [VGPR]), and cytogenetics on PFS. Results A number of relevant factors were different between age groups (median age in ≤60 group 53 years vs 66 years in 〉 60 group), including the HDT regimen received (MEL100 7% vs 10%; MEL140 3% vs 59%; MEL200 88% vs 31%). The rate of double transplantation was similar for the younger and older cohorts (55% vs 59%), likely due to the older patients receiving age-adjusted high-dose melphalan with a lower toxicity, allowing a similar rate of double transplantation as younger patients receiving MEL200. Among the 357 patients included in these analyses, median PFS from start of induction was 33.6 vs 27.8 months with bortezomib consolidation vs observation (log-rank p=0.0243). Median PFS for bortezomib vs observation was 33.6 vs 29.0 months (HR 0.86; p=0.3599) in the younger cohort and 33.4 vs 26.4 months (HR 0.60; p=0.0073) in the older cohort. PFS for older patients who received bortezomib consolidation was very similar to PFS in younger patients (p=0.861); survival curves were superimposable despite the older patients having received less intensive pretreatment. Univariate analysis demonstrated that treatment group (bortezomib vs observation) had an effect on PFS (HR 0.75; exploratory p-value 〈 0.05), as did age ( 〉 60 vs ≤60 years; HR 1.30), melphalan dose (200 vs 〈 200 mg/m2; HR 0.74), single vs tandem ASCT (HR 1.35), and cytogenetics (high-risk vs no change; HR 2.62). On bivariate analysis of treatment group plus other covariates, the PFS benefit of bortezomib consolidation vs observation remained consistent (HR 0.71-0.76) across analyses with other covariates. On multivariate Cox regression analysis (Table), bortezomib consolidation (HR 0.72), prior bortezomib during induction (HR 0.69), ≥VGPR post-ASCT (HR 0.76), high-risk cytogenetics (HR 2.58), and single vs tandem ASCT (HR 1.54) were independent prognostic factors for PFS. Conclusions For patients with NDMM, bortezomib consolidation post-ASCT appeared to equalize the outcome for older patients who had received less intensive pretreatment than younger patients prior to randomization. A consistent PFS benefit was demonstrated with bortezomib consolidation vs observation in the context of other prognostic factors. In a multivariate analysis, the use of tandem transplantation retained independent prognostic relevance, whereas MEL200 as first HDT did not. Table. Table. Disclosures Straka: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel/Accommodation/Expenses, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel/Accommodation/Expenses; Chugai: Research Funding. Knop:Takeda: Consultancy. Vogel:Janssen-Cilag GmbH: Employment. Kropff:Celgene: Consultancy, Other: Travel/Accommodation/Expenses, Speakers Bureau; Janssen: Consultancy, Other: Travel/Accommodation/Expenses, Speakers Bureau; Onyx: Consultancy, Speakers Bureau. Metzner:Amgen: Consultancy; Sanofi: Consultancy; Celgene: Other: Travel/Accommodation/Expenses; Takeda: Other: Travel/Accommodation/Expenses. Langer:Celgene: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Novartis: Consultancy. Sayer:Riemser Pharma: Consultancy. Bassermann:Celgene: Other: Travel/Accommodation/Expenses. Gramatzki:Janssen: Other: Travel/Accommodation/Expenses, Research Funding. Rösler:Janssen: Consultancy, Other: Travel/Accommodation/Expenses. Engelhardt:MSD: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel/Accommodation/Expenses , Research Funding. Fischer:Novartis: Consultancy, Honoraria. Einsele:Celgene: Consultancy, Honoraria, Other: Travel/Accommodation/Expenses , Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: Travel/Accommodation/Expenses , Research Funding, Speakers Bureau; Novartis: Consultancy, Other: Travel/Accommodation/Expenses , Speakers Bureau; Amgen: Consultancy, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.516.516

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 7522-7523

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-168874

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7