Kooperativer Bibliotheksverbund

In: SSRN Electronic Journal, Elsevier BV

Type of Medium: Online Resource

ISSN: 1556-5068

URL: Article

DOI: 10.2139/ssrn.3516132

Language: English

Publisher: Elsevier BV

Publication Date: 2020

In: The Lancet Haematology, Elsevier BV, Vol. 7, No. 6 ( 2020-06), p. e456-e468

Type of Medium: Online Resource

ISSN: 2352-3026

URL: Article

DOI: 10.1016/S2352-3026(20)30099-5

Language: English

Publisher: Elsevier BV

Publication Date: 2020

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 991-991

Abstract: Background The role of single vs double autologous stem cell transplantation (ASCT) in patients with newly diagnosed (ND) multiple myeloma (MM) needs to be prospectively investigated in the novel agent era. Methods The phase III EMN02/HO95 study was designed to compare (first randomization, R1) (stratification according to ISS stage) standard-dose intensification therapy with bortezomib-melphalan-prednisone (VMP) vs high-dose intensification therapy with melphalan at 200 mg/m2 (HDM) followed by ASCT after 3-4 cycles of bortezomib-cyclophosphamide-dexamethasone as induction therapy. A second randomization to consolidation therapy vs no consolidation was performed after intensification therapy, to be followed by lenalidomide maintenance until progression or toxicity in both arms. A primary study endpoint was progression-free survival (PFS) from R1. In centers with a policy of double ASCT, patients were randomized in a 1:1:1 ratio to either VMP or single ASCT (ASCT-1) or two sequential courses (administered 2 to 3 months apart) of HDM and double ASCT (ASCT-2) in order to prospectively compare ASCT-1 with ASCT-2, which was an additional study objective. Results From February 2011 to April 2014, 1510 pts aged ≤65 years with symptomatic NDMM were registered and 1192 of these were eligible for R1. According to the design of the study, 614 eligible patients who received the diagnosis of MM in centers with a double intensification policy were randomly assigned to either VMP (n=199) or ASCT-1 (n=208) or ASCT-2 (n=207). Patients randomized to ASCT-1 or ASCT-2 were included in the current pre-specified analysis. Median age was 59 years for patients in the ASCT-1 group and 57 years for those in the ASCT-2 group. The frequency of ISS stage III was 18% and 19%, while revised ISS stage III was 9% and 11%, respectively. Cytogenetic abnormalities were detected by FISH analysis of CD138+ plasma cells. A high-risk (HR) cytogenetic profile, defined by t(4;14) and/or del(17p) and/or t(14;16) (HR cyto-3), was observed in 26% of evaluable patients who were randomized to ASCT-1 and in 21% of those randomly assigned to ASCT-2. If amp(1q) and/or del(1p) were added for the definition of high-risk disease, a HR cytogenetic profile that included at least 1 of the 5 above mentioned chromosomal abnormalities (HR cyto-5) was reported in 55% of evaluable patients in the ASCT-1 group and in 54% of those in the ASCT-2 group. Median follow-up from R1 was 27 (IQR: 20-35) months. On an intention-to-treat basis, the median PFS was 45 months in the ASCT-1 arm and was not yet reached for patients in the ASCT-2 arm; 3-year estimates of PFS were 60% and 73%, respectively (HR=0.66; 95% CI=0.45-0.96; P=0.030). PFS benefit with ASCT-2 was retained across predefined subgroups, including patients with β2-microglobulin 〉 3.5 mg/L (HR=0.59; CI=0.34-0.99; P=0.005), bone marrow plasma cells 〉 60% (HR=0.41; CI=0.22-0.77; P=0.006), LDH values above the upper limits (HR=0.52; CI=0.28-095; P=0.034), revised ISS stage II (HR=0.50; CI=0.31-0.80; p=0.004), HR cyto-3 (HR=0.49; CI=0.24-1.02; P=0.057) and HR cyto-5 (HR=0.57; CI=0.35-0.93; P=0.024). In a multivariate Cox regression analysis stratified by ISS stage, randomization to ASCT-2 (HR=0.62; CI=0.40-0.95; P=0.027) and HR cyto-5 (HR=2.63; CI=1.63-4.16; P 〈 0.001) were the leading independent predictors of PFS. Overall survival was not yet mature and no difference between the two treatment groups was evident. Conclusions Upfront double ASCT after bortezomib-based induction therapy for newly diagnosed MM was superior over a single ASCT in terms of prolonged PFS. Clinical benefits of double ASCT were mostly seen in patients with disease-related factors predicting for poor prognosis. Disclosures Cavo: Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria. Offidani:Janssen: Honoraria; Celgene: Honoraria, Research Funding. Boccadoro:Janssen: Honoraria, Research Funding; CELGENE: Honoraria, Research Funding; Mundipharma: Research Funding; Amgen: Honoraria, Research Funding; SANOFI: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Abbivie: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.991.991

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 19, No. 10 ( 2019-10), p. e271-

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/j.clml.2019.09.447

Language: English

Publisher: Elsevier BV

Publication Date: 2019

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: Blood Cancer Journal, Springer Science and Business Media LLC, Vol. 10, No. 5 ( 2020-05-18)

Type of Medium: Online Resource

ISSN: 2044-5385

URL: Article

DOI: 10.1038/s41408-020-0326-1

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2020

detail.hit.zdb_id: 2600560-8

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3336-3336

Abstract: Cardio-vascular (CV) events are common in patients (pts) with myeloma (MM) and may occur as a result of age-related comorbidities, the disease itself or as a complication of anti-MM treatment, including proteasome inhibitors.Carfilzomib is a novel second generation proteasome inhibitorapproved as a single agent and in combination with lenalidomide and dexamethasone for the treatment of relapsed MM. Here, we present the results of an integrated CV safety analysis of 148 newly diagnosed, elderly or transplant-ineligible pts enrolled in 3 phase I/II studies with the combination of Carfilzomib, cyclophosphamide and dexamethasone(IST-CAR-506, IST-CAR-561, IST-CAR-601).In all trials cyclophosphamide 300 mg/m2 was administered orally on days 1, 8, 15 and dexamethasone 40 mg was administered orally once weekly. Carfilzomib was administered intravenously at the dose of 36 mg/m2 on days 1, 2, 8, 9, 15, 16 in the IST-CAR-506 trial; at 3 dose levels escalated from 45 to 70 mg/m2 on days 1, 8, 15 in the IST-CAR-561 trial and on days 1, 2, 8, 9, 15, 16 in the IST-CAR-601 trial. In all studies, after completing 9 28-day cycles, pts received 28-day maintenance cycles with Carfilzomib until disease progression or intolerance. Adverse events (AEs) were graded based on NCI-CTCAE v4. Median age was 72 years (range 55-85), 38 pts (26%) were older than 75 years. The median follow-up was 21 months. Overall, any grade CV AEs were reported in 62 pts (42%): 40/110 pts (36%) younger than 75 years and 22/38 (58%) older than 75 years (p=0.02). The more frequent events were hypertension, aggregated cardiac failure events, thromboembolic events and arrhythmia (Table 1). Grade ≥ 3 events occurred in 29 pts (30%): 17/110 pts (15%) younger than 75 years and 13/38 (34%) older than that (p=0.01). Aggregated cardiac failure events of any grade were reported in 10 pts (7%), thromboembolic events in 5 pts (3%), hypertension in 4 pts (3%) and arrhythmia 2 pts (1%). In pts younger than 75 years, the most frequent grade ≥ 3 AEs were hypertension (10 patients, 9%) and dyspnea (11 patients, 10%). In pts older than 75 years, the most frequent grade ≥ 3 AEs were hypertension and pulmonary edema (5 pts each, 13%). Importantly, 34% of pts who experienced CV AEs had hypertension at baseline or developed it during treatment compared to 14% of pts who did not experience CV AEs. Diabetes was more frequent (33%) in pts older than 75 years who developed CV AEs compared to 10% of pts older than 75 years who did not report any CV AEs or those younger than 75 years. No difference was observed among different doses or different schedules of Carfilzomib. Among pts who developed a CV AE, one third had a Carfilzomib dose reduction or discontinuation (Table 1) compared to 12-18% of pts who did not experience CV toxicity (p 〈 0.0001). Overall, the risk of CV toxicity was lower during maintenance: 21 pts of 97 who started maintenance (22%) developed any grade CV events. This improvement was evident only in pts younger than 75 years: 11/75 patients younger than 75 years (15%) had CV events compared to 10/22 (45%) older than 75 years (Figure 1). The most frequent CV AE during maintenance was hypertension (12%), regardless of age. Only 5 pts (5%) reduced Carfilzomib dose during maintenance. Five (3%) CV-related deaths were documented: 4 during induction and 1 during maintenance. All of them were possibly related to Carfilzomib (atrial fibrillation, heart failure, cardiac arrest, sudden death, pulmonary embolism). The occurrence of any CV AE during induction increased the mortality for any cause by twofold, regardless of age: the 2-year overall survival was 70% in patients who experienced CV AE and 82% in those who did not (HR 2.01, 95% CI 0.99-4.07, p=0.04). The risk of CV AEs during treatment with Carfilzomib is significantly higher in pts older than 75 years and the most important risk factor, regardless of age, is hypertension. Developing CV toxicity increases the need for dose reduction or drug discontinuation with a negative impact on overall survival. Elderly pts should be carefully assessed before starting treatment with 24 hour blood pressure monitoring. During treatment, baseline vital signs should be recorded and medications of blood pressure should be targeted promptly to keep blood pressure below 140/80 mmHg. With these simple actions, these AEs may be prevented or managed proactively and pts can derive maximum benefit from their treatment with Carfilzomib. Disclosures Bringhen: Mundipharma: Other: ADVISORY BOARD; Amgen: Other: ADVISORY BOARD; Janssen-Cilag: Honoraria; Celgene: Honoraria; BMS: Honoraria; Karyopharm: Other: ADVISORY BOARD. Petrucci:Janssen-Cilag: Honoraria; Celgene: Honoraria; Sanofi: Honoraria; Bristol-Myers Squibb: Honoraria. Caravita di Toritto:Janssen-Cilag: Honoraria. Ria:BMS: Speakers Bureau; BMS: Speakers Bureau; Italfarmaco: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Research Funding, Speakers Bureau; Janssen-Cilag: Other: Advisory Board, Speakers Bureau; Binding Site: Speakers Bureau. Cavo:Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Foà:Janssen-Cilag: Consultancy, Speakers Bureau; Genetech: Consultancy; Roche: Consultancy, Speakers Bureau; Ariad: Speakers Bureau; Pfizer: Speakers Bureau; BMS: Consultancy; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau. Corradini:Celgene: Honoraria, Speakers Bureau; Janssen-Cilag: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Sanofi Aventis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Gentium: Honoraria, Speakers Bureau. Gaidano:Roche: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Morphosys: Consultancy, Honoraria. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Sonneveld:Celgene: Other: Advisory board, Research Funding; Millennium: Other: Advisory board, Research Funding; Onyx: Other: Advisory board, Research Funding; Janssen-Cilag: Other: Advisory board, Research Funding. Boccadoro:Novartis: Honoraria, Research Funding; SANOFI: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Abbivie: Honoraria; Amgen: Honoraria, Research Funding; Mundipharma: Research Funding; CELGENE: Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.3336.3336

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. 136, No. Supplement 1 ( 2020-11-5), p. 11-12

Abstract: Background. Infections represent a major cause of toxicity in newly diagnosed multiple myeloma (NDMM) patients, and their incidence is higher during the first 4 months of therapy (Dumontet, Leukemia 2018). The use of prophylactic levofloxacin for the first 3 months of therapy demonstrated to reduce rates of infections (Dryson, Lancet Hematol 2019). However, factors predicting the risk of infections in patients treated with novel agents and the need for antimicrobial prophylaxis for all vs selected patients remain under debate. We investigated the incidence of severe infections and associated baseline risk-factors in NDMM patients. Methods. Data from Italian patients enrolled in clinical trials and receiving carfilzomib-based (IST-CAR-506, IST-CAR-561), bortezomib-based (EMN02) and lenalidomide-based (EMN01, RV-MM-PI-0752, RV-MM-EMN-441) treatment were pooled together and analyzed. The primary aim of the analysis was to evaluate the incidence of severe infections, defined as any grade (G) 3-5 event or G2 if involving the lung/lower respiratory tract (CTCAE version 4.0). The rate of early severe infections (i.e. infections occurring during the first 4 months of treatment) was also analyzed. Secondary goals were to identify baseline factors associated with an increased risk of early severe infections and to evaluate the impact of early severe infections on treatment outcome. Results. A total of 1892 patients were included in the analysis. Median age was 65 years, 970 (51%) patients were transplant eligible (TE) and 922 (49%) transplant ineligible (NTE). Overall, 1059 (56%) patients received IMiD-based induction therapy and 833 (44%) a PI-based induction therapy. Median follow-up was 68 months. We recorded 898 infections of any grade, of which 436 (49%) were considered severe. Most frequent severe infections included lung/lower respiratory tract infection (50%), febrile neutropenia (23%) and sepsis/septic shock (10%). Overall, severe infections occurred when myeloma response to treatment was ≤PR in 62% of cases, VGPR in 29% and sCR/CR in 9%. 654 (35%) patients reported at least 1 infection of any grade and 377 (20%) patients at least one severe infection. Early infections (first 4 months) occurred in 243 patients (13%) and early severe infections in 129 patients (6.8%). Overall, 21 patients (1.1%) died due to infection, of whom 6 during the first 4 months. In a multivariate analysis (Table), main factors associated with increased risk of early severe infections were ISS stage 3 (OR 2.14, 95% CI 1.32-3.48), presence of del17p by FISH (OR 1.80, 95% CI 1.1-2.96), intermediate fit status (OR 1.88 95% CI 1.1-3.21) and frail status (OR 2.12, 95% CI 1.08-4.18) according to IMWG frailty score (Palumbo, Blood 2015). No difference in risk of early severe infections was observed according to induction treatment with PI vs IMiD (OR 1.10, 95%CI 0.68-1.78). In a time-dependent Cox regression analysis adjusted for potential confounders (age, RISS stage and performance status), the risk of disease progression/death was significantly higher in patients who had an early severe infection compared to patients without early severe infection (median PFS 21.3 months vs 31.3 months, HR 1.32, 95% CI 1.07-1.63, p & lt;0.01). A significant impact was observed also on survival (median OS 45.8 vs 95.8 months respectively, HR 1.72, 95% CI 1.34-2.21, p & lt;0.01). Conclusions. We found that 34% of patients experiencing severe infections had the event during the first 4 months of therapy. Patients with aggressive disease and elderly frail patients are at higher risk of early severe infections, hampering treatment adherence and efficacy, and eventually affecting PFS and OS. Identifying patients more susceptible to severe infections through easily available parameters could pave the way for the evaluation of risk-adapted antimicrobial prophylaxis in clinical trials. Table 1 Disclosures D'Agostino: GSK: Membership on an entity's Board of Directors or advisory committees. Offidani:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Petrucci:BMS: 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; GSK: 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; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Liberati:JANSSEN: Honoraria; AMGEN: Honoraria; CELGENE: Honoraria; ROCHE: Honoraria, Research Funding; PFIZER: Honoraria, Research Funding; ONCOPEPTIDES AB: Honoraria, Research Funding; TAKEDA: Honoraria, Research Funding; MORPHOSYS: Honoraria, Research Funding; ONCONOVA: Honoraria, Research Funding; ABBVIE: Honoraria, Research Funding; NOVARTIS: Honoraria, Research Funding; KARYOPHARM: Honoraria, Research Funding; BMS: Honoraria; BEIGENE: Honoraria; ARCHIGEN: Honoraria; BIOPHARMA: Honoraria; FIBROGEN: Honoraria; INCYTE: Honoraria; VERASTEM: Honoraria, Research Funding. Benevolo:Amgen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Gaidano:Sunesys: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Galli:Takeda: Honoraria; Janssen: Honoraria; Celgene: Honoraria; BMS: Honoraria. Corradini:Janssen: Consultancy, Honoraria; Incyte: Consultancy; Gilead: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Amgen: Consultancy, Honoraria, Other: Travel and accommodations paid by for; Sanofi: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other; BMS: Other; KiowaKirin: Consultancy, Honoraria; Kite: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations paid by for; F. Hoffman-La Roche Ltd: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Travel and accommodations paid by for. Conticello:Amgen, Takeda, Janssen: Honoraria. Cavo:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau; Karyopharm: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel accomodations, Speakers Bureau. Sonneveld:Skyline Dx: Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Boccadoro:Mundipharma: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria. Bringhen:Bristol-Myers Squibb: Honoraria; Takeda: Consultancy; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, 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. OffLabel Disclosure: The presentation includes discussion of off-label use of a drug or drugs for the treatment of multiple myeloma (including carfilzomib, cyclophosphamide, dexamethasone, bortezomib, melphalan, prednisone and lenalidomide).

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136302

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 105, No. 1 ( 2020-01), p. 193-200

Type of Medium: Online Resource

ISSN: 0390-6078 , 1592-8721

URL: Article

DOI: 10.3324/haematol.2019.219139

Language: English

Publisher: Ferrata Storti Foundation (Haematologica)

Publication Date: 2020

detail.hit.zdb_id: 2186022-1

detail.hit.zdb_id: 2030158-3

detail.hit.zdb_id: 2805244-4

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 197-197

Abstract: Introduction Three-drug induction regimens including a first or second generation proteasome inhibitor are a current standard of care for autologous stem-cell transplantation (ASCT)-eligible, newly diagnosed, multiple myeloma (MM) patients (pts). In the absence of prospective randomized studies comparing different induction regimens, it is difficult to recommend one treatment over another, and the choice is ultimately based upon physician’s preference or single center’s policy. Bortezomib-thalidomide-dexamethasone (VTD) has been recently approved by EMA as induction for previously untreated, ASCT-eligible, MM pts. Bortezomib combined with cyclophosphamide and dexamethasone (VCD) is an attractive alternative to VTD, although efficacy results have not been backed by phase III studies. The present study aimed to evaluate the differences in response rates and toxicity between VTD and VCD induction regimens in preparation for subsequent ASCT. Methods Two hundred and thirty six pts who were randomized to the VTD arm of the GIMEMA-MMY-3006 study were compared with an equal number of pair mates who received induction therapy with VCD as part of the EMN02 trial designed to prospectively compare ASCT up front vs bortezomib-melphalan-prednisone followed by ASCT at the time of relapse or progression. Both groups of pts were treated in Italian centers participating in the two phase III studies. Case matching was performed with respect to the following pt characteristics at baseline: age (± 2 years), ISS stage (1 vs 2 vs 3), t(4;14) (detected by FISH in ≥ 10% vs 〈 10% CD138+ bone marrow plasma cells) and del(17p) (≥ 20% vs 〈 20% positivity). The two groups were also comparable with respect to Hb concentration, Plts and M protein isotype. Induction treatment consisted of three 21-day cycles of either VTD (bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11; thalidomide 100 mg daily for the first 14 days and 200 mg daily thereafter; dexamethasone 40 mg on days 1, 2, 4, 5, 8, 9, 11, and 12) or VCD (bortezomib and dexamethasone as in VTD; cyclophosphamide 500 mg/m2 on days 1 and 8). Evaluation of response and toxicity was performed after the third cycle of induction or the last cycle actually received for those pts who discontinued earlier. Results On an intention-to-treat basis, the overall rate of partial response (PR) or higher, as established according to the IMWG criteria, was 93% (95% CI: 89-96%) with VTD and 84% (CI: 79-89%) with VCD (χ2test p value=0.003). In particular, the complete response (CR) rate was approximately three fold higher for pts randomized to VTD (19%, CI: 14-24%) as compared to those in the VCD group (7%; CI: 4-10%) (p 〈 0.001), while the corresponding values for very good partial response (VGPR) were 43% (CI: 36-49%) vs 32% (CI: 26-38%), respectively (p 〈 0.001). Overall, VTD induction therapy yielded a significantly higher rate of ≥ VGPR (61%, CI: 55-68%) as compared to VCD (39%, CI: 32-45%) (p 〈 0.001), and a two fold lower probability to achieve less than PR (7%, CI: 4-11%) vs 16% (CI: 11-21%) (p=0.003). The superior rate of ≥ VGPR yielded by VTD over VCD was retained both in pts with ISS stage 2+3 (65%, CI: 57-73%) vs 37% (CI: 29-46%) (p 〈 0.001), and in those with t(4;14) and/or del(17p) [79% (CI: 68-90%) vs 44% (CI: 30-58%), p 〈 0.001]. Evaluation of toxicity induced by VTD and VCD induction therapy was focused on peripheral neuropathy (PN) (NCI CTCAE, version 3.0). Grade ≥ 2 PN was slightly higher for pts on VTD (13%, CI: 9-17%) as compared to those on VCD (9%, CI: 6-13%) (p=0.19). When the threshold of grade ≥ 3 PN was considered, the difference between the two groups significantly favoured pts treated with VCD [2% (CI: 0.1-3%) vs 7% (CI: 4-11%) (p=0.004) for pts on VTD] . However, it is worth noting that only a single pt on VCD and 2 pts on VTD discontinued treatment due to PN. Conclusions The triplet VTD induction therapy was associated with significantly higher CR and ≥ VGPR rates compared to VCD, confirming that VTD is one of the most active bortezomib-based induction regimens in preparation for ASCT. Grade ≥ 2 PN rate was similar between the two regimens, although VTD-induced grade ≥ 3 PN was higher with VTD. Data on the impact of VTD and VCD induction therapy on post-ASCT high-quality response rates and additional outcomes will be presented at the meeting. The superiority of VTD over VCD needs to be confirmed by prospective randomized studies, one of which is currently running in Europe. Disclosures Cavo: Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Millennium Pharm.: Consultancy, Honoraria; Bristol-Myers Squib: Consultancy, Honoraria; Onyx: Honoraria. Cavallo:Onyx: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Petrucci:Celgene, Janssen-Cilag, Sanofi, Bristol-Myers Squibb: Honoraria. Ballanti:Janssen: Honoraria. Palumbo:Sanofi Aventis: Honoraria; Onyx Pharmaceuticals: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Genmab A/S: Consultancy, Honoraria; Array BioPharma: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Sonneveld:Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Onyx: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.197.197

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 17, No. 1 ( 2017-02), p. e7-

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/j.clml.2017.03.012

Language: English

Publisher: Elsevier BV

Publication Date: 2017

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3