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In: Leukemia & Lymphoma, Informa UK Limited, Vol. 58, No. 1 ( 2017-01-02), p. 138-144

Type of Medium: Online Resource

ISSN: 1042-8194 , 1029-2403

URL: Article

DOI: 10.1080/10428194.2016.1189547

Language: English

Publisher: Informa UK Limited

Publication Date: 2017

detail.hit.zdb_id: 2030637-4

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2110-2110

Abstract: Introduction : a formal comparison between Lenalidomide-Dexamethasone (Rd) and Lenalidomide-Prednisone plus Melphalan (MPR) or Cyclophosphamide (CPR) has not been performed yet. We compared Rd vs. MPR vs. CPR in newly diagnosed multiple myeloma (NDMM) patients ≥65 years old in a multicenter phase III trial. Per protocol, upfront dose reductions of Dexamethasone, Melphalan and Cyclophosphamide were performed, according to patients age ( ≤75 years vs. 〉 75 years). The primary endpoint was progression-free survival (PFS). Methods : 662 patients with NDMM were randomized to receive nine 28-day cycles of Rd (n=222), MPR (n=218) or CPR (n=222). Rd: lenalidomide 25 mg/day for 21 days; dexamethasone 40 mg on days 1,8,15,22 in patients 65-75 years old and 20 mg in those 〉 75 years; MPR: lenalidomide 10 mg/day for 21 days; melphalan orally 0.18 mg/Kg for 4 days in patients 65-75 years old and 0.13 mg/Kg in patients 〉 75 years; prednisone 1.5 mg/Kg for 4 days; CPR: lenalidomide 25 mg/day for 21 days; cyclophosphamide orally 50 mg/day for 21 days in patients 65-75 years old and 50 mg every other day in patients 〉 75 years; prednisone 25 mg every other day. After induction, patients were randomized to receive maintenance with lenalidomide alone (R) or with prednisone (RP). Results : Patients characteristics were well balanced. Eighty-three (37%) patients in the Rd, 86 (39%) in the MPR and 80 (36%) in the CPR groups were older than 75 years. In intention to treat analysis, after a median follow-up of 31 months, no difference in PFS and overall survival (OS) was observed. Median PFS was 23 months in Rd, 27 months in MPR and 23 months in CPR (Rd vs MPR p=0.216; Rd vs CPR p=0.872; MPR vs CPR p=0.148). Median OS was not reached and was 73% in Rd, 67% in MPR and 72% in CPR at 3 years (Rd vs MPR p=0.663; Rd vs CPR p=0.754; MPR vs CPR p=0.448). A subgroup analysis, according to age was performed. No difference in response rate was observed. In patients ≤75 years, median PFS was 23 in Rd, 30 in MPR and 23 months in CPR (Rd vs MPR, p 〈 0.04; Rd vs CPR p=0.897; MPR vs CPR, p 〈 0.05). Median OS was not reached and was 75% in Rd, 76% in MPR, 77% in CPR at 3 years (Rd vs MPR p=0.251; Rd vs CPR p=0.280; MPR vs CPR p=0.975). In patients 〉 75 years, no PFS difference was noticed: median PFS was 22 in Rd, 18 in MPR, 21 months in CPR (Rd vs MPR p=0.572; Rd vs CPR p=0.699; MPR vs CPR p=0.914). An OS advantage was reported with Rd: median OS was not reached in Rd patients, and was 37 and 43 months in the MPR and CPR groups, respectively (Rd vs MPR p=0.04; Rd vs CPR p=0.430; MPR vs CPR p=0.323). The rate of at least one hematologic grade 3-4 adverse event was 29% in Rd, 66% in MPR, 33% in CPR patients ≤ 75 years and 29% in Rd, 70% in MPR, 33% in CPR patients 〉 75 years (MPR vs Rd/CPR p 〈 0.0001). No difference was observed in extra-hematologic adverse events: 25% in Rd, 24% in MPR and 25% in CPR patients ≤75 years; 29% in Rd, 35% in MPR, 34% in CPR patients 〉 75 years. Conclusion : this trial compared for the first time Rd, MPR and CPR in elderly NDMM. In all patients, the addition of alkylating agent to Lenalidomide-steroid combination did not show any advantage on PFS and OS. In a subgroup analysis, safety and efficacy data suggest that triplet regimens may be indicated in patients ≤75 years, while a doublet regimens for those 〉 75 years. The MPR combination showed a PFS advantage in patients ≤75 years, with a higher incidence of hematologic toxicity and SPM. In patients 〉 75 years an OS advantage was reported with Rd, mainly due to a higher efficacy of salvage treatments. Updated results will be presented at the meeting. Disclosures Off Label Use: Use of Lenalidomide as off label. Bringhen:Onyx: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria. Offidani:Mundipharma: Honoraria; Sanofi: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Patriarca:Merck Sharp & Dohme: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria. Hajek:Janssen: Honoraria; Celgene: Consultancy, Honoraria; Merck: Consultancy, Honoraria. Boccadoro:Onyx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen and Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Palumbo:Onyx Pharmaceuticals: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Genmab A/S: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Honoraria; Amgen: Consultancy, Honoraria; Array BioPharma: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.2110.2110

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 2077-2077

Abstract: The extensive use of new drugs in multiple myeloma (MM) allowed the achievement of unprecedented levels of cytoreduction and major advantages in survival rates, though almost all patients still relapse after a successful treatment. PCR-based minimal residual disease (MRD) studies are powerful prognostic tools, able to indentify patients at high risk of relapse. Thus, there is a growing interest in MRD to modulate therapy also in MM, as already happens in other lymphoid neoplasms. However available reports have a too short follow-up to be conclusive. In particular some points need to be addressed: 1) which is the long-term outcome of patients achieving molecular remission (MR) in the absence of further treatment? 2) What is the prognostic impact of MR loss? 3) How long is the window between MR loss and clinical relapse? These issues have been addressed based on the mature results of the GIMEMA VEL-03-096 trial [EudraCT Number 2004-000531-28], which currently has a median follow-up (mFU) of 93 months. Patients and methods Inclusion criteria and treatment schedule have been already reported [Ladetto et al., J Clin Oncol 2010]. MRD was assessed on bone marrow at diagnosis, study entry, after two VTD courses, at the end of treatment and then every six months up to clinical relapse. Patients underwent MRD detection using both qualitative nested PCR and Real Time Quantitative (RQ)-PCR, employing immunoglobulin heavy chain-derived patient specific primers, as described [Voena et al., Leukemia 1997; Ladetto et al., Biol Bone Marrow Transpl 2000; van der Velden et al., Leukemia 2007] . MR was defined as negative MRD results by nested-PCR or less than 1EE-04 by RQ-PCR. Loss of MR was defined as an increase of MRD levels of at least one log in consecutive samples at whenever timepoint. For survival analysis duration of response (DOR), progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) rates were used, as detailed in IMWG criteria [Rajkumar et al., Blood 2011]. Results Thirty-nine patients were enrolled. So far 27 serological progressions, 22 clinical relapses needing salvage treatment and 12 deaths (two non-MM-related) were observed. Median PFS was 60 months, median TNT 67 months and OS at mFU was 64%. 270 of the planned samples for MRD monitoring (86%) were actually received by the centralized lab. Currently, 26 MR and 11 MR losses have been registered. The achievement of MR was strongly associated with a better outcome, in terms of median DOR (62 vs 9 months, p 〈 0.001), PFS (67 vs 22 months, p 〈 0.001), TNT (108 vs 30 months, p 〈 0.001) and resulted significant for OS, too (72% vs 48% at mFU, p=0.04, Figure 1A-B). Moreover, patients with ongoing MR, MR loss or not achieving MR at all showed increasing risk of relapse, respectively (DOR not reached vs 38 vs 9 months, PFS 92 vs 63 vs 22 months, TNT not reached vs 72 vs 30 months, each p 〈 0.001, Figure 2). Interestingly, the time lag between MR loss and clinical relapse for patients achieving and then loosing MR was comparable to that between end of consolidation and clinical relapse for patients never obtaining MR (TNT 19 vs 11 months p=0.34). Finally, analyzing the relationship between MR achievement, MR loss and need for a salvage treatment, of the 26 patients who obtained MR only 11 (42%) received a retreatment at a median time of 42 months (range: 22-87 months). Of these 11 clinical relapses, 7 were anticipated by a molecular relapse (64%), occurring at a median time of 9 months (range: 2-39 months). The 4 relapses not anticipated by MR loss occurred in cases with inadequate follow-up sampling or at least two years after the end of the planned molecular follow-up. Conclusions Besides confirming the strong prognostic value of PCR-based MRD monitoring in MM, our long-term results indicate the following: 1) the 42 months TNT of patients achieving MR underlines the excellent disease control of MM patients once obtained MR; 2) the occurrence of MR loss heralds relapse, with a TNT from MR loss comparable to TNT of patients not achieving MR; 3) there is a 9 months lag between MR loss and need for salvage treatment. These observations will have increasing relevance considering that ongoing methodological developments will allow effective MRD monitoring in the vast majority of MM patients. Disclosures: Off Label Use: Bortezomib and thalidomide as post-transplant consolidation during first-line treatment of multiple myeloma. Ladetto:Celgene: Research Funding, Speakers Bureau; Jannsen Cilag: Research Funding, Speakers Bureau; Mundipharma: Research Funding, Speakers Bureau; Roche: Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau. Cavallo:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Jannsen Cilag: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Caravita:Celgene: Honoraria, Research Funding; Jannsen Cilag: Honoraria. Guglielmelli:Celgene: Research Funding. Boccadoro:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Jannsen Cilag: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Palumbo:Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Amgen: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.2077.2077

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

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. 9688-9690

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-157914

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. 114, No. 22 ( 2009-11-20), p. 3419-3419

Abstract: Abstract 3419 Poster Board III-307 Background Bortezomib induction before autologous stem cell transplantation (ASCT) has shown its efficacy in newly diagnosed multiple myeloma (MM) patients, both in association with dexamethasone alone (Harousseau JL, et al. Blood 110, 2007, abstr 450) and in combination with doxorubicin and dexamethasone (Popat R, et al. Br J Haematol 141:512-516, 2008). Lenalidomide, a less toxic and more potent thalidomide-derivative, lacks the neurotoxic effects of the parent drug and represents an optimal agent to include in maintenance regimens. Aims These observations provided the rationale for investigating a sequential approach including bortezomib as induction and lenalidomide as consolidation-maintenance in MM patients undergoing ASCT. Methods A hundred and two newly diagnosed patients aged 65–75 years were enrolled in 17 Italian centers. Induction (PAD) included four 21-day cycles of bortezomib (1.3 mg/m2 days 1,4,8,11), pegylated-liposomal-doxorubicin (30 mg/m2 day 4), and dexamethasone (40 mg/day: cycle 1, days 1–4, 8–11, 15–18; cycles 2–4, days 1–4). Autologous transplantation was tandem melphalan 100 mg/m2 (MEL100) followed by stem-cell support. After ASCT, patients received consolidation with four 28-day cycles of lenalidomide (25 mg/day days 1–21 every 28 days) plus prednisone (50 mg every other day) (LP), followed by maintenance (L) with lenalidomide alone (10 mg/day days 1–21 every 28 days) until relapse. Primary endpoints were safety (incidence of grade 3–4 adverse events [AEs]) and efficacy (response rate). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Time-to-event estimates analysis was performed using the Kaplan-Meier method. Results Very good partial response (VGPR) or better was 58% after PAD induction and increased to 82% after MEL100 and to 86% during LP-L. Complete response (CR) rate was 13% after PAD induction, increased to 38% after MEL100 and to 66% during LP-L. After a median follow-up of 2 years, the 2-year PFS was 69%, the 2-year time-to-progression was 75% and the 2-year OS was 86%. During PAD induction, main grade 3–4 AEs were thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%), and pneumonia (10%); treatment-related mortality was 3%. During consolidation-maintenance grade 3–4 AEs included neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash (4%). Consolidation-maintenance treatment was well tolerated: only 4% of patients required Granulocyte-colony stimulating factor support and no patient required platelet transfusion; dermatological toxicity was easily manageable with dose-reduction and supportive therapy; no treatment-related deaths were reported. Updated results will be presented at the meeting. Conclusion This is the first phase II study in newly diagnosed MM patients to date, where a sequential approach including bortezomib as induction, and lenalidomide as post ASCT consolidation-maintenance was explored. Treatment was correlated with an increase in response rate and in the depth of response (CR rate) and was generally well tolerated. These data suggest that this is a safe and effective regimen for newly diagnosed MM patients. Randomized trials are needed to confirm these results. Disclosures Patriarca: Celgene: Honoraria; Janssen Cilag: Honoraria. Bringhen:Celgene: Honoraria; Janssen Cilag: Honoraria. Boccadoro:Janssen Cilag : Consultant, advisory committee, Research Funding; Celgene: Consultant, advisory committee, Research Funding; Pharmion: Consultant, advisory committee, Research Funding. Palumbo:Celgene: Honoraria; Janssen Cilag: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.3419.3419

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4380-4380

Abstract: The role of ASCT in AML appears to be appropriate in patients with favorable cytogenetic features whereas allogeneic SCT is appropriate in those with high-risk cytogenetic features. Gemtuzumab ozogamicin (GO), a monoclonal antibody conjugated to the calicheamicin, targets the CD33+ cell surface marker that is expressed on cells in the majority of AML patients. Clinical trials currently underway are investigating the role of GO in consolidation therapy. We hypothesized that GO could have beneficial effects as maintenance therapy after hematopoietic SCT in high-risk patients. Here we report data on 4 AML patients in CR who received 4 doses of GO as maintenance therapy following ASCT. Our approach differs from previous reports in the literature in that, instead of using GO to induce a first remission or re-induce a second remission after relapse, we administered GO to patients while they remained in remission, two months after undergoing ASCT. Patient #1 was a 64 year-old male with 88% CD33 expression at diagnosis. This patient had previously undergone an ASCT using a conditioning regimen of Bu+Cy. He was in second CR following an induction regimen of 2 cycles of fludarabine + cytarabine + idarubicin. Patient #2 was female, aged 67 years and had 90% CD33 expression at diagnosis. She was in first CR following an induction regimen of 2 cycles of etoposide + cytarabine + idarubicin. Patient #3 was a 69-year old male with 95% CD33 expression at diagnosis. He was in first CR following an induction regimen of 2 cycles of fludarabine + cytarabine. Patient #4 was a 59 year-old male with 93% CD33 expression. He was in first CR after a second line treatment with mitoxantrone, cytarabine and etoposide. Histocompatible donors were not available for any of the patients. Three months after attaining CR, all 4 patients received a myeloablative conditioning regimen with B(A)VC, Bu+Cy, Bu+Cy and TBI+Melphalan, respectively, and underwent ASCT. Two months after the ASCT procedure, patients initiated treatment with GO: GO was administered alone for 4 doses with 28 days between doses (two patients received 6 mg/mq for the two first doses and 3 mg/mq for the two last doses; two patients received 3 mg/mq for four doses). All four patients remain alive and in CR at +17, +13, +11and + 5 months. Overall survival at the time of reporting is +35, +15, +13 and +8 months in patients 1, 2, 3 and 4, respectively. There were no cases of grade 3 or 4 liver toxicity and bleeding was not observed in any of the patients. Thrombocytopenia (50,000–100,000 cells/μL) occurred in all four patients and neutropenia (500–1000 cells/μL) in two patients. In conclusion in our small series GO demonstrated good efficacy when administered in fractionated doses as maintenance therapy after ASCT in patients with CD33+ AML in first or second CR. GO showed an acceptable tolerability profile, with no severe hepatotoxicity and no bleeding. Thrombocytopenia occurred in all three patients and in all cases there was a rapid platelet recovery. A GO dose of 3 mg/m2 appeared to be better tolerated than the higher dose (6 mg/m2) and will be used in future studies. If confirmed in a study involving a larger number of patients, our results could support a new therapeutic role for GO, namely as a maintenance therapy for patients in CR following hematopoietic SCT.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V110.11.4380.4380

Language: English

Publisher: American Society of Hematology

Publication Date: 2007

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 539-539

Abstract: Frail patients represent 30% of the myeloma population, and are more susceptible to adverse events (AEs) with subsequent treatment discontinuations that significantly affect efficacy and dose-intensity. This community-based, phase II, multicenter trial aims to assess the efficacy and safety of 3 reduced-dose intensity subcutaneous (sc) bortezomib-based treatments in newly diagnosed elderly multiple (MM) patients. Methods Patients with symptomatic, measurable MM, older than 75 years were enrolled. No exclusion criteria were planned in the protocol, to avoid patient selection bias. Patients with abnormal cardiac, pulmonary, renal or hepatic function were included. Treatment consisted of nine 28-day cycles with sc bortezomib 1.3 mg/m2 days 1, 8, 15, 22 plus oral prednisone 50 mg every other day (VP) or VP plus oral cyclophosphamide 50 mg every other day (VCP) or oral melphalan 2 mg every other day (VMP) for 28 days, followed by maintenance with sc bortezomib every 2 weeks until progression. A geriatric assessment was performed, including the Charlson index for estimating comorbidities, the Activity of Daily Living (ADL) and the Instrumental Activity of Daily Living (IADL) questionnaires to assess self-care and independence status. Combining these factors with age, patients were classified as fit ( 〈 80 years, ADL= 6, IADL=8, Charlson score= 0), unfit (fit patients 〉 80 years or ADL=5, IADL=6-7, Charlson score=1), or frail (unfit patients 〉 80 years or ADL≤4, IADL ≤5 and Charlson score ≥2). Results A total of 152 patients were enrolled, including 51 patients in the VP, 51 in the VCP and 50 in the VMP group. Median age was 78 years and 30% of patients were older than 80 years. Overall, 53%, 47% and 32% of the patients had ISS stage III disease, 21%, 20% and 24% had an unfavourable FISH profile [at least one chromosomal abnormality: del17, or t(4;14), or t(14;16)], and 88%, 84% and 78% were defined as unfit/frail in the VP, VCP, and VMP groups, respectively. Patients received a median of 9 treatment cycles and 44% of patients started maintenance. All three induction regimens exhibited substantial activity, with an overall response rate (≥partial response) of 67% in the VP, 63% in the VCP, and 80% in the VMP group. After a median follow-up of 17 months, median progression-free survival (PFS) was 14, 16 and 16 months and 1-year overall survival (OS) estimates were 80%, 82% and 80% in the VP, VCP and VMP group, respectively. The incidence of Serious Adverse Events (SAEs) was 22%, 20% and 30% and the discontinuation rate due to AEs was 14%, 16% and 26% in the VP, VCP and VMP groups, respectively. The most common non hematologic grade ≥3 AEs were infections (12%), cardiovascular events (8%), and neurologic events (7%), including 5% of peripheral neuropathy. According to the geriatric classification, and specifically in the fit, unfit and frail patients, the overall response rate was 92%, 67% and 65%, the 1 year OS was 100%, 88% and 73%, rate of SAEs was 4%, 22%, 30% and discontinuation due to toxicity was 40%, 58% and 67%, respectively. Conclusions In this community-based population of elderly newly diagnosed MM patients low-dose intensity VP, VCP and VMP showed similar PFS and OS estimates, while SAEs and discontinuations were higher with VMP, suggesting that a melphalan-free regimen should be preferred in these patients. Geriatric assessment is mandatory, since both efficacy and toxicities are significantly different in fit, unfit and frail patients. Disclosures: Larocca: Janssen and Cilag: Honoraria. Cavallo:Janssen-Cilag: Honoraria. Caravita:Janssen-Cilag: Honoraria. Petrucci:Janssen-Cilag: Honoraria. Sonneveld:Janssen-Cilag: Honoraria; Celgene: Honoraria; Onyx: Honoraria; Janssen-Cilag: Research Funding; Millenium: Research Funding; Onyx: Research Funding; Celgene: Research Funding. Boccadoro:Janssen-Cilag: Membership on an entity’s Board of Directors or advisory committees; Janssen-Cilag: Research Funding; Janssen-Cilag: Consultancy. Palumbo:Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.539.539

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Hematological Oncology, Wiley, Vol. 40, No. 5 ( 2022-12), p. 1009-1019

Abstract: In combination with lenalidomide and dexamethasone (KRd), Carfilzomib has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) on ASPIRE trial. Efficacy and safety of the triplet are still the object of investigation by many groups to confirm ASPIRE results in the setting of RRMM treated in real‐life who don't meet trial restrictive inclusion criteria. Therefore, we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018. The median age was 64 years (range 33–85), and the median number of previous therapies was two (range 1–11). After a median of 11 KRd cycles, the overall response rate was 79.9%. The median progression‐free survival (PFS) was 22 months, and the 2‐year probability of PFS was 47.6%. Creatinine clearance 〈 30 ml/min, 〉 1 line of previous therapy, and high‐risk FISH were all associated with a poor prognosis in multivariate analysis. The median overall survival (OS) was 34.8 months; the 2‐year probability of OS was 63.5%. At multivariate analysis, creatinine clearance 〈 30 ml/min, 〉 1 line of previous therapy, and high‐risk FISH were significantly associated with poor prognosis. After a median follow‐up of 16 months (range 1–50), 259 withdrew from therapy. The main discontinuation reason was progressive disease (81.8%). Seventy‐four patients (12.3%) discontinued therapy for toxicity. The most frequent side effects were hematological (anemia 49.3%, neutropenia 42.7%, thrombocytopenia 42.5%) and cardiovascular (hypertension 14.5%, heart failure 2.5%, arrhythmias 3.6%). Our study confirms the safety and efficacy of KRd in the real‐life setting of RRMM patients and encourages its use in clinical practice.

Type of Medium: Online Resource

ISSN: 0278-0232 , 1099-1069

URL: Issue

URL: Article

DOI: 10.1002/hon.v40.5

DOI: 10.1002/hon.3035

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 2001443-0

In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 22 ( 2022-08), p. S116-S117

Type of Medium: Online Resource

ISSN: 2152-2650

URL: Article

DOI: 10.1016/S2152-2650(22)00479-7

Language: English

Publisher: Elsevier BV

Publication Date: 2022

detail.hit.zdb_id: 2540998-0

detail.hit.zdb_id: 2193618-3

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 763-763

Abstract: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). The introduction of novel agents challenged the role of ASCT at diagnosis. We conducted a multicenter 2X2 randomized trial comparing conventional chemotherapy plus lenalidomide with ASCT followed by maintenance with lenalidomide-prednisone (RP) or lenalidomide (R) alone in newly diagnosed young MM (NDMM) patients. Methods Eligible patients with NDMM ≤ 65 years were enrolled. All patients received Rd induction (four 28-day cycles of lenalidomide 25 mg day 1–21 and low-dose dexamethasone 40 mg day 1,8,15,22) followed by stem cell mobilization. Patients were randomized to receive consolidation with CRD [six 28-day cycles of cyclophosphamide (300 mg/m2 day 1,8,15), dexamethasone (40 mg days 1,8,15,22) and lenalidomide (25 mg days 1–21)] or MEL200-ASCT (melphalan 200 mg/m2 with stem-cell support). Patients were randomly assigned to receive subsequent maintenance with RP (28-day cycles of lenalidomide 25 mg days 1–21 plus prednisone 50 mg every other day) or R alone (28-day cycles of lenalidomide 25 mg days 1–21). Primary study endpoint was progression-free survival (PFS); secondary endpoints included safety, responses and overall survival (OS). Data cut off was May 30th, 2013. Results Three-hundred and eighty-nine patients were enrolled in the trial. Patient characteristics were well balanced between CRD (n=194) and MEL200-ASCT (n=195), and between R (n=195) and RP (n=194) arms. Median follow-up was 31 months. In the intent to treat (ITT) analysis, the median PFS was not reached with MEL200-ASCT and 28 months with CRD (the respective 3-year PFS was 60% vs. 38%, HR=0.62, 95%CI: 0.49-0.85, P=0.003). Median time from enrolment to maintenance was 14 months. In the population of patients eligible for maintenance, 2-year PFS from the start of maintenance was 73% for RP and 56% for R patients (HR= 0.57, 95%CI: 0.34-0.93; P=0.03). In the subgroup of patients who received MEL200-ASCT, 2-year PFS from the start of maintenance was 83% for patients who received RP and 64% for those who received R alone (HR=0.36 95%CI: 0.15-0.87, P=0.02). In the subgroup of patients who received CRD, 2-year PFS from the start of maintenance was 64% for patients who received RP and 47% for those who received R alone (HR=0.75, 95%CI: 0.40-1.39, P=0.36). At present, no differences in OS were noticed between patients randomised to received CRD or MEL200-ASCT, and between patients who received RP or R maintenance. As expected, the rates of grade 3-4 hematologic (85% vs. 26%, P 〈 0.001) and non-hematologic (35% vs. 19%, P=0.003) adverse events (AEs) were higher in the MEL200-ASCT arm compared with the CRD arm. The main non-hematologic AEs were infections (18% vs. 5%, P=0.001) and gastrointestinal AEs (18% vs. 3%, P 〈 0.001). Rates of grade 3-4 hematologic (8% vs. 7%, P=0.85) and non-hematologic (12% vs. 13%, P=0.88). AEs were similar in the RP and R arms. The main non-hematologic AEs in both RP and R groups were infections (3% vs. 3%). At present, 6 second primary malignancies and 3 cases of cutaneous basalioma have been reported. Conclusions MEL200-ASCT significantly prolonged PFS in comparison with CRD. At present no difference in OS was reported, this may be due to the low number of events and to the length of follow-up. The increase in toxicity with MEL200-ASCT did not adversely impact on efficacy. The addition of prednisone to lenalidomide maintenance significantly reduced the risk of progression in comparison with lenalidomide alone, without increasing the toxicity. Updated data with longer follow-up will be presented at the meeting. Disclosures: Palumbo: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria. Gay:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Spencer:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Larocca:Celgene: Honoraria. Caravita:Celgene: Honoraria, Research Funding. Petrucci:Celgene: Honoraria. Hajek:Celgene: Honoraria; Celgene: Consultancy. Boccadoro:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.763.763

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7