scholarly journals Double Immune Checkpoint Inhibitor Blockade with Nivolumab and Ipilimumab with or without Azacitidine in Patients with Myelodysplastic Syndrome (MDS)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1831-1831 ◽  
Author(s):  
Guillermo Garcia-Manero ◽  
Guillermo Montalban-Bravo ◽  
Koji Sasaki ◽  
Naval G. Daver ◽  
Elias J. Jabbour ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Immune Checkpoint Inhibitor ◽  
Overall Response Rate ◽  
Response Rate ◽  
Checkpoint Inhibitor ◽  
Median Number ◽  
Front Line ◽  
Genetics Research ◽  
Number Of Cycles

Abstract Introduction: Myeloid cells express PD1 and CTLA-4. Expression of these molecules is enhanced by azacitidine (AZA). Treatment of patients (pts) with nivolumab (Nivo) and anti-PD1 antibody or ipilimumab (Ipi) and anti-CTLA-4 antibody results in the upregulation of CTLA-4 in patients treated with Nivo and reversely of PD1 in patients treated with Ipi, potentially as a mechanism of evasion. In view of the activity of Nivo and Ipi in MDS (Garcia-Manero, ASH 2016), we hypothesized that dual combination of Nivo + Ipi with AZA could have significant activity in high risk MDS. Methods: To study this, we designed a basket exploratory phase 2 trial of ICPI in MDS. Patients with MDS age 18 or older with adequate renal and hepatic function without history of autoimmune disorders were eligible. Patients were divided into front-line and HMA-failure cohorts. Front-line patients were treated with AZA 75mg/m2 iv daily days 1-5 of a 28 day cycle with Nivo 3 mg/kg iv on days 6 and 20 + Ipi 3 mg/kg iv on day 6. Patients with HMA failure where treated with Nivo 3 mg/kg iv on days 1 and 15 + Ipi 3 mg/kg iv on day 1 of a 28 day cycle. The study design allowed for AZA add-back after 6 cycles of therapy if there was no response or progression. The maximum size per cohort was 20 pts. The primary endpoint was to determine the safety of Nivo or Ipi as single agents or in combination with AZA. Secondary objectives included overall response rate (ORR) and assessment of biological activity. Responses were evaluated following the revised 2006 IWG criteria. The study included stopping rules for response and toxicity. Results: The median follow up was 4.7 months [range 0-10 months]. From January 2017 to April 2018, 14 patients were treated, 6 pts on front-line cohort and 8 on HMA failure. The median age was 69 years [range 52-80]. A total of 4 (29%) pts had Int-1 risk, 6 (43%) had Int-2 and 4 (29%) had High risk by IPSS. Next generation sequencing on whole bone marrow extracted DNA was performed using a 28 gene panel in 5 pts and an 81-gene panel in 9 pts. Cytogenetic abnormalities and identified mutations are shown in Table 1. Median number of marrow blasts was 10 [range 1-16]. Median Hgb was 9.5g/dL [range 7.3-10.9 g/dL], median WBC was 1.5x109/L [range 0.9-4.7] and platelets was 29x109/L [range 8-117]. A total of 13 pts are evaluable for response at the time of analysis. A total of 3 (38%) pts in the HMA failure cohort received AZA after 6 cycles of therapy. The median number of cycles was 4 [range 1-10] with a median number of cycles to response of 3 [range 1-4]. The overall response rate was 50% (3/6) in the frontline cohort, all of them complete responses, and 29% (2/7) in the HMA failure cohort, including 1 complete response and 1 hematological improvement. Adverse events are shown in Table 2. Treatment with Ipi or NIvo had to be held due to rash in 2 pts, due to elevation of creatinine in 2 pts. Early mortality was observed in 1 patient and this was due to pneumonia complicated with respiratory failure and renal failure. The median overall survival is NR in the frontline cohort and is 8.4 months in the HMA failure cohort (Figure 1). Conclusion: Preliminary results suggest double immune checkpoint inhibitor blockade with Ipi and Nivo in combination with AZA in the frontline setting, or in pts with HMA failure is associated with a tolerable safety profile and clinical activity. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Daver:Incyte: Research Funding; Novartis: Consultancy; Alexion: Consultancy; ARIAD: Research Funding; Daiichi-Sankyo: Research Funding; Otsuka: Consultancy; Novartis: Research Funding; Pfizer: Research Funding; Sunesis: Research Funding; Karyopharm: Consultancy; BMS: Research Funding; Incyte: Consultancy; Pfizer: Consultancy; Sunesis: Consultancy; Karyopharm: Research Funding; Kiromic: Research Funding; ImmunoGen: Consultancy. DiNardo:Abbvie: Honoraria; Celgene: Honoraria; Agios: Consultancy; Karyopharm: Honoraria; Medimmune: Honoraria; Bayer: Honoraria. Ravandi:Xencor: Research Funding; Xencor: Research Funding; Astellas Pharmaceuticals: Consultancy, Honoraria; Jazz: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Sunesis: Honoraria; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Amgen: Honoraria, Research Funding, Speakers Bureau; Sunesis: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Abbvie: Research Funding; Orsenix: Honoraria; Jazz: Honoraria; Macrogenix: Honoraria, Research Funding; Orsenix: Honoraria; Abbvie: Research Funding; Bristol-Myers Squibb: Research Funding; Macrogenix: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding. Bose:Incyte Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; CTI BioPharma: Research Funding; Celgene Corporation: Honoraria, Research Funding; Constellation Pharmaceuticals: Research Funding; Pfizer, Inc.: Research Funding; Blueprint Medicines Corporation: Research Funding. Pemmaraju:plexxikon: Research Funding; daiichi sankyo: Research Funding; stemline: Consultancy, Honoraria, Research Funding; novartis: Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; cellectis: Research Funding; abbvie: Research Funding; SagerStrong Foundation: Research Funding; Affymetrix: Research Funding. Cortes:novartis: Research Funding. Kadia:Jazz: Consultancy, Research Funding; BMS: Research Funding; Abbvie: Consultancy; Novartis: Consultancy; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Consultancy; BMS: Research Funding; Celgene: Research Funding; Takeda: Consultancy; Celgene: Research Funding; Takeda: Consultancy; Abbvie: Consultancy; Jazz: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding. Konopleva:Stemline Therapeutics: Research Funding.

scholarly journals Final Report of a Phase II Study of Guadecitabine (SGI-110) in Patients (pts) with Previously Untreated Myelodysplastic Syndrome (MDS)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 232-232 ◽  
Author(s):  
Guillermo Garcia-Manero ◽  
Koji Sasaki ◽  
Guillermo Montalban-Bravo ◽  
Kristy R. Bodden ◽  
Prithviraj Bose ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Research Funding ◽  
Median Number ◽  
Response To Therapy ◽  
Stopping Rules ◽  
Final Report ◽  
Genetics Research ◽  
Number Of Cycles

Abstract Introduction: The hypomethylating agents (HMA) are the standard of care for a majority of patients with higher-risk MDS. SGI-110 is a second generation HMA that molecularly is a dinucleotide derivative of decitabine and therefore a more potent inhibitor of DNA methyltransferase activity. SGI-110 is currently being studied in front-line AML and second-line MDS multicenter studies. Here we present results of a single arm phase II trial of SGI-110 for patients with previously untreated MDS. Methods: Patients, age 18 or older, with adequate renal and hepatic functions, with int-2 or high risk MDS by IPSS or more than 10% blasts in bone marrow were eligible. One prior cycle of azacitidine or decitabine was allowed. No prior other therapies were allowed. SGI-110 was administered at a dose of 60 mg/m2 SC daily x 5 days every 4 weeks. The study was designed with stopping rules for response, toxicity, and mortality (first 3 months). A maximum of 100 patients could be treated. Results: From 11/14/2014 to 7/31/2018, 94 patients have been treated. Median age was 69 years (22.7-91.9), 72 patients (77%) had INT-2, 13 patients (14%) high risk. Median % of marrow blasts was 10 (range, 0-20). Median white blood cell count and platelet count were 2.5 (×106/L), and 52 (×106/L) respectively. Twenty two patients (23%) were diploid, 36 (38%) complex, and 33 (35%) others. Mutation distribution was as follows: TP53, 29 (31%); ASXL1, 26 (28%); TET2, 20 (21%); RUNX1, 19 (20%); RAS, 12 (13%); DNMT3A, 10 (11%); EZH2, 9 (10%); SRSF2, 6 (7%); PHF6, 4 (4%); BCOR, 3 (3%); CEBPA, 3 (3%); SF3B1, 3 (3%); IDH2, 3 (3%); BRAF, 2 (2%); CBL 2 (2%); MPL, 2 (2%); NPM1, 2 (2%); U2AF1, 2 (2%); WT1, 2 (2%); CREBBP, 1 (1%); ETV6, 1 (1%); FLT3-ITD, 1 (1%); GATA2, 1 (1%); IDH1, 1 (1%); SETBP1, 1 (1%); ZRSR2, 1 (1%). The median number of cycles received was 5 (range 1 - 32). Ninety four (100 %) patients are evaluable for toxicity. Early mortality was 0%. Common toxicities were fatigue (61%), infection (46%), nausea (27%), pain (19%), and constipation (16%), mucositis (16%), dyspnea (15%), local injection toxicity (15%), and diarrhea (12%). Eighty seven (93%) patients were evaluable for response. The median number of cycles to response was 3 (range 1 - 11). Overall response rate was 53 (61%); CR 19 (22%), CRp 3 (3%), HI 31 (36%), SD 5 (6%), NR 27 (31%), and died 2 (2%). With a median follow-up of 15 months, the median OS was 15 months and the median EFS was 14 months (Figure 1). By UVA, higher ACE-27 score showed tendency of lower rates of response (p=0.063; hazard ratio [HR], 1.383; 95% confidence interval [CI], 0.982-1946). However, MVA did not show any prognostic factors for response. By MVA characteristics associated with survival were: complex karyotype (p=0.036; HR, 2.345; 95% CI, 1.055-5.210), and response to therapy (p=0.003; HR, 0.272; 95% CI, 0.114-0.648). In conclusion: SGI-110 is well tolerated in previously untreated MDS. ORR appears to be better than expected compared to azacitidine or decitabine. Longer follow-up and randomized trials will be needed to understand effect on survival. Figure. Figure. Disclosures Sasaki: Otsuka Pharmaceutical: Honoraria. Bose:Incyte Corporation: Honoraria, Research Funding; CTI BioPharma: Research Funding; Celgene Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Constellation Pharmaceuticals: Research Funding; Blueprint Medicines Corporation: Research Funding; Pfizer, Inc.: Research Funding. Daver:Pfizer: Consultancy; Karyopharm: Research Funding; Novartis: Consultancy; Daiichi-Sankyo: Research Funding; Karyopharm: Consultancy; ARIAD: Research Funding; Novartis: Research Funding; Incyte: Research Funding; Incyte: Consultancy; BMS: Research Funding; Otsuka: Consultancy; Alexion: Consultancy; Sunesis: Consultancy; Pfizer: Research Funding; Sunesis: Research Funding; ImmunoGen: Consultancy; Kiromic: Research Funding. Ravandi:Bristol-Myers Squibb: Research Funding; Sunesis: Honoraria; Orsenix: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Astellas Pharmaceuticals: Consultancy, Honoraria; Xencor: Research Funding; Seattle Genetics: Research Funding; Abbvie: Research Funding; Orsenix: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Bristol-Myers Squibb: Research Funding; Jazz: Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Jazz: Honoraria; Sunesis: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Macrogenix: Honoraria, Research Funding; Macrogenix: Honoraria, Research Funding; Xencor: Research Funding. Cortes:Pfizer: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Arog: Research Funding. DiNardo:Celgene: Honoraria; Agios: Consultancy; Karyopharm: Honoraria; Abbvie: Honoraria; Bayer: Honoraria; Medimmune: Honoraria. Pemmaraju:SagerStrong Foundation: Research Funding; Affymetrix: Research Funding; plexxikon: Research Funding; daiichi sankyo: Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; abbvie: Research Funding; cellectis: Research Funding; stemline: Consultancy, Honoraria, Research Funding; novartis: Research Funding. Kadia:Novartis: Consultancy; Amgen: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Abbvie: Consultancy; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Celgene: Research Funding; BMS: Research Funding; Celgene: Research Funding; Novartis: Consultancy; Jazz: Consultancy, Research Funding; Abbvie: Consultancy; Takeda: Consultancy; Takeda: Consultancy.

scholarly journals The Efficacy of Cladribine (2-CdA) in Advanced Systemic Mastocytosis

2020 ◽  
Vol 36 (4) ◽  
pp. 661-666 ◽  
Author(s):  
Grzegorz Helbig ◽  
Anna Koclęga ◽  
Władysław B. Gaweł ◽  
Martyna Włodarczyk ◽  
Marek Rodzaj ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Systemic Mastocytosis ◽  
Median Number ◽  
Hemoglobin Level ◽  
Median Dose ◽  
Skeletal Involvement ◽  
Duration Of Response ◽  
Hematological Neoplasm ◽  
Number Of Cycles

Abstract Systemic mastocytosis (SM) is a rare clonal disorder with multi-organ involvements and shortened life expectancy. To date, no curative treatment for SM exists. Cladribine (2-CdA) is a purine analogue showing activity against neoplastic mast cells and its use was found to be effective in some patients with SM. Nine patients (six males and three females) with advanced SM at median age of 63 years (range 33–67) who received at least one course of 2-CdA were included in a retrospective analysis. Study patients were classified as having aggressive SM (ASM; n = 7) and SM with an associated hematological neoplasm (SM-AHN; n = 2). The “C” findings were as follows: (1) absolute neutrophil count (ANC) < 1 × 109/l (n = 1) and/or hemoglobin level < 10 g/dl (n = 4) and/or platelet count < 100 × 109/l (n = 4); (2) hepatomegaly with ascites (n = 4); (3) skeletal involvement (n = 2); (4) palpable splenomegaly with hypersplenism (n = 3) and (5) malabsorption with weight loss (n = 5). Treatment consisted of 2-CdA at dose 0.14 mg/kg/day intravenously over a 2-h infusion for 5 consecutive days. Median dose per cycle was 45 mg (range 35–60). Median number of cycles was 6 (range 1–7). Overall response rate (ORR) was 66% (6/9 pts) including three partial responses and three clinical improvements. ORR was 100% and 66% for SM-AHN and ASM, respectively. Median duration of response was 1.98 years (range 0.2–11.2). At the last contact, five patients died, four have little disease activity, but remain treatment- free. 2-CdA seems to be beneficial in some patients with SM, however the response is incomplete.

A Phase I/II Study of Bortezomib and Low Dose Intravenous Melphalan (BM) for Relapsed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2555-2555 ◽  
Author(s):  
Rakesh Popat ◽  
Heather E. Oakervee ◽  
Nicola Foot ◽  
Samir Agrawal ◽  
Patricia Smith ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Progressive Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Median Number ◽  
Overall Response ◽  
Grade 3 ◽  
Number Of Cycles

Abstract Background: Bortezomib as a single agent has known efficacy in the treatment of relapsed multiple myeloma. The overall response rate (CR+PR+MR) was 35% in the SUMMIT study and 46% in the APEX study. In-vitro studies including our own have demonstrated potent synergy with other chemotherapeutic agents such as melphalan. It therefore follows that responses to bortezomib may be further improved by the combination of such drugs. Aims: The primary objectives of this Phase I/II study was to assess the safety, tolerability and response rates in patients with relapsed multiple myeloma; secondary objectives being time to progression (TTP) and overall surival (OS). Methods: This was a multi-centre, non-randomised trial for patients with relapsed myeloma. Patients received bortezomib 1.3mg/m2 on days 1,4,8 and 11 of each 28 day cycle with melphalan on day 2 at increasing dose levels. This was initially at 10mg/m2, but due to cytopenias subsequently at 2.5 and 5mg/m2 (levels 1a, 1 and 2) and we plan to escalate to 7.5mg/m2. Up to 8 cycles were given with dexamethasone added for stable or progressive disease after 4 or 2 cycles respectively. Responses were determined by EBMT criteria. Results: To date, 18 patients have been enrolled (12 male 6 female; median age 60 [range 44–73]; median number of prior therapies 3 [range 1–5] of which 17 have had at least one autologous stem cell procedure with high dose melphalan; 10 prior thalidomide and 2 prior bortezomib). 12 patients received melphalan at 10mg/m2 but due to unacceptable delays predominantly due to thrombocytopaenia, subsequent treatment levels commenced at 2.5mg/m2. The median number of cycles completed thus far is 4 (range 0–8) and of the 16 evaluable, the overall response rate (CR+PR+MR) across all treatment levels was 50% rising to 75% following the addition of dexamethasone as per protocol. At level 1a (melphalan 10mg/m2 ,N=12, median number of cycles completed =5) the best responses (with dexamethasone as indicated) were: 1CR, 1 VGPR, 5 PR, 2 MR; at level 1 (melphalan 2.5mg/m2, N=4) 1 PR, 2 MR (after 2 cycles only). The median time to any response was 1 cycle (range 1–3 ). Three patients have progressive disease, but the median TTP and OS have not yet been reached (median follow-up 3 months). Non-haematological toxicities have been modest with 7 SAEs reported of which only 1 was possibly drug related (myocardial infarction), and 4 episodes of Grade 3 neuropathy (2 resulting in study withdrawal). The commonest grade 3–4 haematological toxicity was thrombocytopaenia (N=10) complicated by bleeding in one patient, followed by neutropenia (N=6). Summary: The combination of bortezomib and intravenous melphalan can be given safely to patients with relapsed multiple myeloma and dose escalation is ongoing. Myelosupression was the commonest grade 3–4 adverse event. A response rate of 50% was seen, which was further improved to 75% with the addition of dexamethasone. This combination may therefore result in higher responses than single agent bortezomib in heavily pretreated patients.

Oral Clofarabine in the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 118-118 ◽  
Author(s):  
Stefan Faderl ◽  
Guillermo Garcia-Manero ◽  
Zeev Estrov ◽  
Farhad Ravandi ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndrome ◽  
Research Funding ◽  
Optimal Dose ◽  
Oral Formulation ◽  
Median Number ◽  
Infectious Complications ◽  
Molecular Characteristics ◽  
Number Of Cycles ◽  
Almost All

Abstract Abstract 118 Clofarabine (CLO) is a second generation deoxyadenosine nucleoside analog with activity in patients (pts) with acute myeloid leukemia (AML). Early reports also suggestedactivity of iv CLO in myelodysplastic syndrome (MDS), but the role of CLO in MDS therapy remains largely undefined. Due to the molecular characteristics of CLO it can also be administered as an oral formulation with a bioavailability of around 50%. As an oral agent has obvious advantages over parenteral administrations, we designed a phase 2 study to evaluate the activity and safety of oral CLO in patients with MDS. Pts were eligible if they had MDS and ≥ 5% blasts (including RAEB-t by FAB) or IPSS intermediate-2 and high-risk, and CMML. Hematopoietic growth factor support prior to and during the study was permitted. Thirty-two pts (2 RA, 11 RAEB-1, 11 RAEB-2, 2 RAEB-t, 5 CMML-1, 1 CMML-2) were treated. Twenty-two pts (69%) had intermediate-2 or high-risk disease by IPSS. Median age was 70 yrs (range 53–86). Overall, ≥ 27 pts (84%) were older than 60 yrs. Thirteen pts (41%) had a history of a prior malignancy and 20 pts (66%) failed prior hypomethylator therapy (6 pts azacitidine, 12 pts decitabine, 2 pts both). Cytogenetics were intermediate and poor in 9 (28%) and 10 (31%) pts, respectively. The starting dose of CLO was 40 mg/m2 orally daily × 5 days every 4–6 weeks (6 pts), which was decreased due to toxicities to 30 mg/m2 orally daily × 5 days (19 pts), and eventually 20 mg/m2 orally daily × 5 days (7 pts). Twenty-eight pts (88%) received treatment in an outpatient facility and almost all pts (94%) received anti-infectious prophylaxis. Responses of 31 evaluable pts are summarized in the Table: Among 20 pts who failed prior hypomethylator therapy responses were CR in 2 (10%), HI in 2 (10%), and CB in 2 (10%). The median number of cycles to response was 1 (range 1–3). Of 10 pts who received further consolidation cycles, the median number was 1 (range 1–8+). No pts died within 6 wks of induction. Acute renal failure occurred in 4 pts (1 pt 40 mg/m2, 3 pts 30 mg/m2) in the context of myelosuppresssion-associated infectious complications; 4 pts died. Common adverse events were nausea/vomiting, rashes, reversible transaminase elevations and hyperbilirubinemia, and fatigue and were mainly ≤ grade 2. The most frequent ≥ grade 3 toxicity were reversible elevations of transaminases. Myelosuppression was ubiquitous, but prolonged myelosuppression (> 42 days) was rare in responding pts. Infectious episodes occurred in 16 pts and were more frequent in pts receiving CLO at 40 or 30 mg/m2. Oral CLO has an ORR of 46% in pts with higher-risk MDS. Responses are lower in pts failing prior hypomethylator therapy. The optimal dose and schedule to balance activity and toxicity remain to be defined. Disclosures: Faderl: Genzyme: Consultancy, Research Funding. Off Label Use: Clofarabine in MDS. Kantarjian:Genzyme: Consultancy, Research Funding.

5-Azacitidine Therapy in Patients with Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia: a Single Institution Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4963-4963
Author(s):  
Alessandra Freyrie ◽  
Gianluigi Reda ◽  
Daniele Vincenti ◽  
Mariarita Sciumé ◽  
Francesca Binda ◽  
...  
Keyword(s):  
High Risk ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Median Number ◽  
Observation Time ◽  
Chronic Myelomonocytic Leukemia ◽  
Female Ratio ◽  
Number Of Cycles ◽  
Male To Female ◽  
Myelomonocytic Leukemia

Abstract Abstract 4963 Overall survival (OS) is significantly improved by 5-azacitidine in intermediate-2 (int-2) and high risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) with 10–29% marrow blasts, and acute myeloid leukemia (AML) with 20–30% marrow blasts, compared with conventional treatments, and currently appears as the standard of care, at least in patients who are not candidates to allogeneic stem cell transplantation (alloSCT). We retrospectively evaluated the efficacy and tolerability of 5-azacitidine in 25 patients treated at our institution from 2009 to 2012, outside of clinical trial. Our series was composed by 17 cases of MDS with IPSS risk int-2 or high, 6 AML with marrow blasts between 20% and 30% and 2 CMML. Patients were treated with 5-azacitidine at a dosage of 75 mg/m2/d subcutaneously for 7 days every 28 days (schedule 5 day on, 2 day off and 2 day on). Median age of our cohort was 72 years (range 37–81 y), male to female ratio was 0. 6 and the median number of cycles received was 7 (range 1–26). According to the MDS-specific comorbidity index 9 pts (53%) were classified as low-risk, 7 pts (41%) as intermediate risk and 1 pt (6%) as high risk. Seventeen (68%) patients (13 MDS, 3 AML, 1 CMML) who had received at least 4 cycles of therapy were evaluable. Median age of these 17 patients was 71 years (range 37–81 y), male to female ratio was 0. 8 and median number of cycles administered was 8 (range 4–26). The overall response rate (ORR) was 59% (10/17 patients). According to International Working Group (IWG) 2006 criteria, five patients (29%) reached complete remission (CR) after a median of 5 cycles of therapy (range 4–6), two patients (12%) obtained hematologic improvement with bone marrow complete remission (marrow CR) after 6 and 11 cycles of therapy respectively, three patients (18%) showed hematologic improvement (HI) after 5 cycles (range 4–6), while stable disease (SD) and progressive disease (PD) were observed in 4 (23%) and in 3 patients (18%) respectively after 5 cycles (range 4–7). Median duration of response was 12 months (range 6–26 mo); median overall survival from the beginning of 5-azacitidine, for all patients treated, was 14. 4 months (range 7–33 mo). We did not observe any differences in response rate according to age, bone marrow fibrosis, cytogenetics and transfusion requirements. In the responder group (10 patients) we did not observe grade 3 or 4 non-hematologic toxicity after a median observation time of 10 months (range 5–33 mo). Among non-responding patients, four (57%) recurred to hospitalization due to infectious or hemorrhagic complications (median observation time 15 months, range 7–33). 5-azacitidine confirmed to be an active therapy for patients with int-2 and high risk MDS and AML with low marrow blast counts not candidate to high intensity treatment for age and or comorbidities, showing high response rate and good tolerability. The low rate of serious adverse events and need of hospitalization improved patient's quality of life and reduced the utilization of medical resources. Disclosures: No relevant conflicts of interest to declare.

A Phase II Add-on Study of Vorinostat (VOR) in Higher Risk Myelodysplastic Syndrome with Failure of Hypomethylating Agents (HMA): The GFM Azavor Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2900-2900
Author(s):  
Thomas Prebet ◽  
Jacques Delaunay ◽  
Eric Wattel ◽  
Thorsten Braun ◽  
Pascale Cony-Makhoul ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Response Rate ◽  
Standard Of Care ◽  
Median Number ◽  
Current Standard ◽  
Stage Design ◽  
Early Evaluation ◽  
Positive Results

Abstract Background: Azacitidine (AZA) is the current standard of care for patients treated for higher risk MDS, but 40-50% patients do not respond and most responders eventually relapse. Median survival after AZA failure is only 5 months and no standard of care is defined for this population. Preclinical studies and positive results of phase I-II trials support a synergistic effect of the histone deacetylase (HDAC) vorinostat (VOR) and AZA in terms of response, although no survival advantage of the combination has as yet been demonstrated. We hypothesized that adding VOR to AZA in patients with primary or secondary AZA resistance could rescue response and prolong survival. Methods: inclusion criteria inGFM AZAVOR study (NCT 01748240) were: 1/IPSS int 2 or high risk MDS at the time of initiation of AZA 2/treatment with at least 6 cycles of AZA and either failure to achieve any response or loss of response (per IWG2006 criteria) 3/a maximum of 3 months between AZA failure and inclusion with no other treatment in between. Patients received VOR 300mg bid from day 3 to day 9 of each cycle. AZA was given at standard 75mg/m2/d day 1 to 7 or at the maximum previously tolerated dose in case of dose reduction. Patients were evaluated after 6 cycles and responding patients treated until progression. The trial used a two-stage design, and accrual was to be stopped if less than 3 responses were seen in the first 14 evaluable patients. Results 21 patients were included between march 2013 and September 2014. Nineteen patients were treated (1 patient died and 1 progressed before treatment). Median age was 72 years. All pts had higher risk MDS and had received a median of 6 cycles of AZA before entering the trial. The median number of AZA+ VOR cycles administered was 3 (range: 1-12). No unexpected SAEs were seen, and the most common AEs were infection, thrombocytopenia, GI toxicities, and fatigue. After 6 cycles of treatment, only 2 patients (11%) achieved response (1 erythroid hematological improvement, 1 partial remission), , which, per protocol, triggered the stop of accrual. At last follow-up, 18 patients were off study and one patient was still on treatment. Nine patients stopped treatment because of progression (42%), 4 stopped treatment for lack of response (21%), 2 stopped treatment because of intolerance (11%), 1 patient stopped at his request (5%), and 1 patient died of complications of cytopenias while on treatment (5%). Median overall survival was 13 months. Conclusion This is the first report of an add-on study in high risk MDS, a strategy that may be useful for the early evaluation of drugs for which synergy with AZA is expected. Our results show that the proposed regimen of AZA +VOR can be used safely. However, the observed response rate was not above the "background" response rate expected from AZA alone continuation in a comparable patient population, indicating that the addition of VOR cannot reverse resistance to AZA. Disclosures Prebet: CELGENE: Research Funding. Off Label Use: lenalidomide. Wattel:Janssen: Consultancy, Honoraria, Research Funding; PIERRE FABRE MEDICAMENTS: Research Funding; CELGENE: Research Funding, Speakers Bureau; NOVARTIS: Research Funding, Speakers Bureau; AMGEN: Consultancy, Research Funding. Cony-Makhoul:Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau. Fenaux:Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding. Vey:Janssen: Honoraria; Roche: Honoraria; Celgene: Honoraria.

Response Rates of Phase 2 and Phase 3 Trials of Decitabine (DAC) in Patients with Myelodysplastic Syndromes (MDS).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2515-2515 ◽  
Author(s):  
Hussain I. Saba ◽  
Michael Lübbert ◽  
P.W. Wijermans
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Median Duration ◽  
Response Rate ◽  
Response Rates ◽  
Median Number ◽  
Phase 2 ◽  
Phase 3 ◽  
Overall Response ◽  
Number Of Cycles

Abstract Background: MDS is characterized by ineffective hematopoiesis, resulting in cytopenias with dysplastic morphology of peripheral blood cells and bone marrow. Decitabine (Dacogen™ DAC) is a cytosine analog that reverses aberrant DNA methylation, leading to re-expression of silenced tumor suppressor genes. Due to the requirement for DNA synthesis and subsequent demethylation, decitabine may require prolonged administration to achieve maximum benefit. Overall response rates (ORR) (CR+PR) from 1 pivotal Phase 3 (D-0007) and 3 supportive Phase 2 trials (91–01, 95–11 and 97–19) in patients with intermediate and high risk MDS receiving DAC are being presented. Methods: The Phase 2 trials were open-label and single-arm, with a minimum of 4 treatment cycles and a maximum of 8 cycles, while the D-0007 was a 1:1 randomized comparison of DAC plus supportive care (SC) vs. SC alone, with a maximum of 10 cycles of therapy. The D-0007 study design dictated that patients be removed from therapy following 8 cycles of decitabine if CR was not achieved, and 6 cycles in the absence of PR. Patients who maintained a CR for 2 cycles were removed from therapy. Results: A total of 271 unique patients were exposed to DAC in the studies (n= 89 in D-0007, n=29 in 91–01, n = 66 in 95–11, n = 87 in 97–19). Patients receiving DAC had similar demographics and disease characteristics in all trials. Responses were observed in all IPSS and FAB subgroups. The percent of patients classified as intermediate-2 and high risk (according to the International Prognostic Scoring System) in the Phase 3 trial was 69% vs. 72% in the Phase 2 trials. By intent-to-treat analysis, the ORRs were 45%, 26%, and 26% respectively, for the Phase 2 trials. These results were corroborated in the Phase 3 trial, where the response rates were evaluated according to the more robust International Working Group MDS criteria, following a blinded, centralized bone marrow review. The D-0007 overall response rate was 17% for DAC (9% CR, 8% PR) vs. 0% for SC (p<0.001). Responses were durable, lasting a median of 266 days. The 95–11 and 97–19 response rates were also centrally reviewed, while 91–01 responses were investigator-assessed. In the 91–01 trial, the ORR was 45% (28% CR, 17% PR) with a median duration of response of 217 days, the 95–11 ORR was 26% (21% CR, 5% PR) with a median duration of 250 days, and the 97–19 ORR was 26% (22% CR, 5% PR) with a median duration of 146 days. Hematologic improvement (HI) was also evaluated according to varied criteria in conjunction with the response rates in all 4 studies; 12 patients (13%) had HI in D-0007, 2 patients (7%) in 91–01, 8 patients (12%) in 95–11, and 13 patients (15%) in 97–19. The D-0007 trial design dictated that patients who maintained a CR for 2 cycles be removed from therapy. As a result, the median number of cycles delivered was 3, with only 48% of patients receiving ≥4 cycles. In the Phase 2 studies, the median number of cycles is clearly higher (median 4), with the majority of patients receiving at least 4 cycles and approximately one-third of patients receiving ≥6 cycles. Conclusion: While response rates of ≥17% were demonstrated in these trials, the optimization of hypomethylating agents for maximum efficacy is very likely to include prolonged therapy, which may correlate with increases in response rate and duration.

Final Report of GFM-VOR2007 Study: a Phase I/II Study of Vorinostat and Low Dose Cytarabine (LDAC) for MDS Patients with Azacitidine (AZA) Failure

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3825-3825 ◽  
Author(s):  
Thomas Prebet ◽  
Thorsten Braun ◽  
Odile Beyne-Rauzy ◽  
Eric Wattel ◽  
Francois Dreyfus ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Research Funding ◽  
Response Rate ◽  
Single Agent ◽  
Therapeutic Index ◽  
Median Number ◽  
Clinical Activity ◽  
Final Report ◽  
Sequential Administration

Abstract Abstract 3825 INTRODUCTION: AZA is the standard of care for patients (pts) treated for high risk MDS. Outcome of patients with AZA failure is poor with no standard treatment currently available (Prebet, JCO, 2012), and alternative strategies are required for this population. Vorinostat is a histone deacetylase inhibitor with clinical activity in MDS and leukemia, although response rate remains low when used as single agent (Garcia-Manero Blood 2008). By contrast, combinations with cytotoxic or targeted therapies seem promising. METHODS: In this study (clinicaltrials.gov NCT00776503), we combined LDAC (10mg/m2/d in the first cycle, then 20 mg/m2/d) for 14 days SC every 28 day cycle and escalating doses of vorinostat. Two schedules of vorinostat, (400mg/day orally) beginning on day 1 (arm A) or on day 14 (arm B), were tested in 3 cohorts receiving escalating treatment duration (7days, 10 days and 14 days per cycle) with a classical 3+3 phase I schedule. 7 additional pts were included at the dose level recommended by the DSMB for each cohort (arm A and B). Inclusion criteria were age >18, MDS or AML with 20–30% blasts, IPSS≥1.5, prior failure of AZA. Toxicity was assessed using CTCAE V3. Patients with clinical benefit could continue on therapy after cycle 3 until progression. RESULTS: A total of 42 pts were included and 40 were treated, 23 pts in arm A and 17 pts in arm B. 2 pts died before the beginning of treatment. Median age was 74 years (range 46– 88), median number of previous treatments was 2 (1–3), and median number of cycles of previous AZA treatment was 11 (range 1–25). All pts were IPSS Int-2 (n=21) or High risk MDS (n=19). A total of 137 cycles of treatment was administered with a median number of 3 cycles/pt and 11 pts received more than 3 cycles (28%). The recommended dose was determined for arm A at 10 days of vorinostat and for arm B at 14 days. During cycle 1, dose limiting toxicities were grade 3 fatigue (n=2), grade 4 bilirubin (n=1), and grade 4 infection (n=2), all in arm A. The most frequent non-limiting toxicities were myelosuppression (37/40), infections (8/40) moderate fatigue (23/40) and mild GI toxicities (25/40). Response was centrally reviewed according to IWG 2006 criteria. Overall response rate was 17% in 35 evaluable pts including 2 CRi, 2 HI and 2 marrow CR. Median duration of response of 3 months (range [2–6+]). There were 2 responders in arm A (1 in the 7 day cohort and 1 in the 14 day cohort) and 4 responders in arm B (1 in the 7 day cohort, 2 in the 10 day cohort, 1 in the 14 day cohort) including the 2 CRi. 18 pts remained stable without HI and 11 progressed during treatment. Median overall survival of the cohort was 9.2 months and 1-year probability of survival was 36%. CONCLUSIONS: Our results show that 400 mg/day vorinostat can be combined to LDAC and given for 10 days (arm A) to 14 days (arm B) with acceptable side effects. It also suggests that the sequential administration might be associated with an increased therapeutic index since longer vorinostat therapy duration could be tolerated. Response rate remains modest but survival compared favorably with conventional care in this group of patients with dismal outcome. Disclosures: Fenaux: Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

scholarly journals Bortezomib in Combination with Dexamethasone, Cyclophosphamide, Etoposide, and Cisplatin (V-DCEP) for the Treatment of Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2139-2139 ◽  
Author(s):  
Kelly Valla ◽  
Jonathan L. Kaufman ◽  
Charise Gleason ◽  
Lawrence H. Boise ◽  
Leonard T Heffner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Median Time ◽  
Salvage Therapy ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
University Hospital ◽  
High Dose ◽  
Overall Response

Abstract Introduction Despite therapeutic advances in multiple myeloma, disease relapse is common. Combination therapy with dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) has been utilized as an effective salvage regimen for over a decade, and a recent study reported that DCEP provided an overall response rate of 45.1% when used as salvage therapy in patients who had previously received novel agents (Park S, et al. 2014). Aside from hematologic toxicities, DCEP is generally well-tolerated. In fact, the toxicity profile of DCEP has been compared to high dose cyclophosphamide in the setting of stem cell mobilization and is considered less toxic than the latter. Based upon the synergy noted when proteasome inhibitors are combined with genotoxic therapy, we have combined bortezomib with DCEP in a series of relapsed myeloma patients. Herein we report our experience with the addition of bortezomib to DCEP in relapsed/refractory disease. Patients and Methods We performed a retrospective evaluation of patients with relapsed/refractory multiple myeloma treated at Emory University Hospital from October 2011 until March 2014. Patients received dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) at standard doses in combination with bortezomib at either a dose of 1 mg/m2 or 1.3 mg/m2 administered on Days 1 and 4 of each cycle given every 28 days. Indications for receiving V-DCEP are either cytoreduction prior to SCT (cohort 1) or as salvage therapy (cohort 2). Results Among the 51 patients (49% male and 51% female) included in analysis, the median age at the time of diagnosis is 58 years (range 30-78) and the time of treatment with V-DCEP is 62 years (range 33-79). Among patients that received V-DCEP as cytoreduction prior to SCT, median prior lines of therapy were 1 (0-8). Among the patients that received V-DCEP as salvage therapy, median number of prior lines of therapy was 3 (1-6). ISS 3 disease was seen in 70% of patients and high risk disease in 72.5% of pts (del 17p: 31%; PCL: 19%; extramedullary disease: 33%; complex CTG: 11%) and t(4;14): 6%). Median time from diagnosis to initiation of V-DCEP therapy among cohort 1 is 18 months (0-86) and among cohort 2 is 31 months (12-105) months. Median serum creatinine before C1D1 is 1.17 (0.61-6) and serum bilirubin is 0.6 (0.1-2.8). 31% of patients needed dose reductions from our standard protocol due to organ dysfunction. 47% of patients received ≥2 cycles. The median time to next cycle is 28 days (20-46) and time to next treatment after V-DCEP is 35 days (25-451) suggesting good hematologic recovery. The overall response rate (≥PR) amongst both cohorts with V-DCEP is 47.8% (40% and 51.6% overall response for cohorts 1 and 2, respectively). Figure 1 illustrates response rates. 10 patients that presented with renal insufficiency had renal response including 2 of the 5 patients on hemodialysis. While the median PFS for cohort 1, as expected has not reached, for cohort 2, it is 8 months (95% CI 5.7-10.3). At a median follow-up of 17 months, from the time of V-DCEP initiation, median OS for cohort 2 is 10 months (95% CI 5-14.9). Median overall survival for this predominantly high risk group of patients from diagnosis in cohort 1 is 78 months (95% CI 47-108) and 49 (95% CI 17-80.7) months in cohort 2, respectively. While only 1 patient with grade 2 peripheral neuropathy (PN) received V-DCEP, change from baseline existing PN was seen in 19% of patients (no grade 3/4 events). Conclusions During this era where minimizing alkylator therapy is a consideration, certain indications exist for using V-DCEP such as cytoreduction prior to SCT or as salvage therapy serving as bridge to next line of therapy. Addition of bortezomib to DCEP is deemed safe and is an effective cytoreductive regimen in the treatment of multiple myeloma. Figure 1 Figure 1. Disclosures Gleason: Celgene: Consultancy; Novartis: Consultancy. Heffner:Amgen: Honoraria, Research Funding; Biotest: Honoraria, Research Funding; Dana Farber CI: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Idera: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding; Onyx: Honoraria, Research Funding; Spectrum: Honoraria, Research Funding; Talon Therapeutics: Honoraria, Research Funding. Lonial:Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

scholarly journals A Phase 2 Study to Assess the Feasibility and Tolerance of the Combination of Elotuzumab, Lenalidomide, and Dexamethasone (ERd) in the Induction, Consolidation, and Maintenance Treatment of Transplant-Eligible Patients Newly Diagnosed with Multiple Myeloma (MM)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 603-603 ◽  
Author(s):  
Jesus G. Berdeja ◽  
Tara K. Gregory ◽  
Suman Kambhampati ◽  
Bertrand M. Anz ◽  
Stefano R. Tarantolo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Overall Response Rate ◽  
Response Rate ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Overall Response

Background: The introduction of novel agents such as proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs) with and without corticosteroids has revolutionized treatment (tx) and improved survival rates for MM. IMID/PI triplets such as VRD (bortezomib, lenalidomide, dexamethasone), VTD (bortezomib, thalidomide, dexamethasone), or KRD (carfilzomib, lenalidomide, dexamethasone) are preferred inductions for transplant-eligible patients (pts). Unfortunately, the PI often has unique safety events such as peripheral neuropathy (PN) or cardiac issues that can impact the quality of life. Elotuzumab is a mAb with a dual mechanism of action (tagging MM cells and activating NK cells by binding SLAMF7). The combination of elotuzumab, lenalidomide, and dexamethasone (ERd), is active, well-tolerated, and approved by the FDA for pts with relapsed MM. In this study, we will determine the feasibility of incorporating ERd into a transplant-eligible pt population. Methods: Pts with newly diagnosed MM requiring chemotherapy planning to undergo autologous stem cell transplantation (ASCT) were enrolled. Induction of elotuzumab at 10 mg/kg was administered IV on days (D) 1, 8, 15, 22 of the 1st 2 28-day cycles and days 1, 15 of the third and fourth 28-day cycles. Lenalidomide was dosed at 25 mg orally on D 1-21 of each 28 day induction cycle. Dexamethasone was administered IV concurrent with elotuzumab (28mg orally 3-24 hours prior to infusion and 8 mg IV with elotuzumab), with 40 mg orally administered on D 8 and 22 of cycles 3 and 4. After completion of the 4 induction cycles, pts proceeded to mobilization and ASCT though pts who refused transplantation were allowed to proceed directly to consolidation and maintenance if the investigator believed the pt was deriving benefit. 70-120 days after ASCT, 4 cycles of consolidation were administered (dosing similar to cycles 3-4 of induction but with lenalidomide at 15mg). Pts then went on to maintenance with elotuzumab 20 mg/kg IV on D 1, oral lenalidomide 10mg +/- 5 mg D 1-21 and dexamethasone 28mg oral/8 mg IV prior to elotuzumab infusion were dosed in 28-day cycles for up to 24 months. The primary endpoint was the induction feasibility rate (IFR) defined as the percentage of pts successfully completing 4 cycles of induction tx with ERd and able to start ASCT. Secondary end points were complete response rate (≥nCR), overall response rate (≥PR), progression-free survival (PFS) and overall survival (OS). AEs were assessed according to CTCAE V4 and responses were assessed using the revised IMWG criteria. Results: 52 pts were enrolled: 56% male, median age 61 ys, 12% RISS III, 21% high-risk cytogenetics [17p del, t(4;14), and/or t(14;16)]. To date, 26 (50%) pts remain on active tx. 4 pts refused transplantation despite being eligible and were excluded from the IFR calculation. The IFR was 69% and the best overall response rate (ORR) was 92% (69% ≥ VGPR). With a median follow up of 20 mos, median PFS and OS for all pts were not reached. The 18 mo PFS and OS were 83% and 89% respectively. The most common AEs were fatigue (59.6%), diarrhea (42.3%) and nausea (42.3%). PN was seen in 29%, and all events were ≤ G2. There were 28 SAEs in 20 pts, including 12 tx-related SAEs. There was 1 tx-related death due to heart failure in a pt with no history of prior cardiac issues who had subsequent therapy. 29% of pts met the high-risk (HR) criteria (defined as RISS III or high risk cytogenetics) and 29% of pts were considered standard-risk (RISS I and no high-risk cytogenetics). The best ORR was 87% (67% ≥ VGPR) for HR pts and 93% (53% ≥ VGPR) for SR pts and the IFR was 57% for HR pts and 64% for SR pts. The median PFS and OS were 20.5 mos and 22.0 mos respectively for HR pts and have not been reached for SR pts. Conclusions: ERd induction, consolidation and maintenance was feasible and well tolerated in conjunction with ASCT in transplant-eligible pts. Despite high ORR for all pts, HR patients had inferior PFS and OS. This study supports the continued evaluation of this regimen in SR pts. Disclosures Berdeja: Amgen Inc, BioClinica, Celgene Corporation, CRISPR Therapeutics, Bristol-Myers Squibb Company, Janssen Biotech Inc, Karyopharm Therapeutics, Kite Pharma Inc, Prothena, Servier, Takeda Oncology: Consultancy; Poseida: Research Funding; AbbVie Inc, Amgen Inc, Acetylon Pharmaceuticals Inc, Bluebird Bio, Bristol-Myers Squibb Company, Celgene Corporation, Constellation Pharma, Curis Inc, Genentech, Glenmark Pharmaceuticals, Janssen Biotech Inc, Kesios Therapeutics, Lilly, Novartis, Poseida: Research Funding. Gregory:Takeda: Speakers Bureau; Celgene: Speakers Bureau; Poseida: Research Funding; Amgen: Speakers Bureau. OffLabel Disclosure: Yes, this was an investigational clinical study of the combination of elotuzumab, lenalidomide, and dexamethasone in the induction, consolidation, and maintenance treatment of transplant-eligible patients newly diagnosed with multiple myeloma.

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