Phase I/II Study on Cytarabine and Idarubicin Combined with Escalating Doses of Clofarabine in Untreated Patients with Acute Myeloid Leukemia and High Risk for Induction Failure (AMLSG 17-10 CIARA)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4038-4038
Author(s):  
Juergen Krauter ◽  
Walter Fiedler ◽  
Richard F. Schlenk ◽  
Peter Paschka ◽  
Felicitas Thol ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Older Patients ◽  
Research Funding ◽  
Historical Control ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Allogeneic Hct ◽  
Induction Failure

Abstract Background: Clofarabine is a second-generation purine nucleoside analogue, which has shown synergistic activity with cytarabine. We determined the maximum tolerated dose (MTD, primary endpoint), safety and efficacy (secondary endpoints) of clofarabine in combination with cytarabine and idarubicin in newly diagnosed acute myeloid leukemia (AML) patients with high-risk for induction failure stratified in two age groups (< 60 years and ≥ 60 years). Methods: In this prospective, open-label, multicenter phase I/II study (EudraCT 2010-021719-18, CIARA trial), newly diagnosed AML patients with high risk of induction failure (NPM1 wildtype, FLT3-ITD negative), who were eligible for intensive chemotherapy, received two induction courses (cytarabine 750 mg/m2 d1-5, idarubicin 7.5 mg/m2 in patients <60 years or 6 mg/m2 in patients ≥60 years d1+3) with increasing doses of clofarabine (20-35 mg/m2 d1-5) following a 3+3 design with extension cohorts. Consolidation consisted of up to 3 courses of high-dose cytarabine or allogeneic hematopoietic cell transplantation (HCT). Results: Forty-two patients with de novo (n=32) or secondary (n=10) AML were included. Median age was 58.5 years (range 28-73, 24 patients < 60 years, 18 patients ≥ 60 years). Intermediate/adverse risk cytogenetics were found in 22 and 12 patients, respectively (karyotype missing in 8 patients). All patients received induction 1, 27 (64%) received induction 2; 4 (10%) patients died during induction courses 1 or 2. Eight patients developed a dose-limiting toxicity (6 patients with grade 3/4 non-hematologic toxicity and 3 patients with grade 4/5 hematologic toxicity) and the MTD was determined at 30 mg/m2 clofarabine for both age cohorts (younger patients: 2 of 6 patients with DLT at 35 mg/m2, no DLT at 30 mg/m2 (n=9); older patients: 4 of 6 patients with DLT at 35 mg/m2 in the extension phase, no DLT at 30 mg/m2 (n=3). The most frequent grade 3-5 non-hematologic adverse events were febrile neutropenia, sepsis, increased liver enzymes, pneumonia, decreased appetite and diarrhea occurring in 55, 24, 21, 21, 10 and 10% of patients. The median time to neutrophils ≥0.5/nl and platelets ≥50/nl after induction 1 was 25 and 24 days, respectively. Sixteen patients (38%) proceeded to allogeneic HCT in first CR and 8 (19%) received at least one course of high-dose cytarabine consolidation. Complete remission (CR) or CR with incomplete recovery (CRi) was achieved in 67%. After a median follow up of 2.2 years the 2-year overall survival (OS) was 56% and the 2-year event-free survival was 38% (median EFS 11.4 months). Compared to a matched historical control of 197 younger AML patients (SHG 0199 trial, Schlenk et al. NEJM 2008), the CR rate was 79% in the 24 younger CIARA patients compared to 66% in the control cohort (P=.18), and 2-year OS was higher for CIARA than for control patients (74% vs 49%, P=.021, Figure A). The allogeneic HCT rate in first CR (CR1) was higher in younger CIARA compared to younger control patients (58% vs 27%, P=.002). The CR rate in older CIARA patients was 50% compared to 36% in a historical control of 191 older patients, who were selected using the same genetic inclusion criteria as for CIARA patients (HD98B trial, Schlenk et al. Haematologica 2009, P=.23). Two-year OS in older patients was similar between CIARA and control patients (33% vs 17%, P=.31, Figure B). The allogeneic HCT rate in CR1 was 11% vs 2% in CIARA vs control patients (P=.029). Conclusion: Clofarabine can be safely administered at 30 mg/m2 in combination with cytarabine and idarubicin in younger and older newly diagnosed AML patients. Allogeneic HCT in CR1 was feasible in a high proportion of younger AML patients and likely contributed to the favorable outcome compared to historical control patients. Figure Overall survival in younger and older AML patients of the CIARA trial compared to historical controls. Figure. Overall survival in younger and older AML patients of the CIARA trial compared to historical controls. Disclosures Krauter: Genzyme: Research Funding. Schlenk:Amgen: Research Funding; Pfizer: Honoraria, Research Funding. Paschka:Novartis: Consultancy; Medupdate GmbH: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer Pharma GmbH: Honoraria; Celgene: Honoraria; ASTEX Pharmaceuticals: Consultancy. Lübbert:Ratiopharm: Other: Study drug valproic acid; Celgene: Other: Travel Funding; Janssen-Cilag: Other: Travel Funding, Research Funding. Janning:Teva: Honoraria. Becker:BMS: Honoraria; Novartis: Honoraria. Heuser:Tetralogic: Research Funding; Novartis: Consultancy, Research Funding; Celgene: Honoraria; Pfizer: Research Funding; Bayer Pharma AG: Research Funding; BerGenBio: Research Funding; Karyopharm Therapeutics Inc: Research Funding.

Efficacy of a Brief, Cyclophosphamide-Intensive Regimen for Older Patients with Newly Diagnosed Burkitt's or Atypical Burkitt's Lymphoma/Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2685-2685
Author(s):  
Yvette L. Kasamon ◽  
Robert A. Brodsky ◽  
Michael J. Borowitz ◽  
Pamela A. Crilley ◽  
Richard F. Ambinder ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Time ◽  
Older Patients ◽  
Research Funding ◽  
Tumor Lysis Syndrome ◽  
B Cell Lymphoma ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
High Dose ◽  
Newly Diagnosed

Abstract Abstract 2685 Poster Board II-661 Background: Although standard therapies cure most adolescents and young adults with Burkitt's lymphoma/leukemia (BL), older patients (pts) have an inferior prognosis with an estimated 1-year survival of 50%. The inferior outcome is attributable to both insufficient efficacy and excess toxicity. Cyclophosphamide (Cy) has long been recognized to be arguably the most active agent in BL. Prior work at our institution showed that high-dose Cy, equivalent to transplantation doses, could be given without stem cell rescue with minimal toxicity even in older pts. Patients and Methods: A phase II trial for pts age ≥ 30, based on intensive Cy and incorporating rituximab but no anthracycline, was developed with a primary endpoint of 1-year overall survival. Entry requirements included newly diagnosed BL or atypical BL; any performance status (PS); HIV negative; and no significant cardiac dysfunction. Renal failure, even if necessitating dialysis, was permitted if it was acute. Treatment consisted of 3 cycles, with successive cycles beginning on day 15 or when ANC was ≥ 500/μL. Cycles 1 and 2 consisted of Cy 1500 mg/m2 IV day 1; vincristine 1.4 mg/m2 (2 mg cap) day 1; prednisone 100 mg days 1-5; rituximab 375 mg/m2 IV days 1 and 8; methotrexate 3 g/m2 IV day 8 with leucovorin rescue; cytarabine 100 mg intrathecally days 1, 4, and 11; and filgrastim. Cycle 3 consisted of rituximab 375 mg/m2 IV day 1; high-dose Cy (50 mg/kg IV days 2, 3, 4, and 5) with uroprotection; filgrastim; and rituximab 375 mg/m2 IV weekly for 4 weeks once ANC was ≥ 1000/μL. Eligibility for cycle 3 included ECOG PS < 4; no disease progression or uncontrolled meningeal disease; not on dialysis; and transaminases ' 5X upper limit of normal. Results: A prespecified interim analysis of the first 12 of a planned 20 evaluable pts is presented. Diagnosis was BL in 8 and atypical BL/unclassifiable high-grade lymphoma with features intermediate between BL and diffuse large B-cell lymphoma in 4. Median age was 56 (range 34 – 75), 8/12 (67%) had Ann Arbor stage III/IV disease, and all were high-risk by Magrath's criteria. PS ranged from 0 to 4. Two pts received hemodialysis on presentation. For all pts, actuarial event-free survival and overall survival (Figure) are 66% and 75%, respectively, at both 1 year and 2 years after treatment initiation. Three pts died during cycle 1: tumor lysis syndrome on day 1, neutropenic sepsis on day 8, multiorgan failure on day 46 after respiratory arrest on day 20. All of the other 9 pts completed protocol therapy: 8 (89%) achieved anatomic CR/CRu as well as a complete metabolic response by PET, and are event-free at a median of 29 months (range < 1 – 44 months) after therapy completion. The remaining pt had residual marrow disease followed by progression and is in remission 1 year after myeloablative allogeneic BMT. Adverse events in these 9 pts included 7 neutropenic fevers; 1 non-neutropenic bacteremia; and 1 self-limited episode of pericarditis with rapid atrial fibrillation. Grade 3 peripheral neuropathy was limited to 2 pts. The planned dose intensity was achievable: median time to cycle 2 was 15 days (14 – 21), and median time from start of cycle 1 to start of cycle 3 was 31 days (28 – 35). Median time to neutrophil recovery after the last dose of Cy was 16 days (10 – 21); median time to platelets ≥ 20,000/μL, without transfusion in the preceding week, was 22 days (0 – 30). Early stopping criteria for response or all-cause mortality have not been met. Conclusion: A very short regimen based on intensive Cy without anthracycline produces a high rate of durable CR's in older, poorer-risk pts with BL or atypical BL. Disclosures: Kasamon: Genentech: Research Funding. Swinnen:Genentech: Consultancy, Research Funding; Enzon: Consultancy; Abbot: Consultancy, Research Funding.

scholarly journals Utilization of Autologous Stem Cell Transplantation in Older Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5701-5701
Author(s):  
Justin King ◽  
Mark A. Fiala ◽  
Scott R. Goldsmith ◽  
Keith E. Stockerl-Goldstein ◽  
Mark A. Schroeder ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Older Patients ◽  
Research Funding ◽  
Small Sample ◽  
Poor Performance Status ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Equity Ownership

Historically, high-dose therapy in combination with autologous stem cell transplants (ASCT) for multiple myeloma (MM) was reserved for younger patients. In more recent years, the use of ASCT has expanded in the older population. However, there is still limited data on the utilization and efficacy of ASCT in older patients, particularly those over the age of 75. To further evaluate this issue, we retrospectively analyzed all patients with newly diagnosed MM between the ages of 75-78, the institutional cutoff for ASCT eligibility, that were referred to the stem cell transplant unit at our institution for consultation from the years 2012-2018. Baseline characteristics, anti-myeloma treatments, and patient outcomes were abstracted through chart review. Seventy-five patients were referred to our institution. 71% were male, 29% female. 39% patients were considered ineligible for ASCT by the consulting transplant physician. Most patients were considered transplant ineligible due to comorbidities or poor performance status. Of the 46 patients eligible for ASCT, 52% underwent the procedure during their first-line therapy. The majority of those patients received reduced intensity melphalan (140 mg/m2) while 2 patients received conventional dosing (200 mg/m2). The other 22 patients eligible for ASCT declined or elected to defer the procedure and to be treated with conventional therapy. The characteristics of these three groups were similar and are detailed in Table 1. After a median follow-up of 30 months, 25% of the patients had expired. Estimated median overall survival (OS) was 71.3 months (unable to quantitate 95% CI) for all patients. Compared to transplant eligible patients, regardless of transplant receipt, those who were transplant ineligible had a 186% increase risk for death (HR 2.86; 95% CI 1.12-7.35; p = 0.029). There was also a notable trend for longer OS in those who underwent ASCT compared to those who were eligible but declined the procedure, but it was not statistically significant (HR 0.36; 95% CI 0.10-1.28; p = 0.114). At a transplant center, two-thirds of patients referred for newly diagnosed MM between the ages 75-78 were considered eligible for ASCT and one-third underwent the procedure. Outcomes were better for patients eligible for ASCT, regardless of whether they underwent the procedure. There was also a trend for better OS in patients who underwent the procedure compared to those who declined. While small sample sizes and the retrospective nature of the study limit our ability to draw conclusions, it appears that ASCT has an OS benefit among patients age 75-78. Disclosures Fiala: Incyte: Research Funding. Stockerl-Goldstein:AbbVie: Equity Ownership; Abbott: Equity Ownership. Vij:Genentech: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Takeda: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Wildes:Janssen: Research Funding; Carevive: Consultancy.

Comparison Of Sequential Vs Alternating Administration Of Bortezomib, Melphalan and Prednisone (VMP) and Lenalidomide Plus Dexamethasone (Rd) In Elderly Patients With Newly Diagnosed Multiple Myeloma (MM) Patients: GEM2010MAS65 Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 403-403 ◽  
Author(s):  
Maria-Victoria Mateos ◽  
Joaquín Martínez-López ◽  
Miguel T. Hernandez ◽  
Rafael Martinez ◽  
Laura Rosiñol ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Research Funding ◽  
Risk Groups ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Sequential Scheme ◽  
To Receive

Abstract Background VMP and Rd are two of the most efficient and widely accepted regimens in the treatment of elderly newly diagnosed MM patients. In order to further improve the outcome of elderly patients, one possibility would be to use regimens including all these drugs simultaneously, but this may result into high toxicity. Alternatively, the use of these regimens (VMP and Rd) in a sequential or alternating scheme could improve the treatment of elderly patients. We hypothesized the alternating scheme would minimize the emergence of resistant clones, and would reduce the cumulative toxicity. In order to test this hypothesis we decided to compare VMP and RD in a sequential vs an alternating scheme. Patients and methods 241 patients were randomized to receive a sequential scheme consisting on 9 cycles of VMP followed by 9 cycles of Rd or the same regimens in an alternating approach (one cycle of VMP alternating with one Rd (half of the patients started by VMP and half by Rd) up to 18 cycles). VMP included the iv administration of bortezomib 1.3 mg/m2 twice weekly for 1 six-weeks cycle, followed by once weekly for 8 four-weeks cycles in combination with oral melphalan 9 mg/m2 and prednisone 60 mg/m2 once daily on days 1–4 of each cycle. Rd treatment consisted on lenalidomide 25 mg daily on days 1-21 plus dexamethasone 40 mg weekly. Results 121 patients were allocated to receive the sequential scheme and 120 the alternating regimen. Both arms were well balanced according to the baseline characteristics. 52% patients in the sequential arm and 55% in the alternating and had high risk cytogenetic abnormalities (t(4;14), t(14;16), del17p or 1q gains). After 9 cycles of treatment, in the sequential arm, 35 out of 66 (54%) achieved at least VGPR vs 51 out of 65 patients (78%) in the alternating arm (p=0.002), including sCR/CR rate of 28% vs 38% in the sequential and alternating arms, respectively (p=NS). Seven patients in each arm achieved immunophenotypic CR. Moreover, while four patients progressed in the sequential arm under treatment with VMP, no patients in the alternating scheme developed disease progression during the first 9 cycles, After a median follow up of 12 months, there was a trend for shorter TTP in the sequential as compared with the alternating scheme (18 m-TTP of 83% vs 89% (p=NS)). In terms of OS, 83% of patients in the sequential arm were alive at 18 m versus 93% in the alternating (p=NS). Patients who achieved sCR/CR had a significantly longer 18 m-TTP as compared with patients who didn’t achieve it in both sequential (100% vs 71%; p=0.006) and alternating arms (100% vs 79%; p=0.006) and this translated into a significant benefit in OS. No differences were observed in overall response rates and CR rates in standard and high risk patients. The 18 m-TTP was similar in standard and high risk groups in both sequential (86% vs 81%) and alternating arms (84% vs 94%), noting that 94% of patients receiving the alternating scheme were progression-free at 18 months. Regarding hematologic toxicity, the frequency of G3-4 neutropenia was slightly lower in the sequential than in the alternating arm (16% and 23%) and the same trend was observed for G3-4 thrombocytopenia (16% vs 20%). Concerning non-hematologic toxicity, 5% and 4% of the patients in the sequential and alternating arms developed G3-4 infections, respectively; the rate of G3-4 skin rash was 4% in the sequential and 3% in the alternating arm; 4% of patients in the sequential arm developed G3-4 peripheral neuropathy and 3% in the sequential arm. The rate of grade 3-4 thrombotic events was 2% in both arms. Nevertheless, the detailed evaluation of the toxicity will be done at the completion of the trial when all patients will have received the same amount of drugs in either a sequential or an alternating scheme (at the present time, 42 patients in the sequential arm were not yet at risk for the development of lenalidomide-related side effects). Conclusions The administration of melphalan, bortezomib, lenalidomide and steroids in elderly MM patients in a sequential or alternating scheme is feasible. Although longer follow-up is necessary, the alternating scheme may be superior in terms of response rate and outcome, as result of the early exposure of the plasma cell to different agents. Toxicity profile is acceptable. Aparently both schemes of therapy seems to overcome the poor prognosis of high risk cytogenetic. Disclosures: Mateos: Janssen, Celgene: Honoraria. Off Label Use: Lenalidomide plus dexamethasone is not approved for newly diagnosed MM patients. Ocio:Onyx: Consultancy, Research Funding; Novartis: Consultancy; Array Biopharma: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; Celgene: Consultancy, Research Funding. San Miguel:Janssen, Celgene: Membership on an entity’s Board of Directors or advisory committees.

A Phase 1/2 Study of G-CSF, Cladribine, Cytarabine, and Dose-Escalated Mitoxantrone (G-CLAM) in Adults with Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1068-1068 ◽  
Author(s):  
Anna B. Halpern ◽  
Megan Othus ◽  
Emily M Huebner ◽  
Kaysey F. Orlowski ◽  
Bart L. Scott ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Induction Chemotherapy ◽  
Research Funding ◽  
Phase 1 ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Grade 3 ◽  
Dose Levels

Abstract Introduction:"7+3" with standard doses of cytarabine and an anthracycline has remained the mainstay of induction chemotherapy for newly diagnosed AML. Since some studies have shown improved outcomes with high-dose cytarabine, cladribine, or escalated doses of anthracyclines, we conducted a phase 1/2 study (NCT02044796) of G-CLAM using escalated doses of mitoxantrone for newly diagnosed AML or high-risk MDS (>10% blasts). Methods: Patients≥18 years were eligible if they had treatment-related mortality (TRM) scores of ≤6.9 (corresponding to a predicted risk of early death with standard induction chemotherapy of ≤6.9%) and adequate organ function (LVEF ≥45%, creatinine ≤2.0 mg/dL, bilirubin ≤2.5 times upper limit of normal). Excluded were patients with uncontrolled infection or concomitant illness with expected survival <1 year. In phase 1, cohorts of 6-12 patients were assigned to 1 of 4 total dose levels of mitoxantrone (12, 14, 16, or 18 mg/m2/day, days 1-3, compared to 10 mg/m2/day used in standard dose G-CLAM previously established in relapsed/refractory AML). Other drug doses were G-CSF 300 or 480 μg/day (for weight </≥76 kg; days 0-5), cladribine 5 mg/m2/day (days 1-5), and cytarabine 2 g/m2/day (days 1-5). In phase 2, patients were treated at the maximum tolerated dose (MTD) of mitoxantrone. A second identical course of G-CLAM was given if complete remission (CR) was not achieved with cycle 1. Up to 4 cycles of consolidation with G-CLA (mitoxantrone omitted) were allowed if CR or CR with incomplete platelet or blood count recovery (CRp/i) was achieved with 1-2 cycles of induction therapy. Dose-limiting toxicities (DLTs) were: 1) grade 3 non-hematologic toxicity lasting >48 hours that resulted in >7-day delay of the subsequent treatment cycle; 2) grade ≥4 non-hematologic toxicity if recovery to grade ≤2 within 14 days, both excluding febrile neutropenia, infection or constitutional symptoms. Results: Among 33 patients (median age of 57.3 [range: 26-77], median TRM score 2.31 [0.16-5.90]) treated in phase 1, one DLT occurred at dose levels 3 and 4 (respiratory failure in both cases), establishing G-CLAM with mitoxantrone at 18 mg/m2/day as the MTD. Sixty-two patients, including 6 treated in phase 1, received G-CLAM at MTD. Patient characteristics were as follows: median age 58 (21-81) years, median TRM score 2.85 (0.06-6.73), with AML (n=52) or high-risk MDS (n=10). Cytogenetics were favorable in 6, intermediate in 44, and adverse in 12 (MRC criteria); 11 patients had NPM1 and 6 had FLT3 mutations. Fifty-two patients (83.9%, 95% confidence interval: 72.3-92.0%) achieved a CR (n=48 [77.4%: 65.0-87.1%]), or CRp/i (n=4 [6.5%: 1.8-15.7%]) with 1-2 cycles of therapy. Only 3 patients required 2 cycles to best response. Among the 48 CR patients, 43 (89.6%) were negative for measurable residual disease (MRDneg) by flow cytometry. Four patients had morphologic leukemia free state, 1 patient with myeloid sarcoma had a partial remission, 4 had resistant disease, and 1 died from indeterminate cause. One patient died within 28 days of treatment initiation (septic shock). Median times to an absolute neutrophil count ≥500/μL and a platelet count of ≥50,000/μL were 26 and 23 days. Besides infections and neutropenic fever, maculopapular rash, and hypoxia (fluid overload/infection-related) were the most common grade ≥3 adverse events. In addition to the phase 1/2 MTD cohort, there were 15 patients treated in an expansion cohort and 3 eligible patients treated off protocol with mitoxantrone at 18 mg/m2. For these 80 patients combined treated at MTD, the CR and CR/CRp/i rates were 76.3% and 81.2%. After multivariable adjustment, compared to 300 patients treated with 7+3 on the SWOG S0106 trial, G-CLAM with mitoxantrone 18mg/ m2 was associated with an increased probability of CR (odds ratio [OR]= 3.08, p=.02), CR/CRp/i (OR=2.96, p=.03), a trend towards improved MRDnegCR (OR= 3.70, p=.06), and a trend towards improved overall survival ([OS]; hazard ratio=0.34, p=.07). For the entire study cohort, the 6 and 12-month relapse-free survival were 73% (64-83%) and 62% (42-74%) and the 6 and 12-month OS were 89% (82- 96%) and 77% (67-88%). Conclusions: G-CLAM with mitoxantrone up to 18 mg/m2/day is well tolerated and has potent anti-leukemia activity. This regimen may warrant further randomized comparison with 7+3. We also plan to examine the addition of sorafenib to G-CLAM in newly diagnosed AML patients regardless of FLT3 status. Disclosures Othus: Glycomimetics: Consultancy; Celgene: Consultancy. Scott:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Agios: Membership on an entity's Board of Directors or advisory committees. Becker:GlycoMimetics: Research Funding. Erba:Ariad: Consultancy; Gylcomimetics: Other: DSMB; Pfizer: Consultancy; Sunesis: Consultancy; Jannsen: Consultancy, Research Funding; Juno: Research Funding; Novartis: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy; Celgene: Consultancy, Speakers Bureau; Agios: Research Funding; Astellas: Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Celator: Research Funding; Seattle Genetics: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Amgen: Consultancy, Research Funding.

scholarly journals Outcomes of Newly Diagnosed Myeloma Patients Requiring Dialysis: Dialysis Independence Is Associated with Rapid Myeloma Response and Predicts for Longer Survival

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4492-4492
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Roussou ◽  
Maria Gavriatopoulou ◽  
Despina Fotiou ◽  
Dimitrios Ziogas ◽  
...  
Keyword(s):  
Renal Failure ◽  
High Risk ◽  
Supportive Care ◽  
Board Of Directors ◽  
Light Chain ◽  
Research Funding ◽  
High Dose ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
High Dose Dexamethasone

Abstract Renal failure (RF) is a common severe complication of symptomatic myeloma and may be severe enough to require extrarenal dialysis in approximately 1-5% of newly diagnosed patients. Severe RF is associated with high risk of early death and increased morbidity. Immediate effective anti-myeloma therapy and vigorous supportive care are the cornerstones of management. The use of high cutoff hemodialysis to rapidly reduce the load of nephrotoxic light chains seems to offer limited additional benefit in patients requiring dialysis when treated with bortezomib-based therapies (Cook M et al EHA 2016, Abs P270). However, outside clinical trials, there are limited data focusing on the management and outcomes of NDMM patients requiring dialysis. Thus, we analyzed the outcomes of consecutive newly diagnosed patients with RF requiring dialysis, who were managed and treated in a single center. Between 1995 and 2016, 50 patients (6.2% of 796 consecutive NDMM) who were treated in the Department of Clinical Therapeutics (Athens, Greece) presented with severe RF requiring dialysis. The analysis included all patients who received at least one dose of any therapy. All patients received similar supportive care and dialysis with regular filters. The median age of patients requiring dialysis was 69 years (37-88), 68% were >65 years of age. At presentation 92% had Hb <10 g/dl, 5 (10%) had platelet count <100x109/l, 12 (24%) had hypeprcalcemia (Ca ≥11.5 mg/dl) and 24 (48%) had elevated LDH (≥250 IU/l). All patients had elevated β2-microglobulin (median 21.7 mg/L, range 6-60 mg/l) and all were ISS stage 3. High risk cytogenetics (N=40) were present in 38% and per R-ISS, 75% were R-ISS-3 and 25% R-ISS-2. Myeloma was light chain only in 42%, IgA in 26%, IgG in 30% and IgD in 1 patient (2%); light chain was κ in 38 (64%) and λ in 18 (36%). Among patients who retained urine flow at presentation, median 24h Bence Jones proteinuria was 2.2 gr (range 0.1-8.8 gr). Among patients with available FLCs, median level of involved free light chain (iFLC) was 9080 mg/l (range 119-201000 mg/l). Treatment was bortezomib-based in 41 (82%) patients: 11 (22%) had bortezomib + dexamethasone (VD), 21 (42%) VD + cyclophosphamide (VCD), 8 (16%) VD + thalidomide (VTD), 1 (2%) VD + doxorubicin (PAD). Nine (18%) patients received non-bortezomib containing regimens: 5 (10%) thalidomide plus high dose dexamethasone and 4 (8%) VAD with high dose dexamethasone. Twenty-five (50%) patients became dialysis independent at a median time of 158 days from start of therapy (range 4-336 days). Age ≤65 years was associated with higher probability (75% vs 38%) and shorter time to dialysis independence (51 vs 336 days; p=0.027); no other baseline factors were associated with dialysis independence in univariate analysis. Among patients treated with bortezomib, three-drug combinations (n=30) vs VD alone (N=11) were associated with higher probability of dialysis independence (57% vs 27%; p=0.06). Among patients who became dialysis independent 12 received VCD, 4 VTD, one PAD, 3 VD, 2 MDT, 2 VAD and one T-VAD. Median follow up for all patients was 33 months and median survival was 29 months. Early mortality (within 2 months from start of therapy) was 16%, mostly due to infectious complications. On intent to treat, 64% achieved ≥PR (CR: 6%, VGPR: 32%, PR: 26%); among patients who survived >2 months, ≥PR was achieved by 76%. At 2-month landmark, patients who achieved ≥PR within the first 2 months had higher dialysis independence rates (68% vs 27%, p=0.004). Becoming dialysis independent was associated with a significant improvement in survival (median OS of 63 vs 22 months of patients who remained on dialysis; p=0.002), even after exclusion of early deaths. Notably, the survival of patients who discontinued dialysis was similar to that of the rest of patients (57 months). High dose melphalan (HDM) followed by autologous stem cell transplantation was performed in five patients while on dialysis. Four of them (80%) become dialysis independent approximately one month after HDM. In conclusion, about 6% of NDMM present with renal failure requiring dialysis but half of them can become dialysis independent after bortezomib-based therapy, without the use of special filters, especially if they achieve a rapid myeloma response. VD-based triplets increase the probability of renal response over VD alone and independence from dialysis is associated with a significant improvement in prognosis. Disclosures Dimopoulos: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: 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. Terpos:Celgene: Honoraria; Genesis: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria; BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel expenses, Research Funding. Kastritis:Takeda: Consultancy, Honoraria; Genesis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

No Improvement Of Overall Survival After Extended Follow-Up Of Donor Versus No Donor Analysis Of Newly Diagnosed Myeloma Patients Included In The HOVON 50/54 Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2132-2132 ◽  
Author(s):  
Henk Lokhorst ◽  
Bronno van der Holt ◽  
Jan Cornelissen ◽  
Marie José Kersten ◽  
Marinus H.J. Van Oers ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Survival Benefit ◽  
Research Funding ◽  
Phase Iii ◽  
High Dose ◽  
Newly Diagnosed ◽  
Donor Group ◽  
No Donor

Abstract Background The value of Allo-SCT in myeloma is heavily disputed. In our previous Donor versus No Donor (DvND) comparison we found no survival benefit of Allo-RIC in newly diagnosed myeloma. (Lokhorst et al:Blood 2012119: 6219-6225). However, a recent update of the EBMT-NMA 2000 trial (Gahrton el al:Blood 2013121: 5055-506) suggested that extended follow-up (> 5 years) may be necessary for a correct interpretation of a potential survival benefit for Allo-RIC. Here we present the extended follow-up of our trial, in which the median follow-up of patients now exceeds over 7.5 years since the first autologous SCT. Methods Patients with an HLA–identical sibling donor included in the phase III HOVON-50 study, that was designed to assess the role of thalidomide in induction treatment and maintenance after high-dose therapy (HDM 200 mg/m2), could proceed to the Hovon 54 study in which an Allo-SCT was performed after conditioning with low dose TBI only, between 2-6 months after HDM. Among the 536 eligible patients randomized in the HOVON-50 trial, ultimately 260 patients were eligible to be included into the DvND analysis: 122 patients with a donor, of whom 99 patients received an Allo-RIC and 138 without a donor, of whom 115 patients started maintenance therapy with thalidomide. Groups were comparable with regard to age, myeloma stage, and prognostic factors including cytogenetics and ISS stage. Results 93% of the patients in the no donor group achieved at least a PR (38% CR, 71% at least VGPR ), versus 96% of the patients in the donor group (43% CR, 73% at least VGPR). After a median follow-up of 91 months after HDM, PFS and OS were comparable between the two groups. In the intention to treat analysis median PFS was 29 months for the no donor group and 30 months the no donor group (P=0.25). Median OS was 76 for the donor group and 81 months for the no donor group (P=0.61). For the patients who actually received their allocated treatment (Allo-RIC or maintenance), PFS curves started to diverge after 3 years, however no statistical difference was observed (P=0.07). Allo-RIC improved the median overall survival from 73 to 94 months compared to patients receiving maintenance. However, due to frequent late mortality (> after 96 months) in the Allo-RIC group the benefit was not statistically significant (P=0.54). No subgroup including those achieving CR or those with high risk features (ISS, deletion of chromosome 13) did benefit from Allo-RIC. Conclusion This analysis failed to show improvement of tandem Auto Allo-RIC as part of first line therapy in myeloma as compared to Auto-SCT followed by maintenance therapy, even after extended follow-up. Disclosures: Lokhorst: Genmab A/S: Consultancy, Research Funding; Celgene: Honoraria; Johnson-Cilag: Honoraria; Mudipharma: Honoraria. Minnema:Janssen Cilag: Consultancy, Honoraria. Sonneveld:Janssen-Cilag: Honoraria; Celgene: Honoraria; Onyx: Honoraria; Janssen-Cilag: Research Funding; Millenium: Research Funding; Onyx: Research Funding; Celgene: Research Funding.

scholarly journals High Risk Older AML Patients May be Benefited from the Treatment of Decitabine Combined Wih CAG Regimens

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4953-4953
Author(s):  
Xia Xiao ◽  
Mingfeng Zhao ◽  
Qi Deng ◽  
Qing Li ◽  
Juan Mu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Adverse Events ◽  
Older Patients ◽  
Median Overall Survival ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Ecog Performance Status ◽  
Secondary Aml ◽  
Number Of Patients

Abstract Patients over age 60 maked up more than 50% of newly diagnosed patients with acute myeloid leukemia (AML). Futhermore, with an aging population, more and more older AML patients were diagnosed in China. But the treatment approaches of this disease were variable, with many uncertainties and controversies. Treatment options for older patients with adverse prognostic features, such as poor performance status, unfavorable cytogenetics or an antecedent hematologic disorder were limited, and outcomes were poor. Aggres­sive induction chemotherapy had a high mortality and relatively low efficacy in this population. There were several new therapeutic schemes for older patients with AML. CAG regimens consisting of low-dose cytarabine, aclarubicin and granulocyte-colony stimulating factor for the treatment of older patients with AML showed higher rates of CR (42-68%). Decitabine, a DNA-hypomethylating agent induces differentiation and apoptosis of leukemic cells. The current National Comprehensive Cancer Care guidelines suggested decitabine as alterative options for older patients with AML. Previous studies have shown that decitabine demonstrated efficacy in a phase II multicenter study of older patients with AML, with a CR rate of 25%, 30-day mortality of 7%, median overall survival 7.7 months and little extramedullary toxicity. In our study, decitabine(15 mg/m2/d, d1-5) combined with CAG regimens (aclarubicin 20 mg/d, d3-6, Ara-C 10 mg/m2, q12h, d3-9, G-CSF 300ug, qd, d1-9) treated 27 older patients with AML, repeated every 4 weeks. Effectiveness and safety were assessed. 27 older patients with newly diagnosed AML who were in Tianjin First Central Hospital of China from January 2011 to December 2013 were enrolled in our study. They were all treated with decitabine combined with CAG regimens. The characteristics of the 27 patients were described in Table I. The study population included 15 males and 12 females, with a median age of 68 years (range 60-79 years). All patients had Eastern Cooperative Oncology Group (ECOG) performance status of <3. Cytogenetics were classified according to criteria of the Cancer and Leukemia Group B(CALGB), and were adverse in 11 patients (40.7%) and intermediate in 16 patients (59.3%). No patient had favorable cytogenetics. 12 patients (44.4%) had secondary AML or an antecedent MDS or myeloproliferative disorder. Molecular diagnostics with mutations of FLT3-ITD in 6 patients (22.2%), NPM1 in 7 patients (25.9%) patients and JAK-2 in 4 patients (14.8%). Clinical responses, survival and adverse events of all 27 patients were analyzed. The median treatment cycle was 4 cycles. Rate of complete remission, overall response rate and a 30-day mortality rate were 40.1%, 66.7%, 7.4%, respectively. The median overall survival and median recurrence-free survival were 13.0months (95%CI, 7.0-18.0 months ) and 7.0 months (95%CI, 3.0-11.0 months), respectively. Adverse events in the regimens were mainly included myelosuppression, infection, nausea, vomiting and liver dysfunction. The adverse events could be well tolerated after managements. In conclusion, the treatment of decitabine combined with CAG regimens was found to be feasible and useful in high-risk older patients with AML. This regimen was a well-tolerated therapeutic alternative, was effective in producing remissions lasting several months or disease stabilization in high-risk older patients with AML. Table 1. The characteristics of newly diagnosed patients with AML Total number of patients n=27 median age(range) 68 years(60-79 years) Male/female 15/12 (1.25/1) ECOG performance status, n (%) 0 5 (18.5%) 1 10 (37.0%) 2 12 (44.4%) Cytogenetics, n (%) Adverse 11 (40.7%) Intermediate 16 (59.3%) secondary AML, n (%) MDS 6 (22.2%) myeloproliferative 5 (18.5%) Other tumors 1 (3.7%) Molecular mutations, n (%) FLT3-ITD 6 (22.2%) NPM1 7 (25.9%) JAK-2 4 (14.8%) Disclosures No relevant conflicts of interest to declare.

scholarly journals Final Safety and Efficacy Results from the CPX-351 Early Access Program (EAP) for Older Patients with High-Risk/Secondary Acute Myeloid Leukemia (sAML)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1434-1434
Author(s):  
Gail J. Roboz ◽  
Melissa L. Larson ◽  
S. Eric Rubenstein ◽  
Scott R Solomon ◽  
Gary J. Schiller ◽  
...  
Keyword(s):  
High Risk ◽  
Older Patients ◽  
Research Funding ◽  
De Novo ◽  
Newly Diagnosed ◽  
Open Label ◽  
Employment Equity ◽  
Phase 3 ◽  
Equity Ownership ◽  
De Novo Aml

Abstract Background: CPX-351 (Vyxeos®) is a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio. In a large randomized, open-label, multicenter, phase 3 study of CPX-351 versus conventional cytarabine/daunorubicin chemotherapy (7+3 regimen) in adults aged 60-75 years with newly diagnosed high-risk/sAML, patients treated with CPX-351 had significantly longer survival times and higher remission rates (Lancet JE, et al. J Clin Oncol. 2018). Based on these results, CPX-351 was approved by the US FDA in 2017 for the treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes (AML-MRC). This abstract reports the results of an EAP study that provided expanded access to CPX-351 for older patients who met the eligibility criteria for the phase 3 study and collected additional data on safety and efficacy. Methods: In this phase 4, single-arm, open-label EAP, patients were between 60-75 years of age and had confirmed high-risk/sAML (therapy-related AML [tAML], AML with a history of myelodysplasia [MDS] or chronic myelomonocytic leukemia [CMML], or de novo AML with MDS karyotype). Patients could receive up to 2 cycles of induction with CPX-351 100 units/m2 (cytarabine 100 mg/m2 + daunorubicin 44 mg/m2) on Days 1, 3, and 5 (2nd induction: Days 1 and 3). Patients with complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 4 cycles of consolidation with CPX-351 65 units/m2 (cytarabine 65 mg/m2 + daunorubicin 28.6 mg/m2) on Days 1 and 3. The primary endpoint was safety, and the secondary endpoint was the rate of CR+CRi. Results: Overall, 52 patients received ≥1 dose of CPX-351 and were included in the safety analysis. Among these patients, the median age was 70 years (range: 55-75) and 23% had an Eastern Cooperative Oncology Group score of 2. Median time since diagnosis was 0.30 months (range: 0.03-36.14) months. Patients with AML-MRC accounted for 77% of the safety analysis population, including those with antecedent MDS with prior hypomethylating agent (HMA) treatment (25%), antecedent MDS without prior HMA treatment (21%), antecedent CMML (8%), and de novo AML with MDS karyotype (23%); 23% of patients had tAML. All patients received 1 induction cycle and 25% received 2 induction cycles; 17%, 8%, 4%, and 2% of patients received 1, 2, 3, and 4 consolidation cycles, respectively. CR+CRi was achieved in 23 patients (44% [95% CI: 31%, 59%]), including 15 with CR (29% [95% CI: 17%, 43%]) and 8 with CRi (15% [95% CI: 7%, 28%]; Table). The median time to remission was 37 days (range: 15-72). At the end of the study, 47 (90%) of patients were still alive and 11 (21%) patients received transplant. All patients were alive at Day 30, and the mortality rate at Day 60 was 6%. The safety profile observed in this EAP study was consistent with that of the phase 3, randomized study (Table). Treatment-emergent adverse events (TEAEs) of any grade occurred in 96% of patients, including 44% of patients with an TEAE deemed related to treatment; the only treatment-related AE that occurred in >10% of patients was febrile neutropenia (31%). Only 2 patients (4%) discontinued treatment due to an AE (ejection fraction decrease and intercranial hemorrhage [n = 1 each]). Five patients (10%) had grade 5 AEs during the study, including disease progression, multiple organ dysfunction syndrome, acute respiratory distress syndrome, aspiration, and intracranial hemorrhage (n = 1 each). Conclusions: The data from this EAP study were consistent with results from the randomized, phase 3 study. The safety profile in the EAP study was similar to that observed in the phase 3 study and there was a similar CR+CRi rate (44% vs 48%, respectively) in this high-risk/sAML population. Disclosures Roboz: Sandoz: Consultancy; Cellectis: Research Funding; Argenx: Consultancy; Bayer: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Aphivena Therapeutics: Consultancy; Sandoz: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy; Novartis: Consultancy; Celgene Corporation: Consultancy; Celltrion: Consultancy; Jazz Pharmaceuticals: Consultancy; Roche/Genentech: Consultancy; Eisai: Consultancy; Otsuka: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy; Eisai: Consultancy; Otsuka: Consultancy; Orsenix: Consultancy; Celltrion: Consultancy; AbbVie: Consultancy; Daiichi Sankyo: Consultancy; Aphivena Therapeutics: Consultancy; Bayer: Consultancy; Argenx: Consultancy; Jazz Pharmaceuticals: Consultancy; Astex Pharmaceuticals: Consultancy; Cellectis: Research Funding; Orsenix: Consultancy; Pfizer: Consultancy. Rubenstein:Alexion: Consultancy, Honoraria, Speakers Bureau; Cyclacel: Other: Travel support; Astex: Other: Travel support. Schiller:Celator/Jazz Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding. An:Jazz Pharmaceuticals: Employment. Mancino:Jazz Pharmaceuticals: Employment. Chiarella:Celator/Jazz Pharmaceuticals: Employment, Equity Ownership. Louie:Celator/Jazz Pharmaceuticals: Employment, Equity Ownership, Patents & Royalties. Lin:Jazz Pharmaceuticals: Honoraria.

scholarly journals The Incidence of Thromboembolism for Lenalidomide Versus Thalidomide in Older Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 361-361
Author(s):  
Ang Li ◽  
Qian V. Wu ◽  
Greg Warnick ◽  
Edward N. Libby ◽  
David A. Garcia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Propensity Score ◽  
Older Patients ◽  
Research Funding ◽  
The United States ◽  
Immunomodulatory Drugs ◽  
Newly Diagnosed ◽  
Treatment Groups ◽  
To Receive

Abstract Introduction: Chemotherapy backbones with immunomodulatory drugs have become the standard of care for the treatment of multiple myeloma (MM). Despite improved survival outcomes, thrombotic complications remain a concern especially in the older patients with co-morbidities. A meta-analysis showed that lenalidomide might be associated with lower rate of thromboembolism than thalidomide-containing regimen in patients with newly diagnosed MM with (0.7 vs. 2.6 per 100-patient-cycle) or without prophylaxis (0.8 vs. 4.1 per 100-patient-cycle) (JTH 2011;9:653). As thalidomide is still commonly used outside of the United States, it is important to understand if the thromboprophylaxis guideline is generalizable to all immunomodulatory drugs. However, no prior study has directly compared the thrombotic incidence between the two regimens while accounting for confounders. In the current propensity score weighted study, we have examined the incidence of venous (VTE) and arterial (ATE) thromboembolism and survival for older patients with newly diagnosed MM treated with lenalidomide- versus thalidomide-containing regimen. Methods: We performed a retrospective cohort study using the SEER-Medicare database and selected all patients 66 or older with newly diagnosed MM 2007 to 2013. Patients were included if they had a prescription of IMID within twelve months of diagnosis and complete enrollment for fee-for-service and prescription drug coverage. Patients were followed from the IMID index date until first VTE occurrence or death and they were censored for disenrollment from Medicare A/B/D, enrollment in health maintenance organization, or 12/31/2014. We defined VTE (including pulmonary embolism and deep vein thrombosis) and ATE (including acute stroke and myocardial infarction) using previously validated ICD-9-CM codes with positive predictive value of 75-95% (Thromb Res 2010;126:61, Am Heart J 2004;148:99, Stroke 2014;45:3219). We used inverse probability of treatment weighting (IPTW) to balance potential confounders (demographics, year of diagnosis, co-morbidities, concurrent medications) where a standardized difference (SD) of <0.1 was considered adequate balance. Weighted Kaplan-Meier curves and Cox models (HR) were used to compare overall survival. Weighted cumulative incidence curves and Fine-Gray subdistribution hazards models (SHR) were used to compare VTE and ATE incidence where death was treated as a competing risk. Variance was estimated via 200 bootstraps. Results: Among 2397 older MM patients that met the study criteria, 78% received lenalidomide (n=1863) and 22% thalidomide (n=534). There was a strong temporal trend of increasing lenalidomide use over time (Table 1). The lenalidomide group was more likely to receive bortezomib and lower dose of dexamethasone and less likely to receive anticoagulant prophylaxis. All confounders were balanced between the two treatment groups after IPTW. The 12-month incidence of VTE (10%) and ATE (5%) were similarly high in both groups (Figure 1a-b). Lenalidomide vs. thalidomide had a SHR of 1.11 (0.59-2.02) for VTE and a SHR 0.96 (0.45-1.98) for ATE. Overall survival was also not significantly different with a HR of 0.88 (0.60-1.18) for lenalidomide vs. thalidomide. Conclusion: In this propensity score weighted study of older patients with newly diagnosed MM, the cumulative incidences of VTE and ATE were similarly high in both lenalidomide- and thalidomide-treatment groups. The lack of difference in overall survival should be interpreted with caution as residual confounding such as severity of disease could influence this outcome. Our results suggest that appropriate risk stratification and vigilant thromboprophylaxis remain essential for MM patients receiving all types of immunomodulatory drugs. Disclosures Garcia: Retham Technologies LLC: Consultancy; Shingoi: Consultancy; Portola: Research Funding; Boehringer Ingelheim: Consultancy; Bristol Meyers Squibb: Consultancy; Janssen: Consultancy, Research Funding; Incyte: Research Funding; Daiichi Sankyo: Research Funding; Pfizer: Consultancy. Lyman:Amgen: Other: Research support; Halozyme; G1 Therapeutics; Coherus Biosciences: Consultancy; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees.

Analysis of 179 Patients with Newly Diagnosed Multiple Myeloma (MM) Treated with Novel Agents Followed by Autologous Stem Cell Transplantation (ASCT): a Retrospective Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1343-1343
Author(s):  
Joyce Habib ◽  
Neil Dunavin ◽  
Gary Phillips ◽  
Patrick Elder ◽  
Meaghan Tranovich ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Genetic Profile ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Abstract 1343 Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States with an estimated 20,580 new cases in 2009. Over the past decade, the introduction of novel agents (thalidomide, lenalidomide and bortezomib) have played a pivotal role in improving response rates, duration of response, overall survival (OS) and quality of life. In this study we describe a single center experience with novel agents used for induction followed by high dose chemotherapy (HDT) and first autologous stem cell transplant (ASCT) in patients with MM. Method: A retrospective review of the medical records of 179 newly diagnosed patients with MM seen between October 2006 and December 2009 at The Ohio State University was performed. All patients received novel therapy containing thalidomide, bortezomib or lenalidomide as part of an induction regimen followed by ASCT. All patients received melphalan 140mg/m2 or 200mg/m2 as preparative regimen. Kaplan-Meier estimates were used to plot progression free survival and overall survival. Results: Of the 181 patients seen, 2 were excluded because they did not receive a novel agent as part of induction treatment. Of the 179 patients analyzed, median age was 56.8 years (29-80) with 30% of patients older than 60 years. African American represented 19%. Fifty-nine percent were male, 80% had Durie-Salmon (DS) stage III while 25%, 28%, 18% represented International prognostic score (IPS) stage I, II, and III respectively with 27% unknown. Median comorbidity index score was 2 (2-7) and median Karnofsky performance score (KPS) was 90% (70-100). Thirty percent had high risk genetic profile, and 73% received one line of treatment before ASCT. The median time from diagnosis to ASCT was 8.33 months (4-58). The overall response rate (ORR) prior to transplant was 84% (9% complete (CR), 29% very good partial (VGPR), and 46% partial (PR)). The ORR post ASCT was 89% (CR 45%, VGPR 22%, PR 21%). Non relapse mortality was 1% and 3% at 100 days and 1 year respectively. At a median follow up of 31 months (7-90), 69 patients (38%) had relapsed. Median progression free survival (PFS) was 29 months with 1 and 3 years PFS of 79.3% and 61.5% respectively (Fig. 1). The OS was not reached. One and 3 years OS were 93% and 88% respectively (Fig. 1). Univariate analysis showed that time to transplant > 12 months was associated with poor outcome and decreased overall survival (HR 3.30, p = 0.008). High risk genetic profile was also found to be associated with decreased overall survival although this was not statistically significant (HR 2.31, p = 0.070). Multivariate analysis found that only time to transplant > 12 months was an independent predictor of decreased OS. Significant predictors for disease progression were high risk genetic profile and time to transplant > 12 months in patients receiving 2 or more treatments before ASCT. Conclusion: Induction with novel agents followed by HDT and ASCT improves CR rate, in our case from 9% to 45%. Median PFS (29 months) was comparable to other published data. OS was not been reached after a median follow up of 31 months. Predictors of progression include high risk genetic profile and time to transplant > 12 months. The only significant predictor for survival was time to transplant. Our study suggests that an early transplant may improve OS and PFS. An extended analysis will be presented at the meeting. Disclosures: Phillips: NCI/NIH: Research Funding; NCCM Grant: Research Funding; ARRA RC2 Grant: Research Funding. Byrd:Genzyme Corporation: Research Funding.

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