scholarly journals Allogeneic STEM Cell Transplantation in 45 Patients with Myelodysplastic Syndrome: Single-Center Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4913-4913
Author(s):  
Helena Pomares ◽  
Rocio Parody Porras ◽  
Alberto Mussetti ◽  
Mercedes Galiano ◽  
Clara Maluquer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Myelogenous Leukemia ◽  
Advisory Committees ◽  
Allogeneic Hct ◽  
Increased Risk ◽  
First Choice

Abstract Background: Myelodysplastic syndromes (MDS) includes a group of clonal myeloid neoplasms characterized by cytopenias due to ineffective hematopoiesis, abnormal blood and marrow cell morphology, and an increased risk of transformation to acute myelogenous leukemia (AML). Allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapeutic option for patients with MDS. Aim: To analyze the clinical features and evolution of the MDS patients who underwent to HCT in our institution. Methods: Between July 2006 to January 2021, forty-five patients with MDS underwent allogeneic HCT at the Institut Català d'Oncologia, Hospital Duran i Reynals in Barcelona. Median age at HCT was 56 years (range 35 - 69 years). Thirty-two patients (64%) were male. The diagnosis of patients according to the 2016 WHO classification was: 22% MDS-MLD, 29% MDS-EB-1, 18% MDS-EB-2, 20% CMML, 4% MDS with isolated del(5q) and 7% unclassifiable MDS. Seven patients (15%) underwent allogeneic HCT after progression to AML. Treatments received before the transplant were: chemotherapy AML-like 11 patients (24%) and Azacitidine 24 patients (53%). Ten patients (23%) underwent HCT upfront. Results: Median time from diagnosis to allogeneic HCT was 5 months (range 2 - 12 months). Donors were: matched related (MRD) 17 (38%), matched unrelated (MUD) 12 (27%) and haploidentical 16 (35%). For HLA-MRD transplants, 12 patients received busulfan and fludarabine, 2 patients received TBI and cyclophosphamide, and 3 received busulfan, cyclophosphamide and thiotepa. All of them received tacrolimus or cyclosporine with methotrexate. For HLA-MUD transplants, 7 patients received busulfan and fludarabine, 1 received busulfan and cyclophosphamide, 2 received fludarabine and melphalan, and 2 received busulfan, cyclophosphamide and thiotepa. Six patients received tacrolimus or cyclosporine with methotrexate, 3 patients received tacrolimus with sirolimus and 3 patients received posttransplant cyclophosphamide . For recipients of haploidentical transplants, 6 patients received fludarabine, busulfan and cyclophosphamide, 4 patients received busulfan, thiotepa and fludarabine, 5 patients received fludarabine, cyclophosphamide and TBI and 1 patient received TBI and cyclophosphamide. All patients received tacrolimus or cyclosporine with mycophenolate and posttransplant cyclophosphamide. Five patients (11%) received myeloablative conditioning and 40 patients (89%) received a reduced intensity conditioning regimen. According to graft soure,5 patients (11%) received bone marrow grafts and 40 patients (89%) received peripheral blood grafts. Grade II-IV acute GVHD at day +100 was observed in 19/41 patients (39%) and chronic GVHD in 15/35 patients (42%). Four patients (8%) presented veno occlusive disease. Cytomegalovirus reactivation was reported in 19/38 (50%), and possible/probable invasive fungal infection was reported in 4/49 (8.2%) patients. Median follow-up from MDS diagnosis was 47 months (range 9 - 252 months). At the time of last follow up, 23 patients (51%) are still alive. Median overall survival (OS) was 20 months (range 2 - 180 months). Median progression-free survival (PFS) after transplant was 17 months (range 3 - 180 months). No significant differences were found in OS between the donor types (P = .234) (Figure 1). However, there was a trend for improved PFS in the MRD group, with 2-year PFS of 88%, 58% and 66% for MRD, MUD, and haploidentical recipients, respectively (P = .084) (Figure 2). Summary/Conclusion: Although statistical power is limited, these data suggests that MRD should be the first choice as donor transplant. MUD and haploidentical donors are an acceptable approach for patients without an HLA-matched donor. Figure 1 Figure 1. Disclosures Mussetti: GILEAD: Other: Clinical trials participation, Research Funding; TAKEDA: Honoraria; NOVARTIS: Honoraria, Other: Clinical trials participation. Sureda: Roche: Other: Support for attending meetings and/or travel; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; GSK: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Arnan: Jazz: Other: Participation in clinical trials; Takeda: Other: Participation in clinical trials; BMS/Celgene: Consultancy, Other: Participation in clinical trials; Novartis: Consultancy, Other: Participation in clinical trials; Astellas: Consultancy.

Allogeneic Hematopoietic Cell Transplantation for Consolidation of VGPR or CR In Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4581-4581
Author(s):  
Taiga Nishihori ◽  
Jose L. Ochoa-Bayona ◽  
Joseph Pidala ◽  
Kenneth H. Shain ◽  
Daniel Sullivan ◽  
...  
Keyword(s):  
Single Dose ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Induction Therapy ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Advisory Committees ◽  
Allogeneic Hct ◽  
One Year

Abstract Abstract 4581 Allogeneic hematopoietic cell transplantation (HCT) from HLA-identical siblings has been shown to prolong survival of patients with multiple myeloma in some studies. However, all published clinical trials of up front allogenic transplant for myeloma were conducted before thalidomide, lenalidomide and bortezomib became available; as such, less than 10% of the patients were in complete remission (CR) at time of transplantation. With contemporary therapy incorporating novel agents, more than 50% of patients achieve very good partial response (VGPR) or better (VGPR or CR). We summarize our experience with the safety and efficacy of allogeneic transplantation for patients achieving VGPR or better following induction therapy containing novel agent(s). Thirteen myeloma patients with first VGPR or CR received allogeneic HCT between July 2007 and January 2011. Median age at transplant was 45 years (range, 25 – 59), median time from initial therapy to transplant was 236 days (range, 122 – 410). Six patients (46%) have high-risk cytogenetics/FISH. Five patients received bortezomib plus lenalidomide induction therapy and eight patients received bortezomib-induction. Three patients (23%) underwent autologous HCT with melphalan plus bortezomib conditioning (melphalan 100 mg/m2 for 2 days followed by bortezomib 1.3 mg/m2) subsequent to induction therapies to achieve further cytoreduction prior to allogeneic HCT. Median number of prior therapies was 2 (range, 1–2). Disease status at the time of allogeneic HCT was stringent CR (n=5), CR (n=3), and VGPR (n=5). All patients received unmanipulated peripheral blood stem cell grafts from HLA-matched sibling donors (n=5) and HLA-matched unrelated donors (n=8). Six patients received fludarabine 30 mg/m2 for 4 days and melphalan 70 mg/m2 for 2 days followed by a single dose of bortezomib 1.3 mg/m2 (Flu/Mel/Vel). Seven patients received fludarabine 40 mg/m2 for 4 days and melphalan 70 mg/m2 for 2 days (Flu/Mel). Graft-versus-host disease (GVHD) prophylaxis constitutes tacrolimus/methotrexate (n=5), tacrolimus/mycophenolate mofetil (n=4), and tacrolimus/sirolimus (n=4). All patients achieved neutrophil engraftment after a median of 17 days (range, 11 – 19), and all patients achieved platelet engraftment after a median of 17 days (range, 12 – 21). All patients established stable donor cell chimerism. Best responses after allogeneic HCT were sCR (n=10), CR (n=2) and VGPR (n=1). The cumulative incidence of grades 2–4 acute GVHD at day 100 was 57% (95% CI 0.30 – 1.00) with Flu/Mel conditioning and 33% (95% CI 0.11 – 1.00) for Flu/Mel/Vel conditioning, respectively (p=0.24). This observation suggests that a single dose of bortezomib 48 hours before HCT may prevent GVHD. One patient died of GVHD complications, 1 had disease progression and 11 remain alive, progression free with a median follow-up of one year (range 4 months to 4 years). The one year progression-free survival estimate is 90% (95%CI 0.71 – 1.00). These initial data indicate that allogenic transplant for myeloma in VGPR or CR is well tolerated. Longer follow-up is required to assess the efficacy of allogeneic HCT in the era of novel agents in preventing progression of the disease. Disclosures: Baz: Millenium: Research Funding, Speakers Bureau; Celgene: Research Funding. Alsina:Millennium: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Allergan: Research Funding.

scholarly journals Outcome of Autologous Stem Cell Transplantation in Waldenström's Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2149-2149
Author(s):  
Romil Patel ◽  
Neeraj Y Saini ◽  
Ankur Varma ◽  
Omar Hasan ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
First Remission ◽  
Relapsed Disease

Abstract Introduction: The role of autologous hematopoietic stem cell transplantation (auto-HCT) in the management of patients with Waldenström Macroglobulinemia (WM), a rare, indolent lymphoma, has not been established. We had previously published our experience with auto-HCT in a small cohort of WM patients1. Here, we present an updated analysis of auto-HCT with a larger cohort of WM patients. Methods and study population: The study cohort was comprised of 29 patients who underwent high-dose chemotherapy and auto-HCT at MD Anderson Cancer Center (MDACC). The Kaplan-Meier method was used to create survival curves. Overall survival (OS) was defined as the duration from date of transplant to death or last date of follow-up in living patients. Progression-free survival (PFS) was defined as the duration from date of transplant to either progressive disease or death, whichever occurred first. Results: Median age at auto-HCT was 60 (range, 43-75 years). Eight patients (28%) had concurrent light chain amyloidosis (AL). Of the five patients who had MYD88 testing completed, 3 were positive for the MYD88 mutation. Additionally, of these 3 patients, 2 were also positive for CXCR4 mutation. Patients received a median of 2 lines (range 1-6) of therapy prior to auto-HCT; 3(10%) patients had primary refractory disease, 8(28%) were in first remission, and 18 (62%) had relapsed disease. Median time from transplant to last follow-up for the surviving patients was 5.3 years. Preparative regimens received by the patients were: Melphalan (n=20), BEAM-R (n=2), Busulfan/Melphalan (n=1), Cyclophosphomaide/Etoposide/total body irradiation (n=1), Thiotepa/Busulfan/Cyclophosphamide (n=1), and Carmustine/Thiotepa (n=1). Three patients further went on to receive allogeneic transplant either after relapse from auto-HCT or due to disease transformation to aggressive lymphoma. Twenty-eight patients achieved engraftment with a median time to neutrophil engraftment of 11 days (range, 10-15 days). One patient suffered primary graft failure due to progression of disease and died 84 days after transplant. Non-relapse mortality was 3.4% at 1 year. All patients were eligible for response evaluation. The median OS from diagnosis was 12.2 years. Overall response rate was 96%: complete response (n=8, 27.6%), very good partial response (n=5, 17.3%), partial response (n=15, 51.7%), and progressive disease (n=1, 3.4%). PFS and OS at 5 years were 43.3% and 62.9%, respectively. Median PFS and OS from auto-HCT were 4.1 and 7.3 years (Fig. 1A). The median OS from auto-HCT in first remission + primary refractory and relapsed disease was 8.2 years and 4.1 years, respectively.16 patients were alive at the time of censoring while 13 patients had died. Causes of death include relapsed disease (n=6), secondary malignancy (n=2), infection (n=1), chronic graft-versus-host disease (n=1), and unknown (n=3). 8 patients (28%) were positive for concurrent AL amyloidosis. The sites of amyloid involvement were kidneys (n=2), lungs (n=1), bone marrow (n=1), heart(n=1), lymph nodes(n=1), gastrointestinal tract (n=1) and subcutaneous fat aspirate(n=5). The median overall survival for patients with amyloid involvement (n=8) was 12 years. On univariate analyses, the number of chemotherapy regimens prior to transplant (≤ 2 vs >2 lines) was the strongest predictor of overall survival (p=0.03, HR 0.3, CI: 0.09-0.9, log-rank) and PFS (p=0.001, HR 0.24, CI: 0.07-0.85, log-rank). The median PFS in patients with ≤ 2 lines and > 2 lines of therapy was 71 months versus 19 months, respectively (Fig. 1B). Conclusion: Auto-HCT is safe and feasible in selected patients with WM, with a high response rate and durable remission even in patients with relapsed or refractory disease. References: Krina Patel et.al. Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia. Blood 2012 120:4533; Disclosures Thomas: Celgene: Research Funding; Bristol Myers Squibb Inc.: Research Funding; Acerta Pharma: Research Funding; Array Pharma: Research Funding; Amgen Inc: Research Funding. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Orlowski:Takeda: Consultancy; Celgene: Consultancy; Spectrum Pharma: Research Funding; Janssen: Consultancy; Kite Pharma: Consultancy; Sanofi-Aventis: Consultancy; BioTheryX: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. Patel:Poseida Therapeutics, Inc.: Research Funding; Takeda: Research Funding; Abbvie: Research Funding; Celgene: Research Funding.

Stem Cell Transplantation Can Provide Durable Disease Control in Blastic Plasmacytoid Dendritic Cell Neoplasia (BPDC): A Retrospective Study From the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3077-3077
Author(s):  
Sascha Dietrich ◽  
Damien Roos-Weil ◽  
Ariane Boumendil ◽  
Emanuelle Polge ◽  
Jian-Jian Luan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Nk Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Advisory Committees

Abstract Abstract 3077 Blastic plasmacytoid dendritic cell neoplasm (BPDC), formerly known as blastic NK cell lymphoma, is a rare hematopoietic malignancy preferentially involving the skin, bone marrow and lymph nodes. The overall prognosis of BPDC is dismal. Most patients show an initial response to acute leukemia-like chemotherapy, but relapses with subsequent drug resistance occur in virtually all patients resulting in a median overall survival of only 9–13 months. However, anecdotal long-term remissions have been reported in young patients who received early myeloablative allogeneic stem cell transplantation (alloSCT). We therefore performed a retrospective analysis of patients identified in the EBMT registry in order to evaluate the outcome of autologous stem cell transplantation (autoSCT) or alloSCT for BPDC. Eligible were all patients who had been registered with a diagnosis of BPDC or Blastic NK cell lymphoma and had received autologous stem cell transplantation (autoSCT) or alloSCT in 2000–2009. Centres were contacted to provide a written histopathology and immunophenotyping report and information about treatment and follow-up details. Patients who did not have a diagnostic score ≥ 2 as proposed by Garnache-Ottou et al. (BJH 2009) were excluded. RESULTS: Overall, 139 patients could be identified in the database who fulfilled the inclusion criteria (alloSCT 100, autoSCT 39). Of 74 patients for whom the requested additional information could be obtained, central review confirmed the diagnosis of BPDC in 39 patients (34 alloSCT, 5 autoSCT). The 34 patients who had undergone alloSCT had a median age of 41 years (range: 10–70 years), were transplanted from a related (n=11) or unrelated donor (n=23); received peripheral blood stem cells (n=9), bone marrow stem cells (n=19) or cord blood (n=6); and had been treated with a reduced intensity conditioning regimen (RIC, n=9) or myeloablative conditioning (MAC, n=25). Nineteen of 34 patients were transplanted in CR1. After a median follow up time of 28 months (range: 4–77+ months), 11 patients relapsed (median time to relapse: 8 months, range: 2–27 months) of whom 8 died due to disease progression. 9 patients died in the absence of relapse. No relapse occurred later than 27 months after transplant. Median disease free survival (DFS) was 15 months (range: 4–77+ months) and median overall survival (OS) was 22 months (range: 8–77+ months; Figure 1a). However, long-term remissions of up to 77 months after alloSCT could be observed. Patients allografted in CR1 tended to have a superior DFS (p=0.119) and OS (p=0.057; Figure 1b). MAC was associated with a better OS (p=0.001) which was attributable to the significantly higher non-relapse mortality (NRM) rate of patients after RIC (p=0.014), who had been significantly older (age RIC: 56 years, age MAC: 36 years, p=0.0014). The relapse rate was not different in patients after RIC and MAC, respectively. However, there was no survivor after RIC. Median age in the autoSCT group was 47 years (range: 14–62 years). Three of 5 patients were transplanted in CR1 of whom 1 patient relapsed after 8 months, 1 patient experienced treatment related mortality and 1 patient remained in CR for 28 months. The 2 remaining patients had more advanced disease at autoSCT and relapsed 4 and 8 months thereafter. CONCLUSION: AlloSCT is effective in BPDC and might provide curative potential in this otherwise incurable disease, especially when performed in CR1. However, it remains to be shown by prospective studies if the potential benefit of alloSCT in BPDC is largely due to conditioning intensity, or if there is a relevant contribution of graft-versus-leukemia activity. Disclosures: Tilly: Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, Travel/accommodations/meeting expenses; Genentech: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding, Speakers Bureau; Pfizer: Speakers Bureau; Janssen Cilag: Speakers Bureau.

Updated Outcomes of Fludarabine/Melphalan/Bortezomib (Flu/Mel/Vel) Conditioning for Upfront Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5885-5885
Author(s):  
Taiga Nishihori ◽  
Claudio Anasetti ◽  
Rachid Baz ◽  
Jose L Ochoa-Bayona ◽  
Kenneth H. Shain ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Advisory Committees ◽  
Allogeneic Hct ◽  
Genetics Research ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors

Abstract Background: Multiple myeloma remains incurable despite impressive array of available novel agents and therapeutic strategies. Allogeneic hematopoietic cell transplantation (HCT) remains the only potentially curative option for patients with multiple myeloma but it is limited by its toxicities. We previously reported initial result of a phase 2 study of upfront allogeneic HCT in myeloma patients achieving at least very good partial response (VGPR) after initial therapy (Nishihori, et al. ASH 2013 abstract 3390) and here we report more mature results after a median follow up of 3 years. Methods: Twenty seven myeloma patients received allogeneic HCT between 01/2010 and 02/2015 at Moffitt Cancer Center (NCT 00948922). Eligible patients were age ≤ 60, achieving first ≥ VGPR or complete response (CR), and have 8/8 HLA-matched related or unrelated donors. Conditioning regimen consisted of fludarabine 30 mg/m2 for 4 days (days -6, -5, -4, and -3) and melphalan 70 mg/m2 for 2 days (days -4 and -3) followed by a single dose of bortezomib 1.3 mg/m2 on day -3 (Flu/Mel/Vel regimen). GVHD prophylaxis was initially left to the discretion of physicians but later modified to only tacrolimus/methotrexate. No maintenance therapy was prescribed after allogeneic HCT. Results: The median age at transplant was 50 (range, 25-58) years. Disease status at the time of allogeneic HCT was VGPR (n=17: 63%) and CR/stringent CR (n=10: 37%). All patients received unmanipulated peripheral blood stem cell grafts from HLA-matched related donors (n=14) or HLA-matched unrelated donors (n=13). Graft-versus-host disease (GVHD) prophylaxis was tacrolimus plus either methotrexate (n=19: 70%), or mycophenolate mofetil (n=4), or sirolimus (n=4). All patients achieved neutrophil engraftment with a median of 15 (range, 11-19) days. Platelet engraftment was achieved with a median of 17 (range, 13 - 35) days and 2 patients did not recover platelets. The cumulative incidences of grades II-IV and grades III-IV acute GVHD at day 100 were 63.6% (95% confidence interval (CI): 43.1-81.1) and 19.6% (95%CI: 5.4-39.9), respectively. The cumulative incidence of moderate to severe chronic GVHD was 56.4% (95%CI: 36.3-75.5) at 1-year. The cumulative incidences of transplant-related mortality at day 100, 1 year and 2 years were 7.4% (95%CI: 0.8-20.0), 11.1% (95%CI: 2.7-25.4), and 11.1% (95%CI: 2.7-25.4), respectively. Progression-free survival estimates at 1, 2, and 3 years were 74.1% (95%CI: 53.2-86.7), 65.1% (95%CI: 43.3-80.2), and 65.1% (95%CI: 49.9-87.5), respectively. With a median follow up of 39 months for surviving patients, overall survival estimates at 1, 2 and 3 years were 85% (95%CI: 64.9-94.1), 75.4% (95%CI: 52.6-88.3), and 69.1% (95%CI: 53.8-93.5), respectively. Conclusions: The results of the this phase 2 trial of upfront allogeneic HCT with fludarabine/melphalan/bortezomib (Flu/Mel/Vel) conditioning are promising and provide the rationale for reasonable potentially curative option to younger and fit patients who are eligible for upfront intensive consolidation strategy. This approach may be potentially valuable for those with high-risk myeloma and a multicenter study is currently being conducted (BMT CTN protocol 1302:NCT02440464). Disclosures Nishihori: Novartis: Research Funding; Signal Genetics: Research Funding. Baz:Takeda/Millennium: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Novartis: Research Funding; Karyopharm: Research Funding; Bristol-Myers Squibb: Research Funding; Signal Genetics: Research Funding. Shain:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen/Onyx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Signal Genetics: Research Funding; Takeda/Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Alsina:Signal Genetics: Consultancy; Novartis: Research Funding; Takeda/Millennium: Research Funding; Amgen/Onyx: Consultancy, Speakers Bureau.

scholarly journals Allogeneic Stem Cell Transplantation in Patients Aged ≥70 Years: Epidemiology, Outcomes, and Risk Factors Based on the German Registry for Stem Cell Transplantation (DRST)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3926-3926
Author(s):  
Jan Frederic Weller ◽  
Louisa Kaufmann ◽  
Claudia Lengerke ◽  
Jürgen Finke ◽  
Johannes Schetelig ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Underlying Disease ◽  
Advisory Committees ◽  
Elder Patients ◽  
Karnofsky Index

Abstract Introduction. Malignant diseases treated with allogeneic hematopoietic stem cell transplantation (alloHSCT) predominantly occur beyond the 7 th decade of life. Numerical age per se is not regarded an adverse risk factor in alloHSCT. In an aging society, interventions historically deemed high risk are increasingly used in elder patients. Methods. Epidemiology, outcomes and risk factors of patients aged ≥70 years undergoing alloHSCT in Germany 1999-2019 and registered with the DRST/EBMT database were analyzed retrospectively. Baseline patient, disease, and transplant data were collected from MED-A forms. Centers were contacted to provide additional treatment and follow-up information. Results. Between 1999 and 2019, 1648 patients aged ≥70 years (median 72, range 70-79.7; 585 female) were transplanted in 50 German centers. More than 90% of all patients were transplanted 2010-2019. Centers transplanted between 2 and 192 patients, with 14 centers contributing <10 and 4 centers contributing >100 patients each. Most patients suffered acute leukemia (1084, 65.8%) or MDS/MPN (410, 24.9%). Karnofsky index before start of conditioning was 100% (n=230, 14%), 90% (n=651, 39.5%), 80% (n=480, 29.1%), 70% (n=94, 5.7%), <70% (n=55, 3.3%). Myeloablative conditioning was chosen in 25.6%. Total body irradiation was used for 305 patients (18.6%). Conditioning contained antithymocyteglobulin in 49.6%. Donors were unrelated for 85.5%. Median donor age was 37 (18-79) years. Patient CMV IgG was positive in 63.1% and the constellation 'negative donor, positive patient' was present in 19.9%. Median overall survival (OS) and disease free survival (DFS) was 408/ 344 days. With a median follow up of 536 days for surviving patients, Kaplan Meier estimates of OS/ DFS were 52.6%/ 48.5% and 40.9%/ 38.6% at 1 and 2 years. In a competing risk analysis, cumulative incidence of non-relapse-mortality (NRM)/ relapse (RI) was 22.2%/ 29.3% at 365 days. Frequency of acute graft versus host disease (GvHD) II-IV was 25.1% and chronic limited/ extended GvHD 11.7%/ 14.8%. Karnofsky performance score, CMV IgG matching, acute and chronic GvHD and stem cell source showed a prognostic impact on OS, DFS, RI and/ or NRM (Table 1). Underlying disease did not impact outcome, neither did age amongst patients at an age of 70-80 years. To compare with outcome in the decade below (60-69 years), an analysis after matching for underlying disease, CMV relation, and Karnofsky index included 2728 patients (each 1364 patients 60-69 and ≥70 years of age). For each year of life, univariate HR for OS and DFS were 1.01 [95%CI 1.001-1.023, p=0.035] and 1.01 [95%CI 0.99-1.02, p=n.s.], respectively, in this matched-pair analysis. The cumulative HR (OS, DFS) for both age groups was 1.16 [95%CI 1.05-1.28, p<0.01] and 1.13 [95%CI 1.02-1.24, p=0.016] for patients ≥70 years. Conclusion. AlloHSCT is increasingly used to treat elder patients in Germany with a sharp increase during the last decade. Age per se is a modest adverse risk factor for adult patients after alloHSCT with slightly increased mortality in patients 70-80 versus those at 60-69. Further research might concentrate on patient selection and further reduction of procedural toxicity. Figure 1 Figure 1. Disclosures Schetelig: Roche: Honoraria, Other: lecture fees; Novartis: Honoraria, Other: lecture fees; BMS: Honoraria, Other: lecture fees; Abbvie: Honoraria, Other: lecture fees; AstraZeneca: Honoraria, Other: lecture fees; Gilead: Honoraria, Other: lecture fees; Janssen: Honoraria, Other: lecture fees . Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding. Stelljes: Pfizer: Consultancy, Research Funding, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau. Dreger: AbbVie: Consultancy, Speakers Bureau; Bluebird Bio: Consultancy; Novartis: Consultancy, Speakers Bureau; Janssen: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; Gilead Sciences: Consultancy, Speakers Bureau; BMS: Consultancy; Riemser: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Wulf: Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Clinigen: Consultancy, Honoraria. Scheid: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria; Roche: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bethge: Novartis: Consultancy, Honoraria, Speakers Bureau; Kite-Gilead: Consultancy, Honoraria, Speakers Bureau; Miltenyi Biotec: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau.

90Y-Ibritumomab Tiuxetan (Zevalin®) Consolidation of First Remission In Advanced-Stage Follicular Non-Hodgkin's Lymphoma: Updated Results After a Median Follow-up of 66.2 Months From the International, Randomized, Phase III First-Line Indolent Trial (FIT) In 414 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 594-594 ◽  
Author(s):  
Anton Hagenbeek ◽  
John Radford ◽  
Achiel Van Hoof ◽  
Umberto Vitolo ◽  
Ama Z.S. Rohatiner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Research Funding ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Advanced Stage ◽  
Ibritumomab Tiuxetan ◽  
Advisory Committees

Abstract Abstract 594 The FIT trial was conducted to evaluate the safety and efficacy of 90Y-ibritumomab tiuxetan (0.4 mCi/kg; maximum dose 32 mCi) when used as consolidation of first complete or partial remission in patients with previously untreated, advanced-stage follicular lymphoma (FL). Patients were randomly assigned to either 90Y-ibritumomab treatment (n = 207) or observation (n = 202) within 3 months (mo) of completing initial induction therapy (chemotherapy only: 86%; rituximab in combination with chemotherapy: 14%). Response status prior to randomization did not differ between the groups: 52% complete response (CR)/CR unconfirmed (CRu) to induction therapy and 48% partial response (PR) in the 90Y-ibritumomab arm vs 53% CR/CRu and 44% PR in the control arm. The primary endpoint was progression-free survival (PFS) of the intent-to-treat (ITT) population. Results from the first extended follow-up after a median of 3.5 years revealed a significant improvement in PFS from the time of randomization with 90Y-ibritumomab consolidation compared with control (36.5 vs 13.3 mo, respectively; P < 0.0001; Morschhauser et al. JCO. 2008; 26:5156-5164). Here we report a median follow-up of 66.2 mo (5.5 years). Five-year PFS was 47% in the 90Y-ibritumomab group and 29% in the control group (hazard ratio (HR) = 0.51, 95% CI 0.39–0.65; P < 0.0001). Median PFS in the 90Y-ibritumomab group was 49 mo vs 14 mo in the control group. In patients achieving a CR/CRu after induction, 5-year PFS was 57% in the 90Y-ibritumomab group, and the median had not yet been reached at 92 months, compared with a 43% 5-year PFS in the control group and a median of 31 mo (HR = 0.61, 95% CI 0.42–0.89). For patients in PR after induction, the 5-year PFS was 38% in the 90Y-ibritumomab group with a median PFS of 30 mo vs 14% in the control group with a median PFS of 6 mo (HR = 0.38, 95% CI 0.27–0.53). Patients who had received rituximab as part of induction treatment had a 5-year PFS of 64% in the 90Y-ibritumomab group and 48% in the control group (HR = 0.66, 95% CI 0.30–1.47). For all patients, time to next treatment (as calculated from the date of randomization) differed significantly between both groups; median not reached at 99 mo in the 90Y-ibritumomab group vs 35 mo in the control group (P < 0.0001). The majority of patients received rituximab-containing regimens when treated after progression (63/82 [77%] in the 90Y-ibritumomab group and 102/122 [84%] in the control group). Overall response rate to second-line treatment was 79% in the 90Y-ibritumomab group (57% CR/CRu and 22% PR) vs 78% in the control arm (59% CR/CRu, 19% PR). Five-year overall survival was not significantly different between the groups; 93% and 89% in the 90Y-ibritumomab and control groups, respectively (P = 0.561). To date, 40 patients have died; 18 in the 90Y-ibritumomab group and 22 in the control group. Secondary malignancies were diagnosed in 16 patients in the 90Y-ibritumomab arm vs 9 patients in the control arm (P = 0.19). There were 6 (3%) cases of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) in the 90Y-ibritumomab arm vs 1 MDS in the control arm (P = 0.063). In conclusion, this extended follow-up of the FIT trial confirms the benefit of 90Y-ibritumomab consolidation with a nearly 3 year advantage in median PFS. A significant 5-year PFS improvement was confirmed for patients with a CR/CRu or a PR after induction. Effective rescue treatment with rituximab-containing regimens may explain the observed no difference in overall survival between both patient groups who were – for the greater part – rituximab-naïve. Disclosures: Hagenbeek: Roche Global Advisory Board: Consultancy. Radford:Schering (May 2009): Honoraria, Membership on an entity's Board of Directors or advisory committees. Vitolo:Roche Italy: Membership on an entity's Board of Directors or advisory committees; Celgene Italy: Membership on an entity's Board of Directors or advisory committees. Soubeyran:Roche: Honoraria, Research Funding; Cephalon: Research Funding. Bischof Delaloye:Expert Statement (questions of reimbursement in Switzerland): Honoraria. Morschhauser:Roche: Honoraria, Paid expert testimony within the past 2 years; Bayer: Honoraria.

scholarly journals Upfront Autologous Stem Cell Transplantation for Newly Diagnosed Elderly Multiple Myeloma (MM) Patients: A Prospective Multicenter Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1989-1989
Author(s):  
Laurent Garderet ◽  
Cyrille Touzeau ◽  
Anne-Marie Stoppa ◽  
Denis Caillot ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Advisory Committees

Abstract Introduction: Previous trials have shown that autologous stem cell transplantation (ASCT) is superior to conventional chemotherapy in terms of remission rate and PFS in younger MM patients. Concerns about toxicity and potential efficacy of ASCT in older MM patients lead most centers to limit ASCT indications to patients aged <65 years. However, at the era of novel induction regimens, and because of better patient selection and supportive care, ASCT may prove to be a valid treatment option even in older MM patients. Therefore, some investigators are questioning the widely used 65 years age limit. Patients and Methods: We prospectively analyzed the outcomes of 56 consecutive MM patients who had received ASCT between September 2012 and September 2014 in 6 institutions in France (protocol ClinicalTrials.gov Identifier: NCT01671826). Patients were newly diagnosed MM. For induction therapy, all patients received a bortezomib-based induction regimen (VD, VTD, VCD, or VRD, 4 to 6 cycles) according to center's local guidelines. Mobilization was performed with G-CSF or G-CSF+cyclophosphamide and plerixafor whenever needed. High-dose chemotherapy consisted of either 140 mg/m2 or 200 mg/m2 Melphalan. A short two months consolidation phase post ASCT was allowed (lenalidomide-dexamethasone, VD, VTD, VCD or VRD). No maintenance treatment was given. Response, disease progression and relapse were defined according to the IMWG uniform response criteria. All patients signed an informed consent form according to the EBMT guidelines. Results: At time of diagnosis, median age was 67 (range, 64-74) years with 23% of patients being >70 years. There were 30 males and 26 females. The immunoglobulin subtype was IgG (n=29), IgA (n=15), light chain (n=10), other (n=2). The Salmon and Durie stage was III in 89% of cases (n=47), and the ISS score was I (n=18; 35%), II (n=19; 37%), III (n=14; 27%). Patients had high risk cytogenetics features (t(4;14) and/or del17p) in 9 cases (16%). 10% of patients had a serum creatinine level >176 micromol/L. None of the patients underwent hemodialysis. The Sorror comorbidity score was 0 (34), 1 (6), 2 (2), 3 (6), 6 (1), unknown (7). The median age at time of ASCT was 68 years, and the median time from diagnosis to ASCT was 5 months. In an intention to treat analysis, out of 56 patients, 6 patients could not proceed to ASCT because of an early infectious death (n=1), serious comorbidity (n=2), disease refractoriness to induction (n=1), and failure to collect an adequate PBSC graft (n=2). A median of 5.31x106/Kg CD34+ cells could be collected. Disease status at time of ASCT was: CR (n=12; 24%), VGPR (n=19; 38%), PR (n=17; 34%), and SD/non-responding (n=2; 4%). The conditioning regimen consisted of 140mg/m² melphalan in 18 cases (36%) and 200mg/m2 in 32 patients (64%). Moreover, 4 patients (8%) received a tandem ASCT. The median time for neutrophils and platelets engraftment was 12 days. The day-100 post ASCT non-relapse mortality was 0% and the 2-year NRM was 4.2% (95% CI:[0.3-18.3]). The overall response rate at day 100 was 96% (CR: 34%, VGPR: 47%, PR: 15%, SD/non-responsive: 4%). At 3 months post ASCT, 82% patients were able to receive the planned post ASCT consolidation treatment. After a median follow-up of 12 months, the estimated progression-free (PFS) and overall survival (OS) rates at 2 years were 76% (95%CI: [61.6-94.1]) and 88% (95%CI: [76.7-100]), respectively. The incidences of infectious complications post ASCT, and response rates were comparable between the two melphalan dose levels (p=0.28). However, in the univariate analysis, the 200 mg/m2 melphalan conditioning group showed a better OS rate compared to the 140 mg/m2 group (1-year OS: 100% vs. 67%; p=0.012). Conclusion: These prospective multicenter results indicate that ASCT is a safe and effective treatment modality for elderly, but fit MM patients at the era of novel induction agents. Of note, patients above age 70 did not experience a worse prognosis. Thus, age per se should not be used as an exclusion criterion for ASCT. Longer follow-up data will be presented, but these results already set the frame for a randomized comparison to the non-transplant approaches in this patients' subgroup. Disclosures Garderet: Bristol-Myers Squibb: Consultancy. Touzeau:AbbVie: Research Funding. Stoppa:Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Karlin:Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Risk-Adapted Intensive Chemotherapy for Primary ACUTE Myeloid Leukemia during the Last 25 YEARS: Increase in Complete Remission RATE, Hematopoietic Cell Transplantation Access and Decrease in Relapse Incidence Have LED to Improved Survival

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Ana Garrido ◽  
Montserrat Hoyos ◽  
Marina Diaz-Beyá ◽  
Montserrat Arnan ◽  
Susana Vives ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Prognostic Impact ◽  
Intensive Chemotherapy ◽  
Advisory Committees ◽  
Allogeneic Hct

BACKGROUND: The progress in the understanding of pathophysiology of AML has allowed the identification of genetic and immune abnormalities with prognostic impact on outcome and suitable as therapeutic targets. The genetic abnormalities are essential for risk allocation and risk-adapted treatment included the indication of hematopoietic cell transplantation. In the last decade, several studies have shown that persistence of measurable residual disease (MRD) after chemotherapy increases relapse incidence and the probability of leukemia recurrence and survival. Therefore, MRD has been progressively incorporated in prognosis estimation. In the last 25 years the CETLAM cooperative group has promoted 4 consecutive trials for AML patients fit for intensive chemotherapy and eventually HCT. Post-remission treatment was based on genetics of the disease and more recently on MRD. The aim of this study has been to investigate if the survival of patients has improved and, if so, to identify the factors that have influenced on the better outcome. METHODS: We included all patients with primary AML up to the age of 60 years enrolled in 4 consecutive Spanish CETLAM group trials. In brief, induction chemotherapy included idarubicin, cytarabine and etoposide in AML-94, AML-99 and AML-03 protocols and without etoposide in the AML-12. G-CSF priming was allowed in the two more recent trials. Post remission therapy included 1 to 3 consolidations including intermediate or high dose cytarabine. Hematopoietic transplantation indication was based on availability of an HLA-compatible donor, genetic findings and more recently MRD. Follow-up was extended to June 2020. The survival and relapse incidence analyses were censored at 5 years. Informed consent was obtained in all cases and the institutional review boards approved the protocols. RESULTS: Between 1994 and 2019, 1755 primary AML patients between 18 and 60 years-old fulfilled the inclusion criteria. The main characteristics of patients appear in table 1. Median age of the whole group was 46 years old. Overall survival (OS) in the whole group was 45% at 5 years, being significantly better in AML-03 and AML-12 than in AML-94 and AML-99 (image 1). Event free survival (EFS) in the whole group was 37% at 5 years, with also significant differences between trials. Also, the cumulative incidence of relapse (CIR) was 39% in the whole group with less relapses in the two more recent trials (image 2). To understand these findings, we analyzed first the CR rate over time that was higher in the AML-03 and AML-12 protocols (table 2). The results were different depending on genetics of AML with highest CR rate in patients with CBF AML and in those with intermediate-risk cytogenetics and favorable molecular findings; in contrast, patients with adverse cytogenetics had the lowest CR rate mainly because frequent refractoriness to therapy. According to outcomes in each MRC cytogenetic group 5y-OS was: 69±3% (63-76) in favorable group, 46±2% (43-49) in intermediate and 21±3% (16-27) in adverse group (p&lt;0.001). 5y-EFS was 57±3% (51-64), 38±1% (35-41) and 15±2% (11-20) (p&lt;0.001), and 5y-CIR was 30±3% (24-37), 39±2% (36-43) and 51±4% (43-59) (p&lt;0.001), respectively (table 3). Referent to feasibility of allogeneic HCT, there was an increased access to the procedure over the years. A higher proportion of patients allografted in AML-03 and AML-12, 32% and 41% of patients in CR, respectively, compared to 16% in AML-94 and 19% in AML-99. A shortening of the interval between CR and transplantation has been observed in recent years; 3.9 months (mo) in AML-94, 2.7 mo in AML-99, 2.9 mo in AML-03 and 2.2 mo in AML-12. CONCLUSIONS: In adults with primary AML and age up to 60 years-old have improved over the last 25 years. During this period, the CETLAM group has refined the biological characterization of AML patients and tailored the post-remission therapy based on genetic markers with prognostic impact. The increased feasibility of allogeneic HCT may also justify the better results in more recent trials. Even though, there is substantial room for improvement, particularly in patients with AML and adverse genetic features. Disclosures Salamero: Pfizer: Consultancy; Jazz Pharmaceuticals: Consultancy, Honoraria; Daichii Sankyo: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Moraleda:Takeda: Consultancy, Other: Travel Expenses; Sandoz: Consultancy, Other: Travel Expenses; Novartis: Consultancy, Other: Travel Expenses; Gilead: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Research Funding. Tormo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; MSD: Honoraria; Daiichi Sankyo: Honoraria; Servier: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Ribera:Pfizer, Amgen: Research Funding; Pfizer, Amgen, Ariad, Novartis: Consultancy, Speakers Bureau. Sureda Balari:Roche: Honoraria; Incyte: Consultancy; Janssen: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; BMS: Speakers Bureau; Celgene: Consultancy, Honoraria. Sierra:Jazz Pharmaceuticals: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead-Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Patterns of Care and Outcomes in Mantle Cell Lymphoma in the Modern Immunochemotherapy Era

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4140-4140
Author(s):  
Alessia Castellino ◽  
Melissa C. Larson ◽  
Matthew J. Maurer ◽  
Susan L. Slager ◽  
Cristine Allmer ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Board Of Directors ◽  
Research Funding ◽  
High Dose ◽  
Front Line ◽  
Advisory Committees ◽  
Pattern Of Care ◽  
Mantle Cell ◽  
High Dose Cytarabine

Abstract Backgroud. The treatment landscape of mantle cell lymphoma (MCL) has significantly changed in last decades. Improvement in diagnosis and understanding of disease biology has been coupled with emergence of new therapeutic options, including targeted agents. While MCL outcome data comes primarily from clinical trials (CT), the impact of therapeutic advances on pattern of care (POC) and outcome in MCL in the general population is not well characterized. This study sought to characterize changes in pattern of care and outcomes of patients with MCL in a prospective observational series in the rituximab era. Methods. The study included consenting adult patients with newly diagnosed MCL that were prospectively enrolled into the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) Molecular Epidemiology Resource, from 09/01/2002 to 06/30/2015. Demographic, clinical and prognostic factors were abstracted, and all patients were actively followed for re-treatment, relapse and death. Since bendamustine-rituximab (BR) regimen starting to be used in 2010, we defined patients enrolled from 09/01/2002 to 12/31/2009 as era 1 and those enrolled 01/01/2010 to 06/30/2015 as era 2. Baseline characteristics and outcomes, evaluated in terms of event free survival (EFS), overall survival (OS) and cause of death, were analyzed and compared between the two eras identified. Results. 348 patients with newly diagnosed MCL were enrolled. Five patients had no available data for front-line treatment and were excluded. The analysis was thus conducted on 343 patients: 169 patients were diagnosed in era 1 with a median follow-up of 131.2 months vs. 174 in era 2 with a median follow-up of 58.9 months. Baseline clinical characteristics and MIPI score were similar across the two eras ( Table 1). Frontline induction treatment was significantly different in the two eras. BR use was 0 vs 49 (28.2% ), R-CHOP/CHOP like regimen in 89 (52.7%) vs 45 (25.9%), high-dose cytarabine (HiDAC)-based therapy in 1 (0.6%) vs 28 (16.1%), intensified regimens (HyperCVAD) in 16 (9.5%) vs 8 (4.5%), other regimens (including R-cladribine, R-fludarabine-mitoxantrone, rituximab monotherapy) in 35 (20.7%) vs 13 (7.5%) patients in era 1 vs era 2 respectively. Non-systemic treatment (observation, surgery or radiation only) was performed in 25 (14.8%) vs 31 (17.8%), while 9 (8%) vs 12 (7.7%) patients were enrolled in clinical trials, in era 1 vs era 2 respectively. Autologous stem cell transplantation (ASCT) as consolidation of first line treatment or use of Rituximab maintenance was not different between Era 1 and Era 2. Among the entire cohort of 343 MCL patients, 3y-EFS and 3y-OS were 51.9% (95% IC 46.7-57.6) and 73.5 (95% CI 68.8-78.4), respectively (Figure 1). 3y-EFS was 45.9% (95% CI 39.0-54.1%) vs 58.4 (95% CI, 51.2-66.6%) in Era 1 vs Era 2 (HR 0.69 (0.51-0.92), p=0.006), 3y-OS was 70.9% (95% CI, 63.4-78.1%) vs 76.1% (95% CI, 69.7-83.1%) in Era 1 vs Era 2 (HR 0.87 (0.61-1.24), p=0.26), respectively (Figure 1). In a univariate analysis, high risk simplified MIPI was prognostic of lower EFS and OS in both the era groups. Conclusion. The BR regimen entered front line therapy of MCL resulting in decline of R-CHOP use in the MER. While rates of ASCT remain similar over the two eras, high dose cytarabine usage in induction therapy has increased. While POC in MCL continue to evolve, the introduction of bendamustine and high-dose citarabine based regimens resulted in an improvement in EFS but not OS in this observational cohort-based analysis. Findings in this study are important for design and planning of future clinical trials incorporating novel agents in induction therapy of MCL. Figure 1. Figure 1. Disclosures Cohen: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

scholarly journals Systemic Mastocytosis: Management and Outcome. Data Analysis from the Greek Registry

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5463-5463
Author(s):  
Ioannis Tsonis ◽  
Nikolaos Kanellias ◽  
Vasileios Lazaris ◽  
Panayiotis Panayiotidis ◽  
Damianos Sotiropoulos ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Median Time ◽  
Research Funding ◽  
Systemic Mastocytosis ◽  
Cell Leukaemia ◽  
Line Treatment ◽  
Advisory Committees ◽  
Increased Risk ◽  
Travel Grant

Abstract Background and Methods: Systemic Mastocytosis (SM) is a rare haematologic malignancy characterized by the abnormal growth and accumulation of neoplastic mast cells in one or more organs. The cKIT D816V mutation is a common genetic finding in most cases. A subset of patients appears to be at increased risk for mediator release related symptoms as well as organ dysfunction, including skeletal problems such as osteoporosis, osteolytic lesions and fractures. The diversity of clinical manifestations results in both delayed diagnosis and therapeutic dilemmas. SM cases diagnosed in Greece, between 1987 and 2018, are presented. This project is included in the current activities of Myeloproliferative Neoplasm Working Party of Hellenic Society of Haematology for registry and research development. The medical files of the patients were retrospectively evaluated for disease characteristics, treatment and outcome. Results: Overall 59 patients, median age 52.0 years, with SM were included in the study. Median time of symptoms onset to diagnosis was two years. Twenty-one patients were categorized as indolent SM (ISM), 19 as SM with an associated haematological neoplasm (SM-AHN), 18 as aggressive SM (ASM) and one with mast cell leukaemia (MCL). The main characteristics of the disease are shown in Table 1. Several haematologic neoplasms were associated with SM. Although myeloid malignancies were the most common, including MDS or MDS/MPN (n=9), CMML (n=2), AML (n=1), CML (n=1) and ET (n=1), lymphoid malignancies were also reported and included NHL (n=3), HL (n=1) and B-ALL (n=1). SM and the AHN were diagnosed simultaneously in 12 cases. AHN diagnosis preceded the diagnosis of SM in 4 cases (median time: 22 months), while the opposite occurred in three cases (median time: 7.0 months). Most of the patients with ISM (16/21) did not receive any specific treatment. As far as the remaining five are concerned, one was treated with imatinib, one with hydroxyurea and the rest three received corticosteroids to control the mediators' related symptoms. One of the latter had diarrhoea without infiltration of the gastrointestinal tract and received consecutively Interferon alpha (IFNα), imatinib and corticosteroids without resolution of the syndrome. Eight patients with SM-AHN received treatment for both the SM and the co-existing haematological neoplasm, six only for the AHN, three only for SM, while three did not require treatment yet. The most common treatment for SM was IFNα (n=6), followed by imatinib (n=4), cladribine (2-CdA) (n=3) and dasatinib (n=1). Patients with ASM received either IFNα (n=8) or 2-CdA (n=5) as first line treatment. Second line treatment included imatinib (n=2), 2-CdA due to IFNα intolerance (n=1) and corticosteroids (n=2). Two patients with vertebrae fractures required surgical intervention. All patients with skeletal involvement received additionally biphosphonates. The patient with MCL received consecutively 2-CdA, chemotherapy (FLAG-Ida) and dasatinib achieving partial response and proceeded to allogeneic stem cell transplantation. He died 6 months later due to complications related to graft versus host disease. With a median follow-up of 31 months the median overall survival in the entire cohort is not reached. The median follow-up for patients with ISM and ASM is 33.5 and 18.5 months respectively, and all of them are alive with adequate disease control. Seven deaths were reported only in the group of patients with SM-AHN. Six patients died due to acute leukaemia and one due to infection, indicating that the aggressiveness of the underlying haematological malignancy is the strongest factor that affects survival in this group. Conclusion: Systemic Mastocytosis is a rare disease with variable manifestations and outcome. Nowadays, several therapeutic modalities are available for effective disease management over time. Novel targeted therapies seem to be promising to further improve the outcome, but still early and accurate diagnosis, in accordance to WHO classification, remains important. Table 1. Table 1. Disclosures Gavriilaki: European Hematology Association: Research Funding. Terpos:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Genesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document