DOUBLE-EXPRESSOR LYMPHOMAS DO NOT HAVE INFERIOR OUTCOME AFTER AUTOLOGOUS STEM-CELL TRANSPLANT IN THE FIRST LINE TREATMENT

Abstract Abstract 2395 While already tested in T-PLL, the impact of chemo-immunotherapy with alemtuzumab in combination with bi-weekly CHOP on autologous stem cell harvest (ASCH) has not yet been analysed in the context of first line treatment of primary systemic peripheral T-cell lymphoma (PTCL). We therefore evaluated the feasibility of ASCH in the first 23 patients of the ongoing international multicenter ACT-1 study, the first, and so far only, randomized trial in primary systemic PTCL. The ACT trials (ACT-1 + ACT-2) test the addition of alemtuzumab to CHOP followed, in younger patients (ACT-1), by high-dose therapy with autologous stem cell transplant (HDT+ASCT). The aims of the analysis were: (i) feasibility of ASCH in alemtuzumab + CHOP (A-CHOP) treated patients as compared to patients not receiving the antibody, but otherwise treated and managed in the same way, and (ii) comparison of ASCH counts in the two treatment arms. By July 2010, 20 patients, 11 in the standard treatment (arm A) and 9 in the experimental treatment (arm B) cohort, had undergone induction therapy and had been primed for subsequent ASCH according to local guidelines. Histological subtype distribution in the two treatment groups showed: PTCL not otherwise specified N=4 (arm A) and N=5 (arm B), angioimmunoblastic N=5 (arm A) and N=4 (arm B), extranodal NK/T-cell, nasal type N=1 (arm A), hepatosplenic N=1 (arm A). Pre-therapeutic evidence of bone marrow involvement was present in 4 (arm A) and 2 (arm B) patients, respectively. Of the original 23 patients, three did not undergo stem-cell harvest due to progressive disease (1 pt), patient's decision (1 pt), and pre-therapeutic CNS involvement (1 pt). Among the 20 harvested patients, ASCH failure was experienced in three patients (standard arm N=1 and experimental arm N=2; p=0.57). In two patients (one in each treatment cohort) a suboptimal stem cell yield could be optimized by the use of plerixafor according to local guidelines. A comparison of stem cell counts (CD34+ cells × 106/kg body weight) from the two treatment cohorts showed a trend towards moderately lower stem cell yields in alemtuzumab-treated patients (3.34 CD34+ cells × 106/kg body weight in arm B vs 6.54 CD34+ cells × 106/kg body weight in arm A, p=0.03). In conclusion, the addition of alemtuzumab to bi-weekly CHOP in the setting of first-line therapy of primary systemic PTCL does not significantly impair ASCH prior to upfront autologous stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

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Impact of FDA approval of lenalidomide maintenance therapy in the first-line treatment of multiple myeloma after autologous stem cell transplant on total healthcare costs.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e19509 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e19509-e19509 ◽

Cited By ~ 1

Author(s):

Jipan Xie ◽

Kejal Parikh ◽

Christina Chen ◽

Chelsey Yang ◽

Adina Farrukh ◽

...

Keyword(s):

Multiple Myeloma ◽

Maintenance Therapy ◽

Healthcare Costs ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Line Treatment ◽

First Line ◽

Fda Approval ◽

First Line Treatment

e19509 Background: Lenalidomide maintenance therapy after autologous stem cell transplant (ASCT) in the first-line treatment has been shown to improve progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM) patients (pts). This study assessed the impact of FDA approval of lenalidomide maintenance therapy on total healthcare costs of a US health plan. Methods: A model was developed to estimate the incremental (additional) total plan costs (in 2016 USD) for maintenance therapy in each year for the first 3 years after lenalidomide monotherapy (R) maintenance therapy approval. The number of post-ASCT adult MM pts eligible for initiating maintenance therapy was estimated from published epidemiological data and an analysis of Connect MM Registry data. Clinical endpoints for R-maintenance, including time on treatment, PFS and OS, were obtained from a meta-analysis of published clinical trials (CALGB, IFM, and GIMEMA). The use of common off-label maintenance therapies was considered. Types of costs included in the model were drug, drug administration, adverse events (AE), AE monitoring, one-time progression and terminal care costs. Results: In a hypothetical health plan with 1 million members, the number of adult MM pts eligible to initiate post-ASCT maintenance therapy was estimated to be 28. Among them, 14.8 pts initiated R-maintenance in Year 1, 15.2 in Year 2, and 15.3 in Year 3, representing an incremental increase of 2.9%, 4.2% and 4.4% after R-maintenance therapy approval, respectively. After considering additional costs of maintenance, as well as potential offsets resulting from delayed progression the incremental total healthcare costs by year are listed in the table. Conclusions: Approval of lenalidomide monotherapy for maintenance after ASCT in the first-line treatment of MM has minimal impact on total plan costs, primarily due to the small incident population and the already common use of lenalidomide in post-ASCT maintenance. [Table: see text]

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Survival outcomes in blastic plasmacytoid dendritic cell neoplasm by first-line treatment and stem cell transplant

Blood Advances ◽

10.1182/bloodadvances.2020001875 ◽

2020 ◽

Vol 4 (14) ◽

pp. 3435-3442

Author(s):

Seongseok Yun ◽

Onyee Chan ◽

Daniel Kerr ◽

Nicole D. Vincelette ◽

Afshan Idrees ◽

...

Keyword(s):

Stem Cell ◽

Dendritic Cell ◽

Stem Cell Transplant ◽

Plasmacytoid Dendritic Cell ◽

Hazard Ratio ◽

Cell Transplant ◽

Line Treatment ◽

First Line ◽

Cell Neoplasm ◽

First Line Treatment

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with dismal clinical outcomes. Conventional chemotherapies such cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose cytarabine and methotrexate (CVAD) have been commonly used for the BPDCN treatment until a recent study showed promising outcomes in patients treated with SL-401 (Tagraxofusp). In this single-institution retrospective study, we identified a total of 49 consecutive BPDCN patients. Among 42 patients who received treatment, hyper-CVAD regimen was associated with higher complete response rate compared with CHOP-based regimens or SL-401 (91% vs 50% vs 50%), although the difference did not achieve statistical significance. Furthermore, there was no significant overall survival (OS) difference between patients treated with SL-401 vs other chemotherapies as their first-line treatment (hazard ratio = 1.597; 95% CI, 0.460-5.548; P = .431). Of note, patients who received allogeneic stem cell transplant (allo-SCT) had significantly longer OS (hazard ratio = 0.160; 95% CI, 0.0453-0.56; P = .041). Extent of disease (skin vs bone marrow vs both) or younger age (<60 years old) did not have significant prognostic impact on OS. Collectively, our study confirmed the survival benefit of allo-SCT and suggests that conventional and intensive chemotherapies such as CHOP and hyper-CVAD as well as SL-401 would be comparable first-line choice for the BPDCN patients.

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Effectiveness and tolerability of first-line autologous stem cell transplant and maintenance rituximab for mantle cell lymphoma

Bone Marrow Transplantation ◽

10.1038/s41409-017-0054-8 ◽

2017 ◽

Vol 53 (3) ◽

pp. 347-351

Author(s):

Umberto Falcone ◽

Haiyan Jiang ◽

Shaheena Bashir ◽

Richard Tsang ◽

Vishal Kukreti ◽

...

Keyword(s):

Stem Cell ◽

Mantle Cell Lymphoma ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

First Line ◽

Mantle Cell

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Outcomes of Patients with Refractory/Relapsed Diffuse Large B-Cell Lymphoma Who Progress After Autologous Stem Cell Transplantation in the Rituximab Era.

Blood ◽

10.1182/blood.v120.21.2689.2689 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2689-2689

Author(s):

Sarah J. Nagle ◽

Kaitlin Woo ◽

Rosemarie Mick ◽

Stephen J. Schuster ◽

Sunita D. Nasta ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cell Transplant ◽

First Line ◽

Large B Cell Lymphoma ◽

Historical Controls ◽

First Line Treatment

Abstract Abstract 2689 Salvage chemotherapy and autologous stem cell transplant (ASCT) remain the current standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who have primary refractory disease or relapse after initial therapy. The addition of rituximab results in improved overall survival (OS) after first line treatment, but cure rates of salvage therapy and ASCT are inferior when compared to historical controls (Gisselbrecht et al, JCO 2010). In the pre-rituximab era, patients with DLBCL who progressed after ASCT had an extremely poor prognosis, with a median OS of 3 months from the time of progression (Vose et al, Blood 1992). There is a paucity of data regarding outcomes and clinical patterns following progression after ASCT in the rituximab era. We conducted a retrospective analysis using our institutional database of DLBCL patients who underwent ASCT for primary refractory or relapsed disease. For those who progressed after ASCT, we evaluated OS defined as time from date of progression after ASCT to date of death from any cause or last follow-up. We also analyzed OS for various subgroups based on their clinical characteristics and post-progression therapy. The impact of post-progression therapy on outcome was assessed by calculating OS from the time of exposure to a particular treatment to date of death from any cause or last follow-up. Median OS was estimated by the Kaplan-Meier method and subgroup comparisons were performed using the log rank test. We identified 215 patients with primary refractory or relapsed DLBCL who underwent ASCT between January 1, 2005 and December 31, 2011. All patients received rituximab as part of their first line treatment. Fifty-six patients (26% of total) were found to have progression after ASCT. Eight patients were excluded from the analysis because they were not re-biopsied at relapse (n=5) or they had indolent disease at relapse (n=3). Data on the remaining 48 patients (median age 57 years; range 20–74) were further analyzed. The median OS from progression after ASCT for the entire cohort was 10.7 months (95% CI: 6.8–18.0 months). Patients who progressed < 1 year from ASCT (n=39) had a significantly shorter OS than those who progressed ≥ 1 year from ASCT (n=9): 9.5 vs. 26.7 months (p=0.02). Patients with at least stable disease as first assessment after ASCT (n=29) had a significantly longer OS than those who progressed immediately after ASCT (n=19): 18 vs. 6 months (p=0.01). Patients who were exposed to at least one novel agent (lenalidomide, radioimmunotherapy, non-rituximab monoclonal antibodies or tyrosine kinase inhibitors) as part of their post-progression therapy after ASCT (n=20) had a median OS of 11.2 months from treatment initiation. In contrast, patients who were treated with conventional cytotoxic chemotherapy but not novel agents (n=20) had a median OS of 6.7 months. In particular, patients who underwent radioimmunotherapy at some point after progression post-ASCT (n=9) had a median OS of 17.5 months (95% CI: 2.6-n/a months) with one patient in complete response > 48 months after the treatment. Patients who underwent allogeneic stem cell transplant following progression after ASCT (n=6) had a median OS of only 7.1 months (95% CI: 0.8-n/a months). In the rituximab era, the median OS of DLBCL patients who progress after ASCT appears improved when compared to historical controls, especially in those who progress > 1 year from ASCT. Patients with DLBCL progressing after ASCT should be considered for therapy with novel agents, which may result in long term survival. Disclosures: No relevant conflicts of interest to declare.

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Long-Term Results of Cytarabine-Containing Induction Followed By Consolidation with Autologous Stem Cell Transplant and Rituximab Maintenance As Primary Treatment for Mantle Cell Lymphoma

Blood ◽

10.1182/blood.v126.23.1995.1995 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1995-1995

Author(s):

Umberto Falcone ◽

Shaheena Bashir ◽

Khalil Al-Farsi ◽

Laurie Watkins ◽

C. Denise Turvey ◽

...

Keyword(s):

Stem Cell ◽

Median Time ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

High Dose ◽

Cell Transplant ◽

First Line ◽

Rituximab Maintenance ◽

Cd34 Cells ◽

Mantle Cell

Abstract Introduction: Mantle cell lymphoma (MCL) often follows an aggressive course and remains incurable with standard therapies. First-line chemotherapy followed by consolidation with high-dose chemotherapy (HDT) and autologous stem cell transplant (ASCT) has become a standard of care in eligible patients (pts). As relapse remains the main cause of treatment failure, strategies such as intensifying induction therapy with high-dose cytarabine or adding rituximab maintenance (RM) have been tested to reduce the relapse rate (RR) post-ASCT. We evaluated the effect of the addition of cytarabine and RM on the outcome of pts undergoing ASCT. Methods: We conducted a retrospective analysis of consecutive MCL pts who underwent ASCT after first-line chemotherapy at the Princess Margaret Cancer Centre between 2000-2013. Pts received induction with CHOP, RCHOP, or RCHOP alternating with RDHAP (RCHOP/RDHAP), followed by HDT with or without total body irradiation (TBI). All pts had a documented response to induction using Cheson 1999 criteria. After ASCT, pts received maintenance with single-agent rituximab 375 mg/m2 or were simply observed. Results: 98 MCL pts were treated: median age was 56 years (36-66), 15 pts (15%) had blastoid or pleomorphic subtype, 85 pts (87%) had stage IV disease. MIPI was high risk in 18 pts (19%). Induction therapy: CHOP 14 pts (14%), RCHOP 57 (58%), and RCHOP/RDHAP 27 (28%). After induction CR was obtained in 44%, PR in 56% pts. CR rates were: CHOP 7 (50%), RCHOP 25 (44%), RCHOP/RDHAP 12 (44%) (P=ns). 89% pts had collected > 5*106 CD34/kg after RCHOP, and 78% after RCHOP/RDHAP (P=ns). Overall 66/98 pts (67%) had > 5*106 CD34/kg collected with 1 apheresis (Table 1). HDT was melphalan+etoposide for 63% pts, cytarabine+melphalan for 31% pts; 77 (79%) also received TBI. Median time from diagnosis to ASCT was 7.5 months (2.5, 33.4). Post-ASCT responses: CR 92 pts (94%), PR 4 (4%), 2 (2%) PD. Median time to ANC ≥0.5 were 10 days (CHOP), 11 days (RCHOP), and 11 days (RCHOP/RDHAP), while median days to PLT≥20 were 9 (CHOP), 11.5 (RCHOP), and 13 (RCHOP/RDHAP). Post-ASCT, 31% of pts had normal blood counts at 3 months which improved to 52% at 1 year post-ASCT. Maintenance data were available for 95/98 pts. RM was given to 72 pts (74%). Median follow-up from date of transplant for the entire cohort was 3.22 years (range 0.7 - 14.1). The 2-year and 5-year PFS were 85.8% (76.7-91.5) and 52.2% (37.7-64.7), respectively. 32 pts relapsed after ASCT (32.65%). Relapse occurred in 3 (11%) pts after RCHOP/RDHAP, 19 (33%) after RCHOP, and 10 (71%) after CHOP. Median time to relapse was 9 years (95%CI: 4.7-NR). 2-year and 5-year RR were 14.54% and 41.65%, respectively. Median OS was 9.15 years (95%CI: 7.3-NR), 2-year OS was 88.8% (80.2-93.8), and 5-year OS was 74.9% (61.7-84.2%). For patients observed without treatment post-ASCT, median PFS was 2.87 years (1.22-4.63) and median OS 5.19 years (1.66-NR), while for those receiving RM, PFS was 9.06 years (4.97-NR, p<0.001) and median OS has not yet been reached (7.30- NR, p=0.009). Conclusions: Response rate and PFS were similar between different induction regimens. The outcomes of responding pts following ASCT appear superior to previous strategies. Our patients enjoyed a very long PFS and median OS is surprisingly long as well. Within the limits of a retrospective study, our data support the use of rituximab maintenance, showing a significant benefit in both PFS and OS. Table 1. ASCT data Stem cell collection CHOP RCHOP RCHOP/RDHAP P value Pts collecting > 2x106 /Kg CD34+ cells in 1 day 4/14 (29%) 44/57 (77%) 17/27 (67%) 0.002 Pts collecting 2-5 x106 /Kg CD34+ cells N/A 6/57 (11%) 6/27 (22%) Pts collecting >5 x106 /Kg CD34+ cells N/A 51/57 (89%) 21/27 (78%) 0.153 Engraftment median (range) Days to ANC ≥ 0.5 10 (9,11) 11 (9, 12) 11 (9, 12) Pts with ANC ≥ 0.5 ≤ 11 days 13/13 (100%) 45/52 (87%) 21/25 (84%) 0.33 Days to PLT ≥ 20 9 (7, 15) 11.5 (9, 17) 13 (9, 26) Pts with PLT ≥ 20 ≤ 12 days 12/13 (92%) 37/52 (71%) 8/25 (32%) 0.0001* Days from ASCT to discharge 13 (11,26) 14 (11,30) 13 (11,23) PTs requiring RBC Transfusions 11 (79%) 43 (75%) 22 (81%) 0.821 Number of RBC Transfusions 2 (0, 4) 2 (0, 7) 3(0, 6) Pts requiring PLT Transfusions 12 (86%) 52 (93%) 25 (93%) 0.759 Number of PLT Transfusions 1 (0, 4) 2 (1, 9) 3 (1, 5) * comparison CHOP Vs R-CHOP: not significant, p=0.113 Legend. ASCT: autologous stem cell transplant; Pts: patients; ANC: absolute neutrophils count; PLTs: platelets; RBC: red blood cells. Disclosures Kuruvilla: Hoffmann LaRoche: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Gilead: Consultancy; Janssen: Consultancy, Honoraria; Merck: Honoraria; Bristol-Myers Squibb: Honoraria; Lundbeck: Honoraria; Karyopharm: Honoraria.

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PB2125 THE IMPACT OF RVD OR VCD INDUCTION ON RESPONSE 3 MONTH AFTER FIRST LINE AUTOLOGOUS STEM CELL TRANSPLANT IN MULTIPLE MYELOMA. A SINGLE_CENTER RETROSPECTIVE ANALYSIS

HemaSphere ◽

10.1097/01.hs9.0000566984.39649.76 ◽

2019 ◽

Vol 3 (S1) ◽

pp. 957

Author(s):

J. N. Nørgaard ◽

F. Schjesvold ◽

M. Moksnes

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Retrospective Analysis ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

First Line ◽

The Impact

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Zygomycosis After Allogeneic Hematopoietic Stem Cell Transplantation: A French Multicenter Cohort Study (2003-2008)

Blood ◽

10.1182/blood.v116.21.1263.1263 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1263-1263

Author(s):

Alienor Xhaard ◽

Fanny Fanternier ◽

Eric Dannaoui ◽

Anne Bergeron-Lafaurie ◽

Claire Lacroix ◽

...

Keyword(s):

Cohort Study ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Attributable Mortality ◽

Cell Transplant ◽

Line Treatment ◽

First Line ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

First Line Treatment

Abstract Abstract 1263 Background: To evaluate the clinical characteristics and outcome of zygomycosis (ZG) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Methods: Retrospective cohort study involving HSCT patients with ZG diagnosed between 2003 and 2008, from 19 centres. During this period, 4138 allogeneic HSCT were performed in these centers. Results: ZG incidence was 0.56% (n=23). Twenty patients (87%) were male. Median age was 44 years (range: 3 to 63 years). Donors were non HLA-identical in 14 cases and conditioning regimens were reduced intensity in 8. ZG occurred a median of 217 days post transplant (range: 0 to 2693 days). Fifteen patients had active graft-versus-host disease (GVHD). Twenty patients were receiving steroids at a median dose of 1 mg/kg/day (range: 0.1 to 2 mg/kg/day) at ZG diagnosis. Ten patients (43%) had diabetes mellitus. Nine patients (39%) had experienced a previous proven or probable invasive filamentous fungal infection (Aspergillus: 8, Trichoderma:1) a median of 115 days (range: 8 to 392 days) before ZG diagnosis. ZG was a breakthrough infection in 20 cases. Before ZG diagnosis, 13 patients were on voriconazole therapy for a median duration of 61 days (range 3 to 394 days), 4 patients were on posaconazole (PCZ) for a median of 61 days (range 7 to 88 days). Other patients were receiving caspofungin, itraconazole or voriconazole. Lungs were the most common site of infection (65%); two patients had a disseminated infection. Histology was performed in 52% of the patients, and contributed to diagnosis for 83% of biopsies. Culture was positive in 83% of cases. The main causal species were Lichtheimia spp. and Rhizopus spp. Median time between the first clinical symptom and diagnosis was 8 days (range: 2 to 34 days). Twenty patients received an antifungal. All but 2 patients received a lipid formulation of amphotericin B as first-line treatment. Eleven patients received PCZ, two as first-line treatment. Surgery was performed in eight patients. Median treatment duration was 47 days (range: 2 to 730 days). Nine patients responded to treatment. Nineteen patients (83%) died a median of 46 days after ZG diagnosis (range: 0 to 1449 days). ZG attributable mortality was 79% (15/19 patients). Four patients are alive a median of 706 days after ZG diagnosis (range: 705 to 1955 days). Conclusion: ZG is a late event with a poor prognosis after allogeneic HSCT. Because ZG diagnosis is difficult, special attention must be paid to patients on long-term antifungal treatment for a previous mold infection, and with protracted GVHD. Disclosures: No relevant conflicts of interest to declare.

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