Co-Morbidity Score at the Time of Transplant Determines Prognosis in Older Patients Who Develop Acute Graft-Vs.-Host Disease (GVHD).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2244-2244
Author(s):  
Amin M Alousi ◽  
Gabriela Rondon ◽  
Grace-Julia Okoroji ◽  
Uday Popat ◽  
Leandro De Padua Silva ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Acute Gvhd ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Older Age ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Morbidity Score ◽  
Co Morbidity

Abstract Abstract 2244 Poster Board II-221 Background: Older age patients are increasingly being considered for allogeneic hematopoietic cell transplants (HCT). Concerns related to early treatment related mortality (TRM), namely from acute GVHD, often limit referrals. Outcomes for older age patients who develop acute GVHD remain unknown. Methods: We performed a retrospective analysis of 83 adult patients enrolled onto two consecutive trials at MD Anderson to determine predictors for TRM at 6 months following systemic treatment of acute GVHD. These trials enrolled patients with newly diagnosed acute GVHD between 2000-2008 and included a single-center randomized trial of infliximab + methylprednisolone (MP) vs. MP alone and a multicenter trial of MP + one of 4 agents (mycophenolate, etanercept, denileukin diftitox or pentostatin). Results: Median age was 49 yrs (range, 20-70 yrs) and 63% of patients (pts) were male. 52% had acute leukemia and 31% were in remission at the time of transplant. Myeloablative condition and/ or peripheral blood HCT were performed in 52% and 54% of pts, respectively. Matched sibling, matched unrelated and mismatched transplants were 49%, 40% and 11%. GVHD prophylaxis was tacrolimus/ methotrexate in 87% of pts. Grades I/II, III/IV and visceral-organ acute GVHD represented 68%, 32% and 60% of pts occurring at a median time of onset of 25 days post-HCT. Day 28 acute GVHD response (defined as complete or partial response) was 63%. The median co-morbidity score at the time of HCT was 3 (range 0-11). Co-morbidity scores >3 were more common in pts >50 yrs (47%) than in those '50 yrs (24%), p=0.03. The proportion of responders on day 28 was comparable in pts >50 yrs (60%) and those '50 yrs (64%), p=0.7. On univariate analysis, significant predictors of higher TRM rate at 6 months following initiation of systemic therapy for acute GVHD were lack of response on day 28 post therapy (Hazard Ratio (HR) 3.6, p= 0.004), age > 50 yrs (HR 2.9, p=0.03) and co-morbidity score >3 (HR 3.1, p=0.01). There was no significant impact on the rate of TRM for donor type, cell source, intensity of conditioning regimen, donor/recipient sex mismatch, disease status at the time of transplant, GVHD grade at the time of initiation of systemic therapy or protocol assigned therapy. To adjust for potential interaction and confounding effects, multivariate analysis was performed by classifying pts into mutually exclusive groups according to day 28 response status, age, and co-morbidity score (see table). The cumulative incidence of TRM was lowest in pts who were '50 yrs of age and who responded to first line therapy with co-morbidity scores not impacting outcomes. TRM was comparably low (15%) in the absence of co-morbidity scores >3 in pts >50 yrs who responded to first line therapy. In contrast, in the presence of co-morbidity scores >3, TRM rate was high in pts >50 yrs regardless of whether pts responded (40%) or did not respond (100%) to first line therapy. Conclusion: The ability to withstand acute GVHD and/ or its therapy in pts older than 50 yrs depends on co-morbidity scores at the time of transplant. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Overall Survival and Response to Systemic Therapy in Metastatic Extrauterine Leiomyosarcoma

Sarcoma ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
A. N. Shoushtari ◽  
J. Landa ◽  
D. Kuk ◽  
A. Sanchez ◽  
B. Lala ◽  
...  
Keyword(s):  
Overall Survival ◽  
Systemic Therapy ◽  
Objective Response ◽  
Soft Tissue Sarcomas ◽  
Older Age ◽  
First Line ◽  
Risk Of Death ◽  
First Line Therapy ◽  
Line Therapy ◽  
Male Sex

Background. Leiomyosarcomas (LMS) represent a heterogeneous subset of soft tissue sarcomas. Factors influencing prognosis for patients with metastatic extrauterine LMS (euLMS) are not well described. Limited data are available regarding responses to systemic therapy.Methods. We collected clinical and pathologic information for all patients with metastatic euLMS seen at Memorial Sloan Kettering Cancer Center between 1989 and 2012. Objective responses to first-line therapy were analyzed for a subset of patients with available baseline and on-treatment imaging using RECIST 1.1.Results. 215 patients with metastatic euLMS had a median overall survival (OS) of 2.6 years from the time of metastasis. Older age, male sex, and ≥3 initial sites of metastasis were associated with worse OS on multivariate analysis. Objective response rate (ORR) inN=113was 19% overall and 25%, 26%, and 25% for gemcitabine, gemcitabine plus docetaxel, and anthracycline-alkylator combinations. Patients whose tumors objectively responded to first-line therapy had a lower risk of death versus those who did not (Hazard Ratio 0.46; 95% CI: 0.26–0.79,p=0.005).Conclusions. Anthracycline- and gemcitabine-based regimens have similar activity in this cohort of euLMS. Prognostic factors for OS include older age, male sex, and ≥3 initial sites.

scholarly journals Low-dose MTX combined with low-dose methylprednisolone as a first-line therapy for the treatment of acute GVHD: safety and feasibility

2010 ◽  
Vol 46 (6) ◽  
pp. 892-898 ◽  
Author(s):  
Y Wang ◽  
L P Xu ◽  
K Y Liu ◽  
D H Liu ◽  
J Wang ◽  
...  
Keyword(s):  
Low Dose ◽  
Acute Gvhd ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Outcomes of metastatic adrenocortical carcinoma (ACC): A 16-year single institutional experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16088-e16088
Author(s):  
Dwight Hall Owen ◽  
Sandipkumar Patel ◽  
John E Phay ◽  
Lawrence Andrew Shirley ◽  
Lawrence S Kirschner ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Systemic Therapy ◽  
Lung Metastases ◽  
Cox Proportional Hazards ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

e16088 Background: ACC is a rare malignancy with limited data to guide management of metastatic disease. Prior research regarding survival has focused on pts with locoregional disease, but has not offered insight into the management and outcomes of pts with metastatic disease. Methods: We retrospectively reviewed patients (pts) with metastatic ACC who were treated with systemic therapy between January 2000 and October 2016 at The Ohio State University Comprehensive Cancer Center. Kaplan-Meier and Cox proportional hazards regression models were used for survival analysis. Results: A total of 18 pts received systemic therapy for distant metastatic disease. Median age at diagnosis was 51 (range 31 – 72). Median overall survival (OS) from time of diagnosis of ACC was 15.5 months (95% CI 4.8 – 28.2), and from time of systemic treatment (ST) was 7.1 months (95% CI 3.3 – 26). A germline variant of uncertain significance in MSH2 (c.138C > G) was identified in one patient. Baseline FDG-PET scans were obtained in 11/18 pts, and demonstrated avidity in all patients. Maximum SUV ranged from 4.1 to 47.6, with a median of 15. First line therapy was etoposide, doxorubicin, cisplatin, and mitotane (EDPM) in 13/18 pts and clinical trial with IMC-A12 (IGF-1 receptor antibody) in four pts. Median duration of first line therapy was 1.8 months (95% CI 0.9 – 2.8). Survival was not statistically different for patients receiving EDPM as first or second line therapy (median OS 23.3 vs 12.0 months, p = 0.96). Additional lines of therapy included EDPM, IMC-A12, AT-101, mifepristone, OSI-906 (IGF-1R inhibitor), and nivolumab. Median lines of therapy given were 2. The presence of bone metastases (p = 0.69) or lung metastases (p = 0.21) at the time of initiation of ST was not associated with OS from ST. Conclusions: In our experience, the prognosis of pts with metastatic ACC receiving systemic therapy is poor with most pts receiving ≤ 2 lines of therapy. Patients receiving first or second line EDPM seemed to have worse outcomes than noted in previously published trials, possibly due to our patients being sicker at baseline. Metastasis to the lung or bone at initiation of ST did not impact OS.

Progression-free survival in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements: An exploration of response to systemic therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 588-588 ◽  
Author(s):  
Kristen Bibeau ◽  
Luis Féliz ◽  
Scott Barrett ◽  
Ling Na ◽  
Christine Francis Lihou ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Line Therapy

588 Background: Most cholangiocarcinoma (CCA) patients (pts) are diagnosed with advanced disease and are ineligible for surgery. FGFR2 fusions or rearrangements are present in 10–16% of pts with intrahepatic CCA (iCCA) and are reported to be oncogenic drivers. However, little data are available on the role of FGFR2 genetic alterations in the response to systemic cancer therapy. FIGHT-202 is a phase 2 study of pemigatinib (a selective, potent, oral FGFR1–3 inhibitor) in pts with previously treated advanced/metastatic CCA (NCT02924376); primary results were reported at ESMO 2019. FIGHT-202 enrolled pts who progressed on ≥1 prior therapy, allowing the examination of the role of FGFR2 alterations on the response to prior therapy. The objective of this post hoc analysis was to evaluate progression free survival (PFS) on standard systemic therapy received prior to study enrollment among pts with CCA harboring FGFR2 fusions or rearrangements ( FGFR2+). Methods: Case report forms were reviewed to determine disease history and exposure to prior lines of systemic cancer therapies (LOSCT) in the advanced setting before receiving pemigatinib. Only pts with sufficient data on prior LOSCT were included in this analysis. Median PFS was calculated using the Kaplan-Meier method. Results: 102 pts were included in this analysis (median age 54.5, 61.8% female). Median PFS on first-line therapy was 5.5 (95% CI: 4.0, 8.0) months. Among the 38 pts (37.3%) with ≥2 prior LOSCT, median PFS on second-line therapy was 4.4 (95% CI: 3.0, 5.3) months. Conclusions: This analysis provides data about PFS on standard systemic therapies for pts with FGFR2+ CCA. Median PFS on first-line therapy was lower than historical published data, and median PFS on second-line therapy was slightly longer than previously reported, in unselected CCA populations. Limitations of this analysis include retrospective examination of investigator reported data, and that clinical trial participants may not truly reflect a general CCA patient population. The short PFS on standard therapies in pts with FGFR2+ CCA highlights the need for development of other options including targeted therapies to improve outcomes.

The outcome of vincristine, dactinomycin D, ifosfamide and doxorubicin (VAIA) as first-line therapy for adult-patients with metastatic ewing sarcoma; a single-center experience.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23501-e23501 ◽  
Author(s):  
Jean Paul Atallah ◽  
Mahmoud Abdelsatar Elshenawy ◽  
Ahmed ali Badran ◽  
Maaz Kamal Alata ◽  
Ahmed Gad ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ewing Sarcoma ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Objective Response ◽  
Adult Patients ◽  
Categorical Variables ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

e23501 Background: Ewing sarcoma family of tumors (ESFT) is a rare malignancy among adults. Most studies from western countries have reported improvement in outcomes following multi-agent chemotherapy. We report our experience in the management of this disease among Arab ethnicity. The aim of this study is to assess the outcome of VAIA combination as a first-line treatment in Adult-patients with metastatic Ewing sarcoma. Methods: Patients who were newly diagnosed as metastatic Ewing sarcoma between 03/1997 and 11/2016 at King Faisal Specialist Hospital and Research Center, who received VAIA as first-line therapy were eligible. The patient's characteristics were summarized using Medians with interquartile ranges (IQR) and frequencies for continuous and categorical variables, respectively. Variables including age, sex, primary tumor size, site (skeletal vs extraskeletal) and extent of metastasis in correlation with progression and overall survival were analyzed using the Kaplan–Meier method and Cox proportional hazards regression. Results: Thirty-nine patients were identified. Male (26, 66.7%), Female (13, 33.3%). Skeletal (27, 69.2%), Extraskeletal (12, 30.8%). The median longest diameter of the primary tumor 9.75 (IQR 8-15). The most common metastatic sites were Lungs (22, 56.4%) & Bone (10, 25.6%), however, the least common sites were Bone Marrow (3, 7.7%) and liver (2, 5.1%). The median number of VAIA cycles was 10 cycles (IQR 5-14). Objective response rate (ORR) was noticed in 20 patients (51.2%) (Complete Remission (7, 17.9%), Partial Remission (13, 33.3%). One patient had stable disease and 12 (30.8%) patients had progressive disease. The assessment was not feasible in 3 (7.7%) patients. With a median follow up duration of 18 months (1-44).20 patients died (62.5%). The median PFS and OS was 10,18 months respectively with 3,5 years overall survival rate of;35.7%,26.9% respectively. Univariate analysis correlation among different variables were insignificant. Conclusions: VAIA chemotherapy combination showed poor outcomes among our patients in comparison to literature further improvement is needed in this aggressive malignancy in our region.

scholarly journals Bendamustine Adversely Affects Stem Cell Mobilization Among Patients with Mantle Cell Lymphoma (MCL): A Comparison of the BR Vs RCHOP Eras in British Columbia (BC), Canada

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4556-4556
Author(s):  
Hatem Alahwal ◽  
Parv Chapani ◽  
Diego Villa ◽  
Yasser Abou Mourad ◽  
Maryse Power ◽  
...  
Keyword(s):  
Stem Cell ◽  
Platelet Count ◽  
Univariate Analysis ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Risk Of Failure ◽  
Increased Risk ◽  
Cd34 Cells ◽  
Frontline Therapy

Abstract Introduction In 2013, bendamustine/rituximab (BR) replaced RCHOP as standard first line treatment for both transplant eligible and ineligible MCL patients (pts) in BC. Retrospective cohort studies report that bendamustine has no adverse effect on peripheral blood stem cell (SC) mobilization but this is discordant with local experience. We sought to compare rates of failed SC collection in MCL pts planned for high dose chemotherapy and autologous stem cell transplant (ASCT) after BR or RCHOP and identify risk factors for failed SC mobilization and collection. Methods We identified all pts with MCL in BC treated with BR or RCHOP as first line therapy who underwent SC mobilization from Jan. 1 2003-Dec. 31 2017 using the Leukemia/Bone Marrow Transplant Program of BC and Apheresis Database Standard mobilization was with G-CSF alone (G) until difficulties with SC collection were noted after BR. Different mobilization strategies were then used, including delaying SC collection 2-3 mos after BR, G + cyclophosphamide (G+C) mobilization and/or "rescue" plerixafor if Day 1 SC collection was inadequate. Failure of SC collection was defined as yield <1 x106 CD34+ cells/kg on apheresis Day 1 (D1fail). . All variables significant in univariate analysis (P<0.1) were entered into a multivariate analysis (MVA) logistic regression model to identify factors associated with D1 fail. Results A total of 152 pts were identified. 2 were excluded as they had pre-emptive plerixafor prior to apheresis D1 on a trial. Of the remaining 150 pts, 55 (37%) received BR, 95 (63%) RCHOP for a median of 6 cycles (range 1-6). Baseline characteristics were similar between groups (Table 1). Pts receiving BR had higher remission rates compared to RCHOP (CR 58% vs 35%, P=.004) and a longer duration from their last chemotherapy to apheresis D1 (BR 89 d vs RCHOP 39 d, P<0.), reflecting an intentional change in practice. For this same reason, use of G+C mobilization was higher in BR pts (45%) compared with RCHOP pts (1%). Failure on D1 of SC collection was significantly higher after BR compared to RCHOP (45% vs. 10%, P<.001). This difference persisted when only pts mobilized with G alone were included: D1fail 60% BR vs 10% RCHOP (P<.001), Fig. 1. Among BR pts, D1fail was higher for those mobilized with G compared with G+C (60% vs. 28%, P=.03). Of the 25 BR pts with D1fail, 20 pts received rescue plerixafor (P) (1 dose: 18, 2 doses: 1, 3 doses: 1) with 17 successfully collecting > 2.0 x106 CD34+ cells/kg, 2 successfully collected after a 2nd round of SC mobilization (Pt1: G+C+P, Pt2: G+P), and 1 pt did not undergo ASCT due to collection failure. Of the 5 pts who did not receive plerixafor, 2 successfully collected with 1-2 additional apheresis days and 3 successfully collected with a 2nd round of SC mobilization (2: G+P, 1: G+C). Among the 9 RCHOP pts with D1fail, 1 had rescue plerixafor with success, 3 successfully collected after 1-2 more apheresis days and 5 had a 2nd round of SC mobilization (1: G, 4: G+P), of which 1 failed and did not proceed to ASCT. Univariate analysis identified the following associated with D1fail: frontline therapy (BR vs RCHOP, P=<.001), mobilization regimen (G+C vs G, P=.001), gender (P=.002) and D1 platelet count (P=<.001). Delaying SC mobilization in pts who received BR did not improve D1 yield (P=.31). In MVA, frontline therapy with BR had an increased risk of D1fail compared to RCHOP with an odds ratio (OR) of 7.83 (95% CI 2.7-23.1), P<.001. Using G+C significantly improved the odds of a successful collection compared to G alone (OR for D1fail 0.17 [95% CI 0.05-0.62], P=.007). Female gender and low platelet count also increased risk of D1fail in MVA (Table 2). Conclusion MCL pts who receive BR as first line therapy have an almost 8-times higher risk of failure of D1 SC collection compared to those who receive RCHOP. This failure can be overcome largely with "rescue" plerixafor and partially with planned G+C mobilization such that successful collection can be achieved in >90% of pts. However, these agents add cost and potential toxicity. Platelet count on D1 SC collection is a potential indicator of high risk of failure. Delaying SC mobilization in BR pts does not improve collection yield. The impact of bendamustine in pre-transplant chemotherapy regimens, not only for MCL but also for a broad range of lymphomas where it is being increasingly used, must be considered when planning SC mobilization strategies. Disclosures Sehn: Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals Trends in Initial Systemic Therapy for Elderly Patients with Metastatic Clear Cell Renal Cell Carcinoma

Kidney Cancer ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 131-137
Author(s):  
Chelsea K. Osterman ◽  
Allison M. Deal ◽  
Matthew I. Milowsky ◽  
Marc A. Bjurlin ◽  
Tracy L. Rose
Keyword(s):  
Targeted Therapy ◽  
Elderly Patients ◽  
Systemic Therapy ◽  
Clear Cell ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
First Line Therapy ◽  
Line Therapy ◽  
Multivariable Regression ◽  
To Receive

BACKGROUND: The treatment landscape for metastatic clear cell renal cell carcinoma (mRCC) is rapidly changing. It is unknown how adoption of new types of therapies may differ by patient age. OBJECTIVE: To compare trends in first-line therapy use for older (≥70 years) and younger (< 70) patients with mRCC before and after approval of nivolumab in 2015. METHODS: Using the National Cancer Database, we assessed trends in first-line therapy use by calculating the proportion of patients receiving targeted therapy, immunotherapy, or no systemic therapy by year of diagnosis. Initial systemic treatment was compared for patients diagnosed in 2016 with patients diagnosed in 2011 as a control group prior to nivolumab approval. Multivariable regression analysis was used to evaluate the interaction between year of diagnosis and elderly status for use of first-line immunotherapy or targeted therapy. RESULTS: From 2006 to 2016, the proportion of patients receiving any type of systemic therapy increased from 43.7% to 56.5%. On stratified multivariable regression analysis, older patients diagnosed in 2016 were 17.3 times more likely to receive first-line immunotherapy compared to those diagnosed in 2011, while younger patients were 2.3 times more likely. There was no change in targeted therapy use over this time regardless of patient age. CONCLUSIONS: The rate of adoption of first-line immunotherapy was particularly pronounced for elderly compared to younger patients. While first-line use of immunotherapy may have allowed elderly patients to receive systemic therapy that they otherwise would not, the efficacy of these drugs in elderly patients deserves further study.

PET/CT Before Autologous Stem Cell Transplantation Predicts Outcome In High-Risk, Relapsed Follicular Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4370-4370
Author(s):  
Marion Alcantara ◽  
Jehan Dupuis ◽  
Michel Meignan ◽  
Anne Julian ◽  
Stephanie Becker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Follicular Lymphoma ◽  
Conditioning Regimen ◽  
Tumor Burden ◽  
Ct Scans ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Pet Ct ◽  
Group 3

Abstract Introduction First-line immunochemotherapy followed by two years of rituximab (R) maintenance is now the standard of care for high-tumor burden follicular lymphoma (FL). In spite of an old controversy regarding the heterogeneous metabolic activity of FL lesions, either interim or final PET-CT after R-CHOP first-line therapy is now recognize to be strongly predictive of outcome. At the time of relapse, R-chemotherapy and autologous stem cell transplantation (ASCT) is a recommended option. Though, some patients will relapse quickly while others achieve long-term remissions. We investigated the prognostic value of PET-CT in patients with high-tumor burden relapsed FL treated with salvage R-chemotherapy followed by ASCT. Patients and Methods Seventy-five patients with relapsed FL referred to three French institutions were retrospectively analyzed. Patients with grade 3b follicular lymphoma or transformed into diffuse large B-cell lymphoma were excluded. Patients received second-line immunochemotherapy according to the local physician’s choice. We classified these salvage treatments into three groups: fludarabine-based regimen (n=29, group 1), cytarabine-based regimen (n=31, group 2), or ifosfamide-based regimen (n=15, group 3). PET-CT scans performed after salvage therapy (before ASCT) were included in the analyses. The local investigator’s interpretation of the imaging physician’s scan report defined a positive or negative PET. Results Median age was 56 years and 60% were men. Sixty eight patients received ASCT. Among this whole high-risk study population, 87% relapsed before 36 months after R-CHOP and 42% relapsed within 6 months and were therefore considered as R-CHOP refractory, with a median progression free survival (PFS) after R-CHOP first-line therapy of 15 months. Only 21% of the patients received R maintenance after R-CHOP. PET-CT scans after salvage therapy (before ASCT) were considered negative in 57%/76%/47% among the 3 groups respectively (p=0.06). Median stem cell harvest was higher in group 3-ifosfamide-based (8.3.106) than in both fludarabine and cytarabine-based regimens (4.47 and 4.8.106 respectively, Mann-Whitney p=0.15). Conditioning regimen was BEAM (37%) or Zevalin-BEAM (56%). Thirteen patients received R maintenance after ASCT. At a median follow-up of 28 months, 26/75 patients relapsed and 62 are alive. At 2 years, median PFS was 63.8%/66%/53.5% and median overall survival (OS) 68%/94%/92% among the 3 groups, respectively. PFS was only correlated to PET-CT results (p=0.0006). OS was correlated to group of therapy (2-3 versus 1), FLIPI score at relapse and PET-CT negativity. The latter was the strongest OS predictor on a multivariate analysis (p<0.01). On the other hand, age, gender, conditioning regimen, and PFS after R-CHOP (<36 months or even <12 months) were not linked to shorter PFS/OS. We observed 12% of second non-hematologic cancer. Conclusion PET-CT scan negativity after salvage treatment is the most important favourable factor for relapsed/refractory FL patients who receive ASCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Venous Thromboembolic Events in Diffuse Large B Cell Lymphoma. Incidence, Risk Factors and Outcomes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3968-3968
Author(s):  
Sabarish Ayyappan ◽  
Dhivya Prabhakar ◽  
Vinita Gupta ◽  
Brenda Cooper ◽  
Hillard M. Lazarus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Patient Characteristics ◽  
Hematologic Malignancies ◽  
P Value ◽  
First Line ◽  
Bulky Disease ◽  
First Line Therapy ◽  
Line Therapy

Abstract Venous thromboembolism (VTE) is a frequent complication of hematologic malignancies, including lymphoid malignancies. VTE results in significant morbidity and mortality in lymphoma patients. There is limited information regarding the factors affecting the risk of VTE in diffuse large B cell lymphoma (DLBCL) patients treated with chemoimmunotherapy. We conducted a retrospective analysis to identify risk factors affecting the incidence of VTE and the effect of this complication on patient outcome. Methods: We searched the hematologic malignancies database of University Hospitals Seidman Cancer Center for patients newly diagnosed with DLBCL between 2004 and 2014. Records were reviewed for baseline demographics, evidence of known risk factors for VTE, disease characteristics, treatment history and baseline laboratory values. The univariate probability of overall survival (OS) and progression free survival (PFS) was estimated using the Kaplan-Meier method. The cumulative incidence procedure was used to estimate the incidence of VTE. To identify risk factors for VTE, univariate analysis was conducted on the potential risk factors for VTE and variables with P-value .25 were selected for analysis in the multivariate logistic regression model. Results: 204 patients diagnosed with DLBCL were included. Patient characteristics are presented in table 1. The median age at diagnosis was 66 years and 63% had advanced stage at diagnosis. After a median follow up was 27 months, 34 patients (16.6%) presented a VTE, with a 3-year cumulative incidence of 13.7% (95% CI 9.2-20.3%). The VTE was a pulmonary embolism in 12 subjects (35%) and deep venous thrombosis in 22 patients (65%). The diagnosis of VTE was done in the presence of active disease in 23 subjects (67%) and the first VTE occurred during the first line of chemotherapy in 16 patients (47% of VTE). Risk factors identified by univariate analysis (table 2) included previous history of VTE, coronary artery disease and congestive heart failure, bulky disease, and absence of a complete response. Treatment with an anthracycline - containing regimen resulted in decreased risk of VTE. In multivariate analysis, only the presence of bulky disease, progressive disease after first line therapy and treatment with anthracyclines retained statistical significance (p = 0.05, 0.05 and 0.006, respectively). After a median of 27 months of follow up 113 patients had presented progression after first line therapy and 72 had died. Overall, 3-year PFS was 58.6% (95% CI 51-66.2%), with lower PFS in patients experiencing VTE (3-year PFS: VTE 34.8%; no VTE 64.4%, p=0.002). 3-year OS for the whole cohort was 70.2% (95% CI 63.1-77.3%). Patients who presented VTE had a 3-year OS of 51.3% vs. 74.8% in patients without VTE (p=0.002). DLBCL patients present a high risk of VTE, with approximately half of all VTE events occurring early in the course of the disease. We were able to identify the presence of bulky disease at diagnosis and the absence of response to first line therapy as risk factors for developing VTE. The use of anthracycline-containing regimens was protective against VTE, likely because of the increased rates of disease response. Patients with VTE had worsened outcomes, likely a result of the presence of persistent disease, although a direct effect of VTE on long-term outcomes cannot be ruled out. Our results highlight the need for a heightened awareness of the increased risk of VTE in DLBCL patients and the need for prevention strategies. Table 1. Baseline patient characteristics Median age, years (range) 66 (20-92) Gender (%) Male Female 115 (56.3%) 89 (43.6%) Stage I II III IV 32 (15.9%) 43 (21.4%) 41 (20.4%) 85 (42.3%) R-IPI 0 1-2 3-5 18 (8.8%) 104 (51.0%) 80 (39.2%) Table 2. Risk Factors and results of univariate analysis Risk factor Odds Ratio p value Age > 65 1.179 0.661 Male gender 0.847 0.659 Prior congestive heart failure 5.69 0.009 Prior VTE 4.016 0.07 Increased creatinine 3.479 0.181 Morbid obesity 5.121 0.252 Prior malignancy 1.283 0.674 Bulky disease 2.425 0.035 Stage II vs. I III vs. I IV vs. I 3.742 1.343 1.906 0.058 0.703 0.338 Elevated LDH 1.329 0.450 Hemoglobin <10g/dl 0.902 0.236 Platelets < 150,000/mcl 1 0.108 Non - GCB molecular subtype 0.658 0.439 Positive FISH for t(8;14) 1.668 0.568 Anthracycline 0.383 0.050 Rituximab 5.454 0.265 Response PR vs. CR PD vs. CR SD vs. CR 0.843 0.986 0.850 0.863 1.013 1.550 Disclosures No relevant conflicts of interest to declare.

scholarly journals Duration of Therapy Is Independently Associated with Improved Progression Free and Overall Survival Following First Line Therapy for Non-Transplant Eligible Patients with Multiple Myeloma: Retrospective Analysis from a Single Centre

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5684-5684
Author(s):  
Dunnya De-Silva ◽  
Adam Bloomfield ◽  
Nicholas Counsell ◽  
Simon Cheesman ◽  
Ali Rismani ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Total Duration ◽  
Novel Agents ◽  
First Line ◽  
Disease Response ◽  
Duration Of Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Stage 1

Abstract Background. Survival for older patients with multiple myeloma (MM) has improved with novel agents such as Proteasome inhibitors (PIs) and Immunomodulatory drugs (IMiDs) . Outcomes in this heterogeneous population are also affected by pre-morbid fitness, comorbidities and tolerance of therapy. We analysed the outcomes of first line systemic therapy in this older patient group, aiming to explore the influence of patient, disease and regimen factors on outcomes. Methods. Non-transplant eligible patients undergoing first line therapy between April 2008 and April 2016 were identified retrospectively from electronic prescribing records; patient and disease features, toxicity and dose modifications were obtained from clinical records. FISH was performed on CD138+ cells using standard probes, and adverse risk was defined as per IMWG criteria. Survival was estimated using Kaplan-Meier methods and disease response by IMWG criteria. Cox Regression (univariate and multivariate) analysis was performed to identify factors influencing progression free (PFS) and overall survival (OS). Results. 84 patients were identified with median age 76 years (range 52-97); 24(28.6%) had cardiac and 12(14.3%) had pulmonary comorbidities. There was an equal spread of ISS stage and 26(31.0%) patients had extramedullary disease (EMD). Of 44 patients with FISH results at diagnosis, 18 (40.9%) had high risk features including 9(20.5%) with del(17p). Patients received a range of treatments; 51(60.7%) had PI-based regimens mainly with Bortezomib, 18(21.4%) received IMiDs (13 Thalidomide, 5 Lenalidomide) and 13(15.5%) chemotherapy. The median total duration of therapy including maintenance was 7.7months (range 0.7-24.1); this was longer (9.6months) in patients receiving IMiDs. The median PFS was 13.1 months (95% CI 10.6-15.5) and median OS was 40.5months (95% CI 30.3-50.7). The overall response rate (ORR) was 70.2%, and was higher in patients treated with novel agents (IMiD 72.2%, PI 72.0%) compared to patients treated with chemotherapy (61.6%). Younger age (70-80years vs. ≥80years), ISS stage 1, disease response ≥PR, maintenance therapy and longer total duration of therapy were associated with longer PFS in univariate analysis, and EMD was associated with shorter PFS(p's <0.1). On multivariate analysis, only total duration of therapy (HR=0.89; 0.81-0.96, p=0.005), ISS stage 1 (HR=0.28; 0.12 -0.63, p=0.002) and younger age (70-80years vs. ≥80years HR=0.50; 0.24-1.05, p=0.068) independently predicted longer PFS. Looking at factors predicting OS on univariate analysis, ISS stage 1, IMiD therapy, maintenance therapy and longer duration of therapy were associated with prolonged OS (p's <0.1). Only longer duration of therapy (HR=0.84; 0.76-0.93, p=0.001) and ISS stage 1 (HR=0.25; 0.08-0.80, p=0.020) remained significantly associated with OS on multivariate analysis. Although adverse genetic risk was associated with shorter OS on univariate analysis, the effect was not seen after adjusting for ISS stage, induction regimen and duration of therapy, where only duration of therapy remained significant (HR=0.69; 0.56-0.87, p=0.001). 18 (21.7%) patients discontinued therapy early due to toxicity; this was more frequent with PI (23.5%) and chemotherapy regimens (20.5%) compared to IMiD regimens (16.7%). 48(57%) patients required dose alterations due to toxicity, and this was commoner with IMiD (72%) compared to chemotherapy (38%) or PI (55%) based regimens. Conclusion. We report a sequential cohort of non-transplant eligible patients undergoing first line therapy in the era of novel agents. Our results indicate a consistent benefit for PFS and OS with longer duration of therapy, independent of response, regimen or adverse risk disease. ISS 1 was also an independent predictor of prolonged PFS and OS. Treatment regimen type and response did not correlate independently with PFS or OS. Despite the presence of comorbidities and discontinuations for toxicity, the PFS and OS outcomes are encouraging. This review of real-world outcomes highlights the potential benefit of continuous therapy in older patients. Improved ways of identifying patients susceptible to toxicity and use of frailty-adjusted treatment schedules would further improve outcomes in this patient group. Disclosures Yong: Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor; Janssen: Research Funding.

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