Bendamustine in Monotherapy and in Combination Regimens in the Treatment of Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma – a Retrospective Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4602-4602
Author(s):  
Iwona Hus ◽  
Dariusz Jawniak ◽  
Magdalena Gorska-Kosicka ◽  
Aleksandra Butrym ◽  
Justyna Dzietczenia ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Lymphocytic Leukaemia ◽  
Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Rank Test ◽  
Indolent Lymphoma ◽  
Advisory Committees ◽  
Log Rank Test ◽  
Combination Regimens

Abstract Abstract 4602 Purpose: In this study, we carried out a retrospective analysis of the efficacy and toxicity of bendamustine in patients with B-cell lymphoproliferative diseases. Methods: Bendamustine was administered both in monotherapy and combined protocols in 111 patients, including 81 patients with chronic lymphocytic leukaemia (CLL), 20 patients with indolent lymphoma, and 10 patients with aggressive lymphoma (8 mantle cell lymphoma and 2 diffuse large B-cell lymphoma). Median age of patients was 61 years (range: 44 – 87 years). Almost all patients, except 3 previously untreated patients with CLL had relapsed (78 patients) or refractory disease (30 patients). 60.4% of patients were treated with bendamustine plus rituximab, while 28.2% received bendamustine in monotherapy, and 31.4% received other combined regimens. Results: Overall response rate (ORR) was 65.8%, including 20.7% of complete response (CR) and 45.1% of partial response (PR). In CLL patients, ORR was 59.3% with 16% of CR and 43.2% of PR. In patients with indolent NHL, ORR was 80%, including 30% of CR and 50% of PR. In patients with aggressive lymphoma, OR and CR rates were respectively: 90% and 40%. In patients with CLL, a likelihood of response was significantly lower in patients with ZAP-70 expression (p=0.006) and 17p deletion (p=0.009). Median overall survival (OS) for all patients was 11.5 months (range 1–40). For CLL patients, median OS was 11 months (range 1–40), for patients with indolent lymphoma 15.5 months (range 5–29 ) and for patients with aggressive lymphoma - 10 months (6–38). Median OS was significantly longer in patients responding to therapy as compared to non-responders (15 months vs. 8 months; p=0.0001). Median progression-free survival (PFS) in all patients was 6 months (0–38), including 4 months (0–38) for CLL patients, and 8.5 months (0–33) for patients with both aggressive and indolent lymphoma. Among pre-treatment parameters, β2-microglobulin (RR=1.234; p=0.002), haemoglobin level (RR=0.803; p=0.03) and PLT count (RR=1.005; p=0.03) significantly influenced survival. Also, the higher number of bendamustine cycles was associated with longer overall survival (RR=0.715; p=0.003). In patients with CLL, 17p deletion was associated with reduced overall survival (p=0.021; log-rank test). OS was significantly longer in patients who received ≤ 2 lines of previous therapies as compared to > 3 lines (p=0.018; log-rank test), and who received ≥ 4 courses of therapy (p=0.02; log-rank test). In patients with NHL, both OS and PFS were significantly longer in patients with lactate dehydrogenase level <250 U/l (p= 0.01; p=0.02; respectively), and who received ≥ 4 cycles of treatment (P= 0.03). Toxicity was predominantly haematological, including grade III/IV neutropenia in 32%, thrombocytopenia in 15% and anaemia in 16% of patients. Conclusion: Bendamustine, both in monotherapy and combination regimens, is an effective therapy with a favourable toxicity profile even in heavily pretreated patients. Disclosures: Hus: Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria; Glaxosmithkline: Consultancy. Off Label Use: In Europe bendamustine is indicated for first-line treatment of chronic lymphocytic leukaemia (Binet stage B or C) in patients for whom fludarabine combination chemotherapy is not appropriate and indolent non-Hodgkin's lymphomas as monotherapy in patients who have progressed during or within 6 months following treatment with rituximab or a rituximab containing regimen. Wiktor-Jedrzejczak:Genzyme: Speakers Bureau; Celgene: Speakers Bureau; Genopharm: Speakers Bureau; Bayer: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy; Janssen-Cilag: Consultancy; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Walewski:Roche: Honoraria, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Cephalon: Research Funding; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Dmoszynska:Millenium Pharmaceuticals: Consultancy; Celgene: Consultancy; Mundipharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.

The Transcriptional Signature of Kinases Inhibited by the Multi-Targeted Kinase Inhibitor AS703569 Is Associated with Clinical Outcome in Multiple Myeloma (MM): Anti-MM Activity of AS703569 in Preclinical Studies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 730-730
Author(s):  
Jake Delmore ◽  
David N. Cervi ◽  
Douglas McMillin ◽  
Efstathios Kastritis ◽  
Jana Jakubikova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
Kinase Inhibitor ◽  
Rank Test ◽  
Preclinical Studies ◽  
Advisory Committees ◽  
Transcriptional Signature ◽  
Log Rank Test

Abstract Abstract 730 Multi-targeted kinase inhibitors, when associated with manageable toxicity, offer the therapeutically desirable option of targeting, through a single chemical entity, several pathways that may contribute to the complexity and heterogeneity of molecular lesions harbored by neoplasias such as multiple myeloma (MM). However, intractable questions often emerge while prioritizing for preclinical studies different multi-targeted agents with extensive and/or only partially overlapping of sets of known targets. We have hypothesized that the potential therapeutic relevance of a multi-targeted inhibitor may be reflected on the prognostic relevance of its targets' transcriptional signature. We applied this concept in the case of the orally bioavailable multi-targeted kinase inhibitor AS703569, which targets (with IC50 in low nM range) all 3 Aurora kinase (AK) isoforms as well as various other kinases (e.g. cSRC, FGFR1, Flt3, Fyn, Lyn, Rsk1-3, Yes, Axl, et.c.) and evaluated the transcriptional signature of AS703569 kinase targets (with IC50 <10 nM) in MM cells of patients receiving Bortezomib as part of Phase II/III trials (specifically SUMMIT/APEX). We observed that patients with high transcriptional signature of AS703569 targets had inferior progression-free and overall survival (p=0.005 and p=0.012, log-rank test) and also validated that, in a study of tandem autologous transplant, a subset of patients with high levels of this AS703569 target transcriptional signature also have inferior overall survival (p=0.032, log-rank test) compared to cases with low levels of the signature. These observations supported the notion that the kinome space targeted by AS703569 is enriched for targets associated with adverse clinical outcome in MM. In preclinical assays, we observed that AS703569 decreased the viability of MM cell lines and primary CD138+ MM tumor cells in a time- and dose-dependent manner, with IC50 values <50 nM for the majority of cell lines tested; and without evidence of cross-resistance with established anti-MM agents. Combinations of AS703569 with dexamethasone, doxorubicin, or bortezomib did not exhibit antagonism, suggesting that AS703569 can be incorporated in regimens with these established anti-MM drug classes. Interestingly, in vitro compartment-specific bioluminescence imaging (CS-BLI) assays showed that against MM cells which respond to stromal cells with increased proliferation and survival, the anti-MM activity of AS703569 is more pronounced when these MM cells are co-cultured with bone marrow stromal cells than in conventional cultures in isolation. This indicated that AS703569 is capable of overcoming the protective effects that BMSCs confer to MM tumor cells and prompted in vivo validation studies in our orthotopic SCID/NOD model of diffuse MM bone lesions established by i.v. injection of MM-1S-GFP/Luc cells monitored by whole body bioluminescence imaging. AS703569 (50 mg/kg p.o. once weekly)-treated mice had longer overall survival than vehicle-treated mice (median 50.0 days, 95% C.I. 40.3-59.7 days vs. 39.0 days, 95% C.I., 35.4-42.6 days, p=0.019, log-rank test). An alternative schedule of AS703569 at 16.7 mg/kg 3 times/week also resulted in longer overall survival (median 54.0 days, 95% C.I. 33.2-74.8 days, p=0.023, log-rank test). These data indicate that AS703569 exhibits anti-MM activity in vitro and in orthotopic in vivo MM models, and suggests that this multi-targeted inhibitor merits considerations for further preclinical studies, as well as potential clinical studies in MM, especially given the otherwise adverse outcome associated with the inhibitor's target transcriptional signature. Disclosures: Laubach: Novartis: Consultancy, Honoraria. Rastelli:EMD Serono: Employment. Clark:EMD Serono: Employment. Sarno:EMD Serono: Employment. Richardson:Millenium: (Speakers' Bureau up to 7/1/09), Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: (Speakers' Bureau up to 7/1/09), Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Anderson:Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mitsiades:Millennium: Consultancy, Honoraria; Novartis : Consultancy, Honoraria; Bristol-Myers Squibb : Consultancy, Honoraria; Merck & Co: Consultancy, Honoraria; Kosan Pharmaceuticals: Consultancy, Honoraria; Pharmion: Consultancy, Honoraria; PharmaMar: Patents & Royalties; Amgen: Research Funding; AVEO Pharma: Research Funding; EMD Serono : Research Funding; Sunesis Pharmaceuticals: Research Funding.

Impact Of The Proportion Of Metaphases With Isolated Del(5q) On Clinical Outcomes In Lenalidomide (LEN)-Treated Patients With IPSS Low-/Int-1-Risk Myelodysplastic Syndromes (MDS) In MDS-003 and MDS-004

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1538-1538
Author(s):  
Aristoteles Giagounidis ◽  
Alan List ◽  
Eva Hellström-Lindberg ◽  
Mikkael A. Sekeres ◽  
Ghulam J. Mufti ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Clinical Outcomes ◽  
Research Funding ◽  
Rank Test ◽  
Employment Equity ◽  
Advisory Committees ◽  
Log Rank Test ◽  
Equity Ownership ◽  
Baseline Characteristics ◽  
Rbc Transfusion

Abstract Introduction The proportion of aberrant metaphases is prognostic for overall survival (OS) in MDS patients with trisomy 8 (Mallo M, et al. Leuk Res. 2011;35:834-6). The impact of the proportion of metaphases with del(5q) on clinical outcomes, including OS, disease progression and response to therapy with LEN in MDS remains undefined. In two large multicenter studies of LEN (MDS-003 and MDS-004) in RBC transfusion-dependent patients with International Prognostic Scoring System (IPSS) Low- or Intermediate (Int)-1-risk del(5q) MDS, RBC transfusion independence (TI) ≥ 8 weeks was achieved in 51–67% of patients (List A, et al. N Engl J Med. 2006;355:1456-65; Fenaux P, et al. Blood. 2011;118:3765-76). This retrospective analysis evaluated response to treatment, progression to acute myeloid leukemia (AML) and OS by proportion of del(5q) metaphases in patients with isolated del(5q) from the MDS-003 and 004 studies. Methods In order to allow sufficient patient numbers for analysis, ≥ 16 metaphases were evaluated for del(5q) by standard karyotyping (MDS-003 and MDS-004) and 200 interphase nuclei were evaluated by fluorescence in situ hybridization (FISH; MDS-004 only) using a probe for the commonly deleted region 5q31 (LSI EGR1/D5S721, Abbott, Wiesbaden, Germany). Patients received LEN on days 1–21 of each 28-day cycle (10 mg) or continuously (5 mg or 10 mg), or placebo. In MDS-004, patients randomized to placebo could cross over to LEN 5 mg by week 16. RBC-TI ≥ 26 weeks, time to AML progression and OS were analyzed by the proportion of del(5q) metaphases or interphases (≤ 60% vs > 60%) using standard karyotyping and FISH, respectively. Results Of the 353 patients from MDS-003 and MDS-004, 194 had isolated del(5q) by standard karyotyping; median proportion of del(5q) metaphases was 96% (range 4–100). Baseline characteristics including age, time from diagnosis, RBC transfusion burden, hemoglobin level, platelet and absolute neutrophil counts were comparable among patients with ≤ 60% (n = 21) and > 60% (n = 173) del(5q) metaphases. Rates of RBC-TI ≥ 26 weeks were similar across patients in the ≤ 60% and > 60% groups (P = 0.6515). Time to AML progression was comparable for patients in the ≤ 60% group versus the > 60% group (log-rank test P = 0.9802); 2-year rates were 22.2% (95% confidence interval [CI]: 7.7–54.5%) and 14.6% (95% CI: 9.9–21.2%), respectively. Time to AML progression was similar when analyzed with death without AML as competing risk (Gray’s test P = 0.5514). OS was longer in the > 60% versus the ≤ 60% group (log-rank test P = 0.0436); median OS was 3.7 years (95% CI: 3.0–4.2) and 2.4 years (95% CI: 1.5–4.9), respectively. In MDS-004, the proportion of del(5q) interphases was analyzed using FISH in 106 patients, including 46 with ≤ 60% and 60 with > 60%. When analyzed by FISH, rates of RBC-TI ≥ 26 weeks were similar across patients in the ≤ 60% and > 60% groups (P = 1.000). Time to AML progression and OS were similar across these groups (log-rank test P = 0.7311 and P = 0.8639, respectively) when analyzed by FISH. In the ≤ 60% and > 60% groups respectively, 2-year AML progression rates were 14.8% (95% CI: 6.9–30.1%) and 18.6% (95% CI: 10.4–32.0%), and median OS was 3.1 years (95% CI: 2.3–4.8) and 2.9 years (95% CI: 2.3–4.4). Time to AML progression was similar when analyzed with death without AML as competing risk (Gray’s test P = 0.8631). Conclusions In IPSS Low- or Int-1-risk MDS patients with isolated del(5q) treated with LEN in MDS-003 and MDS-004 studies, baseline characteristics, RBC-TI ≥ 26 weeks and AML progression were comparable in patients with > 60% versus ≤ 60% del(5q) metaphases. Although similar across groups when analyzed by FISH in a subset of patients, surprisingly, OS was longer in patients with > 60% del(5q) metaphases than in those with ≤ 60% del(5q) metaphases by standard karyotyping. However, the number of patients with ≤ 60% del(5q) metaphases was limited and no adjustment was made for multiple testing. These findings suggest that the number of cells with the isolated del(5q) abnormality measured by FISH does not impact clinical outcome in this RBC transfusion-dependent study population, but this finding could not be confirmed for OS by standard karyotyping. Disclosures: Giagounidis: Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. List:Celgene: Serve on Celgene Data Safety & Monitoring Committee Other. Hellström-Lindberg:Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Sekeres:Celgene: Membership on an entity’s Board of Directors or advisory committees; Amgen: Membership on an entity’s Board of Directors or advisory committees. Mufti:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Schlegelberger:Celgene: Consultancy. Morrill:Celgene: Employment, Equity Ownership. Wu:Celgene: Employment, Equity Ownership. Skikne:Celgene: Employment, Equity Ownership. Fenaux:Celgene: Honoraria.

Center Experience and Calendar Year Of Transplantation Strongly Influence Short Term Survival After Autologous Peripheral Blood Transplantation In 1315 Patients With Light Chain Amyloidosis: An EBMT Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 417-417
Author(s):  
Stefan O Schonland ◽  
Ute Hegenbart ◽  
Simona Iacobelli ◽  
Jennifer Hoek ◽  
M Rovira ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Performance Status ◽  
Rank Test ◽  
High Dose ◽  
Al Amyloidosis ◽  
Advisory Committees ◽  
Term Survival ◽  
Log Rank Test ◽  
One Year ◽  
Short Term Survival

Abstract Introduction High-dose chemotherapy and autologous stem cell transplantation (ASCT) is a treatment option for eligible patients with systemic light chain (AL) amyloidosis. Compared to patients with multiple myeloma (MM), the risk for complications and transplant-related mortality is increased. However, in this fragile patient group it is often not possible to distinguish between treatment- and amyloidosis-related deaths in the post-transplant period. The CIBMTR reported a one year survival (1-yr OS) of 66% of patients transplanted between 1995 and 2001. Another multicenter analysis from Great Britain reported a one year survival of 75% (Goodman et al., BJH, 2006); interestingly, they could show a significant reduction of day 100 all-cause mortality from 32% to 13% after 1998. In recent single center studies 1-yr OS was better ranging from 80% to 90% (reviewed by Schönland et al., BMT, 2011). The amyloidosis groups of Mayo Clinic and Boston Medical School could also show a survival improvement over time (Tsai et al., Blood, 2012 and Gertz et al., BMT, 2010). Specific Aim The aim of this retrospective study was to analyze the 1-yr OS after ASCT for patients with AL amyloidosis in Europe. Of special interest were calendar year of transplants and center experience. Methodology Patient-, disease-, and transplant-related variables were collected according to the data entries in the EBMT database. Inclusion criteria were as follows: first autologous transplant with peripheral blood stem cells performed between 1997 and 2010. Center experience was measured for each patient by the number of previous MM ASCT done in the center until the year of AL transplant. Results 1315 patients from 259 centers fulfilled the entry criteria and were included in the analysis (for patient characteristics see table). The conditioning regimen was high-dose melphalan in most cases. Median follow up was 47 months. 1-yr OS after ASCT was 80.7% (CI 78.5 – 82.9). In univariate analysis age, gender, time from diagnosis to ASCT had no influence on 1-yr OS. Bad performance status (57% (50-65) vs. 90% (87-92); p<0.001) and progression/relapse as status at conditioning (61% (53-69) vs. 85% (83-87); p<0.001) significantly reduced 1-yr OS. A strong and significant influence of the transplant period (see figure 1, log-rank test, p<0.001) and higher center experience (see figure 2; log-rank test, p<0.001) could also be demonstrated. Interestingly, the proportion of patients with bad performance status decreased from 28% to 13% in most recent years (p=0.001). These results hold in multivariate analysis. Bad performance status (HR 4.3; p<0.001), progression/relapse as status at conditioning (HR 1.96; p<0.001) and earlier transplant period (HR 1.1; p<0.001) retained their highly significant negative influence on 1-yr OS. In an alternative multivariate model replacing transplant period with center experience, the latter has also a beneficial effect (HR 0.99 for 10 additional previous MM transplants; p=0.015) and all other prognostic factors retained the estimated effects. Conclusion This is the first report from the EBMT about the results of ASCT in AL amyloidosis from 259 European centers and the largest retrospective analysis for this rare entity. It clearly shows that short term survival has been improved over time probably due to better patient selection and increase of center experience. Of note, in the most recent cohort (2009 to 2010) the 1-yr OS was 91% (CI 87-96) supporting the further use of ASCT in eligible AL amyloidosis patients. Disclosures: Leblond: Roche : Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Mundipharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau.

Long-Term Responders after Brentuximab Vedotin: Experience on 57 Patients with Relapsed and Refractory Hodgkin and Anaplastic Large Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2725-2725 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Letizia Gandolfi ◽  
Beatrice Casadei ◽  
Cinzia Pellegrini ◽  
Alessandro Broccoli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Median Number ◽  
Brentuximab Vedotin ◽  
Advisory Committees ◽  
Large Cell Lymphoma

Abstract Brentuximab vedotin (BV) is an antibody drug-conjugate targeting CD30 linked to monomethyl auristatin E. Several studies have shown the efficacy of BV in patients with refractory or relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). We reviewed our clinical database to evaluate the long-term efficacy of this treatment. From July 2009 to February 2015, 57 patients were treated with BV in our Institute: 43 with a diagnosis of HL and 14 with sALCL. Thirty-six were males and 21 were females, with a median age of 33 years (range 16-77). All of them had been heavily pretreated before BV with a median number of previous therapies of 3 (range 2-10). Thirty-nine had refractory disease and 18 were relapsed. Autologous stem cells transplantation had failed in 30 patients. BV was administered at a dosage of 1.8 mg/mq, every 21 days, for a maximum of 16 cycles. The median number of cycles was 8 (range 2-16); 13 patients completed the entire schedule. The best overall response rate was globally 57,8% (33 of 57 patients), including 25 (43.8%) complete responses (CR): 18 with HL and 7 with sALCL. At present, 20/25 (80%) patients are still in continuous CR (CCR) with a median follow up of 9 months (range 3-41): 10 of them have consolidated the response with a stem cell transplantation (SCT) (4 auto-SCT and 6 allo-SCT) and 10 patients have remained in CR without any other therapy after BV. Among these long-term responders without any consolidation (7 patients with HL and 3 with sALCL), the median follow-up is 12 months (range 3-37); in particular there are 3 patients in CCR after at least 24 months. The global overall survival rate at 68 months is 71% (no patients with sALCL dead) and the median overall survival has not been reached yet. The global progression-free survival rate at 48 months is 30%, the median is achieved at 11,7 months. Toxicity was primarily neurological with peripheral sensory symptoms (30%) and motor neuropathy (5%); the majority was grade 3 in severity (8 patients). This study confirms the safety and the high efficacy of BV that can be considered an effective treatment in patients with relapsed or refractory HL or sALCL. This drug can induce a durable complete response representing a "bridge" to auto-SCT or allo-SCT. However our data show a subset of patients that can be considered "long-term responders", who have remained in CCR without any consolidation after BV. Disclosures Zinzani: Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; J&J: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Cavo:Janssen: Honoraria; Celgene: Honoraria, Speakers Bureau; Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria.

Distribution and Impact of Comorbidities on Survival and Leukemic Transformation in Myeloproliferative Neoplasm (MPN)-Associated Myelofibrosis (MF)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4264-4264
Author(s):  
Justyna Bartoszko ◽  
Tony Panzarella ◽  
Caroline Jane McNamara ◽  
Anthea Lau ◽  
Aaron D. Schimmer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Primary Outcome ◽  
Secondary Analysis ◽  
Rank Test ◽  
Leukemic Transformation ◽  
Advisory Committees ◽  
Log Rank Test ◽  
Comorbidity Scores ◽  
The Impact

Abstract Introduction. Myelofibrosis is a disease characterized by aberrant bone marrow function with eventual fibrosis. Current widely-used disease prognostic indices, such as the Dynamic International Prognostic Scoring System (DIPSS) do not take into account comorbidities, which may have significant effects on patient survival as well as disease course. We sought to describe the comorbidity distribution in this patient population and assess the impact of comorbidities as scored by two different widely used scales in clinical practice, the Adult Comorbidity Evaluation 27 (ACE-27) and the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), on overall survival and leukemic transformation in myelofibrosis. A score of 3 on ACE-27 or ≥3 on HCT-CI generally indicates a high burden (severe) comorbidities. Methods. We conducted a retrospective study of 309 patients seen at the MPN program at the Princess Margaret Cancer Centre, with a confirmed diagnosis of myelofibrosis [primary myelofibrosis (PMF), post-essential thrombocytopenia (PET-MF) or post-polycythemia vera (PPV-MF)]. Patients were seen from 1999-2014 with a median follow-up time of 2 years. Time to death and leukemic transformation was examined from the date of first presentation to our centre. Our primary aim was to examine the impact of comorbidity scores, as assessed by ACE-27 and the HCT-CI, on overall survival. In a secondary analysis we examined the impact of comorbidity scores on leukemic transformation. Multivariable Cox proportional hazards models were constructed for the primary and secondary outcomes. A series of descriptive analyses were carried out examining the distribution of various comorbidities as captured by the two scales. Results. The most common comorbidities captured by ACE-27 were hypertension (n=92, 22.3%), diabetes mellitus (n=43, 10.4%), venous disease (n=26, 6.3%), solid tumour including melanoma (n=26, 6.3%), and angina/coronary artery disease (n=23, 5.6%). The most common comorbidities captured by HCT-CI were cardiac (n=49, 17.3%), diabetes (n=43, 15.2%), mild hepatic (n=28, 9.9%), cerebrovascular disease (n=25, 8.8%), prior solid tumour (n=24, 8.5%). The distribution of comorbidity scores as compared between scales is shown in Table 1. A total of 78 patients (25.2%) experienced the primary outcome of interest, which was all-cause death. For the primary outcome of overall survival, there were differences across groups of patients with different comorbidity scores using ACE-27 or HCT-CI, with the highest severity groups having worse outcomes (Figure 1). Progressively increasing DIPSS categories (Low, Intermediate-1, Intermediate-2, and High risk) were also associated with worse overall survival. On multivariable survival analysis, an ACE-27 score of 3 when compared to a lower score of 0-1 was associated with an almost two-fold increase in the risk of all-cause death [HR 1.95 (95% CI 1.06-3.58), p=0.03]. On multivariable analysis, an HCT-CI score of 3+ when compared with 0-1 was marginally significantly associated with an increased risk of all-cause death [HR 1.60 (95% CI 0.96-2.68), p=0.07]. Interaction terms were tested between the scores and age at presentation and no effect of age on survival across varying severities of comorbidities was found. In our secondary analysis, there was no impact of the ACE-27 or HCT-CI on leukemic transformation. Conclusions. ACE-27 picked up severe co-morbidities in 13% of patients in our cohort while HCT-CI picked up severe comorbidities in 23%. Although the incidence of severe co-morbidities was lower when assessed by ACE-27, the overall impact on survival of severe comorbidities as assessed by both scores is likely to be similar. The presence of severe comorbidities at the time of diagnosis conferred a significant survival disadvantage in patients with myelofibrosis, but had no impact on progression to leukemic transformation. Table Overall survival by ACE-27 comorbidity category, showing differences between categories of comorbidity severity (p=0.047, log rank test). Table. Overall survival by ACE-27 comorbidity category, showing differences between categories of comorbidity severity (p=0.047, log rank test). Figure Figure. Disclosures Panzarella: Cellgene: Consultancy. Schimmer:Novartis: Honoraria. Schuh:Amgen: Membership on an entity's Board of Directors or advisory committees. Yee:Novartis Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gupta:Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Research Funding.

scholarly journals Busulfan/Fludarabine- or Treosulfan/Fludarabine-Based Conditioning Regimen in Patients with Wiskott-Aldrich Syndrome Given Allogeneic Hematopoietic Cell Transplantation — an EBMT Inborn Errors Working Party and Scetide Retrospective Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2175-2175 ◽  
Author(s):  
Michael H. Albert ◽  
Mary Slatter ◽  
Andrew Gennery ◽  
Tayfun Guengoer ◽  
Henric-Jan Blok ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Rank Test ◽  
Unrelated Donor ◽  
Advisory Committees ◽  
Secondary Procedure ◽  
Log Rank Test ◽  
Secondary Procedures

Abstract PV and AL contributed equally Multiple studies from the EBMT registry and others have shown excellent survival rates after allogeneic haematopoietic stem cell transplantation (HSCT)for Wiskott-Aldrich syndrome (WAS) patients (Ozsahin et al, Blood 2008). The importance of myeloid engraftment for full disease correction has also been demonstrated (Moratto et al, Blood 2011). However, the vast majority of HSCTs in these studies were performed with (oral) busulfan/cyclophosphamide-based conditioning and in the early 2000 years or before. In 2005, the inborn errors working party (IEWP) of EBMT and ESID first recommended busulfan/fludarabine (BuFlu) or treosulfan/fludarabine (TreoFlu) based conditioning for primary immunodeficiencies such as WAS, with some centers deciding to add thiotepa (TT) to the conditioning. We performed a retrospective analysis via the EBMT and SCETIDE registries of WAS patients transplanted between 01/01/20006 and 12/31/2016 with these two regimens. The primary objective was to compare the overall (OS) and event-free survival (EFS) after HSCT with either BuFlu±TT or TreoFlu±TT conditioning. Secondary objectives included the influence of either conditioning regimen on acute and chronic GVHD, the degree of donor chimerism, incidence of secondary procedures after HSCT (2nd HSCT, stem cell boost, DLI, gene therapy or splenectomy) and rates of disease-specific complications after HSCT. At the time of this interim analysis, 174 patients were included, 92 (53%) with BuFlu±TT and 82 (47%) with TreoFlu±TT conditioning with a median age of 1.57 years (range 0.21-29.96) at HSCT and a median follow-up of 32.9 months (range 1.5-128.9). The donor was an HLA-matched sibling (MSD) in 30, a matched related donor (MRD) in 5, a matched unrelated donor (MUD, 9/10 or 10/10) in 105, a mismatched unrelated donor (MMUD, <9/10) in 9 and a mismatched family donor (MMFD) in 25 (18 with ex-vivo T-cell depletion). Stem cell source was bone marrow in 93 (53%), peripheral blood in 62 (36%) and cord blood in 18 (10%). Two year overall survival (OS) of the entire cohort was 88.6% (95% confidence interval 83.5%-93.6%). There was no significant difference in OS between patients treated with BuFlu±TT or TreoFlu±TT conditioning (2-year OS 88.1% vs. 89.5%; log-rank test p=0.7). Patients aged >5 years had a worse OS as compared to those 5 years or younger at HSCT (74.9% vs. 90.8%; log-rank test p=0.005). The type of donor had no influence on OS: 96.4% for MSD/MFD, 86.8% for MUD/MMUD and 87.7% for MMFD (log-rank test p=0.4). Whole blood chimerism was complete (>90% donor) in 60/75 evaluable patients (80%) at last follow-up or before secondary procedure (if a patient had one), 39/40 (98%) in the BuFlu±TT group and 21/35 (60%) in the TreoFlu±TT group. Twenty-six patients required a secondary procedure: stem cell boost in 4 patients, donor lymphocyte infusion in 9, 2nd HSCT in 15 and splenectomy in 1. Twenty-two of these 26 (84.6%) are alive and 14 of 16 with available chimerism data have a complete donor chimerism (>90%donor) at last follow-up. The 2-year cumulative incidence (CI) of secondary procedures was higher at 33.9% in the TreoFlu±TT versus 12.8% in the BuFlu±TT group (Gray's test p=0.017), and 2-year EFS (secondary procedure or death as event) was 61.4% in the TreoFlu±TT and 75.0% in the BuFlu±TT group (log-rank test p=0.2). Grade II-IV acute GVHD had the same incidence in both groups (100 day CI 24.4% vs. 26.3%; Gray's test p=0.849) and chronic GVHD of any grade was borderline more frequent in the TreoFlu±TT group (2 year CI 17.2% vs 6.7%; Gray's test p=0.054). The cumulative incidence of disease-specific complications occurring more than 6 months post HSCT (severe infections, bleeding, autoimmunity) was not different between the two groups (6.5% vs. 6.4%; Gray's test p=0.92). There was no malignancy reported after HSCT except for one EBV-post-transplant lymphoproliferative disorder (PTLD) 2.7 months after HSCT. In summary, HSCT with either BuFlu±TT or TreoFlu±TT conditioning reliably cures almost 90% of patients with WAS regardless of donor type. WAS-related complications are very rare events more than 6 months post HSCT. More patients required secondary procedures after treosulfan-based than busulfan-based conditioning. These data confirm the feasibility and efficacy of the regimens currently recommended by the IEWP. Disclosures Slatter: Medac: Other: Travel assistance. Chiesa:Gilead: Consultancy; Bluebird Bio: Consultancy. Kalwak:Sanofi: Other: travel grants; medac: Other: travel grants. Locatelli:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria. Sykora:Aventis-Behring: Research Funding; medac: Research Funding. Zecca:Chimerix: Honoraria. Veys:Pfizer: Honoraria; Servier: Research Funding; Novartis: Honoraria.

scholarly journals Neutropenia in Children Treated with Deferiprone or Deferasirox: A Report of the Largest Randomized Trial of Oral Chelators in Transfusion-Dependent Pediatric Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3552-3552
Author(s):  
Fernando Tricta ◽  
Mariagrazia Felisi ◽  
Oscar Della Pasqua ◽  
Amal El-Beshlawy ◽  
Hoda Hassab ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Neutrophil Count ◽  
Severe Neutropenia ◽  
Rank Test ◽  
Cumulative Hazard ◽  
Advisory Committees ◽  
Treatment Groups ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Oral Chelators

Introduction: Agranulocytosis/severe neutropenia is an established adverse event during deferiprone (DFP) use. Less is known about milder episodes, which are frequently transient despite continuous deferiprone use. To provide further insight into this topic, we compared the incidence of neutropenia during DFP or deferasirox (DFX) treatment in the randomized Deferiprone Evaluation in Paediatrics (DEEP-2) trial, where blood neutrophil count was regularly monitored in patients randomized to be treated with DFP or DFX. Methods: DEEP-2 was a multicenter, randomized, 12-month, open-label trial comparing DFP vs DFX in pediatric (&lt;18 years old) patients with transfusion-dependent hemoglobinopathies. 390 patients from 22 centers in 7 countries were randomized (1:1 DFP:DFX) and received at least one dose of the study medication (193 on DFP and 197 on DFX). Neutrophil count was regularly assessed every 7 +/-7 days in all patients. Neutrophil counts &lt;500/mm3 were classified as agranulocytosis/severe neutropenia, 500 - &lt;1,000 /mm3 as moderate neutropenia, and 1,000 - &lt;1,500 /mm3 as mild neutropenia. The incidence of neutrophil counts below the threshold of neutropenia (1,500/mm3) and the rate of reported episodes of neutropenia as identified by the treating physician were compared between the two treatments. An ANOVA model was used to compare the time to neutropenia and time for its resolution between the two treatment groups. To compare the cumulative hazard curves was used the Kaplan-Meier log rank test. Results: 3579 and 4027 neutrophil counts were available for DFP- and DFX-treated patients, respectively. 47 (1.3%) of the total counts in 24 (12.4%) of the 193 DFP-treated patients versus 48 (1.2%) of the total counts in 27 (13.7%) of the 197 DFX-treated patients were below 1,500/mm3. Of these, 28 cases in 23 DFP-treated patients and 15 cases in 11 DFX-treated patients were reported by the treating physician as neutropenia, corresponding to a global incidence rate 11.9% for DFP and 5.6% for DFX (p=0.081, Chi-Square test). 23 (82.1%) of the 28 episodes of neutropenia during DFP use were considered drug related vs 2 (13.3%) of the 15 episodes during DFX use (p-value &lt; 0.001, Fisher Exact test) (table 1). The mean (SD) treatment duration with either DFP or DFX prior to diagnosis of mild or moderated neutropenia was 127 (96.1) days and 101 (85.7) respectively. All those episodes, except for 2, resolved within a mean time of 13 days (1 - 42 days) in DFP-treated patients and 18 days (6 - 46 days) in DFX-treated patients. The 2 cases where neutropenia did not resolve were diagnosed as constitutional neutropenia and bone marrow suppression. There was no significant difference in those results between the two treatment groups as assessed by one-way ANOVA(p = 0.379), Log-Rank test (p = 0.065) or cumulative-hazard and Kaplan-Meier. During the study 3 events of agranulocytosis occurred, all in patients treated with DFP and not included in the present analysis. All 3 episodes resolved. Conclusion: Data from the largest randomized trial of oral chelators in transfusion-dependent pediatric patients provide evidence that, a drop in the neutrophil count below the threshold for mild neutropenia is very common (&gt;10% of patients) for both DFP and DFX treated patients. All episodes of neutropenia, except for 2 with specific etiology, resolved, irrespective of their severity and of chelator used. A causal relationship of neutropenia to chelator use varied based on the chelator; the majority of events observed during DFP use were assessed by the clinician as drug related, whereas the majority of events observed during DFX use were assessed unrelated to its use. These data indicate that while agranulocytosis rate in DFP patients is not changed from previous reports, moderate/mild neutropenia represent discrete events in patients undergoing oral iron chelation therapy. Disclosures Tricta: ApoPharma: Employment. Della Pasqua:GlaxoSmithKline: Employment. Kattamis:Ionis: Membership on an entity's Board of Directors or advisory committees; ViFOR: Membership on an entity's Board of Directors or advisory committees; Vertex: Membership on an entity's Board of Directors or advisory committees; Apopharma: Honoraria; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Reggiardo:CVBF: Consultancy. Spino:ApoPharma: Employment. Tsang:Apotex Inc.: Employment.

Results of a Phase I-II Clinical Trial of Oxaliplatin, Fludarabine, Cytarabine, and Rituximab (OFAR) Combination Therapy In Patients with Aggressive, Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) and Richter Syndrome (RS)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 923-923 ◽  
Author(s):  
Apostolia Maria Tsimberidou ◽  
William G. Wierda ◽  
Sijin Wen ◽  
William Plunkett ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Phase I ◽  
Board Of Directors ◽  
Clinical Outcomes ◽  
Median Survival ◽  
Phase Ii ◽  
Research Funding ◽  
Response Rate ◽  
Rank Test ◽  
Advisory Committees ◽  
Log Rank Test

Abstract Abstract 923 Background: To enhance the response rate with a decrease in myelosuppression that were observed with oxaliplatin, fluradabine, Ara-C, and rituximab (OFAR1) (Tsimberidou et al, J Clin Oncol, 2008;26:196), the daily dose of oxaliplatin was increased from 25 to 30mg, the daily dose of Ara-C was decreased from 1 g/m2 to 0.5 g/m2 and the optimal number of days of fluradabine and Ara-C administration was explored (OFAR2). Methods: OFAR2 consisted of oxaliplatin 30mg/m2 D1-4; fludarabine 30mg/m2; Ara-C 0.5g/m2; rituximab 375mg/m2 D3; and pelfigrastim 6mg D6. Fludarabine and Ara-C were given on D2-3 (level 1) D2-4 (level 2) or D2-5 (level 3) every 4 weeks. Tumor lysis, DNA virus, and PCP prophylaxis was administered. A “3+3” design was used (Phase I) and and the planned number of patients in the Phase II was 90 (CLL, 60; RS, 30). Results: Overall 102 patients (rel. CLL 67, RS 35) were treated. Twelve patients were treated in the Phase I portion of the study. Dose-limiting toxicities were noted in 2/3 patients at level 3 (G4 diarrhea and G4 sepsis). Level 2 was the maximum tolerated dose. Ninety patients (CLL, 60; RS, 30) were treated in Phase II portion of the study (age > 60 years 67%, 17p del 37.5%, 11q del 15%, 13q del 18%, +12, 17%; neg. 12.5%; unmutated IgVH 81.5%, ZAP70-positive 77%, and CD38 30%, 63%). Response in 80 of 90 patients (Phase II) is shown in Table (too early, n=10). The overall response rates in patients (Phase II) with 17p deletion and 11q deletion were 29% and 41%, respectively. Twenty-nine patients underwent SCT after OFAR2 (response status to OFAR2 at the time of SCT: CR, n=3; nPR, n=2; 15; no response, n=9). With a median follow-up of 20.8 months, the median survival was 19 months (95% CI, 13–37+) and the median FFS was 6 months (95% CI, 3.4 – 8.2). Overall, 238 cycles were administered. G3-4 neutropenia, thrombocytopenia, and anemia were noted in 67%, 74%, and 44% of patients (51%, 64%, and 25% of cycles); and G3-4 infections in 19% of patients. Clinical outcomes of OFAR2 were compared with those of OFAR1. In patients with RS, the overall response rate was 41% (11/27) with OFAR2 and 50% (10/20) with OFAR1 (p = 0.57, Fisher's test); the median survival with OFAR2 and OFAR1 was 8.3 months and 18+ months, respectively (p = 0.92, log-rank test); and the respective median FFS was 3.0 months and 4.1 months (p = 0.40, log-rank test). In patients with CLL, the overall response rate was 55% (29/53) with OFAR2 and 33% (10/30) with OFAR1 (p = 0.36, Fisher's test); the median survival with OFAR2 was 21.4 months and 13.8 months with OFAR1 (p = 0.19, log-rank test); and the respective median FFS was 6.6 months and 4.9 months (p = 0.69, log-rank test). Conclusion: OFAR2 induced response in 41% of patients with RS and 55% of patients with relapsed/refractory CLL in the phase II study. Antileukemic activity was also noted in patients with 17p deletion. Although the numbers of patients are small, OFAR1 was associated with a trend towards superior clinical outcomes in patients with RS compared to OFAR2; and OFAR2 was associated with a trend towards superior clinical outcomes compared to OFAR1 in patients with relapsed/refractory CLL. Disclosures: Tsimberidou: Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; ASCO: Career Development Award, Research Funding. Off Label Use: Drug: Oxaliplatin. Oxaliplatin combined with fludarabine, cytarabine, and rituximab has antileukemic activity in patients with relapsed/refractory Chronic Lymphocytic Leukemia and Richter Syndrome. Wierda:Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Micromet: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Research Funding; Abbott Laboratories: Research Funding. O'Brien:Biogen Idec: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Kipps:Sanofi Aventis: Research Funding. Jones:GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbott Laboratories: Research Funding.

Grade 3 Follicular Lymphoma: Outcomes in the Rituximab Era

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1520-1520 ◽  
Author(s):  
Moaath Mustafa Ali ◽  
Basel Rouphail ◽  
Robert M. Dean ◽  
Brian T. Hill ◽  
Deepa Jagadeesh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Board Of Directors ◽  
Statistical Difference ◽  
B Cell Lymphoma ◽  
Large Series ◽  
Aggressive Lymphoma ◽  
Advisory Committees ◽  
Grade 3

Abstract Background: Follicular lymphoma (FL) is a heterogeneous disease commonly graded as 1, 2, 3A and 3B based on percentage of large cells. While FL grade 3A is often considered as an indolent disease and grouped with grades 1-2, data suggest that FL grade 3B has clinical behavior similar to diffuse large B-cell lymphoma (DLBCL) so is approached as an aggressive lymphoma. At the Cleveland Clinic, we reviewed a large series of patients (pts) diagnosed with FL grade 3A, 3B and FL grade 3 with areas of DLBCL and reported characteristics and outcomes in the rituximab era. Methods: Patients: We performed a retrospective IRB-approved analysis of patients diagnosed with FL 3A, 3B, or FL3 with concomitant areas of DLBCL. 72 subjects were identified with FL grade 3; including: 3A, 3B, FL 3/DLBCL, or unclassified FL3. We excluded subjects who had no follow-up data or diagnosed as unclassified FL 3, thus we analyzed a cohort of 46 patients. These 46 were divided into two groups. The aggressive lymphoma group (n=21) included subjects diagnosed with FL3B (n=11) and FL3 (A or B) with concomitant areas of DLBCL (n=10) (termed aggFL). The indolent lymphoma group (n=25) included subjects diagnosed with FL3A. All patients started their 1st treatment between 1998-2014. The aim of this study was to assess the clinical outcomes by comparing the progression free survival (PFS) and overall survival (OS) between the two groups. Results: Of the 46 patients, 25 (54%) had FL 3A, 11 (24%) FL 3B, and 10 (22%) FL3/DLBCL. Thus, the aggressive group (aggFL) had 21 patients (46%). For the entire cohort, 37 (49%) were male and 35 (51%) female; 78% were Caucasian. Table 1 compares FL 3A and combined 3B and FL 3/DLBCL cohorts. With median follow-up of 54 and 62 months for FL3A and aggFL, respectively; 75% of FL 3A and 86% of aggFL patients were alive. Among the FL3A and combined aggFL groups, 23 of 25 (92%) and 18 of 21patients (85%) received R-CHOP, respectively. There was no statistical difference in PFS between the 2 groups, and each group has apparent PFS plateau after ~ 3 years (Figure2). Similarly, we found that no statistical difference in Overall Survival between the groups of indolent FL (F3A) and aggFL (FL3B or FL3/DLBCL) lymphoma. Conclusion: The outcomes of the 1st large series of FL grade 3 patients in the rituximab era, primarily treated with R-CHOP, show no statistically significant difference in PFS or OS between FL 3A vs. aggFL with predominantly large cells (FL 3B/DLBCL). As expected, aggFL, FL3B and FL3/DLBCL, showed a plateau confirming that these pts should be treated with curative intent. Surprisingly, FL3A pts mainly managed with R-CHOP also show a plateau in survival; however, indicating the possibility of long term unmaintained remission in this histology and raising the issue of potential under-treatment with less aggressive regimens. Table 1. Clinical and Demographic Characteristics FL 3A FL 3b FL 3/ DLBCL N=25 % N=21 % P Age 0.45* Mean+ SD 61 ± 15.6 58 ± 11 Range 65 (19- 85) 55 (39-80) Gender 0.56** Male 14 54% 9 43% Female 12 46% 12 57% ECOG Performance Status 1** Good (ECOG 0,1) 18 72% 17 81% Poor (ECOG >1) 2 8% 1 5% Unknown 5 20% 3 14% B Symptoms 0.74** Present 8 32% 5 24% Not Present 17 68% 16 76% BM Involvement 0.47** Involved 6 24% 3 14% Not Involved 16 64% 16 76% Unknown 3 12% 2 10% Stage 0.76** I, II, III 17 68% 13 62% IV 8 32% 8 38% 1st Line Regimen 1** R-CHOP) 22 88% 18 85% Other 3 12% 2 9% Median/Average Follow-up (Months) From DX 54/60 62/65 0.68* From TX 55/58 59/56 0.91* *Anova **Fisher's Exact Figure 1. Figure 1. Disclosures Hill: Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Smith:celegene, spectrum, genentech: Honoraria.

scholarly journals Analyzing Patient Characteristics Who Received (DA) EPOCH-R for High Risk Diffuse Large B-Cell Lymphoma: MD Anderson Cancer Center Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4208-4208 ◽  
Author(s):  
Kristin A. Simar ◽  
Vishwanath Sathyanarayanan ◽  
Amir K Issa ◽  
Mohamed Amin Ahmed ◽  
Mansoor Noorani ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Neutropenic Fever ◽  
Rank Test ◽  
Cancer Center ◽  
P Value ◽  
Outpatient Therapy ◽  
Advisory Committees ◽  
Log Rank Test ◽  
The Difference

Abstract Background: Due to ~50% risk of relapse with standard therapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, R-CHOP), an increasing number of patients with high risk diffuse large B-cell lymphomas (DLBCL) are being treated with dose-adjusted (DA) EPOCH-R (rituximab, etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide). DA-EPOCH-R contains a 96-hour continuous infusion can be delivered either in the inpatient or outpatient setting, via use of ambulatory infusion pumps. Potential advantages of outpatient therapy include reduced inpatient burden for routine chemotherapy, less exposure to resistant bacterial infections, increased patient satisfaction, and reduced cost. The ability to administer outpatient DA-EPOCH-R is dependent on the ability of the healthcare facility to administer the regimen safely while maintaining dose adjustments and schedule. We hypothesize that patients who receive DA-EPOCH-R as an outpatient have similar outcomes and toxicity rates as patients who receive the regimen as an inpatient. We further hypothesize that there is a significant cost benefit for patients to receive DA-EPOCH-R as an outpatient. Methods: This was a retrospective database analysis of newly diagnosed consecutive DLBCL patients ≥ 18 years of age who received DA-EPOCH-R chemotherapy at MD Anderson Cancer Center between 2010 and 2014. Patients with double hit lymphoma defined as having a MYC and BCL2 or BCL6 translocation were excluded due to their aggressive nature. We descriptively analyzed demographic variables in this population including, age, gender, international prognostic index (IPI)) and outcome (overall response rates (ORR), complete response (CR), progression free survival (PFS), overall survival (OS), and hospital admission for neutropenic fever events). Additionally, we evaluated the number of outpatient cycles received in relation to survival outcomes and neutropenic fever events. Statistical analysis was done using Fisher's exact test or Chi-square test to evaluate the association between two categorical variables and Wilcoxon rank sum test was used to evaluate the difference in a continuous variable between patient groups. Kaplan-Meier method was used for time-to-event analysis including overall survival and progression free survival. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Results: A total of 196 patients had data available for analysis, with 138 patients (70.4%) receiving all cycles as an inpatient, while 58 patients (29.6%) received at least 1 outpatient cycle of DA-EPOCH-R (Table 1). Compared with patients who received no outpatient cycle, the patients who received any outpatient therapy were younger, had a lower proportion of high IPI, and experienced fewer episodes of febrile neutropenia. The median OS and PFS for the entire population has not been reached, with a median follow-up time for the censored observations of 2.78 years (range: 0.24 - 8.64 years). The difference in OS between the patients who had any outpatient therapy and no outpatient therapy was not significant by the log-rank test (p-value=0.11). The difference in PFS between the patients who had any outpatient therapy and no outpatient therapy was marginally significant for OS by the log-rank test (p-value=0.07). Our cost analysis for 6 cycles of inpatient DA-EPOCH-R is estimated to be ~$88K, or $14.6K/cycle. The cost savings incurred for chemotherapy only expenses for each outpatient cycle is at least $3.3K/cycle or $19.8K for a total of 6 cycles. Conclusion: DA-EPOCH-R is a highly effective regimen for treating aggressive DLBCL which can be administered in an outpatient setting safely, efficaciously, and in a cost-effective manner without any apparent effect on outcome or rate of admission for neutropenic fever. There can be savings of about of nearly $20K per patient for a 6-cycle course of therapy. In our series, patients who received outpatient therapy were younger and may have had greater social support, which could potentially confound results. This retrospective analysis supports the use of outpatient DA-EPOCH-R, but additional studies are warranted to evaluate which patients may benefit most. Disclosures Oki: Novartis: Research Funding. Nastoupil:Janssen: Other: Travel, Accommodations, Expenses, Research Funding; TG Therapeutics: Research Funding; Celgene: Honoraria; AbbVie: Research Funding. Fowler:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Wang:Asana BioSciences: Research Funding; Acerta: Consultancy, Research Funding; Dava Oncology: Honoraria; BeiGene: Research Funding; Kite Pharma: Research Funding; Juno Therapeutics: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Asana biosciences, Beigene, Celgene, Juno, Kite, Onyx, Pharmacyclics: Research Funding. Fayad:Seattle Genetics: Consultancy, Research Funding. Westin:Celgene: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; ProNAi: Membership on an entity's Board of Directors or advisory committees.

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