scholarly journals Role of Neutrophil Lymphocyte Ratio [NLR] As a Biomarker of Frailty and Predictor of Survival Among Older Adults with Multiple Myeloma (MM)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Smith Giri ◽  
Susan Bal ◽  
Kelly N. Godby ◽  
Joshua Richman ◽  
Adam J Olszewski ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Research Funding ◽  
First Line ◽  
Targeted Interventions ◽  
First Line Therapy ◽  
Systems Research ◽  
Line Therapy ◽  
Race Ethnicity ◽  
The Impact

Introduction: NLR combines a marker of inflammation (neutrophilia) and immune senescence (lymphopenia) to reflect aging related alterations in the immune systems. Prior studies have shown that NLR can serve as a marker of frailty and predict survival among older adults with solid tumors and lymphomas, its role among older adults with MM remains unclear. Methods: We used the Flatiron Health electronic health record-derived de-identified database to source older adults (age ≥60y) with incident MM diagnosed between 1/1/2011 and 2/1/2020. We limited our study cohort with known first line therapy and absolute neutrophil and lymphocyte count (cells//µL) up to 90 days before the start of treatment. We constructed a modified frailty index (Facon et al Leukemia 2020) at MM diagnosis combining age, comorbidity and ECOG performance status, captured within 90 days from the start of first line therapy categorizing patients into frail vs nonfrail. We examined the association between NLR (stratified into quartiles, Q1-Q4) and frailty using logistic regression model adjusted for age, sex and race/ethnicity. We used Kaplan Meier methods and multivariable Cox regression to assess the impact of NLR on overall survival adjusting for age, sex, race/ethnicity, international staging system (ISS) stage, high-risk cytogenetics (HRCA; del17p, t4;14 or t14;16), and first-line therapy. Results: Of 2792 eligible patients, the median age at MM diagnosis was 73y (IQR: 67-78y), with 53% males and 61% non-Hispanic whites. Of these, 56% had IgG isotype, 22% ISS stage-III and 13% had HRCA. The median NLR was 2.29 (IQR: 1.5 to 3.59). Of the 1,743 evaluable for frailty, 1042 patients (59.8%) were frail. Overall, 45% received proteasome inhibitor (PI) + Immunomodulatory agent (Imid) based first line therapy and 19% received autologous stem cell transplantation. Patients in the highest NLR quartile were at a 2.1-fold higher odds of being frail (95% CI 1.52-2.86; p <0.001) when compared with those in the lowest NLR quartile (after adjusting for age, sex and race/ethnicity). NLR was poorly correlated with age (Pearson's r= 0.02). Patients in the highest NLR quartile had an inferior overall survival vs those in the lowest quartile (median OS/3y-OS in Q4 3.3y/53% vs 4.7y/69% in Q1; log-rank p <0.01). Similar results were seen when limiting to patients receiving first line PI & Imid triplet and PI or Imid based doublet regimens (Fig 1). In a multivariable analysis, patients in the highest NLR quartile had a 1.5 times increased hazards of death (95% CI 1.28-1.85, p <0.001) when compared with those in the lowest NLR quartile, after adjusting for potential confounders (Table 1). Conclusion: NLR is an easily available laboratory biomarker associated with frailty as well as inferior overall survival among older adults with MM. Future studies should explore its value as a screening tool to identify frail older adults with MM and guide appropriate treatment selection and targeted interventions to prevent excess toxicities and improve outcomes. Table 1 Disclosures Giri: Pack Health: Research Funding; Carevive Systems: Research Funding; Carevive Systems: Honoraria. Olszewski:Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Costa:Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; AbbVie: Consultancy; Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Genentech: Consultancy.

Lenalidomide Treatment For Lower Risk Non-Deletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Prior To Azanucleosides

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1507-1507
Author(s):  
Rami S Komrokji ◽  
Maria G. Corrales-Yepez ◽  
Najla H Al Ali ◽  
Eric Padron ◽  
Jeffrey E Lancet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Research Funding ◽  
Response Rates ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction Lenalidomide (LEN) is the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndromes (MDS) with chromosome 5q deletion (del 5q). In the MDS-002 study, 26% of lower risk transfusion dependent MDS patients became red blood cell transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment alternative for transfusion dependent anemia in lower risk non-del 5q MDS after azanucleosides failure. The response rate to LEN after azanucleosides failure, however, is not known given that the MDS-002 study preceded FDA approval of azanucleosides. To address the best sequence of LEN to optimize response potential in lower risk MDS, we examined the response rates to LEN in non-del 5q lower risk MDS when offered as first line after (erythroid stimulating agents) ESA's or after azacitidine failure. Methods This was a retrospective study conducted using the Moffitt Cancer Center (MCC) MDS database. We identified patients with lower risk MDS who received both LEN and azacitidine as first or second line therapy after erythroid stimulating agents. Lower risk MDS was defined according to the international prognostic scoring system (IPSS) Low or intermediate-1 (int-1) risk groups. The primary endpoint was to compare rates of erythroid hematological improvement (HI-E) between the group of patients who received LEN as first line therapy followed by azacitidine as second line (LEN 1st line group) and those who received LEN as second line therapy after azacitidine (LEN 2nd line group). HI was defined according to international working group criteria (IWG 2006). Chi- square test was used for categorical variables, T-test was used for continuous variables, and Kaplan Meier estimates for overall survival. All analyses were conducted using SPSS statistical software (IBM version 21) Results We identified 63 patients who received both azacitidine and LEN as first and second line where 37 patients were in group 1 (LEN 1st line) and 26 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table-1. There were no statistically significant differences between the 2 groups in terms of mean age at diagnosis, gender, WHO subtype, revised IPSS, or mean blood counts. The majority of patients had refractory cytopenia with multilineage dysplasia (RCMD) and had low risk revised IPSS . The rate of HI-E was 38% (n=14) among LEN 1st line group compared to 12% (n=3) in LEN 2nd line group. (p=0.04). There was no difference in overall survival (OS) among the two groups with a median OS of 104 months and 87 months, respectively, p=0.55. There was no difference in AML transformation rate, 5.4% (n=2) and 11% (n=3) among the two groups, respectively, p=0.33. There were no differences in response rates to azacitidine among the two groups. Among the Len 1st line group response to 2nd line azacitidine was 38% (n=14) compared to 35% (n=9) among those who received azacitidine as first line followed by LEN as 2nd line. (p=0.69). Conclusion LEN yields a higher rate of HI-E in non-del 5q lower risk MDS when used as first line therapy. If validated in a larger cohort, LEN should be considered for 1st line therapy after ESAs rather than after azacitidine failure. Responses to azacitidine were similar among the two groups, indicating no adverse effect of LEN on azacitidine response. Disclosures: Komrokji: Celgene: Research Funding, Speakers Bureau. Off Label Use: use of lenalidomide in non del 5q. Lancet:Celgene: Research Funding. List:Celgene: Research Funding.

scholarly journals Use of Zidovudine and Interferon Alfa With Chemotherapy Improves Survival in Both Acute and Lymphoma Subtypes of Adult T-Cell Leukemia/Lymphoma

2011 ◽  
Vol 29 (35) ◽  
pp. 4696-4701 ◽  
Author(s):  
Andrew Hodson ◽  
Siobhan Crichton ◽  
Silvia Montoto ◽  
Naheed Mir ◽  
Estella Matutes ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Interferon Alfa ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
First Line ◽  
Adult T Cell Leukemia ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Impact

Purpose Adult T-cell leukemia/lymphoma (ATLL) is a mature (post-thymic) T-cell lymphoma associated with human T-lymphotropic virus type 1 infection. Survival in aggressive subtypes remains poor, and treatment resistance is frequent. Use of zidovudine (ZDV) and interferon alfa (IFN-α) has been associated with improved response rates in small studies and prolonged overall survival in leukemic ATLL subtypes in a recent meta-analysis. Patients and Methods We report the clinicopathologic characteristics, treatment, and outcome of 73 patients with aggressive ATLL (acute ATLL, 29; lymphoma ATLL, 44) diagnosed and treated in England between 1999 and 2009. The impact of ZDV/IFN-α on treatment response and survival was assessed. Results The overall response rate ranged from 49% with chemotherapy alone to 81% with combined first-line therapy (chemotherapy with concurrent/sequential ZDV/IFN-α). Median overall survival (OS) was 9 months: 7.5 months for acute ATLL and 10 months for lymphoma ATLL. Use of ZDV/IFN-α at any time prolonged survival in acute (P < .001) and lymphoma ATLL (P < .001) and was the sole factor associated with reduction in risk of death in aggressive ATLL (hazard ratio, 0.23; 95% CI, 0.09 to 0.60; P = .002). Combined first-line therapy prolonged median OS in acute (P = .0081) and lymphoma ATLL (P = .001) compared with chemotherapy alone. Conclusion These data support the use of low-dose ZDV/IFN-α with chemotherapy in first-line treatment of acute and lymphoma ATLL.

scholarly journals Outcomes in Advanced-Stage Plasmablastic Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2519-2519
Author(s):  
Sophia Lee ◽  
Christen Dillard ◽  
Raphael E Steiner ◽  
Babak Soltanalizadeh ◽  
Lei Feng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Progression Free Survival ◽  
Plasmablastic Lymphoma ◽  
Advanced Stage ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: Plasmablastic lymphoma (PBL) is a rare subtype of non-Hodgkin B-cell lymphoma (NHL), often characterized by immunoblastic morphology and plasmacytic immunophenotype. PBL was initially described in HIV-positive patients (pts) and is now often diagnosed in post-transplant and HIV-negative pts with other immunodeficiency. Pts with limited stage disease treated with induction chemotherapy and consolidative radiotherapy have a good prognosis; however, pts with advanced stage have poor outcome. Previously studied treatment regimens vary and include CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone), HyperCVAD (cyclophosphamide, vincristine, Adriamycin, dexamethasone alternating with methotrexate and cytarabine), and DA-EPOCH (etoposide, vincristine, cyclophosphamide, Adriamycin, prednisone) with or without radiation and autologous stem cell transplant, with no current standard therapy, largely due to the rarity of PBL. Methods: We conducted a retrospective analysis of pts diagnosed with PBL between April 2003 and August 2020 to describe outcomes for pts treated at our center over the past 2 decades. We hope to use this to improve outcomes with novel therapies in the future. We evaluated the baseline demographics, stage, therapy, response rate, progression-free survival (PFS) and overall survival (OS). We used descriptive statistics including mean, standard deviation, median, and range for continuous variables, and frequency counts and percentages for categorical variables. Best response and its 95% exact confidence interval were calculated. Kaplan-Meier method was used to estimate the time-to-event endpoints including progression free survival, and overall survival. Results: 39 pts with PBL were identified, with a median age of 51 years (range 27-91). 16 were HIV+, and 5 were on immunosuppression for autoimmune disease (2), infectious hepatitis (2), or liver transplant (1); the other 18 had no apparent immunosuppression other than advanced age (defined as 70 years and older) in 13. Among those with HIV, 14 were on antiretroviral therapy at time of diagnosis of PBL. The median CD4 count was 140 (range 15-391) and 5 patients had an active viral load. 24 pts were EBV/EBER positive. 6 pts had stage III disease and 33 had stage IV disease. The primary sites of disease included head and neck (13), lymph node (7), gastrointestinal tract (6), other soft tissue (3), abdomen (3), breast (2), gynecologic (2), skin (2), and bone (1). The median LDH was 629 IU/L (313-618). A serum protein electrophoresis was checked in 21 pts and the median was 1.4 g/dL (range 0.2-2.6 g/dL, normal = 0). A beta 2 microglobulin was checked in 28 pts and the median was 3.95 (range 2.55-10.4, normal =0.8 to 2.3 mg/L). The median Ki-67 proliferation index was 85%, and the PBL cells were invariably CD20 negative. 12 cases showed MYC overexpression; 2 had MYC rearrangement by FISH. 32 pts received systemic therapy and were evaluable with 2 median lines of treatment (range 1-6). First line therapy included Hyper-CVAD (n=7), CHOP (n=3), EPOCH (n=19), and other (n=3). The antimyeloma therapy, bortezomib, a proteasome inhibitor, was added to EPOCH for 4 patients or used with dexamethasone in one pt, while the CD38 antibody daratumumab was added to hypercytoxan for the first cycle of an elderly pt with poor performance status (PS). He responded well with improvement in his PS, and subsequently completed 5 cycles of DA-EPOCH and remains in CR. After first line therapy, 59% pts achieved complete response, 13% partial response, and 9% stable disease. 20 pts received intrathecal chemotherapy, 9 pts received radiation, and 8 pts underwent autologous stem cell transplantation (7 as consolidation and 1 at relapse). Please see figure for PFS and OS based on different treatment modalities. Median PFS and OS were 21 and 35.2 months, respectively. Median follow up time was 25.85 months. Conclusions: The majority of our pts (87%) with advanced stage PBL were immunocompromised with HIV (16), requiring immunosuppression (5), or elderly (13). Despite a 56% CR rate with induction, 69% of patients relapsed. Median PFS was less than 2 years and OS was less than 3 years. The dismal outcomes of pts with PBL suggests that this rare and aggressive subtype of NHL with plasmacytic differentiation requires further evaluation with therapies against plasma cell directed antigens such as CD38, BCMA or SLAMF7. *S Lee & C Dillard contributed equally. Figure 1 Figure 1. Disclosures Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Loghavi: Abbvie: Current equity holder in publicly-traded company; Curio Sciences: Honoraria; Gerson Lehrman Group: Consultancy; Guidepoint: Consultancy; Peerview: Honoraria; Qualworld: Consultancy. Ahmed: Seagen: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Xencor: Research Funding. Patel: Pfizer: Consultancy; Janssen: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Oncopeptides: Consultancy.

Analysis of an Online Decision Support Tool for Chronic Lymphocytic Leukemia: Disparities in Treatment Selection Between Experts and Community Practitioners

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5958-5958
Author(s):  
Kristen M Rosenthal ◽  
Farrukh T. Awan ◽  
Jacqueline C. Barrientos ◽  
Steven E. Coutre ◽  
Kevin L Obholz ◽  
...  
Keyword(s):  
Research Funding ◽  
Treatment Plan ◽  
Decision Support Tool ◽  
Treatment Recommendations ◽  
Treatment Selection ◽  
First Line ◽  
Support Tool ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Impact

Abstract Background. Rapid advances in clinical discovery and availability of new treatment options have increased the complexity of treatment decisions for patients with CLL. Guidelines list multiple agents and combinations as recommended therapeutic options for CLL but often do not provide specific treatment recommendations for individual patients. We developed an online treatment decision tool that provides treatment recommendations from CLL experts for specific patient cases. We hypothesized that these individualized recommendations from recognized experts would affect treatment plans. Here we report on an analysis of data entered into this CLL decision support tool, including variance between intended treatment of tool users and the recommendations made by the experts and the impact of the tool on subsequent therapy decisions. Methods. In December 2015, 5 experts provided treatment recommendations for 1380 case variations based on key factors that guide treatment choice. Expert-selected factors for newly diagnosed CLL included age, fitness (based on ECOG PS, CIRS, and renal function), and cytogenetic abnormalities (del[17p], del[11q], or other). Additional variables for patients with relapsed/refractory (R/R) disease after first-line treatment included previous treatment, response duration, and burden of comorbidities. To use the tool, drop-down menus allowed users to select from choices for each variable and their intended treatment for that patient. The corresponding treatment selection from 5 experts was then displayed and users were asked about the tool's impact on their planned treatment. Results. An analysis of 883 patient scenarios (67% treatment naive and 33% with R/R CLL) entered into the tool from February 2016 through July 2016 found substantial variation between the intended therapy choice among tool users and the recommendations from the experts.For example, in every patient case with del(17p), all 5 of the experts recommended ibrutinib as first-line therapy whereas only 49% of tool users planned to use ibrutinib for these patients. Of those users whose intended first-line therapy for del(17p) CLL did not match the experts' recommendation, 54% indicated that this tool would change their original treatment plan and 17% indicated a barrier to implementing this treatment. For either elderly or unfit patients without del(17p), 4 of 5 experts recommended obinutuzumab plus chlorambucil, but only 41% of tool users planned to use this regimen with 50% citing barriers to this treatment approach. For patients with del(17p) CLL and disease relapse or recurrence after chemoimmunotherapy, all 5 experts recommended ibrutinib for these cases with the exception of patients with a history of atrial fibrillation, anticoagulation, or difficult-to-control hypertension where 4 of 5 experts recommended idelalisib/rituximab. Again, the intended treatment plan of approximately 50% of tool users failed to match the experts' recommendation for these cases, and half of these users indicated that this tool would change their original treatment plan. At the time of tool development, all experts recommended either idelalisib/rituximab or clinical trial for patients with R/R CLL and del(17p) who previously received ibrutinib, but 61% of users indicated that they were unsure of the next appropriate treatment. All users who answered the impact question indicated that they now intended to use the expert-recommended treatment for these patients. For patients without del(17p) cytogenetics, treatment selection was more variable among experts and users and changed based on age, fitness, and previous therapy. For patients with del(11q) or other cytogenetics, approximately 20% of tool users were unsure of the appropriate treatment after progression on first-line therapy but 71% of those who answered the impact questions indicated that they remained unsure of their treatment approach despite viewing expert recommendations. Conclusions. Our analysis demonstrates that this interactive online therapy decision tool providing expert recommendations for specific case scenarios in CLL can support optimal decision making and change intended treatment for a majority of cases in which the planned therapy differed from the experts. Detailed comparisons of expert and user responses from the online tool will be presented. Disclosures Awan: Innate Pharma: Research Funding; Pharmacyclics: Consultancy; Novartis Oncology: Consultancy. Barrientos:AbbVie: Consultancy, Research Funding; Janssen: Consultancy; Gilead: Consultancy, Research Funding. Coutre:AbbVie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Research Funding. Zelenetz:Gilead Sciences: Research Funding.

scholarly journals Optimal Treatment Order of Lenalidomide and Hypomethylating Agents for Lower-Risk Myelodysplastic Syndromes: A Report on Behalf of the MDS Clinical Research Consortium

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4322-4322 ◽  
Author(s):  
Rami S. Komrokji ◽  
Mikkael A. Sekeres ◽  
John Barnard ◽  
Najla Alali ◽  
Amy E. DeZern ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lower Risk ◽  
Research Funding ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Baseline Characteristics ◽  
Research Consortium ◽  
Treatment Order

Abstract Introduction While lenalidomide (LEN) is the standard of care for treatment of red blood cell (RBC) transfusion-dependent (TD) lower-risk myelodysplastic syndromes (LR-MDS) with chromosome 5q deletion (del 5q), it is widely used off-label in the non-del5q setting. In the MDS-002 and MDS-005 studies, 26% of TD non-del5q LR-MDS patients became RBC transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment option for TD anemia in lower-risk non-del 5q MDS after hypomethylating agents (HMAs). Thatrecommendationhas led to wide use of HMAs as frontline therapy after erythroid stimulating agents (ESA) failure in LR-MDS. The response rate to LEN after HMA failure, however, is not known, as MDS-002 and MDS-005 excluded patients previously treated with HMAs. To assess the best order of LEN and HMA in optimizing response potential in lower-risk MDS, we examined response rates to each drug when treatment order (LEN followed by HMA or HMA followed by LEN) differed. Methods We identified patients with LR- MDS (International Prognostic Scoring System (IPSS) low or intermediate-1 (int-1) risk groups) within the MDS Clinical Research Consortium database who received both LEN and HMA as first or second line therapy after ESA failure or patients who had low chance of response to ESA. We excluded patients with isolated del5q or del q + one additional cytogenetic abnormality. The primary objective was to compare rates of erythroid hematological improvement (HI-E), defined using 2006 International Working Group criteria (IWG 2006), between patients who received LEN as first line therapy followed by HMA as second line (LEN 1st line group) versus those who received LEN as second line therapy after HMA (LEN 2nd line group). Results We identified 144 patients who received both HMA and LEN as first and second line therapies: 80 patients were in group 1 (LEN 1st line) and 64 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table 1. There were no statistically significant differences between the 2 groups. The rate of HI-E was 20% (16/80) for the LEN 1st line group compared to 11% (7/64) in the LEN 2nd line group. (p=.046). There were no differences in response rates to HMA between the two groups: In the LEN 1st line group, response to 2nd line HMA was 30% (24/78) compared to 39% (25/64) for those who received HMA as first line (p=.2). There was no difference in overall survival (OS) between the two groups, The median OS was 79 months (mo) the LEN 1st line group compared to 61 mo in Len 2nd line group (p= .4). The rate of AML transformation was 9% in Len 1st line group compared to 22% in Len 2nd line group rate (p=.03). There was no difference in AML free survival (78mo versus 61mo respectively, p=0.4). In multivariable analyses adjusting for age, sex, and IPSS-R order of treatment still did not impact overall survival. Conclusion LEN yields a higher rate of HI-E in LR- MDS when used as first line therapy, but responses to HMAs were similar when used before or after LEN. The rate of AML transformation was lower when LEN was used as first line. The order of treatment does not impact overall survival. Lenalidomide should be used prior to HMA if it is to be considered for treatment of anemia in non-del5q LR-MDS. Table 1 Baseline characteristics Table 1. Baseline characteristics Disclosures Komrokji: Novartis: Consultancy, Speakers Bureau; Incyte: Consultancy; Boehringer-Ingelheim: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Roboz:Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy; Cellectis: Research Funding.

Treatments and Outcomes of Patients with Multiple Myeloma (MM) Older Than 75 Years of Age: A Single Institution Experience

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4756-4756
Author(s):  
Elizabeth Finley-Oliver ◽  
Kenneth Shain ◽  
Taiga Nishihori ◽  
Jose-Leonel Ochoa-Bayona ◽  
Melissa Alsina ◽  
...  
Keyword(s):  
Older Adults ◽  
High Risk ◽  
Research Funding ◽  
Novel Agents ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
High Risk Disease ◽  
Causes Of Mortality ◽  
Competing Causes

Abstract Abstract 4756 Background: Considerable advances in the treatment of myeloma patients have culminated in the approval of novel agents (thalidomide, bortezomib, lenalidomide) with survival benefits noted for each. The outcomes of patients younger than 65 years have been shown to be improved with the availability of novel therapies. However, older adults, who comprise the majority of patients with myeloma, have not experienced the same improvement in outcomes as noted in epidemiologic studies (Brenner et al. Hematologica 2009. 94(2): 270 and Schaapveld et al, Eur J Cancer. 2009. 46(1):160.). We postulated that lack of access to novel agents, difference in disease biology, or competing causes of mortality might explain this finding. Method: We conducted a retrospective review of electronic medical records for patients 75 years of age or older at the time of diagnosis with symptomatic myeloma after 2004 (to allow for the availability of novel agents). Demographic information including comorbid conditions, disease characteristics (including risk features and cytogenetics), treatment information as well as survival data was collected. Risk stratification (standard or high risk) was based on the Mayo criteria (Steward et al. Leukemia 2007; 21: 529). Result: 72 patients (median age 78 years, range 75–89, 58% were older than 80 years) with symptomatic myeloma were the subjects of this study. Seventy-two percent were males and 28%, 15%, 60% and 29% had a history of cardiac dysfunction (defined as CAD or CHF), diabetes, hypertension and another malignancy (excluding non melanoma skin cancer) respectively. While 31 patients had missing information to determine the International Staging System; 29%, 32% and 39% had ISS stages 1, 2, and 3, respectively (similar to what is expected in younger cohorts). Moreover, using the Mayo risk model, 31% of patients had high risk disease. The median number of systemic therapies received was 2 (range 0–6). First line therapy did not include a novel agent in 29% of patients (who received alkylating agents 12%, anthracyclines 4%, corticosteroids alone 13%) and at the time of relapse, all but 4 patients had received a novel agent. First line therapy consisted of lenalidomide based regimens (30%), bortezomib based regimens (12%), thalidomide based regimens (28%) and a combination of novel agents (1%). The median overall survival for the entire cohort was 46 months (95% CI: 36.4–56.2 months). Conclusion: Older adults (greater than 75 years of age) with multiple myeloma continue to experience a shortened survival despite the use of novel agents and without a discernable higher incidence of high risk disease suggesting competing causes of mortality and tolerance to therapy may significantly limit the benefit of novel therapies in this age group. To address these limitations, we have initiated a clinical trial evaluating a sequential response adapted lenalidomide based therapy for older adults with newly diagnosed myeloma in order to minimize treatment related toxicities. Disclosures: Alsina: Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Ortho Biotech: Research Funding. Baz:celgene: Consultancy, Research Funding; millenium: Research Funding; orthobiotec: Research Funding.

Oral Fludarabine and Intravenous Rituximab (FR) for Chronic Lymphocytic Leukemia (CLL): Long Term Outcomes and Secondary Malignancies in 673 Patients Treated in British Columbia (BC)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4300-4300
Author(s):  
Elysha Vanderveer ◽  
Steven J.T. Huang ◽  
Helene Bruyere ◽  
Tanya Gillan ◽  
Charles H. Li ◽  
...  
Keyword(s):  
Median Time ◽  
Research Funding ◽  
Secondary Malignancies ◽  
Long Term Outcomes ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Impact

Background: Oral fludarabine and intravenous rituximab (FR) was the standard first-line therapy for CLL or small lymphocytic lymphoma (SLL) patients (pts) in BC from 2003-2015. Ibrutinib for relapsed/refractory (R/R) CLL was introduced and publicly funded in 2015. Our aim was to review long term outcomes of all CLL/SLL pts treated with FR in BC, including the impact of 2nd line therapy with ibrutinib versus chemoimmunotherapy and to report the risk of secondary malignancies in this population based cohort. Methods: The BC Provincial CLL Database was used to identify all CLL/SLL pts who received first-line FR from 2003-2017. The BC Cancer Registry was used to identify secondary malignancies occurring after FR. Primary outcomes were overall survival (OS) and treatment free survival (TFS), defined as start of FR to next-line therapy or death/last follow-up. Variables examined for impact on OS/TFS included age at FR, gender, primary diagnosis (CLL vs SLL), B symptoms, advanced stage (Rai stage 3-4 CLL, Ann Arbor 1-2 SLL), baseline hemoglobin, lymphocyte count, platelets, LDH and FISH abnormalities. All variables significant on univariate analyses (P<.1) were included in multivariate Cox proportional hazard regression models to identify significant predictors of OS/TFS. Results: 673 pts were identified as receiving FR as first-line therapy for CLL (86%) or SLL (14%). Median time from CLL/SLL diagnosis to FR was 2.5 years (y) (range 0.1-27.3). Median age at FR was 67 y (range 26-91) with 73% ≥ 60 y and 39% ≥ 70 y. Most pts were male (66.1%), had early stage disease (84.2%) with no B symptoms (89.7%) and normal LDH (81.1%). Of 411 pts with pre-treatment FISH testing, prevalence of FISH abnormalities were: 48.5% del13q, 25.7% trisomy 12, 12.9% del11q, 8.0% del17p. Median number of FR cycles was 6 (range 1-10). Median follow-up of living pts from FR was 6.4 y (range 0.2-12.7). 2 y and 5 y OS were 89.4% (95% CI: 86.8-91.6) and 73% (95% CI: 69.0-76.6) respectively; median OS 11.6 y (95% CI: 4.6-13.7 y). 2 y and 5 y TFS were 72% (95% CI: 68-75%) and 37% (95% CI: 33 - 41) respectively, median TFS 3.8 y (95% CI: 1.78-7.09). Those with del17p had significantly worse OS and TFS compared to those without (median OS 5.7 vs 13.7 y, P<.001; median TFS 1.4 vs 3.9 y, P<.001), Fig. 1. Multivariate analysis identified only del17p (HR 4.35, 95%CI: 2.10-9.01, P<.001) and age at FR (HR 1.04, 95% CI: 1.01-1.07, P=.007) as significant predictors of OS, and del17p (HR 4.3, 95% CI: 2.5-7.5, P<.001) as a significant predictor of TFS. During the follow up period, 351 pts (52%) went on to 2nd-line therapy: ibrutinib 87 (including 2 with BR and 1+R), cyclophosphamide-based (CVP/CHOP) +/- R 102, repeat FR 71, FCR 6, F alone 21, bendamustine +/-R 13, chlorambucil+/-R 38, steroids 3, R alone 3, alemtuzumab 2, other chemotherapy 3 and allotransplant 2. Median follow-up after 2nd-line therapy was 2.8 y (range 0.1-10.8). Median OS and TFS from 2nd-line treatment (TFS2) for ibrutinib (n=87) vs. for other treatments (n=264) was: OS not reached vs 5.3 y, P<.001; TFS2 not reached vs 1.2 y, P<.001. These significant differences persisted when analyses were restricted to those who received ibrutinib vs. chemoimmunotherapy (n=169): median OS not reached vs. 6.3 y (P=.002); median TFS not reached vs. 1.7 y (P<.001), Fig. 2. 2 y OS and TFS2 after ibrutinib were 91% (95% CI: 80-96%) and 78% (95% CI: 65-87%), respectively. A total of 202 malignancies were recorded after initiation of FR in 166 pts (24.7%), Table 1. The median time from FR to 2nd malignancy was 2.3 y (range 0.1-13.5). Richter's transformation (RT) occurred in 36 pts (5.3%) at median 1.9 y (range 0.1-13.2) from FR. Most frequent 2nd malignancies were: non-melanoma skin cancer (11.7%), lung (2.5%), colon (2.1%), other heme (1.9%), and prostate (1.8%). There were 4 cases of acute myeloid leukemia (AML), 2 of which received alkylator therapy after FR prior to AML diagnosis. Conclusions: In this large, homogeneous cohort of CLL/SLL pts treated with first-line FR, including nearly 40% of pts ≥ age 70, we demonstrate a short median TFS of 3.8 y; however, a long OS of 11.6 y. Rates of 2nd malignancies are low after this non-alkylator based chemoimmunotherapy regimen. Ibrutinib for R/R CLL/SLL after FR resulted in significantly improved survival over alternate therapy, with excellent 2 yr OS 91% and TFS 78%. These data demonstrate the efficacy of FR and the benefit of ibrutinib over chemoimmunotherapy as second-line therapy for CLL/SLL in the real-world. Disclosures Bruyere: Jenssen: Other: Travel Grant; Celgene: Honoraria. Villa:Roche, Abbvie, Celgene, Seattle Genetics, Lundbeck, AstraZeneca, Nanostring, Janssen, Gilead: Consultancy, Honoraria. Scott:Celgene: Consultancy; Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Savage:BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Connors:Takeda Pharmaceuticals: Honoraria; Seattle Genetics: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Sehn:TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria.

Early Autologous Stem Cell Transplantation (autoSCT) May Overcome the Adverse Impact of Del 11q- in Poor-Risk Chronic Lymphocytic Leukemia (CLL): Results From the GCLLSG CLL3 Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 879-879 ◽  
Author(s):  
Peter Dreger ◽  
Hartmut Döhner ◽  
Hildegard Greinix ◽  
Fabienne McClanahan ◽  
Manfred Hensel ◽  
...  
Keyword(s):  
Research Funding ◽  
Hazard Ratio ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
Female Ratio ◽  
Poor Risk ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mutational Status ◽  
The Impact

Abstract Abstract 879 As previously reported, dose-escalated first-line therapy with autoSCT as conducted in the GCLLSG CLL3 protocol is a feasible and effective therapy option for younger patients with poor-risk CLL. Purpose of the present analysis was to study the impact of FISH karyotype according to the hierarchical model, and of IGHV mutational status on progression-free (PFS) and overall survival (OS) in this trial. Trial design and patients: The protocol comprised optional cytoreduction with CHOP, fludarabine, or FC; PBSC mobilization using the Dexa-BEAM regimen; and myeloablative therapy with TBI/CY followed by reinfusion of purged (CD34+) stem cells. Inclusion criteria were age <61 years, stage Binet B/C or poor-risk stage A as defined by short lymphocyte doubling time plus elevated TK, and one line of pretreatment or less. From December 1996 through September 2002, 216 patients were registered with the protocol. As 47 cases had to be excluded due to screening failure (n=21), withdrawn consent (n=19) or other reasons (n=7), 169 patients were eligible for the current analysis. Male to female ratio was 5:1 and the median age at diagnosis was 51 years (range 27-60). Results: SCT was performed in 131 patients (78%) at a median time of 17 months (range 4-159) after initial diagnosis, whereas 38 patients did not proceed to SCT due to mobilization failure (n=14), disease progression (n=4), early death (n=3), patients preference (n=6), or unknown reasons (n=11). At a median follow-up of 99 months (range 4-137) after initiation of first cytoreductive therapy within the protocol, median OS of all 169 patients was 10.5 years, with 10.5 years for those treated with and 6.1 years for those treated without autoSCT, yielding a hazard ratio of 0.26 (95% CI 0.13-0.54; p<.0001). Median PFS was 6.3 years, with 6.8 years for those treated with and 4.8 years for those treated without autoSCT (HR 0.39; 95% CI 0.23-0.67; p=0.0007). The 10-year incidence rate of t-MDS/ t-AML was 9% (1-18%). Diagnostic samples for assessment of the IGHV mutational status were available for 143 of 169 patients (85%). An unfavorable (unmutated of V3-21-containing) IGHV rearrangement was present in 104 patients (73%). Compared to the 39 patients with favorable IGHV, those with unfavorable VH had significantly worse PFS and OS (median PFS 5.1 years vs not reached, hazard ratio (HR) 2.47 (1.56-3.92), p=0.0001; median OS 9.1 years vs not reached, HR 2.0 (1.14-3.68), p=0.017). FISH was possible in 160 patients (95%) with results as follows: del 17p- 4 patients (3%), del 11q- without del 17p 40 patients (25%), trisomy 12 without del 17p- and del 11q- 20 patients (13%), del 13q- as sole abnormality 48 patients (30%), other karyotypes 20 patients (13%), normal karyotype 28 patients (17%). All 4 patients with del 17p- showed progressive disease after Dexa-BEAM mobilization and did not proceed to autoSCT. Whereas PFS (p <0.0001) and OS (p <0.0001) thus was strongly reduced in the 4 patients with del 17p-, no significant differences between the other subsets became evident: median PFS 1.0 years (del 17p-), 5.9 years (del 11q), 4.8 years (+12), 7.5 years (del 13q-), 7.7 years (normal); median OS 1.5 years (del 17p-), 10.5 years (del 11q-), not reached (+12), not reached (del 13q-), 10.3 years (normal). Conclusions: Unmutated IGHV remains an adverse prognostic factor after dose-escalated first-line therapy with autoSCT. In contrast, this strategy may overcome the unfavorable impact of the FISH karyotype del 11q- seen with conventional therapy. Disclosures: Hopfinger: Roche: Honoraria. Schmitz:Roche: Honoraria, Research Funding. Stilgenbauer:BayerScheringAG: Honoraria, Research Funding.

Patterns Of Care, Survival, and Costs Of Second-Line Treatment In Medicare Beneficiaries With Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2936-2936
Author(s):  
Mark Danese ◽  
Robert Griffiths ◽  
Michelle Gleeson ◽  
Tapashi Dalvi ◽  
Jingyi Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Patterns Of Care ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Factors

Abstract Background DLBCL is the most common subtype of non-Hodgkin's lymphoma. Approximately 50% of DLBCL patients are over age 65. Patterns of care and outcomes in older patients receiving second-line therapy for DLBCL have not been well-characterized. Objective We analyzed patterns of care, overall survival and costs of care in a cohort of older DLBCL patients receiving second-line therapy. Methods Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified a cohort age ≥66 with DLBCL diagnosed between 2000 and 2007. Patients had to receive first-line therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen, with or without rituximab. Second-line treatment was defined as either (a) ≥1 new agents < 90 days after discontinuing all first-line agents (refractory disease), or (b) ≥1 agents (including first-line agents) ≥90 days after completion of first-line therapy (relapsed disease). Rituximab monotherapy was excluded (n=736). Patients were enrolled from 12 months prior to diagnosis and followed through 12/31/2009. Observation ended at death, change from coverage, or 12/31/2009. We reviewed the therapies of each patient and classified them into 1 of 3 groups: aggressive, conventional, or palliative. Direct costs to Medicare were calculated using paid amounts over the 24-month period after initiating second-line therapy, weighted to account for censoring, and inflated to 2009 US dollars. Results There were 5,716 first-line DLBCL patients of whom 632 (11%) received second-line therapy (206 refractory and 426 relapsed). The most common aggressive regimens were methotrexate (n=60), [carboplatin, cyclophosphamide and etoposide (n=54)] and [cisplatin, cytarabine, and etoposide (n=23)]. The most common conventional regimens were [cyclophosphamide, doxorubicin, and vincristine (n=74)], [cyclophosphamide and etoposide (n=31)]. The most common palliative regimens were etoposide (n=68), [cyclophosphamide and vincristine (n=56)], fludarabine (n=26), and gemcitabine (n=25). Median survival was 13.4 months. Overall, survival was not statistically significantly different among the different treatment approaches in multivariate-adjusted survival models. However, patient characteristics differed significantly between these treatment groups with patients receiving aggressive treatment being younger than in the palliative treatment group (>80 years: 9.1% vs 30.6%; p<0.0001). Similarly refractory patients were more frequent in the aggressive vs. conventional treatment group (53.4% vs. 11.3%; p<0.0001). Significant factors affecting survival included female gender (hazard ratio [HR] 0.65, 95% CI 0.53-0.80), absence of B symptoms at diagnosis (HR 0.69, 95% CI 0.53-0.89), and presence of anemia at diagnosis (HR 1.26, 95% CI 1.02-1.55. Multivariate adjusted, cumulative 24-month costs for the reference group for all model variables was $117,442 (95% CI $78,270 to $156,615). Significant factors that modified this cost were age 75-79 (relative to age 66-69; $-28,860), age ≥80 ($-42,262), extranodal involvement at diagnosis ($-15,421), and anemia at diagnosis ($+23,047). Conclusions Second-line therapy for refractory and relapsed DLBCL was associated with high mortality and costs in the Medicare population. While selection bias limits comparison of aggressive vs. conventional therapies, our findings suggest a substantial unmet need in the second-line setting. Disclosures: Danese: Genentech: Consultancy, Research Funding; Medimmune: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Griffiths:Amgen, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MedImmune: Consultancy, Research Funding. Gleeson:Amgen, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MedImmune: Consultancy, Research Funding. Dalvi:Medimmune: Employment, stock Other. Li:Medimmune: Employment, stock Other. Deeter:Medimmune: Consultancy, Employment, stock Other.

Efficacy of different anti-HER2 drugs in first-line therapy for advanced breast cancer: Systematic review and meta-analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11500-e11500
Author(s):  
Andre Deeke Sasse ◽  
Flavio Mavignier Carcano ◽  
Lucas Vieira dos Santos ◽  
Joao Paulo Da S.N. Lima
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Advanced Breast Cancer ◽  
Meta Analysis ◽  
Advanced Breast ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Impact

e11500 Background: Anti-HER2 therapy has brought major gains to therapy of advanced breast cancer (ABC), however it is still not know if there are difference in efficacy between trastuzumab and lapatinib. We execute a systematic review and meta-analysis in order to measure the impact of anti-HER2 therapy on ABC outcome and to assess if any particular drug is more effective in this scenario. Methods: Randomized controlled trials comparing first-line antineoplastic drug plus minus antiHER2 therapy (either trastuzumab or lapatinib) in ABC patients were searched in major meeting proceedings and databases. The outcomes were overall survival (OS), progression-free survival (PFS), tumor response and safety. Meta-analyses were performed using random-effects model and outcomes measured by hazard ratio (HR) and pertinent 95% confidence intervals were calculated. Subgroup analyses and meta-regression were undertaken to compare and measure the impact of anti-HER2 drug used over the estimated effect size. Results: eight trials (1848 patients) were included, two trials used lapatinib whereas six used trastuzumab. In two trials, anti-HER2 therapy was combined to hormone therapy. All trials, except the one by Slamon, demanded tumors to be ISH+ or IHC 3+. The methodological quality of included trials was moderate to good. Either trastuzumab or lapatinib improved overall survival (HR 0.79; 95% CI 0.69-0.91; P=0.0008; I2=0%) with no difference bet drugs (test for difference P=0.75). PFS was also increased with antiHER2 addition with similar activity of trastuzumab and lapatinib (HR = 0.58; 95% CI 0.51-0.66; P<0.0001; I2=0%, test for difference P= 0.42). Conclusions: The present meta-analysis confirmed the role of antiHER2 drugs as a valid first-line therapy for ABC. Furthermore, we failed to show any difference in efficacy between lapatinib and trastuzumab when combined to systemic therapy, both being acceptable options for antiHER2 therapy for ABC.

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