Outcomes according to involved free light chain (FLC) levels in patients with normal FLC ratio after initial therapy in light chain amyloidosis (AL).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8049-8049
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
Angela Dispenzieri ◽  
Morie A. Gertz ◽  
Martha Lacy ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Light Chain ◽  
Plasma Cells ◽  
Renal Involvement ◽  
Progression Free Survival ◽  
Complete Response ◽  
Initial Therapy ◽  
Rank Test ◽  
Amyloid Formation ◽  
Line Treatment

8049 Background: Complete response in AL is defined as normal FLC ratio with negative serum and urine immunofixation. It is not clear if high involved serum FLC (hIFLC) in a patient with normal ratio may contribute to ongoing amyloid formation and hence affect outcomes. Methods: Data of 1308 patients (pts) with systemic AL seen within 90 days of diagnosis, at Mayo Clinic between 2006-2015, was analyzed retrospectively. Among these, 369 pts had 2 consecutive normal FLC ratio values after 1st line treatment and form the study population. Log rank test was used to estimate survival differences. Results: Among these 369 pts, pts with hIFLC at 1streading of normal FLC ratio (hIFLC1; n=170; 46.1%) were compared to those who did not (n=199; 53.9%). At diagnosis, the median age [61.5 vs 60.8 years (y); p=0.2], proportion of males (62.4 vs 58.3%; p=0.4), percentage of pts with renal involvement (73.5 vs 64.8%; p=0.07), in mayo stage I / II / III / IV (32.9% / 23%/ 27.3% / 16.8% vs 43.6 %/ 22.9% / 18.1% / 15.4%; p=0.1), with bone marrow plasma cells >10% (24.2 vs 30%; p=0.2) and with presence of t(11; 14)(48.4 vs 60; p=0.08) was similar, while cardiac (67.5 vs 53.3%; p=0.006) and hepatic (18.2 vs 9.1%; p=0.01) involvement was higher in hIFLC1 group. The median follow-up from diagnosis was 6.1 y (95% CI; 5.6, 6.8). The median progression free survival (PFS) in pts who had hIFLC1 was lower than for those who did not; 2.6 y (95% CI; 1.9, 4.5) vs 5.2 y (95% CI; 4.6, 6.4), p<0.0001, as was the median overall survival [OS; 6.7 y (95% CI; 4.5, 8.3) vs not reached (NR), p<0.0001]. We performed a more stringent comparison for pts with 2 consecutive hIFLC values (hIFLC2; n=112; 30.4%) versus not (n=257; 69.6%). The median PFS (3.2 y; 95%CI; 2.2, 4.5 vs 5.6 y; 95% CI; 4.7, 7.1; p<0.0001) and OS (7.8 y; 95% CI; 6.4, NR vs NR; 95%CI; 9.5, NR; p<0.0001) were significantly reduced in pts with hIFLC2 versus not as well. A multivariate analysis confirmed an impact of hIFLC1 and hIFLC2 on PFS/OS independent of serum creatinine. Conclusions: In pts with systemic AL, persistent elevation of the involved FLC predicts for poor prognosis (independent of serum creatinine) even among those who achieved normal FLC ratio after 1st line treatment.

Phase III Study of VCAP-AMP-VECP vs. Biweekly CHOP in Aggressive Adult T-Cell Leukemia-Lymphoma (ATLL): Japan Clinical Oncology Group Study, JCOG9801.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 812-812 ◽  
Author(s):  
Kunihiro Tsukasaki ◽  
Takuya Fukushima ◽  
Atae Utsunomiya ◽  
Syuichi Ikeda ◽  
Masato Masuda ◽  
...  
Keyword(s):  
Cox Regression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Rank Test ◽  
P Value ◽  
Minimization Method ◽  
Adult T Cell Leukemia ◽  
Non Hodgkin Lymphoma

Abstract Background: In our study for non-Hodgkin lymphoma (NHL) in 1980’s (JCOG8701), human T-lymphotropic virus type-1- associated ATLL was the poorest prognostic subtype in NHL. The complete response (CR) rate was 42%, the median survival time (MST) was 8 months, and the 4-yr overall survival (OS) was 12% (Proc ASCO13:378, 1994). Our previous phase II study (JCOG9303) of G-CSF-supported, dose-intensified multi-agent chemotherapy with VCAP (vincristine, cyclophosphamide, doxorubicin, prednisolone), AMP (doxorubicin, ranimustine, prednisolone) and VECP (vindesine, etoposide, carboplatin, prednisolone) with intrathecal prophylaxis for aggressive ATLL, showed promising results with response rate (RR) of 81% and MST of 13 months (Br J Haematol113:375,2001). To test the superiority of this VCAP-AMP-VECP regimen over biweekly-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), we conducted a phase III trial. Methods: Previously untreated patients (pts) with aggressive ATLL, acute-, lymphoma- or unfavorable chronic-type, were randomized either to receive 6 courses of VCAP-AMP-VECP every 4 weeks (arm A) or 8 courses of biweekly-CHOP (arm B) with minimization method balancing performance status and institution. Both regimens were supported with G-CSF and intrathecal prophylaxis using cytarabine, methotrexate and prednisolone. Eligibility included preserved organ functions and aged 15–69 years. Primary endpoint was OS to be compared by log-rank test. Assuming 60 eligible pts in each arm, the study had 0.8 power to detect a 15% difference in 3-year OS at 0.05 one-sided alpha. Results: 118 pts (57 in arm A, 61 in arm B) were randomized between 07/98 and 10/03. Median follow-up time in all randomized pts was 11.0 months at 12/04. 72 % of the pts responded, with 23 pts achieving CR (40%) and 18 achieving partial response (PR; 32%) in arm A. The RR was 66%, with 15 pts achieving CR (25%) and 25 achieving PR (41%) in arm B. The median progression-free survival (PFS) time and PFS at one-year in arm A were 7.0 months and 28.1%, respectively, whereas 5.4 months and 16.2% in arm B. The MST and OS at 3 years in arm A were 12.7 months and 23.6%, respectively, whereas 10.9 months and 12.7% in arm B. Log-rank p-value for primary end point, OS, was 0.085. After adjustment of patients’ characteristics at registration by Cox regression, the p value became 0.029 because of unbalanced prognostic factors such as bulky lesion. In arm A vs. arm B, %G4 neutropenia, %G4 thrombocytopenia and %G4 infection were 98% vs. 83%, 74% vs. 17% and 7% vs. 3%, respectively. Three toxic deaths were reported in arm A. Conclusions: These results demonstrate that VCAP-AMP-VECP yields longer OS time than biweekly-CHOP but with higher toxicity profiles that are acceptable, and suggest that the former regimen should be the standard therapy for aggressive ATLL.

Defining Complete Response in Multiple Myeloma: Role of the Serum Free Light Chain Assay and Multiparameter Flow Cytometry.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1479-1479 ◽  
Author(s):  
Roger G. Owen ◽  
J. Anthony Child ◽  
Andy C. Rawstron ◽  
Sue Bell ◽  
Kim Cocks ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Light Chain ◽  
Plasma Cells ◽  
Complete Response ◽  
Free Light Chain ◽  
Multiparameter Flow Cytometry ◽  
High Dose ◽  
Reference Laboratory ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract It is becoming increasingly clear that the use of immunofixation (IF) to define complete response (CR) in MM has its limitations. Paraprotein concentration is not a direct measure of tumour bulk and maximal responses may take many months to achieve which inevitably underestimate CR rates in therapeutic schedules that contain the sequential use of different agents. The purpose of this study was to prospectively assess the applicability and value of the serum free light chain (SFLC) assay and multiparameter flow cytometry (MFC) to assess CR in the intensive pathway of the MRC Myeloma IX Trial. In this trial patients are initially randomised to induction with CVAD or CTD and patients with stable disease or better proceed to high dose melphalan (HDM) with stem cell support. There is a second randomisation to maintenance thalidomide or no further therapy. SFLC as well as standard serum and urine paraprotein assessments were performed in a central reference laboratory at the following time points: presentation, end of induction, day 100 post HDM and 3 monthly until relapse. Similarly MFC in which neoplastic plasma cells are identified and differentiated from normal plasma cells on the basis of CD19 and CD56 expression was evaluated (again in a central laboratory) at presentation, end of induction and day 100 following HDM and annually until relapse. An initial analysis of 207/1114 randomised patients was performed and the results are detailed below - End of induction Day 100 post HDM IF negative 16.3% 49.4% SFLC normal 46.1% 78.6% MFC negative 10.2% 50.7% The SFLC assay was informative in 95% of patients and provided for a more rapid assessment of response than conventional methods. A normal SFLC assay at the end of induction appeared to predict for attainment of an IF-neg CR at day 100 (70% IF-neg CR if SFLC normal vs 30% when SFLC abnormal at the end of induction). It should however be noted that 58% of patients who failed to achieve an IF-neg CR at day 100 had a normal SFLC assay. MFC provides for a direct assessment of residual neoplastic plasma cells. The assay was informative in 96.7% of patients and has a reproducible sensitivity of 0.01%. The majority of patients (89.8%) had detectable disease at the end of induction with a median of 0.7% neoplastic plasma cells (range 0.01–14%). Further cytoreduction was provided by the HDM such that 49.3% had flow detectable disease at day 100 with a median of 0.26% neoplastic plasma cells (range 0.02–8%). 30% of patients with IF-neg CR had detectable disease while 21% of patients with a persistent paraprotein had no detectable disease in their marrow. The majority of the latter patients had IgG paraproteins and it is postulated that many of these pts will ultimately achieve an IF-neg CR. We would conclude that given the kinetics of paraprotein clearance in MM it may be more appropriate to define CR on the basis of a normal SFLC assay and the absence of minimal residual disease by MFC. In this way it should be possible to more accurately define the CR rate achieved by individual components of multi-agent sequential regimens.

Effectiveness of Second Line Treatment in AL Amyloidosis Patients Refractory to M-Dex.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4930-4930
Author(s):  
Julie Abraham ◽  
Houria Debarri ◽  
Amelie Penot ◽  
Estelle Desport ◽  
Claire Aguilar ◽  
...  
Keyword(s):  
Light Chain ◽  
Complete Response ◽  
Free Light Chain ◽  
New Drugs ◽  
Al Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
Front Line ◽  
Multicentric Study ◽  
Hematological Response

Abstract Abstract 4930 Purpose AL amyloidosis is a monoclonal disorder responsible for secretion of a monoclonal free light chain which will deposit as aggregated fibrils and cause organ dysfunction. Prognosis without treatment is poor with median survival around 1 year. Since our multicentric randomized trial comparing M-dex (oral Melphalan and Dexamethasone combination) and high dose treatment with stem cell support (Jaccard et al, NEJM 2007), M-Dex is our reference front line therapy in AL patients, whatever the risk group. Median survival with this strategy has dramatically improved, reaching 5 years in our study as well as in the Italian one (Palladini et al, Blood 2007). Nevertheless survival of refractory patients was poor in the absence of valuable rescue treatment between 2000 and 2005(Figure 1). New drugs as Thalidomide, Lenalidomide or Bortezomib, whose efficacy has been proven in multiple myeloma, has been reported to be effective and tolerable in AL patients. We performed a retrospective multicentric study to determine outcome of M-Dex refractory patients in the era of these new drugs. Patients and methods Patients with biopsy proven AL amyloidosis, treated with M-Dex, front line, since June 2006 were included if they were considered as refractory by there referent physician in 10 centres belonging to the French network for AL amyloidosis. We recorded the hematological response with second line treatment. Survival was analyzed from the first treatment date using Kaplan Meier model. Results We included 29 patients with a median age of 60 years (32-76), 16 patients had cardiac involvement, 19 renal involvement. The median number of organ involvement was 2 (1-5). Isotype of monoclonal light chain was kappa in 38% of cases, and lambda in 62%. Median abnormal free light chain level was 158 mg/L (25.9-2100). Twenty patients (69 %) were considered as non responders because they did not reached a 50% decrease in free light chain serum level and 9 patients (31%), who achieved a partial hematological response, because they did not have a clinical response. The median time between the first M-Dex cycle and the second line treatment was five months (1-17). Second line consisted in thalidomide in 5 patients, lenalidomide in 7 patients, and Bortezomib in 17 patients, in combination with sequential Dexamethasone. Hematological response occurred in 69% of the whole series, with 27% complete response. Depending on treatment, partial hematological response was obtained in 4/5 patients with thalidomide, 2/7 patients with lenalidomide, and 14/17 patients with bortezomib responded with 8 complete responses. With a median follow-up of 21 months (0-32) 69% of patients are alive (Figure 2). Conclusion As expected introduction of new drugs for treatment of refractory AL patients gives a high level of hematological response leading to a better survival. Bortezomib seems to be particularly attractive with hematological response rate of 82%, and 47% complete response. The combination of M-Dex and bortezomib will be compared soon with M-Dex in a prospective international multicentric study. Disclosures No relevant conflicts of interest to declare.

Renal Heavy Chain and Heavy+Light Chain Amyloidosis: A Report of 17 Cases and Comparison with Renal Light Chain Amyloidosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3992-3992 ◽  
Author(s):  
Samih H. Nasr ◽  
Samar M. Said ◽  
Anthony M. Valeri ◽  
Sanjeev Sethi ◽  
Lynn D. Cornell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Serum Creatinine ◽  
Light Chain ◽  
Cardiac Involvement ◽  
Plasma Cells ◽  
Kidney Biopsy ◽  
P Value ◽  
Fat Pad ◽  
Monoclonal Protein ◽  
Light Chain Amyloidosis

Abstract Abstract 3992 Little is known about the rare entities of heavy and light chain amyloidosis (AHL) and heavy chain amyloidosis (AH). In this study, we report the renal and hematologic characteristics, pathology, and outcome of 17 patients with renal AH/AHL including 5 with AH (4 IgG and 1 IgA) and 12 with AHL (7 IgGλ, 3 IgAκ, 1 IgAλ, and 1 IgMλ), and compare them with 202 patients with renal AL amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red-positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) (12 patients) or by immunofluorescence (5 patients). All patients with renal AH/AHL were Caucasians, with a M:F ratio of 2.4 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal Ig, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematologic and renal responses to chemotherapy were comparable to renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. In conclusion, renal AH/AHL is an uncommon but under-recognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications. Table 1. Demographics and hematologic characteristics AH/AHL AL p value No. of patients 17 202 Gender: Male/female 12/5 (71%/29%) 126/76 (62%/38%) 0.61 Age, median (range) 63 (50–77) 62 (36–86) 0.73 Additional organ involvement 8 (47%) 126 (62%) 0.3 Cardiac involvement 3 (18%) 100 (50%) 0.01* % of plasma cells in bone marrow, median (IQR) 8 (5–15) 6 (5–10) 0.82     ≥30 plasma cells 4 (24%) 11/198 (6%) 0.02* Positive SPEP/SIF for paraprotein 15 (88%) 158/200 (79%) 0.53     Presence of whole monoclonal protein on SPEP 14 (82%) 108/200 (54%) 0.04* Positive UPEP/UIF for paraprotein 13/16 (81%) 158/189 (84%) 0.73     Presence of whole monoclonal protein on UPEP 10/16 (63%) 61/189 (32%) 0.03* Abnormal serum FLC ratio (<0.26 or >1.65) 9/12 (75%) 150/188 (80%) 0.71 Markedly abnormal FLC ratio (< 0.125 or > 8) 5/12 (42%) 100/188 (53%) 0.55 Positive bone marrow for amyloid 6/16 (38%) 135/183 (74%) 0.004* Positive fat pad biopsy for amyloid 2/14 (14%) 105/145 (72%) <0.001* IQR, interquartile range. Table 2. Renal characteristics at kidney biopsy AH/AHL AL p value No. of patients 17 202 24h urine protein in g, median (IQR) 5.1 (3.2–9.0) 6.0 (3.2–10.0) 0.9 Full nephrotic syndrome 9/16 (56%) 132/197 (67%) 0.42 Serum albumin in g/dl, median (IQR) 2.7 (2.2–3.3) 2.5 (1.9–2.9) 0.29 % albuminuria on UPEP, median (IQR) 68 (61–72) 70 (60–76) 0.47 Serum creatinine in mg/dl, median (IQR) 1.4 (1.1–2.1) 1.2 (0.9–1.8) 0.25 Serum creatinine >1.2 mg/dl 10/16 (63%) 92/201 (46%) 0.3 eGFR, median (IQR) 47 (27–67) 58 (36–75) 0.29 Decreased eGFR 10/16 (63%) 103/201 (51%) 0.44 Microscopic hematuria 9/16 (56%) 44/169 (26%) 0.02* IQR, interquartile range. Disclosures: No relevant conflicts of interest to declare.

Predictors of Early Relapse Following Initial Therapy for Systemic Immunoglobulin Light Chain Amyloidosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2082-2082
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Light Chain ◽  
Research Funding ◽  
Initial Therapy ◽  
Al Amyloidosis ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Early Relapse ◽  
First Line Treatment

Abstract Introduction Immunoglobulin light chain amyloidosis (AL Amyloidosis) is a monoclonal plasma cell proliferative disorder that is characterized by tissue deposits of misfolded insoluble κ or λ light chain derived amyloid fibrils, leading to organ dysfunction. The prognosis of patients depends on the number and severity of organ involvement, especially cardiac involvement. Autologous stem cell transplant (ASCT), if eligible, alkylator (melphalan) and novel drugs like proteasome inhibitors (PI) and immunomodulators (IMiD) have improved the overall survival (OS) during the past decades. But still, nearly half of the patients die within a year of diagnosis. We analyzed the factors predicting early relapse / progression or death (within 12 months) after first line therapy for systemic AL amyloidosis. Methods Clinical and laboratory data of all consecutive patients with systemic AL amyloidosis seen at Mayo Clinic within 90 days of their diagnosis, between 2006 and 2015, was collected by chart review and analyzed retrospectively. Patients who died within 3 months of starting the first line treatment were excluded from analysis. Early relapse (ER) was defined as relapse / progression requiring treatment change / re-institution or death within 12 months of starting first line treatment. Patients in the cohort with ER were compared with patients with a follow up of more than 12 months who had a relapse / progression beyond 12 months or had continuing response at the time of analysis. Categorical variables were analyzed using chi - square and Fisher's exact test and continuous variables using Kruskal- Wallis test and Wilcoxon rank sum test. Multivariate analysis was done using logistic regression model. Results Seven hundred and eighty six patients with newly diagnosed systemic AL amyloidosis met the study criteria and were included in the analysis. Among these, 230 (29.3%) patients had ER within 12 months of starting initial therapy while 556 (70.7%) patients either relapsed after 1 year or had continuing response at the time of analysis. Baseline demographics, organ involvement and type of first line therapy are presented in Table1. The median estimated follow up for the entire cohort from start of initial therapy was 62.9 months (95% CI; 59.9, 67.3). The variables included in the univariate and multivariate analyses for factors predicting ER were age at diagnosis (≤ vs > 70 years ), revised mayo stage (I and II vs III and IV), bone marrow plasma cell percentage (BMPC; ≤ 10% vs > 10%), presence of any chromosomal abnormalities, trisomies or IgH translocations by fluorescence in situ hybridization (FISH), multiorgan involvement [(>1 vs 1) (heart, liver, kidney, gastrointestinal tract, autonomic neuropathy), incorporation of ASCT in initial therapy. In univariate analysis, mayo stage (p<0.0001), multiorgan involvement (p=0.0008) and inclusion of ASCT as part of initial therapy (p<0.0001) were significantly associated with ER, while age (p=0.06), BMPC(p=0.9), FISH abnormalities (p=0.2) were not. However, in multivariate analysis, only mayo stage (III + IV vs I + II; p=0.01) and non-inclusion of ASCT in first line treatment (p=0.0001) were significantly predictive of ER. Conclusions Despite the introduction of ASCT and novel drugs, the early mortality in systemic AL amyloidosis remains high. This study demonstrates that patients with ER are older with higher prevalence of cardiac involvement and multiorgan involvement and higher Mayo stage (III and IV). Incorporation of ASCT as part of the initial therapy was associated with reduced early relapse, but it is difficult to separate the influence of the eligibility for ASCT from the effect of ASCT itself. This will help us in characterizing these patients to better understand their mechanisms of resistance to therapy and gives an insight to the type of initial therapy that benefits them. Disclosures Dispenzieri: GSK: Membership on an entity's Board of Directors or advisory committees; Jannsen: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Alnylam: Research Funding; pfizer: Research Funding. Kapoor:Takeda: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Kesios: Consultancy; BMS: Consultancy; Sanofi: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Glycomimetics: Consultancy; Millennium: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; AbbVie: Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding.

A pooled analysis of 1,144 patients with HIV-associated lymphoma: Assessment of lymphoma-, HIV-, and treatment-specific factors on clinical outcomes.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8005-8005 ◽  
Author(s):  
Stefan K. Barta ◽  
Xiaonan Xue ◽  
Roni Tamari ◽  
Jeanette Y Lee ◽  
Nicolas Mounier ◽  
...  
Keyword(s):  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Complete Response ◽  
Initial Therapy ◽  
Pooled Analysis ◽  
Cd4 Count ◽  
Therapeutic Interventions ◽  
Hiv Viral Load ◽  
Clinical Phase

8005 Background: Non-Hodgkin Lymphoma (NHL) remains the most common malignancy in patients with HIV. Outcomes have significantly improved over the last decade, but there is no accepted consensus regarding the optimal initial therapeutic approach. Our objective was to assess the effects of clinical factors on response and survival. Methods: We performed a systematic review to search for prospective clinical phase II or III trials that assessed therapeutic interventions for HIV-associated NHL and assembled individual patient data from 16 trials published between 2000 and 2011 including 1144 patients (median N=62/trial, range 17-195). Treatment factors included type of chemotherapy (CHOP, N=642; EPOCH, N=178; CDE, N=191; intensive regimens, N=155) and rituximab use (N=542). Endpoints included complete response (CR), progression-free survival (PFS), and overall survival (OS). We used logistic regression and Cox proportional hazard models adjusted for age, sex, age-adjusted International Prognostic Index (IPI), baseline CD4 count, baseline HIV viral load, use of concurrent antiretroviral therapy, and histology. Odds ratios (OR) > 1 for CR denote improved CR, and hazard ratios (HR) < 1 indicate reduced risk of progression or death. Results: Among the lymphoma- and HIV-specific covariates evaluated, only a higher IPI score was associated with inferior CR rate, PFS and OS (p<0.001). Rituximab was associated with a higher CR rate (OR 1.75; p=0.017), better PFS (HR 0.39, p<0.001) and OS (HR 0.39, p<0.001); patients with a higher baseline CD4 count benefited more from rituximab (HR for OS 0.57 if baseline CD4 count ≥100/ul vs. <100/ul; p<0.001). For all histologies, initial therapy with the EPOCH regimen resulted in a better CR rate (OR 1.78, p=0.039), PFS (HR 0.61, p=0.032) and OS (HR 0.47, p<0.001) when compared to CHOP. Conclusions: In this pooled analysis including 1144 patients with HIV-associated NHL, the addition of rituximab to chemotherapy was associated with significantly improved CR rate, PFS, and OS, specifically for patients with a baseline CD4 count ≥100/uL. Treatment with infusional EPOCH was also more effective than CHOP.

Cisplatin (CDDP) and radiation versus cetuximab (Cx) and radiation in locally advanced head and neck squamous cell cancer (SCHNC): A retrospective review.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16009-e16009 ◽  
Author(s):  
Prakash Peddi ◽  
Runhua Shi ◽  
Lori Panu ◽  
Fred Ampil ◽  
Cherie-Ann Nathan ◽  
...  
Keyword(s):  
Performance Status ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Rank Test ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Chi Square ◽  
Group A

e16009 Background: SCHNC is a common malignancy and approximately 60% of patients present with locally advanced disease. There is paucity of data directly comparing Cx and CDDP with concurrent radiation in locally advanced SCHNC. We retrospectively reviewed charts of patients treated with CDDP and/or Cx along with radiation in locally advanced SCHNC comparing efficacy and outcomes in an academic cancer center. Methods: Ninety-five patients with locally advanced SCHNC were treated with concurrent CDDP (100 mg/m2 day 1, 22, 43) or Cx (400mg/m2 on day -7 and 250mg/m2 weekly) at our institution between January 2006 and June 2011. Forty-four patients were treated with CDDP (group A), 24 with Cx (group B) and 27 were initially started on CDDP but were switched to Cx secondary to toxicity (group C). All patients received concurrent radiation treatments (66-70 Gy, 2.0 Gy/fraction). The selection of CDDP versus Cx was largely based on ECOG performance status (PS) and baseline renal function of the patients. Chi-square test, analysis of variance, and log-rank test was used for analysis. The three groups had similar baseline characteristics except for mean age of 61, 56 and 55 years in group A, B and C respectively; T4 tumors consisted of 44%, 75% and 41% in groups A, B and C respectively. Groups A, B and C had a combined ECOG 0 and I (PS) of 93%, 75% and 92%. Patients with ECOG III PS were excluded. Results: Oropharynx was the most common treated site (38%) followed by Larynx (35%). Complete response (CR) was seen in 77%, 17% and 67% in groups A, B and C respectively (P<0.001). Median progression free survival (PFS) was 16.6, 4.3 and 22.8 in groups A, B and C respectively (P<0.001) and median overall survival (OS) was >35, 11.6 and >32 months in groups A, B and C respectively (P<0.0001). Conclusions: Concurrent CDDP with radiation leads to better response rate PFS and OS as opposed to Cx though many patients treated with CDDP could not complete treatment due to toxicity. Randomized trial comparing the two should be considered.

Efficacy of pertuzumab in combination with trastuzumab and a taxane in first-line treatment for metastatic breast cancer (MBC): A multicenter, retrospective, observational study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12504-e12504 ◽  
Author(s):  
Teresa Gamucci ◽  
Lucia Mentuccia ◽  
Isabella Sperduti ◽  
Alain Gelibter ◽  
Loretta D'Onofrio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Observational Study ◽  
Real World ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Rank Test ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

e12504 Background: Pertuzumab (P) , Trastuzumab (T) and Docetaxel (D) is standard first-line treatment in patients (pts) with HER2 + metastatic breast cancer (MBC). This multicenter retrospetive observational study was performed to evaluate the activity of P and T in combination with D or Paclitaxel (Tx) in real world HER2 + MBC pts. Methods: We identified HER2 + MBC pts treated with P, T and D or Ptx optionally followed by P, T and endocrine therapy (ET) maintenance in hormone positive (HR+) BC, in 17 Italian cancer centres between 09/2012 and 08/2016. Overall Survival (OS) and Progression Free Survival (PFS) were calculated by the Kaplan-Meier product-limit method. Log-rank test was used to assess differences between subgroups. Results: 191 pts were included in our analysis. Pts characteristics: median age 54 years (range 29-80); PS 0 in 127 (67%) pts and PS 1 in 54 (28%); 107 (56%) had visceral metastases (mts), 23 (12%) only bone mts and 28 (15%) brain mts, 130 (68%) were ER/PgR +. 76 pts (40%) were metastatic at diagnosis; 148 (78) were treated with D while 43 (22%) with Tx. The ORR was 78% (CI 95% 72-84), RC 18% and RP 60%, only 10 (5%) had PD. To date, of the 54 pts treated with ET maintenance, 26% had a further improvement of response (7 pts had RC). At median follow-up of 17 months (mo) (range 6- 52), median PFS was 20 mo (95% CI 14-26) and median OS at 2 years was 80%. No differences in PFS were found for age (p = 0.92), PS (p = 0.18), receptor status (p = 0.57), visceral mts (p = 0.54) and chemotherapy (cht) type (p = 0.47), whereas number of mts site (1 vs > 1) affected PFS (28 vs 16 mo, p = 0.002). Moreover median PFS in naïve pts and in pts pretreated with only cht was 28 mo (95% CI, 20-36) and 27 mo (95% CI, 16-38) respectively, whereas in pts pretreated with T it was 12 mo (95% CI 16-38 p 0.002). In HR+ pts ET maintenance together with P and T had an impact on PFS (28 vs 15 mo, p = 0.01). Conclusions: Our analysis confirms, in real world HER2 MBC pts, the efficacy of P, T and a taxane combination in first line treatment; in this population PFS was shorter in pts pretreated with T. ET maintenance in association with P and T in HR+ pts improved PFS. Data collection is ongoing and update results will be presented.

scholarly journals Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma

Blood ◽  
2016 ◽  
Vol 127 (6) ◽  
pp. 681-695 ◽  
Author(s):  
Niels W. C. J. van de Donk ◽  
Philippe Moreau ◽  
Torben Plesner ◽  
Antonio Palumbo ◽  
Francesca Gay ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Plasma Cells ◽  
Blood Compatibility ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Therapeutic Antibody ◽  
Drug Discontinuation ◽  
Therapeutic Antibodies

AbstractImmunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM, and preliminary results from studies with relapsed/refractory patients have shown enhanced therapeutic efficacy when daratumumab and isatuximab are combined with other agents. Furthermore, although elotuzumab (anti-SLAMF7) has no single agent activity in advanced MM, randomized trials in relapsed/refractory MM have demonstrated significantly improved progression-free survival when elotuzumab is added to lenalidomide-dexamethasone or bortezomib-dexamethasone. Importantly, there has been no significant additive toxicity when these monoclonal antibodies are combined with other anti-MM agents, other than infusion-related reactions specific to the therapeutic antibody. Prevention and management of infusion reactions is important to avoid drug discontinuation, which may in turn lead to reduced efficacy of anti-MM therapy. Therapeutic antibodies interfere with several laboratory tests. First, interference of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting antibodies, interfere with blood compatibility testing and thereby complicate the safe release of blood products. Neutralization of the therapeutic CD38 antibody or CD38 denaturation on reagent red blood cells mitigates daratumumab interference with transfusion laboratory serologic tests. Finally, therapeutic antibodies may complicate flow cytometric evaluation of normal and neoplastic plasma cells, since the therapeutic antibody can affect the availability of the epitope for binding of commercially available diagnostic antibodies.

scholarly journals Benchmark of Progression Free Survival for Multiple Lines of Therapy in Follicular Lymphoma Treated in the Rituximab Era

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2955-2955 ◽  
Author(s):  
Anna Alperovich ◽  
Connie Batlevi ◽  
Katy Smith ◽  
Zhitao Ying ◽  
Jacob D Soumerai ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Progression Free Survival ◽  
Complete Response ◽  
Line Treatment ◽  
Advisory Committees ◽  
Free Survival ◽  
Third Line ◽  
Third Line Treatment

Abstract Introduction In their lifetime, patients with follicular lymphoma frequently require multiple treatments, which have improved their survival over the past few decades. The expected treatment outcome based on lines of treatment in the post-Rituximab era is currently unknown. We analyzed the progression free survival and event free survival by line of treatment to aid estimating clinical endpoints when designing future clinical trials for multiply relapsed patients. Patients and Methods Adults (≥18 years) with de novo follicular lymphoma (FL) treated at our center between 1998 and 2007 were eligible (N=1134). 236 patients with ≤2 visits, mixed histology at initial diagnosis, and active concurrent malignancy were excluded. Of the remaining 898 patients, 105 were observed and did not require treatment during the timeframe of this dataset, and 2 had incomplete data, therefore 791 patients were eligible for response, progression and event free survival (PFS and EFS) analysis (Figure 1). Response was documented by investigators based on clinical or radiographic assessment. Complete response was based on radiographic assessment. PFS was defined as start of treatment to progression of disease or death. Patients with inadequate response to treatment, change of treatment, or stable disease without subsequent documented relapse were censored in the PFS analysis. Events for EFS were defined as progression, change of treatment, and death. PFS and EFS of sequential lines of treatment were evaluated by Kaplan-Meier method and compared across lines using log-rank test with adjustment for within-patient correlation. PFS and EFS were compared by other clinical variables using regular log-rank tests. Results Median age of diagnosis was 57.3 years with 1:1 male to female ratio. Median overall survival was not reached with median follow up of 9 years (N=898, range 0.2 - 16.8 years, Figure 1A). Median time to first treatment for the entire group was 2.3 months (range 0 - 13.3 years). In first line treatment of the 791 patients, 51% (N=406) received Rituximab with chemotherapy (R-Chemo), 13% (N=101) received chemotherapy only (Chemo), 19% (N=150) received Rituximab monotherapy (R-Mono), and 17% (N=129) received other treatments including radiation and surgery. For second line treatment, 405 patients were treated with about 37% receiving R-Chemo and 34% receiving R-Mono. As line of treatment increased, the percentage of patients with radiographically assessed complete response diminished from 71% at first line treatment to 25% by fifth line treatment (Figure 1B). Median PFS for first, second and third line treatment are 4.8, 1.6, and 1 year, respectively (Figure 2A). Median EFS for first, second and third line treatment are 3.8, 1.1, 0.8 year, respectively (Figure 2B). For subsequent lines of treatment, both median PFS and EFS were <1 year. Conclusion Follicular lymphoma is an indolent disease often requiring multiple lines of treatment. However, PFS and EFS for multiple lines of treatment in FL has not been described in the post-Rituximab era. The work has benchmarked the median response by line of treatment. After third line treatment, the PFS was ≤1 year. This analysis serves to aide comparison of different therapies for future drug approval in relapsed FL. Disclosures Hamlin: Xencor: Membership on an entity's Board of Directors or advisory committees; Portola: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees. Horwitz:Spectrum: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Huya: Consultancy; Infinity: Consultancy, Research Funding; Kyowa Hakka Kirin: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy; ADCT Therapeutics: Research Funding. Kumar:Celgene: Honoraria, Other: Scientific Advisory Board; Celgene: Research Funding; Adaptive Biotechnologies: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding. Moskowitz:Merck: Honoraria; Seattle Genetics: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria. Moskowitz:Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Palomba:Pharmacyclics: Consultancy. Zelenetz:Gilead Sciences: Research Funding.

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