The Natural History and Treatment Outcome of De-Novo Chromosome 17p Deletion CLL: A Single Institution Experience with 48 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2041-2041
Author(s):  
Constantine S. Tam ◽  
Michael J. Keating ◽  
Susan O’Brien ◽  
Alessandra Ferrajoli ◽  
Lynne V. Abruzzo ◽  
...  
Keyword(s):  
De Novo ◽  
Prognostic Significance ◽  
Bone Marrow Examination ◽  
Cancer Center ◽  
Dismal Prognosis ◽  
Response Table ◽  
Risk Of Progression ◽  
Progression Risk ◽  
Actuarial Risk ◽  
Md Anderson

Abstract The adverse prognostic significance of chromosome17p deletion (del17p) was established in CLL patients (pts) with pretreated disease, and its significance in patients with previously untreated CLL (“de-novo del17p”) is not well defined. We identified 48 consecutive pts with de-novo del17p within a cohort of 708 previously untreated pts tested by FISH for common CLL aberrations and followed prospectively at the MD Anderson Cancer Center. Characteristics of de-novo 17p pts: median age 61 yrs; Rai 0 31%, I–II 44%, III–IV 25%; B2M≥2N 42%; unmutated IGVH 32/45. The proportion of del17p cells were ≥20% in 35 (73%) pts. Twenty-five (52%) pts had stable disease not requiring immediate therapy, and were observed prospectively; for these pts, the actuarial risk of requiring therapy was 41% at a median follow-up of 19 months. Pts in Rai stage 0 had a low risk of progression to therapy (9%) regardless of IGVH status, whereas the progression risk for Rai I–II pts depended on their IGVH status (figure). Thirty-two pts had commenced therapy, of which 25 were assessable for treatment response (table). Overall (OR) and complete clinical response (CCR) rates were 67% and 33% for rituximab-based therapy, and 84% and 50% for fludarabine & rituximab combinations. Bone marrow examination in 8 CCR pts confirmed that 7 were in flow cytometry negative CR, with normalization of cytogenetics and FISH in 6 of 6 tested. Time to progression for CCR pts was 79% at 18 months, with only 3 relapses to date: notably, 2 relapses were with Richter transformation (one of which was confirmed to be del17p negative), and the only indolent relapse was with a non-del17p clone. Survival for all pts (n=48) from FISH date was 85% at 18 months, and survival from start of therapy (n=32) was 86% at 18 months. Five deaths have occurred to date: two pts died of unrelated causes prior to requirement for CLL therapy, two pts in remission died of complications of therapy, and one pt died of obstructive jaundice related to an undiagnosed pancreatic mass. De-novo del17p does not necessarily imply a dismal prognosis in CLL: the disease course may be indolent especially in Rai 0 disease, and therapy with standard regimens can achieve durable clinical and cytogenetic remissions. All pts who commenced therapy in this study received rituximab, and our favorable survival compared to that reported by the German and United Kingdom trials of F vs FC (median survival 18 months or less) suggest that rituximab may be an important agent in the therapy of del17p CLL. Figure Figure Evaluable Response Comp Clin Resp Flow–CR Remission (months) Rit & GMCSF 4 2 1 1 9, 18+ Rituximab 1 1 1 n/a 42+ Rit & Pred 1 1 0 0 3+ RIT-BASED 6 4 (67%) 2 (33%) 1/5 (20%) 53% @ 18mth Evaluable Response Comp Clin Resp Flow- CR Remission (months) FCR ±GMCSF 11 10 5 3/9 2+,6+,8+,9+,11+,12+,15,22+,22,41+ FCMR 2 1 1 0 3+, 18+ FR 1 0 0 0 n/a PCR 1 1 1 1 19+ CFAR 4 4 2 2 11,11,12,12+ 19 16 (84%) 9 (50%) 6/17 (35%) 62% @ 18mth

scholarly journals Prognosis of aggressive lymphomas: a study of five prognostic models with patients included in the LNH-84 regimen

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 558-564 ◽  
Author(s):  
B Coiffier ◽  
E Lepage
Keyword(s):  
Performance Status ◽  
Prognostic Significance ◽  
Staging System ◽  
Prognostic Models ◽  
Cancer Center ◽  
Malignant Lymphomas ◽  
Prognostic System ◽  
Ann Arbor ◽  
Md Anderson ◽  
Better Than

Abstract Four prognostic models described for aggressive malignant lymphomas and the classical Ann Arbor staging system were used to compare the survival of 737 patients treated with the LNH-84 regimen. The aim of the study was to determine the optimal prognostic system at the time of diagnosis. Three institutions have described these models after multivariate analyses: the Dana Farber Cancer Institute (DFCI1 and DFCI2), the MD Anderson Hospital (MDAH), and the Memorial Sloan- Kettering Cancer Center (MSKCC). The models were constructed with the following variables: performance status, LDH level, and tumor extension. The latter is the most difficult to assess: it was considered as the number of extranodal sites and the diameter of the largest mass in DFCI1, stage and the diameter of the largest mass in DFCI2, the number of extranodal and extensive nodal sites in MDAH, and the number of nodal sites and their localization in MSKCC. Univariate studies with LNH-84 regimen patients showed all these variables to have major prognostic significance (logrank tests: P less than 10(-4)). All five prognostic systems divided patients into three subgroups: good, intermediate, and poor prognosis. Logrank analyses of survival showed highly significant differences (X2 greater than 90 and P less than 10(- 6)) between the subgroups. No gross difference was found between the models, and none was better than the others. A new, internationally accepted prognostic system for the expression and comparison of treatment results in aggressive malignant lymphomas should include major univariate prognostic parameters and must be reliable and easy to use in clinical practice. Until such time, stage or LDH level are the best alternatives.

Prognostic Significance of Serial Determinations of LDH Levels in Primary (De Novo) Myelodysplastic Syndromes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4828-4828
Author(s):  
Friedrich Wimazal ◽  
Wolfgang R. Sperr ◽  
Anja Vales ◽  
Michael Kundi ◽  
Alexandra Boehm ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lactate Dehydrogenase ◽  
Disease Progression ◽  
Myelodysplastic Syndromes ◽  
Prognostic Value ◽  
De Novo ◽  
Prognostic Significance ◽  
Bone Marrow Examination ◽  
Probability Of Survival

Abstract An increased lactate dehydrogenase (LDH) level at diagnosis is associated with a reduced probability of survival and an enhanced risk of AML development in primary (de novo) myelodysplastic syndromes (MDS). However, so far, little is known about the prognostic value of an increase in LDH levels during the follow up in these patients. We have serially determined LDH levels in 221 patients (102 males, 119 females) with de novo MDS (median age 70 years; FAB-types: RA, n=62; RARS, n=46; RAEB, n=48; RAEBT, n=36; CMML, n=29), and examined the prognostic value of LDH as a follow-up parameter. Confirming previous data, an elevated LDH level at diagnosis was found to be associated with a significantly increased probability of AML evolution and a significantly decreased probability of survival (p<0.05). In the follow up, an increase in LDH (from normal to elevated) was found to be associated with progression of MDS and AML evolution in most cases. Moreover, in those patients who progressed to AML, LDH levels were found to be significantly higher in the two three-months-periods preceding progression compared to the two initial three-months-periods examined (p<0.005). In most patients, the increase in LDH was accompanied or followed by other signs of disease progression, such as the occurrence of thrombocytopenia or an increase in blasts. Together, our data show that LDH can be employed as a prognostic follow-up variable in patients with MDS. In those patients in whom an increase in LDH is noted, a thorough re-evaluation of the progression-status of the disease including a bone marrow examination should be considered.

The influence of PET/Gallium (P/G) status and high-dose rituximab (HDR) in patients (pts) with aggressive, large, B-cell lymphoma (LBCL) receiving autologous stem cell transplants (ASCT)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6518-6518 ◽  
Author(s):  
A. M. Alousi ◽  
R. M. Saliba ◽  
G. Okoroji ◽  
C. Hosing ◽  
B. I. Samuels ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
De Novo ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Disease Status ◽  
High Dose ◽  
Risk Of Progression ◽  
Cell Transplants ◽  
Md Anderson

6518 Background: P/G status has been suggested to be an important predictor of outcome in pts with LBCL who receive an ASCT. Newer conditioning regimens which include HDR have been shown to improve results (Khouri, JCO, 2005). The influence of HDR on the outcome of pts based on P/G status has not been determined. Methods: A retrospective review of pts with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Results: A total of 188 pts were identified. Median age was 49 yrs with 108 (57%) male pts. 147 (78%) had de novo LBCL and 41 (22%) had an LBCL of follicular origin (LBCL-F). 83 (39%) pts received HDR with ASCT. At transplantation 95 pts (50%) were in PR, 71 pts (38%) in CRU and 22 pts (12%) in CR. 142 (76%) pts were P/G negative, 37 (20%) pts P/G positive and 9 (4%) pts unknown. The median follow-up was 44 months. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and P/G status. On multivariate analysis, P/G status and HDR were the only predictors for progression and PFS. Pts who were P/G negative and those that received HDR had a hazard ratio (HR) of 0.3 (p<0.001) and 0.5 (p=0.02) for progression, respectively. The cumulative incidence (CI) of progression and progression free survival (PFS) at 54 months according to HDR and P/G status are shown in the table below. P/G Status and HDR were also found to be predictive for pts with LBCL- F on univariate analysis, however due to the small numbers in this subset of pts, multivariate analysis could not be performed. Conclusions: These results suggest that pre-transplant P/G positive status increases the risk of progression of LBCL after ASCT. The addition of HDR to the transplant regimen decreases this risk irrespective of P/G status. [Table: see text] No significant financial relationships to disclose.

scholarly journals Investigating the Natural History and Prognostic Nature of NTRK Gene Fusions in Solid Tumors

2021 ◽  
Author(s):  
Limin Zhu ◽  
Brian Hobbs ◽  
Jason Roszik ◽  
Vijaykumar Holla ◽  
David S. Hong
Keyword(s):  
Natural History ◽  
Solid Tumors ◽  
Gene Fusion ◽  
Early Stage ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Gene Fusions ◽  
Risk Of Progression ◽  
Md Anderson ◽  
Trk Inhibitors

Abstract BackgroundSeveral TRK inhibitors have demonstrated clinical efficacy in patients with solid tumors harboring NTRK gene fusions. However, the natural history and prognostic implications of NTRK fusions in solid tumors remain unknown.MethodsA cohort of 77 MD Anderson Cancer Center patients (MDACC) with NTRK gene fusions was identified and retrospectively compared to a second cohort from the Cancer Genome Atlas (TCGA) database. Due to paucity of events in early stage cancers and lack of TCGA data in rare tumors, 25 randomly selected MDACC patients were matched to 122 TCGA patients without NTRK gene fusion. Next we assessed the associations between NTRK gene fusion and overall (OS) and progression-free survivals (PFS).ResultsAmong the 77 MDACC patients with NTRK gene fusions, 18 NTRK fusion partners were identified. There were insufficient OS events for analysis in the matched cohort. PFS was not significantly different (p=0.49) between the NTRK-fusion positive MDACC patients (median PFS 786 weeks, 95% CI 317-NE) and the NTRK-fusion negative TCGA patients (median PFS NE). The adjusted hazard ratio comparing TCGA patients to MDACC patients was HR=0.72 (95% CI: 0.23-2.33), which trended towards a reduced rate of progression or death experienced by TCGA patients.ConclusionsThis study did not identify statistically significant associations between NTRK fusion and PFS. Nonsignificant trends estimated increases in the risk of progression or death events for patients with NTRK fusions when compared to matched controls. Our findings help illuminate the influence of NTRK fusions on the natural history of a variety of solid tumors.

scholarly journals Prognosis of aggressive lymphomas: a study of five prognostic models with patients included in the LNH-84 regimen

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 558-564
Author(s):  
B Coiffier ◽  
E Lepage
Keyword(s):  
Performance Status ◽  
Prognostic Significance ◽  
Staging System ◽  
Prognostic Models ◽  
Cancer Center ◽  
Malignant Lymphomas ◽  
Prognostic System ◽  
Ann Arbor ◽  
Md Anderson ◽  
Better Than

Four prognostic models described for aggressive malignant lymphomas and the classical Ann Arbor staging system were used to compare the survival of 737 patients treated with the LNH-84 regimen. The aim of the study was to determine the optimal prognostic system at the time of diagnosis. Three institutions have described these models after multivariate analyses: the Dana Farber Cancer Institute (DFCI1 and DFCI2), the MD Anderson Hospital (MDAH), and the Memorial Sloan- Kettering Cancer Center (MSKCC). The models were constructed with the following variables: performance status, LDH level, and tumor extension. The latter is the most difficult to assess: it was considered as the number of extranodal sites and the diameter of the largest mass in DFCI1, stage and the diameter of the largest mass in DFCI2, the number of extranodal and extensive nodal sites in MDAH, and the number of nodal sites and their localization in MSKCC. Univariate studies with LNH-84 regimen patients showed all these variables to have major prognostic significance (logrank tests: P less than 10(-4)). All five prognostic systems divided patients into three subgroups: good, intermediate, and poor prognosis. Logrank analyses of survival showed highly significant differences (X2 greater than 90 and P less than 10(- 6)) between the subgroups. No gross difference was found between the models, and none was better than the others. A new, internationally accepted prognostic system for the expression and comparison of treatment results in aggressive malignant lymphomas should include major univariate prognostic parameters and must be reliable and easy to use in clinical practice. Until such time, stage or LDH level are the best alternatives.

Independent Validation of the MD Anderson Cancer Center Risk Model for Myelodysplastic Syndromes (MDS), and Comparison to the International Prognostic Scoring System (IPSS) and the World Health Organization-Based Prognostic Scoring System (WPSS).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3814-3814 ◽  
Author(s):  
Sarah E Hugo ◽  
Sarah C Bundrick ◽  
Curtis A Hanson ◽  
David P Steensma
Keyword(s):  
Mayo Clinic ◽  
Scoring System ◽  
Proportional Hazards ◽  
Risk Model ◽  
Risk Group ◽  
Prognostic Significance ◽  
World Health ◽  
Cancer Center ◽  
Secondary Mds ◽  
Md Anderson

Abstract Abstract 3814 Poster Board III-750 Introduction The 1997 IPSS remains the most widely used prognostic scoring system for patients with MDS, and it has important strengths, but several other prognostic systems have been proposed recently to overcome some of the well-recognized IPSS limitations. These systems include a new risk model for patients with MDS and CMML – including previously treated patients and those with secondary (treatment-related) MDS – proposed by Kantarjian and colleagues at the MD Anderson Cancer Center (MDACC) (Cancer 2008; 113:1351), as well as the WPSS, proposed by Malcovati and colleagues in Europe (J Clin Oncol 2007; 25:3503) To date, the MDACC risk model has not been validated in a large external independent cohort or directly compared to the WPSS. We assessed the performance of the MDACC model compared to the WPSS and the IPSS in a 12-year Mayo Clinic MDS/CMML cohort. Patients and Methods We reviewed the medical records of 1,503 adult patients (pts; 984 males; median age 71 years, range 17-98) with MDS (n=1,249) or CMML (n=254) evaluated at Mayo Clinic between January 1996 and December 2007. Pediatric pts (age ≤16 and pts with ≥30% marrow blasts were excluded. IPSS and WPSS scores were calculated, and data collected for MDACC risk model assignment (age, performance score, platelet count, hemoglogbin, marrow blast proportion, white blood cell count, karyotype, and transfusion history). Data were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression models. Results The overall median survival was 17.8 months (mos) – 13.7 mos for CMML, 19.1 mos for WHO-defined MDS, and 9.6 mos for RAEB-t – similar to the 14.1 mos observed in the test cohort used to derive the MDACC risk model. Follow-up was complete until death in 1,122 (74.7%) pts. Pts excluded from the cohort stratified using IPSS included 122 patients with CMML and leukocytosis (>12 × 109/L), and 176 pts with secondary MDS/CMML (there were 12 pts with secondary CMML with leukocytosis) – total excluded, 286 pts. Patients excluded from the WPSS cohort included 27 pts with RAEB-t, 254 pts with CMML, and 148 pts with secondary MDS – total excluded, 429 pts. Survival by IPSS risk group was 38.9 mos for Low (n=413), 17.9 mos for Int-1 (n=541), 9.6 mos for Int-2 (n=206), and 6.6 mos for High (n=57). Survival by WPSS risk group was 39.0 months for Very Low (n=352), 26.6 months for Low (n=276), 15.9 months for Intermediate (n=185), 11.2 mos for High (n=221), and 4.9 months for Very High (n=40). Survival by MDACC risk group was 45.6 mos for Low (n=426), 20.0 mos for Int-1 (n=552), 12.3 mos for Int-2 (n=325), and 4.9 mos for High (n=200). When the MDACC risk model was used to classify only the 1,074 pts with conditions for which the WPSS has been validated, survival was 51.4 mos for Low (n=336), 21.2 mos for Int-1 (n=411), 13.3 mos for Int-2 (n=213), and 4.6 mos for High (n=114) (p<0.001 for all comparisons). In a multivariable proportional hazards model, all of the MDACC risk model components except WBC>20 × 109/L retained independent prognostic significance. Conclusions All 3 systems stratify patients accurately, but the MDACC risk model best identifies the lowest-risk patients, and also classifies the broadest group of patients (i.e., primary and secondary MDS, and primary and secondary CMML with or without leukocytosis). The revised IPSS that is currently in development should include the patient factors accounted for by the MDACC risk model, with the possible exception of leukocytosis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparative analysis of international prognostic index for chronic lymphocytic leukemia, progression-risk score, and MD Anderson Cancer Center 2011 score - a single center experience

2021 ◽  
pp. 47-47
Author(s):  
Biljana Mihaljevic ◽  
Vojin Vukovic ◽  
Natasa Milic ◽  
Teodora Karan-Djurasevic ◽  
Natasa Tosic ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Risk Score ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Prognostic Models ◽  
Risk Scores ◽  
Cancer Center ◽  
Progression Risk ◽  
Md Anderson

Introduction/Objective. Prognostication of chronic lymphocytic leukemia (CLL) has been substantially improved in recent times. Among several prognostic models (PMs) focused on the prediction of time to first treatment (TTFT), Progression-Risk Score (PRS) and MD Anderson Cancer Center score 2011 (MDACC 2011) are the most relevant, while CLL-International Prognostic Index (CLL-IPI), although originally developed to predict overall survival (OS), is also being used to estimate TTFT. The aim of this study was to investigate CLL-IPI, PRS, and MDACC 2011 prognostic values regarding TTFT and OS. Methods. The analyzed cohort included 57 unselected Serbian CLL patients from a single institution, with the basic characteristics reflecting more aggressive disease than in general de novo CLL population. The eligible patients were assigned with investigated PMs, and TTFT and OS analyses were performed. Results. Patients with higher risk scores according to CLL-IPI, PRS, and MDACC 2011 underwent treatment significantly earlier than patients with lower risk scores (p = 0.002, p = 0.019, and p<0.001, respectively). In multivariate analysis, MDACC 2011 and CLL-IPI retained their significance regarding TTFT (p = 0.001 and p = 0.018, respectively), while PRS did not. CLL-IPI was the only significant predictor of OS both at the univariate (p = 0.005) and multivariate (p = 0.013) levels. Conclusion. CLL-IPI, PRS, and particularly MDACC 2011 are able to predict TTFT even in cohorts with more advanced-disease patients, while for prediction of OS, CLL-IPI is the only applicable among the three PMs. These results imply that prognostic models should be investigated in more diverse CLL populations, as it is in real-life setting.

scholarly journals Should We Look beyond Revised International Prognostic Scoring System: A Retrospective Observational Study of Progression of Myelodysplastic Syndrome to Acute Leukemia

2021 ◽  
Vol 42 (05) ◽  
pp. 431-438
Author(s):  
Bangalore Rammohan Nagarjun ◽  
Rajashekar Kalaharaghini ◽  
Jyoti Sawhney ◽  
Pina J. Trivedi ◽  
Karthik Dhandapani ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Myelodysplastic Syndrome ◽  
Scoring System ◽  
De Novo ◽  
International Prognostic Scoring System ◽  
Cancer Center ◽  
Western India ◽  
Cytogenetic Finding ◽  
Risk Of Progression ◽  
Cytogenetic Profile

Abstract Introduction Myelodysplastic syndrome (MDS) is a clonal stem cell disorder and heterogeneous condition resulting in peripheral cytopenias with marrow dysplasia due to ineffective hematopoiesis. The revised International Prognostic Scoring System (IPSS-R) predicts the risk of progression to acute leukemia (AL). Indian data on MDS and its progression to AL are limited. Additionally, the cytogenetic findings are dictated by patients' racial background. Study intended to analyze the cytogenetic profile of the patients with MDS. Objectives This study aimed to (1) evaluate the clinicohematologic and morphologic spectrum of newly diagnosed MDS cases, (2) evaluate the cytogenetic profile of these cases, and (3) study the cases progressed to AL. Materials and Methods MDS cases diagnosed and followed-up during a 5-year study period, from January 2015 to December 2019, were included in the study and the study was conducted at regional cancer center in Western India. De novo diagnosed MDS cases with complete workup were considered and MDS due to secondary causes were excluded. Baseline clinical, hematologic findings were tabulated along with cytogenetics and risk stratified as per IPSS-R, and their progression was studied. Results A total of 63 cases of de novo MDS were diagnosed over a period of 5 years with 45 cases on follow-up and 15 cases (33.3%) progressed to AL. Maximum number of cases belonged to MDS-excess blast (EB) category accounting to 48 cases (76.1%). Apparently normal karyotyping was the commonest cytogenetic finding in 33 MDS cases (61.2%) and in 8 cases that progressed to AL (53.4%). Conclusion MDS cases diagnosed at relatively early age were at higher risk of progression to AL. Majority of the cases that progressed to AL were risk stratified in high and very high risk groups and 10 cases which progressed to AL belonged to good category, interestingly apparent normal karyotyping was the commonest cytogenetic finding in more than 50% of the cases progressed to AL. Molecular mutations could only explain this progression and studies integrating molecular mutations with present IPSS-R scoring system should be conducted, as it could translate into better risk stratification and help in early identification and better management of cases at risk in progression to AL.

Prognostic Significance of the French-American-British (FAB) Morphologic Subclassification of “Acute Myeloid Leukemia, Not Otherwise Specified” in the 2008 WHO Classification: Analysis of 5,848 Newly Diagnosed Patients From HOVON, MRC/NCRI, SWOG, and MD Anderson Cancer Center

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 540-540
Author(s):  
Roland B. Walter ◽  
Megan Othus ◽  
Alan K. Burnett ◽  
Bob Löwenberg ◽  
Hagop M. Kantarjian ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Who Classification ◽  
Prognostic Significance ◽  
Early Death ◽  
Cancer Center ◽  
Newly Diagnosed ◽  
Not Otherwise Specified ◽  
Fab Classification ◽  
Md Anderson ◽  
French American British

Abstract Abstract 540 Background: The World Health Organization (WHO) classifies acute myeloid leukemia (AML) via genetic, immunophenotypic, biologic, and clinical features. Nevertheless, in the subgroup “AML, not otherwise specified (NOS)”, cases are subdivided based on morphologic criteria similar to those of the previous French-American-British (FAB) classification, but the clinical relevance of this practice is unknown. Assuming that part of a classification system's value derives from its clinical relevance, we used data from adults with newly diagnosed AML treated on trials conducted by the Dutch-Belgian Cooperative Trial Group for Hematology/Oncology (HOVON), the U.K. Medical Research Council/National Cancer Research Institute (MRC/NCRI), the U.S. cooperative group SWOG, and MD Anderson Cancer Center (MDA) to assess the prognostic significance of FAB in the WHO “AML, NOS” category. Patients and Methods: We reviewed information on patients with newly diagnosed AML other than acute promyelocytic leukemia receiving curative-intent treatment on HOVON (1987-2008), MRC/NCRI (1988-2010), or SWOG (1987-2009) protocols or at at MDA (2000-2011) and had information on FAB classification available. We used multivariate analyses to assess whether the FAB type was independently associated with early death (i.e. death within 28 days of initiation of chemotherapy or study registration), achievement of complete remission (CR), relapse-free survival (RFS), and overall survival (OS). The following pre-treatment covariates were used in the regression modeling: FAB category, age at diagnosis, white blood cell count, platelet count, bone marrow blast percentage, gender, performance status (0 vs. 1 vs. ≥2), karyotype (normal vs. abnormal), and treatment site. Results: After exclusion of patients with therapy-related neoplasms, AMLs with myelodysplasia-related changes, and leukemias with recurrent cytogenetic abnormalities but ignoring information on NPM1 and CEBPA, our cohort included 5,848 predominantly adult patients (median age: 54 years [range: 12–91 years] with “AML, NOS”. After multivariate adjustment, FAB M0 AML was independently associated with significantly lower likelihood of achieving CR and inferior RFS as well as OS as compared to FAB M1, M2, M4, M5, and M6 (FAB “M1-M6”), and inconclusive data regarding M7. Specifically, relative to patients with FAB M1-6, those with FAB M0 the hazard ratios (HRs) were 1.66 (95% confidence interval: 1.30–2.12) for achievement of CR (p<0.001), 0.86 (0.73–1.01) for RFS (p=0.068), and 0.82 (0.72–0.92) for OS (p=0.0013). In contrast, FAB M0 was not associated with risk of early death (HR: 1.01 [0.67–1.53], p=0.96). After exclusion of cases fitting the entity of “AML with mutated NPM1” (n=987) and cases with unknown NPM1 status (n=3,584), FAB M0 was no longer associated with worse outcome relative to other FAB subtypes in the remaining 1,277 patients, with HRs of 1.19 (0.75–1.91; p=0.46) for achievement of CR, 0.98 (0.74–1.31; p=0.89) for RFS, 0.91 (0.72–1.16; p=0.45) for OS, and 1.03 (0.35–3.03; p=0.95) for early death. Although data were limited by sample size, additional exclusion of cases fitting the provisional entity of “AML with mutated CEBPA” and cases with unknown CEBPA status did not further affect this result. Conclusion: In the 2008 WHO classification scheme, our data suggest that FAB subclassification of “AML, NOS” cases does not provide prognostic information if molecular data on the mutational status of NPM1 and CEBPA are available. This finding leads us to question the utility of continued use of the FAB system in this subset of AML patients. Disclosures: No relevant conflicts of interest to declare.

657 Interleukin-6 receptor blockade for management of immune checkpoint inhibitor related adverse events in patients with melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A694-A694
Author(s):  
Chantal Saberian ◽  
Faisal Fa’ak ◽  
Jean Tayar ◽  
Maryam Buni ◽  
Sang Kim ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Activity ◽  
Median Time ◽  
Interleukin 6 ◽  
Immune Checkpoint ◽  
Activity Index ◽  
Critical Role ◽  
Cancer Center ◽  
Interleukin 6 Receptor ◽  
Md Anderson

BackgroundManagement of certain immune mediated adverse events (irAEs) can be challenging and may require prolonged/chronic immune suppression with corticosteroids or other immunosuppressant which could compromise and even reverse the efficacy of immune checkpoint inhibitors (ICI). While the exact immunobiology of irAEs is not fully understood there is enough evidence that IL-6 induced Th-17 that may play critical role in the pathogenesis. Herein, we describe our clinical experience using interleukin-6 receptor (IL-6R) blockade in management of irAEs in melanoma patients.MethodsWe searched MD Anderson databases to identify cancer patients who had received ICIs between January 2004 and March 2020. Of 11,391 ICI-treated patients, 21 patients with melanoma who received IL-6R blockade after ICI infusion were identified and their medical records were reviewed.ResultsMedian age was 61 years (41–82), 52% were females, 90% received anti-programmed cell death-1 antibodies. Fourteen patients (67%) had de novo onset irAEs (11 had arthritis, and 1 each with polymyalgia rheumatica, oral mucositis, and CNS vasculitis), and 7 patients (33%) had flare of their pre-existing autoimmune diseases (5 had had rheumatoid arthritis, and 1 each with myasthenia gravis and Crohn’s disease). Median time from ICI initiation to irAEs was 91 days (range, 1–496) and to initiation of IL-6R blockade was 6.6 months (range, 0.6–24.3). Median number of IL-6R blockade was 12 (range, 1–35), and 16 patients (76%) were concomitantly receiving corticosteroids of median dose of 10 mg (range, 5–20 mg). Of the 21 patients, irAEs improved in 14 (67%) (95% CI: 46%-87%). Of 13 evaluable patients with arthritis, 11 (85%) achieved remission or minimal disease activity as defined by the clinical disease activity index. Median time from initiation of IL-6R blockade till improvement of irAEs was 2.9 months (range, 1.5–36.9). Nineteen patients tolerated well IL-6R blockade, while two patients stopped treatment due to abdominal pain and sinus tachycardia. The median CRP levels at irAEs was 84 mg/L (0.6–187) and decreased to 1.9 mg/L (0.56–12) at 10 weeks after initiation of IL-6R blockade (P=0.02). Of the 17 evaluable patients, the overall tumor response rate by RECIST-1.1 criteria was similar before and after IL-6R blockade initiation (41% vs. 53%).ConclusionsOur data demonstrated that IL-6R blockade could be an effective therapy for irAEs management without dampening the efficacy of ICIs. Prospective clinical trials with longitudinal blood, tumor, and inflamed tissue biopsies are planned to accurately validate these findings and better study the immunobiology of irAEs.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition’s Ethics Board, approval number PA19-0089

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