The Impact of Thalidomide Maintenance Therapy Varies Dependent Upon Biological Risk Grouping

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 199-199
Author(s):  
Annamaria Brioli ◽  
Fiona M Ross ◽  
Martin F Kaiser ◽  
Charlotte Pawlyn ◽  
Ping Wu ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Data Set ◽  
Biological Risk ◽  
Additional Lesion ◽  
Aggressive Disease ◽  
The Impact

Abstract Abstract 199 Recent studies have shown a clinical benefit for maintenance therapy in myeloma, however, the impact may vary dependent upon the underlying biology of the disease. An important question is whether maintenance can facilitate progression of high risk disease. Genetic alterations, such as t(4;14), del(17p) and +1q, can be used to define different biological behaviours, and we have shown that the presence of more than one adverse iFISH lesion can define a group of patients with very aggressive disease. We have studied the impact of thalidomide maintenance dependent upon risk status in the MRC IX study. The trial comprised an intensive and a non-intensive pathway based on patient eligibility for autologous transplant. Patients were subsequently randomized to receive maintenance thalidomide versus no maintenance. iFISH results with a complete data set for adverse IgH translocations, +(1)(q21) and del(17)(p13) were available in 368 cases. Patients were characterized as having standard (SR), high (HR) or ultra-high risk (UHR) disease based on the number of co segregating iFISH lesions (0, 1 or >1). We also looked at defined biological subtype of disease: t(4;14), t(11;14) and hyperdiploidy were considered in isolation or plus an additional adverse lesion. In isolation del(13q) was not of prognostic significance and was not considered in the analysis. Progression free survival (PFS) and overall survival (OS) were calculated from maintenance randomization. Results are summarized in Table 1. On overall population the median PFS and OS for maintenance and for control arm were 19.7 vs 14.7 months (p=0.066) and 37.4 vs 42.9 months (p=0.168), respectively. In the control arm the median PFS of SR, HR and UHR was of 20.2; 13.4; 6.7 (p=0.008) and the median OS was of 48.2; 44.7; 26.8 months (p=0.014), respectively. In the maintenance arm the median PFS was 29.6; 11.7; 6.5 (p=0.008) and for OS was 48.6; 29.6; 23.5 months (p=0.000). Compared to the control arm, SR patients receiving maintenance had a longer PFS with a similar OS, while the HR patients had similar PFS yet impaired OS. The outcome of the UHR was poor irrespective of whether maintenance was given or not. The outcome of t(4;14) was unfavorable in the control arm. Thalidomide maintenance improved the outcome of patients t(4;14) negative (n=325) or with t(4;14) in isolation (n=13), with a trend towards a better PFS; in particular, for t(4;14) positive patients, median PFS for maintenance and controls were 24.6 vs 7.2 months, respectively. OS was similar between treatment arms. t(4;14) plus an additional lesion (n=30) identified a group with a particularly poor outcome irrespective of whether maintenance was given or not. t(11;14) positive patients (n=54) had a favorable outcome; thalidomide maintenance did not discernibly affect PFS and OS. The impact of maintenance was similar whether the translocation was present in isolation (n=39) or in association with another lesion (n=15). The outcome of hyperdiploid patients (n=134) was favorable with a median PFS and OS of 21.2 and 44.4 months, respectively; cases receiving maintenance had an improved PFS (p=0.003), with similar OS. Low risk FISH with hyperdiploidy receiving maintenance had the best PFS and OS (median 36.7 and 50.1 months respectively). Hyperdiploidy associated with another lesion (n=85) behaved as the HR group. Maintenance thalidomide is effective in prolonging PFS in biological LR patients and in patients with t(4;14) in isolation. Conversely, in patients with biologically defined HR disease maintenance thalidomide may not impair PFS but can impair OS. The outcome of cases with very aggressive disease (UHR or t(4;14) plus an additional lesion) is governed by factor others than thalidomide maintenance. Table 1. PFS and OS (in months) according to biological risk groups PFS OS Thalidomide No maintenance p Thalidomide No maintenance p SR 29.6 20.2 0.004 48.6 48.2 0.718 HR 11.7 13.4 0.904 29.6 44.7 0.022 UHR 6.5 6.7 0.475 23.5 26.8 0.612 p 0.008 0.008 0.000 0.014 No t(4;14) 23.0 16.1 0.060 37.5 44.4 0.195 t(4;14) 24.6 7.2 0.280 31.1 36.1 0.588 t(4;14)+1 5.3 6.0 0.813 24.1 16.7 0.185 p 0.000 0.000 0.052 0.045 No t(11;14) 22.1 14.7 0.362 37.9 43.2 0.138 t(11;14) 18.8 18.8 0.455 41.3 42.8 0.883 t(11;14)+1 11.7 12.2 0.145 29.6 37.1 0.138 p 0.621 0.136 0.735 0.843 No hyperdiploidy 14.0 13.3 0.417 36.0 39.6 0.348 Hyperdiploidy 36.7 22.7 0.003 50.1 48.6 0.527 Hyperidiploidy+1 8.7 11.1 0.197 26.4 42.4 0.025 p 0.000 0.081 0.000 0.246 Disclosures: Off Label Use: Thalidomide used as maintenance therapy for myeloma. Cavo:Celgene: Honoraria. Davies:Celgene: Honoraria. Morgan:Celgene: Honoraria.

scholarly journals Differential Impact of ALK Mutations in Neuroblastoma

2021 ◽  
pp. 492-500
Author(s):  
Tara O'Donohue ◽  
Nitya Gulati ◽  
Audrey Mauguen ◽  
Brian H. Kushner ◽  
Neerav Shukla ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Tyrosine Kinase Receptor ◽  
Differential Impact ◽  
Mutation Site ◽  
Free Survival ◽  
Anaplastic Lymphoma ◽  
The Impact

PURPOSE The tyrosine kinase receptor anaplastic lymphoma kinase (ALK) can be abnormally activated in neuroblastoma, and somatic ALK mutations occur in 6%-10% of patients. The differential clinical impact of these mutations has not been clearly elucidated. METHODS Data on patients with neuroblastoma harboring ALK mutations were retrospectively analyzed. ALK sequencing was performed by whole-genome sequencing, hybrid-based capture of targeted exomes, or hotspot ALK mutation profiling. The differential impact of ALK mutation site on clinical characteristics, response to treatment, and survival was analyzed. In a subgroup of patients with locoregional neuroblastoma diagnosed after 2014, the impact of all ALK mutations was compared with wild-type ALK. RESULTS Of 641 patients with neuroblastoma with ALK status analyzed on at least one tumor sample, 103 (16%) had tumors harboring ALK mutations. Mutations existed across all ages (birth to 67.8 years), stages (30% locoregional and 70% metastatic), and risk groups (20%, 11%, and 69% with low-, intermediate-, and high-risk disease, respectively). Mutation sites included F1174 (51%), R1275 (29%), R1245 (10%), and others (10%). Mutation site was not prognostic for progression-free survival or overall survival in the entire cohort, high-risk subgroup, or locoregional subgroup. Locoregional tumors with any ALK mutation were generally invasive: L2 by International Neuroblastoma Research Group staging in 30/31 patients with a 2-year progression-free survival (59%, 95% CI, 37.4 to 80.5) that was inferior to historical controls. This observation was corroborated in the post-2014 subgroup in which gross total resection was less likely for ALK-mutated tumors. CONCLUSION Somatic ALK mutations are present across all stages and risk groups of neuroblastoma. No specific mutation carries differential prognostic significance. Locoregional neuroblastoma has an invasive phenotype when harboring somatic ALK mutations in this population.

Co-Existent Hyperdiploidy Does Not Abrogate The Poor Prognosis Associated With Adverse Cytogenetics In Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 529-529 ◽  
Author(s):  
Charlotte Pawlyn ◽  
Lorenzo Melchor ◽  
Eileen M Boyle ◽  
Annamaria Brioli ◽  
Martin F Kaiser ◽  
...  
Keyword(s):  
High Risk ◽  
Single Cell ◽  
Conflicts Of Interest ◽  
Significant Proportion ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
High Risk Population ◽  
Data Set ◽  
Translocation Event ◽  
The Impact

Abstract The development of the cytogenetic abnormalities hyperdiploidy or a translocation involving the immunoglobulin heavy chain are initiating events in the pathogenesis of myeloma. Previous studies have shown that hyperdiploidy is associated with a more favorable outcome whilst the presence of specific translocations (4;14), (14;16) and (14;20) are associated with poor clinical outcomes especially when they occur in association with other high risk features such as del17p and 1q+. While it has been generally accepted that these events are mutually exclusive, review of a number of clinical datasets shows that they occur together in a significant proportion of cases. This raises the mechanistic issue of which cytogenetic abnormality occurs first as well as the more practical issue of what it means for prognosis. In order to address these important questions we have investigated these cases with interphase FISH (iFISH) as well as determining their outcome in the Myeloma IX study. Myeloma IX is a large study (1960 newly diagnosed myeloma patients) that has been extensively described. iFISH results with a complete data set for hyperdiploidy, adverse IgH translocations, 1q+ and del17p were available for 847 patients with a median follow up of 5.9 years. 58% of patients (499/847) had hyperdiploidy and had a significantly improved survival compared with non-hyperdiploid patients (Median OS 49.7 vs 42.8 months, p=0.016 and PFS 18.8 vs 16.3 months, p=0.028). Hyperdiploid patients were divided into those who had one or more of the adverse lesions t(4;14), t(14;16), t(14;20), del17p and 1q+ (61%, 304/499) and their outcome was compared to those with none (39%, 195/499). The overall and progression free survival was significantly worse for those with hyperdiploidy plus an adverse lesion compared to those with hyperdiploidy alone (Median OS 60.9 vs 35.7 months, p<0.001, median PFS 23 vs 15.4 months, p<0.001). These results remained significant on multivariate analysis. When subdivided into those patients with hyperdiploidy plus: del17p alone, 1q+ alone, an adverse translocation alone or >1 adverse lesion, there remained a significant detrimental effect on survival (OS and PFS) for the del17p, 1q+ and >1 lesion groups and a trend towards worse survival for those with an adverse translocation (numbers too small to prove significance) when compared to those with hyperdiploidy and no adverse lesion. (table 1) Table 1 HD = Hyperdiploidy No. of patients PFS (months) OS (months) HD, no adverse lesions 304 23 60.9 HD plus del 17p 20 19.1 (p=0.019) 35.2 (p=0.003) HD plus 1q+ 142 15.4 (p<0.001) 38.1 (p<0.001) HD plus adverse translocation 9 15.4 (p=0.272) 40.1 (p=0.180) HD plus >1 lesion 24 12.1 (p<0.001) 19.9 (p<0.001) The converse situation was also examined by taking each population with an abnormal lesion and dividing them by the presence or absence of hyperdiploidy. 409/847 (48%) of patients had at least one adverse lesion and they had a significantly worse outcome within the whole data set than those without any adverse lesions (OS 60.6 vs 33.7 months, p<0.001, PFS 23.3 vs 15 months, p<0.001). When the impact of hyperdiploidy within the high-risk population (195/409 hyperdiploid, 214/409 non-hyperdiploid) was examined there was no difference in survival, (OS 35.7 vs 33.6 months p=0.64, PFS 15.4 vs 14.5 months, p=0.58). This remained true across each adverse lesion when individually analysed. A group of patients with hyperdiploidy and a (4;14) translocation were analysed at a single-cell level using iFISH. Within each case the percentage of cells with a translocation was consistently high, whereas the frequency of individual chromosomal trisomies varied. This suggests that the translocation event may occur earlier. Single cell genetic analysis using the Fluidigm technology is ongoing in order to confirm this finding. In conclusion, patients with co-existent hyperdiploidy and adverse cytogenetics have worse outcomes than those with hyperdiploidy alone. The progression of their disease is not different to those patients with adverse cytogenetics alone and our data suggests that the presence of hyperdiploidy is not able to abrogate or even ameliorate this adverse prognostic feature. It is important that this is recognised when designing treatment strategies for this group of patients as they should be treated with more aggressive chemotherapy regimens to maximize their response and control disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma

2019 ◽  
Vol 3 (5) ◽  
pp. 744-750 ◽  
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
S. Vincent Rajkumar ◽  
Morie A. Gertz ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Light Chain ◽  
Progression Free Survival ◽  
Early Response ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Best Response ◽  
Light Chain Disease ◽  
The Impact

Abstract We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and &lt;VGPR after 2 cycles (PFS, 28 vs 30 months, P = .6; OS, 78 vs 96 months, P = .1) and 4 cycles (PFS, 31 vs 29 months; OS, 89 vs 91 months, P = .9), although both were improved, with ≥VGPR as best response (PFS, 33 vs 22 months, P &lt; .001; OS, 102 vs 77 months, P = .003). On multivariate analysis stratified by transplant status, achievement of ≥VGPR after 2 cycles was not associated with improved PFS (hazard ratio [95% confidence interval]; transplant cohort, 1.1 [0.7-1.6]; nontransplant cohort, 1.2 [0.8-1.7]) or OS (transplant cohort, 1.6 [0.9-2.9]; nontransplant cohort, 1.5 [1.0-2.4]). Covariates in the model included high-risk cytogenetics, ISS stage III, triplet therapy, creatinine ≥2 mg/dL, light chain disease, and age. Although patients with high-risk disease are more likely to achieve early response, a rapid achievement of a deep response by itself does not affect long-term outcomes.

Detection of 13q14 Deletion by FISH Is Not Sufficient to Define a Group of Good Prognosis Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2332-2332
Author(s):  
Virginie Eclache ◽  
Vincent Levy ◽  
Fanny Baran-Marszak ◽  
Remi Letestu ◽  
Florence Cymbalista
Keyword(s):  
Prognostic Markers ◽  
Prognostic Significance ◽  
Genetic Alterations ◽  
Large Cohort ◽  
Fish Analysis ◽  
Prognostic Impact ◽  
Trisomy 12 ◽  
Conventional Cytogenetics ◽  
The Impact ◽  
13Q Deletion

Abstract Abstract 2332 Poster Board II-309 Deletion of a 13q14.3 region is by far the most common genomic alteration in CLL. In a large cohort of CLL patients, the presence of deletion 13q as sole anomaly detected by FISH was predominantly found in Binet stage A CLL and associated with a favorable outcome (Dohner et al., N Engl J Med 2000). Further studies have evidenced some heterogeneity among CLL cases with 13q deletion, such as the size of the clone carrying the deletion, the existence of mono versus biallelic deletions, and the presence of other concomitant genetic aberrations. Therefore, we aimed at analysing the impact of this heterogeneity on the prognostic value of 13q14 deletion (del13q) in CLL. Patients and methods In a cohort of 329 previously untreated newly diagnosed stage A CLL, we detected del13q by FISH in 172 patients (52%) using the D13S319 probe. Conventional cytogenetics was performed in the 105 cases with del13q followed in our institution. The other important prognostic markers ( ZAP70, IgVH, CD38, proliferation markers) and clinical progression were also available for all patients. Results We first studied the large cohort of stage A patients and found that deletion 13q had no prognostic impact on PFS. When considering more specifically the presence of deletion 13q as sole anomaly (n=143), PFS was not significantly different from that of patients with no aberration detected by FISH analysis (del 13q, del11q, del17p and trisomy 12) (n=98). Moreover, the distribution of prognostic factors (ZAP70, sTK, mutational status, CD38 expression, lymphocytosis) was not statistically different among these two groups. We aimed at deciphering further these del13q cases through analysis of the percentage of deleted cells, the presence of mono versus biallelic deletions, and the presence of additional aberrations as detected by FISH and conventional cytogenetics in the 105 del13q cases followed in our institution. The size of the del13q clone, as reflected by the percentage of del13q cells by FISH, was highly variable, ranged from 7 to 90 %, and had no prognostic significance on PFS. Monoallelic deletions were present in 77 cases, fully biallelic deletions in 9 cases, and concomitant bi and monoallelic deletions in 19 cases. The 9 cases with biallelic deletions had a significantly shorter PFS and were associated with other unfavorable prognostic markers. As biallelic deletions are most likely to represent progression from monoallelic cases, it is understandable that no clear prognostic impact was evidenced between cases with monoallelic deletions and with concomitant variable amount of bi and monoallelic deleted cells. Twenty cases (20 monoallelic and 6 biallelic) were further studied by array-CGH. Minimal deleted region (MDR) was included in all deletions but the size of the deletion was variable and in most cases much larger than MDR. Among the 6 bi allelic cases, one of the deletions was restricted to the MDR in all cases, pointing out to the importance of the level of miRNA expression. Additional aberrations were found in 44/105 del13q cases. In 17 patients, one or more alterations were detected by FISH techniques : del11q (n=8), trisomy 12 (n=8) or del17p (n=5). By conventional cytogenetic all these aberrations were also detected, as well as other rare ones in 16 additional cases, either isolated or associated in a complex karyotype in 5 cases. Presence of additional aberrations had a significant unfavourable impact on PFS, even when excluding del11q, del17p and tri12, and considering the non recurrent aberrations that were detected by conventional cytogenetics only. Conclusion Presence of 13q deletion should not be considered as a good prognostic marker by itself among stage A patients. Moreover, del13q cases are highly heterogeneous, and the presence of deletion 13q should not be interpreted without considering both alleles or the presence of concomitant genetic alterations. Disclosures: No relevant conflicts of interest to declare.

Age-related efficacy and safety of apalutamide (APA) plus ongoing androgen deprivation therapy (ADT) in subgroups of patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Post hoc analysis of SPARTAN.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5024-5024 ◽  
Author(s):  
Julie Nicole Graff ◽  
Matthew Raymond Smith ◽  
Fred Saad ◽  
Boris A. Hadaschik ◽  
Hiroji Uemura ◽  
...  
Keyword(s):  
High Risk ◽  
Safety Profile ◽  
Age Groups ◽  
Progression Free Survival ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Cox Models ◽  
Free Survival ◽  
Age Related ◽  
The Impact

5024 Background: SPARTAN, a randomized phase 3 placebo (PBO)-controlled study in pts with high-risk nmCRPC and PSA doubling time ≤ 10 mo, showed that, compared with PBO, addition of APA to ongoing ADT treatment (tx) prolonged metastasis-free survival (MFS) by > 2 y, reduced the risk of symptomatic progression by 55%, and increased second progression-free survival (PFS2), which is the time from randomization to disease progression on first subsequent anticancer tx, or death. The impact of APA in terms of benefit and safety profile was evaluated in pts aged < 65, 65-74, and ≥ 75 y. Methods: Pts with nmCRPC were randomized 2:1 to APA (240 mg QD) or PBO; ADT was continuous. APA effect was analyzed by Cox models and Kaplan-Meier methods across age subgroups. Results: Baseline characteristics among age groups were similar, although ECOG PS 1 vs 0 increased with age. MFS benefit with APA was highly significant for all age subgroups (Table). In pts ≥ 75 y, MFS risk with APA vs PBO was reduced by 59%; MFS risk was reduced by 86% and 76% for pts < 65 and 65-74 y, respectively. Risk of PFS2 with APA vs PBO was reduced across all age subgroups. PFS2 in pts < 65, 65-74, and ≥ 75 y: HR, 0.09 (p < 0.0001); HR, 0.56 (p = 0.0343); HR, 0.59 (p = 0.0092), respectively. Risk of symptomatic progression was lessened with APA vs PBO for all age subgroups (Table). There was a similar increase in incidence of tx-emergent adverse events (TEAE) with age in both tx arms that remained higher with APA. Incidence of grade 3/4 TEAE (≥ 75 vs < 65 y): APA, 50% vs 37%; PBO, 37% vs 28%. Conclusions: Pts in all age subgroups with high-risk nmCRPC had significant improvement in MFS with APA + ongoing ADT. The safety profile of APA was similar across age subgroups. Clinical trial information: NCT01946204. [Table: see text]

Tumor mutational burden (TMB) may be a promising predictive biomarker of response to PD-1/PD-L1 targeting in MSI-H colorectal cancer.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 43-43 ◽  
Author(s):  
Marwan Fakih ◽  
Jaideep Singh Sandhu ◽  
Ching Ouyang ◽  
Ethan Sokol ◽  
Jeffrey S. Ross ◽  
...  
Keyword(s):  
Clinical Investigation ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Large Data ◽  
Predictive Biomarker ◽  
Continuous Variable ◽  
Data Set ◽  
Cut Point ◽  
The Impact

43 Background: PD-1 targeting with pembrolizumab or nivolumab leads to durable clinical benefits in patients (pts) with microsatellite instability-high (MSI-H) tumors. However, 30-35% of mCRC pts with MSI-H tumors will experience progressive disease (PD) as a best response when treated with anti-PD1 agents, highlighting the need of additional predictive biomarkers. Methods: We performed a retrospective multi-center clinical investigation to evaluate the impact of TMB, age, gender, stage at initial presentation, pattern of metastatic disease, tumor grade, and RAS/RAF status on response to anti-PD1/PD-L1 in MSI-H mCRC. TMB and MSI status were determined by hybrid capture-based next-generation sequencing (Foundation Medicine [FM]). The TMB distribution in MSI-H CRC was estimated from a large data set from FM. Results: 22 eligible MSI-H mCRC pts were identified across 5 cancer centers: 19 pts received pembrolizumab, 1 pt received nivolumab, 1 pt received nivolumab + ipilimumab, and 1 pt received durvalumab + tremelimumab. Among tested variables, TMB (as a continuous variable) showed the strongest association with an objective response (OR; p < 0.001). Also, both univariate and multivariate analyses supported that TMB serves as an independent prognostic variable in predicting progression-free survival (PFS; p < 0.001 and p < 0.01, respectively). Using log-rank statistics, the optimal predictive cut-point for TMB was estimated between 37-41 mutations/Mb to dichotomize pts into TMBhigh and TMBlow groups. All 13 pts (100%) with TMBhigh had an OR, while only 2/9 (22%) pts with TMBlow had an OR and 6/9 had PD. The median PFS for TMBhigh pts has not been reached (no progressors, median follow-up > 18 mos), while the median PFS for TMBlow pts was 2 mos. Amongst 821 MSI-H CRC cases tested at FM, the 25th, 35th, 50th and 75th percentile TMB cutoffs were 33.1, 37.4, 46.1, and 61.8 mutations/Mb, respectively. Our optimal TMB cut-point range suggests that MSI-H mCRC with the lowest 35th percentile of TMB have a low likelihood of benefit from anti-PD1. Conclusions: These TMB findings require validation in prospective trials and may guide the sequencing of PD-1 inhibitor monotherapy in MSI-H mCRC.

scholarly journals AL Amyloidosis: The Effect of Maintenance Therapy on Autologous Stem Cell Transplantation Outcomes

2020 ◽  
Vol 9 (11) ◽  
pp. 3778
Author(s):  
Michael Ozga ◽  
Qiuhong Zhao ◽  
Don Benson ◽  
Patrick Elder ◽  
Nita Williams ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Maintenance Therapy ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Prognostic Significance ◽  
Al Amyloidosis ◽  
Effective Treatment Option ◽  
Significant Difference ◽  
The Impact

Background: Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic light chain (AL) amyloidosis. While maintenance post ASCT in multiple myeloma is now standard, the decision to utilize maintenance in AL amyloidosis remains largely unexplored. The present study aims to determine the prognostic significance of utilizing maintenance therapy following ASCT and assess the impact of fluorescent in situ hybridization (FISH) abnormalities, bone marrow plasma cell burden (BMPC), and degree of organ involvement on this decision. Methods and results: This is a retrospective analysis of fifty AL amyloidosis patients who underwent ASCT at The Ohio State University. Twenty-eight patients received maintenance and twenty-two did not. Kaplan–Meier survival analysis was used to compare the effect of maintenance therapy with no significant difference in PFS (p = 0.66) and OS (p = 0.32) between the two groups. There was no difference in survival based on maintenance when further categorized by FISH, PFS (p = 0.15), and OS (p = 0.65); BMPC ≥ 10%, PFS (p = 0.49), and OS (p = 0.32); or with 2 or more organs involved, PFS (p = 0.34) and OS (p = 0.80). Conclusion: Maintenance therapy post ASCT did not impact PFS or OS when categorized by FISH abnormalities, increasing BMPC, or ≥2 organs involved in AL amyloidosis patients.

The impact of FLIPI on outcome of frontline treatment with single-agent I-131 tositumomab for follicular lymphoma (FL)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7509-7509 ◽  
Author(s):  
M. S. Kaminski ◽  
D. Hamstra ◽  
J. Estes ◽  
R. Wahl
Keyword(s):  
High Risk ◽  
Bone Marrow Involvement ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Intermediate Risk ◽  
Frontline Treatment ◽  
Baseline Variable ◽  
The Impact

7509 Background: The FLIPI is potentially useful in predicting clinical outcome and comparing treatment results among clinical studies in FL. We recently reported the results of I-131 tositumomab as frontline treatment in 76 pts with advanced-stage FL (NEJM 325:441, 2005). A single 1-week course resulted in a 95% and a 75% overall and complete response (CR) rate, respectively, and at a median follow-up of 5.1 years median progression-free survival (PFS) was 6.1 yrs. In multivariate analyses, bone marrow involvement was the only baseline variable that had a significant effect on PFS. Methods: To evaluate whether baseline FLIPI scores in this study could predict outcome and to compare this pt population with that in other frontline studies, the records of all 76 patients were reviewed. Results: FLIPI scores were available for 74 of the 76 pts: 11 pts (15%) low risk, 37 (50%) intermediate risk, and 26 (35%) high risk. CR rates for each risk group were 82%, 73%, and 73%, respectively. 5-yr PFS were 63% (35–92%, 95% CI), 63% (47–78%), and 52% (33–71%), respectively, p = 0.322. Grouping low + intermediate risk vs. high for PFS: p = 0.134. 5-yr overall survival (OS) rates were 100%, 95% (87–100%), 78% (62– 93%), respectively, p = 0.072, but grouping low + intermediate risk vs. high p = 0.028. A comparison to other frontline studies is below. Conclusions: The FLIPI did not predict for PFS or OS in FL pts treated with single-agent I-131 Tositumomab. However, an OS difference was seen when low + intermediate risk pts were grouped and compared with high risk pts. The distribution of FLIPI scores amongst pts in this study is similar to that observed in other front-line FL studies. Further studies exploring single-agent radioimmunotherapy vs. chemo/radioimmunotherapy combinations are warranted. [Table: see text] [Table: see text]

Liver metastases (LM) to predict for short overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4655-4655 ◽  
Author(s):  
William Kevin Kelly ◽  
Susan Halabi ◽  
Michael Anthony Carducci ◽  
Daniel J. George ◽  
John Francis Mahoney ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Data Set

4655 Background: Patients withCRPC with LM represent a subset of patients with a poor prognosis. An exploratory analysis was performed to evaluate the difference in baseline characteristics and clinical outcomes in patients with and without LM from a randomized phase III trial (CALGB 90401) in men with mCRPC. Methods: Data from 1,050 men treated with docetaxel, prednisone with either bevacizumab or placebo were used. Pts were chemotherapy naïve, and had evidence of progressive mCRPC despite castrate testosterone levels and anti-androgen withdrawal, ECOG performance status ≤ 2, and adequate bone marrow, hepatic and renal functions. The proportional hazards model was used to assess the prognostic significance of LM in predicting OS and progression free survival (PFS) adjusting for stratification factors. Results: Fifty-nine (5.6%) of the 1045 pts with a complete data set had documented LM. Patients with LM had higher baseline alkaline phosphatase (ALK, 167 vs 117 U/L, p =0.0205) and lactate dehydrogenase (LDH, 262 vs 205 U/L, p =0.0001) compared to patients without LM. There were strong associations between LM status and lung metastasis (p=0.0004) and other visceral disease (p=<0.001) but not with bone disease. Clinical outcomes as a function of LM status are listed in the table. The median OS time in LM pts was 14.4 compared to 22.6 months, with a hazard ratio (HR) 1.4. The HR for treatment effect (DP+B vs. DP) for LM was not statistically significant for either group. Conclusions: Compared to pts without LM, mCRPC with LM are characterized by higher LDH and ALK and have a poor OS despite having similar PFS and objectivebiochemical response to docetaxel based therapy. [Table: see text]

Maintenance therapy with bevacizumab with or without erlotinib in metastatic colorectal cancer (mCRC) according to KRAS: Results of the GERCOR DREAM phase III trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3515-3515 ◽  
Author(s):  
Christophe Tournigand ◽  
Benoist Chibaudel ◽  
Benoit Samson ◽  
Werner Scheithauer ◽  
Gérard Lledo ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Phase Iii Trial ◽  
Kras Status ◽  
Secondary Endpoints ◽  
The Impact ◽  
Egfr Tki

3515 Background: The primary analysis of DREAM demonstrated that a maintenance therapy (MT) with bevacizumab (Bev) + EGFR TKI erlotinib (E) significantly improved progression-free survival (PFS) after a 1st-line Bev-based induction therapy (IT) in patients (pts) with unresectable mCRC. Methods: Pts were randomized to MT after an IT with FOLFOX-bev or XELOX-bev or FOLFIRI-bev between Bev alone (Bev 7.5 mg/kg q3w; arm A) or Bev+E (Bev 7.5 mg/kg q3w, E 150 mg/d ; arm B) until PD or unacceptable toxicity. Primary endpoint was PFS on MT. Secondary endpoints included PFS from inclusion, overall survival (OS) and safety. The impact of KRAS tumor status on treatment efficacy was evaluated in an exploratory analysis. Results: 700 pts were registered and 452 pts were randomized (228 in arm A, 224 in arm B). KRAS status was available for 413/452 (91%) pts. The median duration of MT was 3.6 m. Results for MT are presented below (Table). In the registered population, median OS was 24.9m (22.5 – 27.3). Conclusions: Maintenance treatment with bev + erlotinib increases PFS over maintenance with bev alone in pts with mCRC but does not prolong OS. Further follow-up will determine the impact of 2nd or 3rd line anti-EGFR Mabs in this study. Contrasting with anti-EGFR Mabs, KRAS tumor status is not mandatory to select pts with mCRC for treatment with erlotinib. Clinical trial information: NCT00265824. [Table: see text]

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