scholarly journals Bone Marrow Involvement Detected By Multi-Parameter Flow Cytometry Predicts Poor Outcome after Autologous Stem Cell Transplantation for Peripheral T-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1972-1972
Author(s):  
Jordan Gauthier ◽  
Leona Holmberg ◽  
David Wu ◽  
William I. Bensinger ◽  
Ajay K. Gopal ◽  
...  

Abstract BACKGROUND: Peripheral T-cell lymphomas (PTCL) encompass a heterogeneous group of neoplasms accounting for 10 to 15% of non-Hodgkin lymphomas worldwide. Prognosis for PTCL patients is poor and consolidation in first remission with autologous stem cell transplantation (ASCT) is widely used. Most patients though still relapse after transplant. We hypothesized that pre-ASCT bone marrow (BM) involvement detected by multi-parameter flow cytometry (FC) would identify patients with inferior outcome after ASCT. METHODS: We retrospectively analyzed the outcome of 29 consecutive PTCL patients who underwent ASCT at the Fred Hutchinson Cancer Research Center from April 2004 through July 2014. Pre-ASCT BM involvement by flow cytometry (FC) was defined as the presence of an abnormal T-cell population detected by multi-parameter FC analysis in a BM aspirate obtained within 30 days prior to ASCT. An abnormal T-cell population accounting for a percentage equal or greater than 0.01% of total leukocytes after red blood cell lysis was considered significant. RESULTS: Ten patients (34%) with angioimmunoblastic T cell lymphoma (AITCL), 8 (27%) with ALK-negative anaplastic large cell lymphoma (ALCL), 8 (27%) with peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) and 3 (12%) with other PTCL sub-types were included. Median age at transplant was 54 (range: 29-71). Twenty patients (76%) presented at ASCT in complete remission (CR) per 1999 Cheson criteria and 9 (31%) were in first CR (CR1). Fifteen patients (50%) underwent ASCT upfront. Pre-ASCT BM involvement was detected by FC analysis in 7 patients (24%, 3 patients with AITCL, 1 patient with ALCL and 3 patients with PTCL-NOS) and by morphology in 2 patients (7%, 2 patients with AITCL). The 7 patients with pre-ASCT BM involvement detected by FC experienced a significantly higher 4-year cumulative incidence of relapse (CIR) (85% versus 36%, p < 0.001) and lower overall survival (OS) (19% versus 89%, p < 0.001) with a median follow-up of 51 months. These findings were confirmed in multivariable analysis for CIR (HR = 7.37, CI = 1.14 - 47.61, p = 0.03) and OS (HR = 7.04, CI = 1.29 - 38, p = 0.024). The IPI score, absence or presence of CR1 and the number of prior therapies were included in a multivariable model for CIR, while age and the IPI score at diagnosis were taken into account for OS. ASCT performed in CR1 was associated with lower CIR (HR = 0.11, CI = 0.03-0.041, p < 0.001). Histologic subtypes did not impact CIR (p = 0.97) nor OS (p = 0.91) and they did not significantly differ between the groups with and without pre-ASCT BM involvement detected by FC (p = 0.60) after applying Fisher's exact test. Further analysis of the 22 patients presenting in CR at ASCT revealed that in this subgroup, pre-ASCT BM involvement by FC (n = 4) was also associated with higher CIR (75% versus 32%, p = 0.002) and lower OS (25 versus 94%, p <0.001). The prognostic impact of pre-ASCT BM involvement by FC persisted in multivariable analysis for CIR (HR = 16, CI = 1.11-228.70, p = 0.042, IPI score at diagnosis and number of prior therapies considered as covariables) but not for OS (HR = 0.15, CI = 0.65-65.40, p = 0.10, multivariable model including age and the IPI score at diagnosis). CONCLUSION: Pre-ASCT BM involvement by FC correlated with dramatically higher relapse rates and an inferior OS in PTCL patients after ASCT. Furthermore, we demonstrate that residual disease, detected only in patients meeting Cheson 1999 criteria for CR at ASCT is capable of predicting a higher risk for relapse. These findings should encourage further evaluation of minimal residual disease in PTCL patients achieving complete remission as defined per Cheson 1999 and 2007 criteria. Figure 1. Cumulative incidence of relapse Figure 1. Cumulative incidence of relapse Figure 2. Overall survival Figure 2. Overall survival Disclosures Gopal: Merck: Research Funding; Emergent/Abbott: Research Funding; Cephalon/Teva: Research Funding; BioMarin: Research Funding; Sanofi-Aventis: Honoraria; Millenium: Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Piramal: Research Funding; Biogen Idec, BMS: Research Funding. Maloney:Juno Therapeutics: Research Funding; Roche/Genentech: Honoraria; Janssen Scientific Affairs: Honoraria; Seattle Genetics: Honoraria. Till:Roche-Genentech: Research Funding.

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5363-5363
Author(s):  
Brady E. Beltrán ◽  
Denisse A. Castro ◽  
Yesenia M. Huerta- Collado ◽  
Eduardo Sotomayor ◽  
Jorge J. Castillo

Abstract Introduction: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) accounts for 15-20% of NHL and is characterized by a poor survival. The IPI and PIT scores are prognostic factors in survival in B-cell and T-cell lymphomas, but not without limitations. The aim of this study is to evaluate the prognostic value of the NCCN-IPI score in patients with PTCL-NOS. Methods: We included patients with a pathological diagnosis of PTCL-NOS who were diagnosed and treated at our institution between 1997 and 2017. IRB approval was obtained prior to research. Pathological samples were reviewed by hematopathologists at our institution to confirm the diagnosis. Pertinent clinicopathological data were collected through chart review and are presented using descriptive statistics. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazard regression models were fitted to evaluate hazard ratios (HR) for overall survival (OS). Results: A total of 173 patients with diagnosis of PTCL-NOS were included in this analysis. The median age at diagnosis was 58 years (range 18-91 years) with a male predominance (58%). Clinically, 47% of patients were 60 or older, 52% presented with ECOG >1, 82% had elevated serum LDH, 74% had extranodal disease, and 34% had stage I/II and 66% had stage III/IV. IPI score distribution was low-risk in 55% of patients, low-intermediate in 36%, high-intermediate in 48% and high-risk in 33%. PIT score distribution was low-risk in 53%, low-intermediate in 67%, high-intermediate in 38% and high-risk in 14%. NCCN-IPI score distribution was low risk in 40%, low-intermediate in 56%, high- intermediate in 63% and high risk in 11%. 22% of patients received CHOEP, 23% received CHOP, and 55% received other regimens. The overall response rate was 59%; 47% had a complete response and 12% had a partial response. The 5-year overall survival (OS) rate was 32% with a median OS of 12 months. PTCL-NOS patients with low, low-intermediate, high-intermediate and high-risk NCCN-IPI had 5-year OS rates of 46%, 36%, 26% and 0%, respectively (p<0.001). When compared with patients with low-risk NCCN-IPI, patients with low-intermediate (HR 3.2, 95% CI,1.1-9.5; p=0.044) and high-intermediate /high risk NCCN-IPI (HR 6.0, 95% CI 2.1-17; p=0.001) had worse OS. Conclusions: We have validated the NCCN-IPI score as a prognostic tool in patients with PTCL-NOS. This work can serve to address future prospective designs that allow selection of groups of patients at greater risk and thus lead to more individualized therapy. Figure. Figure. Disclosures Castillo: Janssen: Consultancy, Research Funding; Genentech: Consultancy; Abbvie: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Millennium: Research Funding; Beigene: Consultancy, Research Funding.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5364-5364
Author(s):  
Brady E. Beltrán ◽  
Denisse A. Castro ◽  
Yesenia M. Huerta- Collado ◽  
Eduardo Sotomayor ◽  
Jorge J. Castillo

Abstract Introduction: Red blood cell distribution width (RDW) has emerged as a potential prognostic factor in solid tumors and lymphomas. Previous studies have shown an association between increased levels of RDW and inflammatory diseases, being a surrogate marker of inflammation and a predictor of poor outcome. Data on the impact of RDW in outcomes of patients with aggressive peripheral T-cell lymphoma (PTCL) are scarce. Methods: We performed a retrospective study on consecutive patients with a de novo diagnosis of aggressive PTCL diagnosed and treated at our institution between 2010 to 2016. All patients included were treated with chemotherapy with a curative intent. The RDW was collected from the hemogram of PTCL patients at diagnosis. RDW-CV >14% and RDW-SD >49 fL were our cut-offs for the categorical analysis. We fitted univariate and multivariate Cox proportional hazard regression models for overall survival (OS). P<0.05 were considered statistically significant. Results: A total of 101 patients with de novo aggressive PTCL were included. This study included 53 patients (52%) with PTCL, not otherwise specified, 16 patients (16%) with extranodal natural killer/T-cell lymphoma,15 (15%) with adult T-cell lymphoma/leukemia,14 patients (14%) with anaplastic large cell lymphoma, 2 patients (2%) with angioimmunoblastic T-cell lymphoma, and 1 patient (1%) with enteropathy-associated T-cell lymphoma. Median age was 57 with a male predominance (69%). Clinically, 45 patients (45%) were 60 years or older, 41 patients (34%) had ECOG ≥2, 63 patients (65%) had increased LDH levels, 68 patients (67%) had > 1 extranodal site, 65 patients (64%) had stage III/IV disease, and 55 patients (54%) had B symptoms. RDW-CV was >14% in 64 patients (64%). RDW-SD was >49 fL in 35 patients (35%). 38% of patients received CHOEP, 29% received CHOP, and 33% received other regimens. The overall response rate was 68%; 50% had a complete response and 18% had a partial response. At 5 years, median overall survival (OS) was 46%. In the univariate Cox regression analysis, ECOG ≥2 (p<0.001), high RDW-CV >14% (p<0.001), high RDW-SD >49 fL (p=0.007) and high neutrophil-lymphocyte ratio (NLR >4) (p=0.002) were associated with a worse survival. In the multivariate Cox regression analyses, ECOG ≥2 (HR 3.1 CI 1.6-6.0; p=0.001) and high RDW-CV >14% (HR 2.7, 95% CI 1.2-6.0; p=0.01) were independent predictors of poor survival. RDW-CV was an independent factor of survival when was compared with IPI and NCCN-IPI score. Conclusions: RDW is an independent marker for adverse prognosis in aggressive patients with aggressive PTCL treated with curative intent. Figure. Figure. Disclosures Castillo: Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Millennium: Research Funding.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Monica Mead ◽  
Henrik Cederleuf ◽  
Thomas Relander ◽  
Mats Jerkeman ◽  
Fredrik Ellin ◽  
...  

Background: Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphoid neoplasms with poor outcomes. Many patients are elderly with increased comorbidities. Single-center retrospective studies describe outcomes in elderly PTCL patients and suggest comorbidity adversely affects outcomes. Little is known about the treatment, outcomes and impact of comorbidity in a large cohort of elderly PTCL patients. This study aims to describe outcomes of elderly PTCL patients in a large unselected international patient cohort. Methods: Patients with PTCL age ≥ 70 diagnosed from January 1, 2010 - December 31, 2015 in the Swedish Lymphoma Registry (SLR) and California Cancer Registry (CCR) were identified. The SLR covers ~ 95% of adult lymphoma patients in Sweden and the CCR includes information on all cancers diagnosed in California. Patients with precursor T-cell malignancies, primary cutaneous lymphomas, and leukemic subtypes were excluded. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI) and clinical outcomes of the cohort were extracted. Statistical analysis: Patient characteristics, clinical variables and outcomes were summarized using descriptive statistics and compared by Chi-square or Fisher's exact test. Outcomes of interest included overall survival (OS) and cause of death. Kaplan-Meier estimates of OS stratified by groups were calculated and presented in figures. Median OS was reported with 95% confidence interval (CI). Comparisons between groups for OS were done by log-rank test. Univariate and multiple Cox proportional hazards models provided hazards ratio estimates and 95% CI for risk factors. Tests for significance were two-tailed and a p-value less than the 0.05 significance level was considered statistically significant. Analyses were performed using software SAS version 9.4 (2013). Results: A total of 839 patients were included (SLR, n = 176, CCR, n = 663). Median age was 78 (SLR) and 79 (CCR) years, respectively. Included subtypes were AITL, n = 226; ALCL, n = 122; EATL, n = 31; Hepatosplenic TCL, n = 7; NK/T-cell lymphoma, n = 10; and PTCL NOS, n = 443. ECOG performance status was not available. CCI data was available in 731 patients (87 %), and CCI scores were divided into groups = 0-1 (61 %) and CCI &gt; 1 (39 %). Male patients more often had a CCI score &gt; 1 (p = 0.024). No other significant baseline differences were seen between the 2 groups (Table 1). Patients in the SLR more often received multiagent treatment compared to the CCR (63 % vs 44 %, p &lt; 0.001). Age &gt; 80 years, CCI &gt; 1 and advanced Ann Arbor stage (III-IV) were significant prognostic factors for worse outcome. No difference in survival was seen between men and women nor the SLR and CCR (Table 2). Patients with a CCI &gt;1 had a statistically significant worse survival compared to patients with a CCI =0-1 (0.36 years v 0.91 years, p=0.0001). Of the PTCL subtypes, AITL patients had a significantly better outcome (median OS = 1.26 years) compared to ALCL (OS = 0.57 years) and PTCL NOS (OS = 0.66 years). Patients receiving multiagent therapy had improved survival compared to patients not receiving multiagent therapy. When comparing OS in patients diagnosed in 2010-2012 with 2013-2015, no improvement was seen for the later period (Figures 1-4). Lymphoma was the most common cause of death with &gt; 70 % of deaths related to lymphoma irrespective of CCI score (Table 3). Discussion: At the time of submission, this study presents the largest international cohort of elderly patients with PTCL. Prognosis is poor and comorbidity seems to further worsen . In contrast to younger patient series, patients with AITL had a better survival than patients with PTCL NOS and ALCL, and were more common in the CCR than in the SLR. Multiagent treatment was associated with improved outcome. A possible confounder could be that fit patients are also the ones receiving treatment, and it is a setback that adjustment for ECOG was not possible, making treatment data somewhat difficult to interpret. As expected, advanced stage (Ann Arbor III-IV) was associated with worse survival. Conclusion: We believe this is one of the largest cohorts presented in elderly patients with PTCL. Comorbidity is an important adverse factor in this group, whereas treatment seems to improve outcome. The majority of these patients die of lymphoma within a year from diagnosis, and development of new treatments represents an unmet clinical need. Disclosures Jerkeman: Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Roche: Research Funding.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1614-1614 ◽  
Author(s):  
Francine M. Foss ◽  
Kenneth R. Carson ◽  
Lauren Pinter-Brown ◽  
Steven M. Horwitz ◽  
Steven T. Rosen ◽  
...  

Abstract 1614 Background: Registries can be invaluable for describing patterns of care for a population of patients. COMPLETE is a registry of peripheral T-cell lymphoma (PTCL) patients designed to identify the lymphoma-directed treatments and supportive care measures that PTCL patients receive. We report here the first detailed findings of initial therapy. Methods: This is a prospective, longitudinal, observational registry that is led by a global steering committee. Patients with newly diagnosed PTCL and providing written informed consent are eligible. Patients are entered into the registry from time of initial diagnosis and followed for up to 5 years. Only locked records are reported. Results: As of July 2012, 330 patients have been enrolled from the United States. The first patient was enrolled in February 2010. Locked baseline and treatment records are available for 124 and 81 patients, respectively. Of the 124 patients with locked baseline records, 67 patients (54%) were male, the mean age was 59 (range: 19–89), and race/ethnicity was recorded as: White (87 patients; 70%), Black (19; 15%), Asian (5; 4%) and other/unknown (13; 11%). Histology was reported as follows: PTCL-not otherwise specified (27%), anaplastic large cell lymphoma-primary systemic type (18%), angioimmunoblastic T-cell lymphoma (17%), transformed mycosis fungoides (7%), T/NK-cell lymphoma-nasal and nasal type (6%), adult T-cell leukemia/lymphoma, HTLV 1+ (6%) and other (19%). 25 patients (20%) had received another diagnosis, including B-cell lymphoma, Hodgkin's disease and other T-cell lymphomas, prior to their current diagnosis of PTCL. 49 patients (40%) had B symptoms, 102 patients (82%) had an Ann Arbor stage of III/IV, 116 patients (94%) had ECOG performance status of 0–1, and international prognostic index (IPI) score was distributed as follows: IPI 0 (7% of patients), 1 (15%), 2 (43%), 3 (26%), and 4 (9%). Of the 81 patients with locked treatment records, details on initial treatment can be found in table below. Conclusions: This first detailed analysis of primary treatment of PTCL indicates that this disease is still largely being treated with regimens derived primarily from studies of B-cell lymphomas and that a single standard of care does not exist. The fact that a meaningful proportion of patients were initially diagnosed with something other than their current diagnosis of PTCL points out the challenges of diagnosing the disease. While the intent of initial treatment for most patients is to affect a cure, more than 20% of patients were noted as deceased at the end of initial treatment, underscoring the need for more effective, disease-specific therapy. Disclosures: Foss: Merck: Study Grant, Study Grant Other; Celgene: Study Grant, Study Grant Other; Eisai: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; Allos: Consultancy. Carson:Allos: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Pinter-Brown:Allos: Consultancy, Membership on an entity's Board of Directors or advisory committees. Horwitz:Allos: Consultancy, Research Funding. Rosen:Allos: Consultancy, Honoraria. Pro:Celgene: Honoraria, Research Funding; Spectrum: Honoraria; Allos: Honoraria; Seattle Genetics: Research Funding. Gisselbrecht:Allos: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hsi:Allos: Research Funding; Eli Lilly: Research Funding; Abbott: Research Funding; Cellerant Therapeutics: Research Funding; BD Biosciences: Research Funding; Millenium: Research Funding.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1608-1608
Author(s):  
Brady E Beltran ◽  
Erick Cotacallapa ◽  
Jorge J Castillo

Abstract Abstract 1608 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous family of entities with a worse prognosis, stage by stage, than their B-cell counterparts. We have previously reported that an absolute lymphocyte count (ALC) <1000/uL is associated with a worse prognosis in Peruvian patients with PTCL (Castillo et al. 2010). The goal of this study is to investigate the prognostic value of absolute monocyte count (AMC) in the survival of patients with PTCL. Methods: A total of 251 cases of aggressive, non-primary cutaneous PTCL diagnosed at our institution between January 1997 and January 2012 were reviewed, reevaluated according to their morphological, immunological and clinical characteristics, and reclassified according to the 2008 WHO classification of lymphoid neoplasms. Characteristics will be presented descriptively. Kaplan-Meier method was used to estimate overall survival (OS) curves, which were compared using the log-rank test. The multivariate analysis was performed using the Cox proportional-hazard regression test. Results: According to the new WHO classification of lymphoid neoplasms, 104 cases (41%) were classified as adult T-cell leukemia/lymphoma (ATLL), 103 cases (41%) as PTCL, unspecified (PTCLU), 27 cases (11%) as analplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), 11 cases (4%) as extranodal NK/T-cell lymphoma (NKTCL), nasal type, 4 cases (2%) as angioimmunoblastic lymphoma (AIL), and 2 cases (1%) were diagnosed with ALK+ ALCL. The median age at diagnosis was 57 years (range 14–92 years); 47% of patients were >60 years. The male-to-female ratio was 1:1. ECOG performance status >1 was seen in 51%, LDH was elevated in 67%, advanced stage was seen in 73%, and >1 extranodal sites were seen in 22% of the patients. Bone marrow involvement was reported in 30% and B symptoms in 64% of patients. An International Prognostic Index (IPI) score 3–5 was seen in 55%, and a Prognostic Index for PTCLU (PIT) score of 2–4 in 63%. The median overall survival (OS) for the whole group was 10 months. The IPI score, the PIT score, ALC <1000/uL and AMC >800/uL (Figure) showed statistical significance in the univariate survival analysis (p<0.001, p<0.001, p=0.001 and p=0.001, respectively). In the multivariate analysis, PIT score and AMC >800/uL showed statistical significance (p=0.006, p=0.046, respectively). Conclusions: Monocytosis, defined as AMC >800/uL, and the PIT score were independent prognostic factors for OS in patients with aggressive, non-primary cutaneous PTCL. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1706-1706
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Marianne Castro Goncalves ◽  
Rodrigo Santucci ◽  
Renata Oliveira Costa ◽  
Debora Levy ◽  
...  

Abstract Background: Peripheral T-cell lymphoma (PTCL) are a biologically and clinically heterogeneous group of rare diseases arising from mature or activated post-thymic T lymphocytes. Correspond to 10% to 15% of lymphoid malignancies with marked geographical variation in incidence. According to the WHO classification they are divided into nodal, extranodal, primary cutaneous and leukemic or disseminated and encompass 18 distinct entities. The nodal group involves the peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic lymphoma (AITL), anaplastic large cell lymphoma ALK positive (ALCL-ALK+) and anaplastic large cell lymphoma ALK negative (ALCL-ALK-). The literature of PTCL is scarce, especially in our country where data of epidemiology, clinical features and outcomes are usually rarely available. So, to better understand PTCL we performed a retrospective study with patients treated in a reference service for cancer treatment in Brazil. Methods: Eight-seven nodal PTCL patients treated with anthracyclne-based regimen (CHOP or, CHOEP) from January 2000 to June 2014 were evaluated retrospectively at the Medicine School of Sao Paulo University, Brazil. All patients lower than 60 years were consolidated with autologous hematopoietic stem cell transplantation (ASCT) in first CR or PR except that with ALCL-ALK+ diagnosis. Refractory and relapsed patients were salvaged with 3-4 cycles of IVAC (Ifosphamide 1.5 g/m2 i.v D1-D5, etoposide 100mg/m2 i.v D1-D5, aracytin 2g/m2 i.v twice a day D1-D2) regimen and submitted to ASCT. It was performed a central histopathological review and clinical and epidemiological data were obtained from medical records. Patients were evaluated for overall response (OR) including complete response (CR) and partial response (PR), overall survival (OS) and progression free survival (PFS). Statistical analysis was performed using the STATA-3 program using and a p-value ≤ 0.05 was considered statistically significant. Results: Of the 87 patients, 34 (39.08%) cases were classified as ALCL-ALK-, 27 (31.03%) as PTCL-NOS, 16 (18.39%) as ALCL-ALK+, 6 (6.89%) as AITL and in 4 (4.1%) cases the diagnosis could not be performed and an expansion of the immunohistochemical is ongoing. Thirty-six (45.38%) cases were female and 51(54.62%) were male, 59(67.81%) patients were lower than 60 years. Seventy-six (87.35%) patients presented in advanced stage (III or IV) at diagnosis but 73(83.90%) patients presented an ECOG < 2 and 14(16.10%) ≥ 2. Eighteen (20.70%) patients were of low-risk, 26 (29.88%) of low-intermediate risk and 43(49.42%) of high-intermediate and high-risk of international prognostic index (IPI). The CR and PR was obtained for 44(50.57%) and 8(9.19%), respectively with 59.76% OR. Thirty (34.48%) patients were primary refractory and five remain under treatment. In a median of follow of 30 months, ALCL-ALK+ show higher OS (median 140.98 months) than ALCL-ALK- (44.20 months), PTCL-NOS (median 20.62 months) and AITL (median 7.24 months) (p=0.41) (Figure 1A). The median of PFS was 3.84 months for AITL, 23.44 months for ALCL-ALK+, 40.03 months for PTCL-NOS and was not yet reached for ALCL-ALK- (p=0.0006) (Figure 1B). Figure 1: Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 1:. Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 2 Figure 2. Conclusion: In this study we showed that ALCL-ALK+ as well as found in the literature presented a better OS in comparison to others nodal T-cell lymphoma as AITL, PTCL-NOS and ALCL-ALK-. Surprisingly the PFS of ALCL-ALK+ was statistically significant lower than of ALCL-ALK-. We thought that this result may be explained because in our service until to perform this analysis we did not indicate ASCT in first CR for ALCL-ALK+, but for all ALCL-ALK-. This hypothesis may be reinforced as the most of our cases presented high-intermediate and high-risk of IPI and that could equalize the favorable effect of ALK expression. In addition, we changed our approach and we are also indicating ASCT in first line for patients with ALCL-ALK+ with intermediate-high and high-risk of IPI . Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1501-1501
Author(s):  
Matthew J Maurer ◽  
Fredrik Ellin ◽  
James Cerhan ◽  
Stephen Ansell ◽  
Brian K Link ◽  
...  

Abstract Background: Peripheral T-Cell lymphomas (PTCLs) constitute approximately 10% of lymphoid malignancies and consist of several distinct entities based on pathologic and clinical characteristics. With the exception of a few subtypes (e.g., ALK-positive anaplastic large cell lymphoma (ALCL) and some primary cutaneous or leukemic forms of PTCL), a majority of PTCLs are aggressive as characterized by poor treatment response, rapid disease progression and poor overall survival. We have shown that landmark timepoints of event-free survival after diagnosis can stratify subsequent overall survival (OS) in diffuse large B-cell and follicular lymphoma. Here we evaluate this approach in newly diagnosed aggressive PTCLs treated with anthracyline-based or related chemotherapy. Methods. Newly diagnosed PTCL patients were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002-2012. Clinical data were abstracted from medical records using a standard protocol. For this analysis, we included patients receiving anthracycline-based or other multiagent chemotherapy for the following PTCL subtypes: ALK-negative ALCL (N=24); angioimmunoblastic T-cell lymphoma (AITL, N=34); PTCL, not otherwise specified (NOS; N=60); enteropathy-associated T-cell lymphoma (EATL, N=8); extranodal NK/T-cell lymphoma, nasal type (ENKTL, N=11); and hepatosplenic T-cell lymphoma (HSTCL, N=1). Patients were prospectively followed, and event-free survival (EFS) was defined as time from diagnosis to progression, re-treatment, or death due to any cause. Landmark EFS timepoints were assessed at 12 (EFS12) and 24 (EFS24) months after the date of diagnosis. Subsequent OS was defined as time from a specific endpoint (diagnosis, event or EFS landmark). Replication was performed in a population-based cohort of T-cell lymphomas diagnosed from 2000-2009 from the Swedish Lymphoma Registry. Results. 138 eligible patients were enrolled in the MER from 2002-2012, the median age at diagnosis was 58 years (range, 19-88), 66% were male, 73% had Stage III-IV disease, and 33% had IPI 0-1. At a median follow-up of 47 months (range 11-120), 87 patients (63%) had an event and 70 patients (51%) had died. From diagnosis, only 60 patients were event-free at 12 months (EFS12 45%). Patients who failed to achieve EFS12 had a poor subsequent OS from event (median OS = 6.8 months, 95% CI: 5.3-14.0, figure 1). In contrast, patients who achieved EFS12 had a favorable subsequent OS (median unreached, figure 2). Of the 427 eligible patients in the Swedish registry, the median age at diagnosis was 66 years (range, 18-88), 63% were male, 68% had Stage III-IV disease, and 25% had IPI 0-1. PTCL subtypes were: ALK-negative ALCL (N=89); AITL (N=80); PTCL, NOS (N=183); EATL (N=44); ENKTL (N=24); and HSTCL (N=7). At a median follow-up of 86 months (range 40-158), 333 patients (79%) had an event and 316 patients (74%) had died. From diagnosis, 183 patients were event-free at 12 months (EFS12 44%). Similar to the MER cohort, Swedish patients failing EFS12 had poor subsequent survival (median OS = 3.7 months, 95% CI: 2.9-5.3, figure 1). Swedish patients achieving EFS12 had a favorable subsequent OS (median OS = 89 months, figure 2). Similar results were obtained when conducting landmark analysis at 24 months after diagnosis (EFS24). Conclusion. Relapse and re-treatment events within the first 12 months of diagnosis are associated with very poor OS in PTCL treated with anthracyclines or related chemotherapy, while patients achieving EFS12 have encouraging subsequent OS. Stratifying patients into prognostically distinct subsets using EFS12 may help focus biologic and biomarker studies. EFS12 has potential as an early endpoint for studies of newly diagnosed PTCL. Further investigation of determinants related to post-EFS12 survival is needed. Disclosures Maurer: Kite Pharma: Research Funding. Cerhan:Kite Pharma: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Link:Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Thompson:Kite Pharma: Research Funding. Relander:Respiratorius: Patents & Royalties: valproate for DLBCL.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3000-3000 ◽  
Author(s):  
Andrea Janikova ◽  
Robert Pytlik ◽  
Pavel Klener ◽  
Zbynek Bortlicek ◽  
Vit Campr ◽  
...  

Abstract INTRODUCTION: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with usually poor prognosis. Age was identified as the independent risk factors in many studies. Elderly patients suffer from comorbidities, impaired organ functions, and poor performance status resulting in worse tolerance of therapy and its efficacy. Data on outcome, prognosis and treatment efficacy for elderly patients with PTCLs are sparse. METHODS: We used data of 941 newly diagnosed PTCLs registered into CLSG database between January 1999 and March 2015 with last follow-up in February 2016. CLSG database covers approximately 85% of all newly diagnosed NonHodgkin´s lymphomas (NHLs) in Czech Republic. For the analysis, 208 patients with age >70 years at diagnosis were selected. RESULTS: Totally, PTCLs accounted for about 8.7% (454/5210) patients of all NHLs in population younger 60 years, but only about 5.8% (208/3561) NHL patients older 70 years. Median age was 76ys (71-91ys), 94 (45%) were women, lactate dehydrogenase (LDH) was elevated in 130/208 (62.5%) pts., ECOG ≥2 had 80 (38%) pts., and advanced clinical stage III-IV presented 132/208 (63.5%) pts. We identified following PTCL subtypes: PTCL-NOS (Peripheral T-cell lymphoma not otherwise specified) 89/208 (43%), Anaplastic large cell lymphoma (ALCL) 34/208 (16.3%), Cutaneous Anaplastic large cell lymphoma (C-ALCL) 10/208 (4.8%), Mycosis fungoides/ Sézary syndrome (MF/SS) together 29/208 (14%), NK/T nasal lymphoma (NK/T) 2/208 (1%), Angioimmunoblastic lymphoma (AITL) 17/208 (8.1%), Cutaneous CD30+ T lymphoproliferative disease 1/208 (0.5%), T-lymphoblastic lymphoma/leukemia (T-LBL) 3/208 (1.4%), T-cell lymphoma without specification (T-NHL) 17/208 (8.1%). Distribution of PTCL subtypes changed significantly with age. There was higher proportion of PTCL-NOS (43% vs. 34%; p.001) and MF/SS (14% vs. 4.8%; p<.001) in elderly patients (>70ys) compared to younger cohort (≤70ys; n=725). Contrary, percentage of ALCL (16.3% vs. 27%; p<.001) with main difference in ALK+ cases (2% vs. 11%; p<.001), and NK/T (1% vs. 5%; p.003) was lower in elderly PTCLs, whereas the incidence of AITL (8.1% vs. 6.6%) or EATL (3.4% vs. 3%) was similar in both age subgroups. For the whole cohort of PTCLs (>70ys), the 5-year overall survival (OS) was 30% and 5-year progression free survival (PFS) was 21% regardless of subtype or stage. Progression is fatal event in elderly patients with median survival about 8 months only. There were significant survival differences between patients (>70ys vs. ≤70ys) according to PTCL subtype; PTCL-NOS 5 yr-OS 23% vs. 43% (p.00001), ALCL ALK+ 5-yr OS not reached vs. 79% (p.01), ALCL ALK- 5 yr-OS 24% vs. 50% (p.001). Patients with AITL or EATL showed no age-related survival differences. First-line chemotherapy was administered in majority of cases (67%); CHOP-like regimen was given in 78 (37%) pts., COP-like in 44 (21%) pts., and other chemotherapy in 18 (9%) cases. Local therapy (surgery, radiotherapy) was administered in first line in 17 (8%) pts., no or palliative therapy (corticoids) was given in 34 (17%) pts., initial therapy was unknown in 17 (8%) cases. We compared two subgroups of patients according to first line chemotherapy CHOP (n=75) vs. COP (n=41). Median age was 74ys (71-84) vs. 79ys (71-89), high IPI was presented in 29% vs. 50% of patients (p.001). Complete response (CR) was achieved in 35/75 (47%) CHOP treated patients, and in 7/41 (17%) patients managed with COP (p.001). Contrary, there were 12/75 (16%) progression in CHOP arm compared to 10/41 (24%) COP treated pts. Five-year OS was 28% vs. 15% better in CHOP group (p.029) and 5-yr PFS 25% vs. 10%, respectively. CONCLUSIONS: In population-based analysis of adult Caucasian PTCL patients, we identified mild decreasing incidence with age. There were significant age-related distribution differences of PTCL subtypes with shift to preponderance of PTCL-NOS, Mycosis fungoides, and NK/T nasal lymphoma in elderly. Worse survival in elderly PTCLs in comparison to younger patients was evident especially for PTCL-NOS and ALCL subtypes. Despite the baseline differences (COP managed pts. had higher IPI), there is tendency that anthracycline-based chemotherapy (CHOP) brings better results with higher proportion of CR and lower progression/relapse rate projected in longer survival. Disclosures Belada: Seattle Genetics: Research Funding. Mayer:AOP Orphan Pharmaceuticals: Research Funding; Novartis: Research Funding.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1401-1401
Author(s):  
Deepa Jagadeesh ◽  
Scott Knowles ◽  
Steven M. Horwitz

Abstract Background Brentuximab vedotin (BV) was the first antibody-drug conjugate to be approved in multiple cancer types (Gauzy-Lazo 2020). The combination of a CD30-directed monoclonal antibody, a protease-cleavable linker, and the microtubule-disrupting agent monomethyl auristatin E drives the anticancer activity of BV by inducing CD30-targeted cell cycle arrest and apoptosis as well as the bystander effect on adjacent cells (Sutherland 2006, Hansen 2016, Schönberger 2018). In the ECHELON-2 phase 3 clinical trial, BV, cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed efficacy in patients with peripheral T-cell lymphoma (PTCL) across a range of CD30 expression levels, including the lowest eligible level of 10% by immunohistochemistry when compared with patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (Advani 2019). It is hypothesized that A+CHP will demonstrate efficacy in PTCL with &lt;10% CD30 expression because i) clinical responses to BV have occurred in patients with PTCL, cutaneous T-cell lymphoma, or B-cell lymphoma with low (&lt;10%) and undetectable CD30 expression (Jagadeesh 2019) and ii) CD30 expression levels were not predictive of A+CHP responses in non-systemic anaplastic large cell lymphoma (sALCL) (Advani 2019). Study Design and Methods SGN35-032 is a dual-cohort, open-label, multicenter, phase 2 clinical trial (NCT04569032) designed to evaluate the efficacy and safety of A+CHP in patients with non-sALCL PTCL and CD30 expression of &lt;10% on tumor cells. Up to approximately 40 patients will be enrolled in each of the CD30-negative (expression &lt;1%) and the CD30-low (expression ≥1% to &lt;10%) cohorts. Patients will be enrolled based on local results but only patients with CD30 expression &lt;10% per central confirmation will be analyzed for the primary and secondary endpoints. Patients will receive 21-day cycles of A+CHP for 6-8 cycles. Key inclusion criteria include adults with newly diagnosed PTCL, excluding sALCL, per the World Health Organization 2016 classification; CD30 expression &lt;10% by local assessment; and fluorodeoxyglucose-avid disease by positron emission tomography (PET) and measurable disease of at least 1.5 cm by computed tomography (CT), as assessed by the site radiologist. Patients with previous exposure to BV or doxorubicin will not be eligible. The primary endpoint of this trial is objective response rate (ORR) per blinded independent central review (BICR) using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Secondary endpoints include ORR by BICR using the modified Lugano criteria (Cheson 2014), complete response rate, progression-free survival (PFS), and duration of response per BICR using the Revised Response Criteria for Malignant Lymphoma (Cheson 2007), overall survival, and safety and tolerability. A PET scan is required at baseline, after Cycle 4, and after the completion of study treatment. Follow-up restaging CT scans will be performed over the next 2 years. In both the CD30-negative and the CD30-low cohorts, efficacy and safety endpoints will be summarized using descriptive statistics to describe continuous variables by cohort. Time-to-event endpoints, such as PFS, will be estimated using Kaplan-Meier (KM) methodology and KM plots will be presented. Medians for time-to-event analyses (e.g., median PFS) will be presented and two-sided 95% confidence intervals will be calculated using the log-log transformation method. Enrollment is planned for 15 US sites and 32 sites across the Czech Republic, France, Italy, and the UK. Disclosures Knowles: Seagen Inc.: Current Employment. Horwitz: ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.: Consultancy, Research Funding; Affimed: Research Funding; Aileron: Research Funding; Acrotech Biopharma, Affimed, ADC Therapeutics, Astex, Merck, Portola Pharma, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, Shoreline Biosciences, Inc, Takeda, Trillium Th: Consultancy; Celgene: Research Funding; C4 Therapeutics: Consultancy; Crispr Therapeutics: Research Funding; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kura Oncology: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; Millennium/Takeda: Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Research Funding; Secura Bio: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Takeda: Consultancy; Trillium Therapeutics: Consultancy, Research Funding; Tubulis: Consultancy; Verastem/Securabio: Research Funding.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4623-4623
Author(s):  
Amandeep Salhotra ◽  
Liana Nikolaenko ◽  
Lu Chen ◽  
NI-Chun Tsai ◽  
Diane Lynne Smith ◽  
...  

Background: Mature T cell and NK cell neoplasms collectively known as peripheral T-cell lymphomas (PTCL) comprise 15-20% of Non-Hodgkin lymphomas in adults and have a poor prognosis with a 5-year survival of less than 30% for the most aggressive subtypes. Allogeneic HCT (allo-HCT) is offered to eligible patients as a potentially curative modality in the salvage setting or in high risk patients to consolidate an initial response to frontline therapy. There are few studies that report clinical outcomes derived from large sample size and long-term follow up data. Methods: We retrospectively reviewed medical records of 87 consecutive patients with PTCL including transformed mycosis fungoides and NK/T-cell lymphoma without prior autologous transplant who underwent allo-HCT at City of Hope from January 2000 to June 2018 after IRB approval was obtained. Descriptive statistics were used to summarize baseline patient demographic, treatment, and disease characteristics. Kaplan-Meier curves and the log-rank test were used to evaluate the overall survival (OS) and progression-free survival (PFS). Cumulative incidences of time to relapse and time to non-relapse mortality (NRM) were calculated with relapse and NRM as competing risks. Cumulative incidences of acute and chronic GVHD were calculated as time to onset of GVHD with relapse and death as competing events for GVHD. Results: 87 patients were included for the analysis. Median age at the time of allo-HCT was 49 years (range 2-70 years). Histologies were PTCL-NOS (n=21); transformed CTCL (n=19); NK T-cell lymphoma (n=17); AITL (n=15), ALCL (n=7); gamma delta T-cell lymphoma (n=6) and other rare subtypes (n=2). None of the patients had a prior auto transplant. 42 patients (48%) received myeloablative conditioning, with the majority of patients receiving FTBI based conditioning (n=39) and three patients received BEAM regimen for conditioning. 45 patients (52%) received reduced intensity conditioning; fludarabine/melphalan based-conditioning was the most common regimen used (n=39). Sibling HCT was performed in 47 patients (54%), while MUD HCT was performed in 36 patients (41%) with fully matched HLA unrelated donor in 15 (17%) and HLA mismatched in 21 (24%) patients; 4 (5%) received haploidentical HCT. GVHD prophylaxis consisted of tacrolimus/sirolimus (n=54), tacrolimus/sirolimus/MTX (n=11), tacrolimus or cyclosporine/MTX (n=7), tacrolimus or cyclosporine/MMF (n=7), post-transplant cyclophosphamide/tacrolimus/MMF (n=5) and other (n=3). Source of stem cells was PBSC in 77 (88%), bone marrow in 5 (6%), and cord blood in 5 (6%) patients. At the time of allo-HCT, there were a total of 25 (29%) patients in complete remission (CR1 n=15, CR2+ n=10), 25 (29%) patients in partial remission 22 (25%) with induction failure and 14 (16%) with relapsed disease. The median follow-up among survivors was 6.9 years (range 1.1-15.5). The 5- and 10-year PFS was 47% (95% CI: 36%-58%) and 38% (95% CI: 26%-50%), respectively. The 5- and 10-year OS was 53% (95% CI: 41%-63%) and 42% (95% CI: 29%-54%), respectively (Fig.1). Relapses at 5 and 10 years were both 24% (95% CI: 16%-34%), while NRM at 5 and 10 years was 28% (95% CI: 19%-39%) and 37% (95% CI: 25%-50%), respectively. At day 100 after allo-HCT, the rates of acute GVHD grade II-IV were 41% (95% CI: 30%-51%) and grade III-IV of 16% (95%CI: 9%-25%). Chronic GVHD rates at 3 years were 62% (95% CI: 51%-72%), with extensive GVHD of 55% (95% CI: 44%-65%). On univariate analysis, age (> 60 or not), sex, TBI-based conditioning, donor type (MSD vs MUD), stem cell source or remission status prior to allo-HCT did not predict for overall survival in our study. Conclusions: Our results constitute the largest reported single-institution series with a long-term follow-up on allo-HCT outcomes in patients with aggressive T-cell NHL. The 5-year PFS and OS of 47 and 53%, respectively, are encouraging for the high-risk T-cell NHL patients with limited treatment options. Disclosures Salhotra: Celgene: Other: Research Support; Kadmon Corporation: Other: Non paid consultant. Popplewell:City of Hope: Employment. Herrera:Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Mei:Seattle Genetics, Inc.: Research Funding. Zain:spectrum: Honoraria; Seattle Genetics: Honoraria, Speakers Bureau.


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