Fasting Blood Glucose As Prognostic Factor In Peripheral T-Cell Lymphoma: A Study Of 250 Cases

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5080-5080
Author(s):  
Brady E Beltran ◽  
Jorge J Castillo
Keyword(s):  
Blood Glucose ◽  
T Cell ◽  
Prognostic Factor ◽  
Who Classification ◽  
Cell Lymphoma ◽  
Fasting Blood Glucose ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Anaplastic Lymphoma

Abstract Background Peripheral T-cell lymphoma (PTCL) is a heterogeneous familyof entities with a worse prognosis, stage by stage, than theirB-cell counterparts. Fasting blood glucose (FBG) level at diagnosis has recently been described as a novel, independent prognostic factor for survival in patients with extranodal natural killer/T-cell lymphoma (NKTCL). The goal of this study is to retrospectively investigatethe prognostic value of FBG at lymphoma diagnosis in the survival of patientswith PTCL. Methods A total of 250 cases of aggressive, non-primary cutaneous PTCLdiagnosed at our institution between January 1997 and December 2012 were reviewed,reevaluated according to their morphological, immunologicaland clinical characteristics, and reclassified according tothe 2008 WHO classification of lymphoid neoplasms. Characteristics are presented descriptively. For the evaluation of FBG, patients were divided in 2 categories; those patients with an FBG at diagnosis >100 mg/dl (hyperglycemia) and those with an FBG at diagnosis <100 mg/dl (normoglycemia). Overall survival (OS) was defined as the time elapsed between lymphoma diagnosis and death or last follow-up. The Kaplan-Meiermethod was used to estimate OS curves, which were then comparedusing the log-rank test. P-values less than 0.05 were considered statistically significant. Results According to the new WHO classification, 104 cases (41%) were classified as adult T-cell leukemia/lymphoma (ATLL), 103 cases (41%) as PTCL, unspecified (PTCLU), 26 cases (11%) as anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL), 10 cases (4%) as extranodal NKTCL, nasal type, 4 cases (2%) as angioimmunoblastic lymphoma (AIL), 2 cases (1%) as ALK-positive ALCL, and 1 case (0.4%) as hepatosplenic T-cell lymphoma. 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. FBG >100 mg/dl was seen in 34% and FBG <100 mg/dl in 66%. An International Prognostic Index (IPI) score 3-5 was seen in 52%, and a Prognostic Index for PTCLU (PIT) score of 2-4 in 62%.  Response evaluation was performed only in patients who received chemotherapy (n=161). The overall response rate (ORR) was 47% (n=76) with complete response (CR) in 32% (n=52) and partial response (PR) in 15% (n=24). FBG was no associated with ORR or CR (p=0.25 and p=0.43, respectively. We then evaluated FBG separately in patients with ATLL and PTCL except ATLL. In ATLL patients, the median OS was 8 months with a 3-year OS of 33%. In PTCL patients, the median OS was 17 months with a 3-year OS of 49%. FBG >100 appeared as an adverse prognostic factor only in PTCL patients with a median OS that was not reached vs. 27 months in patients with FBG <100 mg/dl (Figure; log-rank p=0.035). No difference was seen in patients with ATLL; patients with FBG >100 mg/dl has a median OS of 16 months vs. 18 months in patients with FBG <100 mg/dl (log-rank p=0.95). Conclusions Based on the results of our single-center retrospective study, FBG >100 mg/dl appears as a prognostic factor in PTCL but not in patients with ATLL. Additional studies are needed to investigate the role of hyperglycemia in patients with PTCL, and to evaluate if controlling hyperglycemia during therapy could improve the survival on such patients. Disclosures: No relevant conflicts of interest to declare.

Low Absolute Lymphocyte Count Predicts Chemotherapy Response and Survival In Peripheral T-Cell Lymphoma, NOS

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3135-3135
Author(s):  
Yu Ri Kim ◽  
yun Deok Kim ◽  
Jin Seok Kim ◽  
June-Won Cheong ◽  
soo Jeong Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Factor ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Independent Prognostic Factor ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Overall Response

Abstract Abstract 3135 Peripheral T cell lymphoma, not otherwise specified (PTCL, NOS) is heterogenous groups of aggressive T-cell lymphoma and treatment outcome is dismal. Lymphopenia is an independent prognostic factor for survival for B-cell lymphoma. The ALC at diagnosis on survival in T-cell lymphoma has not been studied. Thus, we studied the role of ALC at diagnosis on clinical outcome in patients with PTCL, NOS. Between 2001 and 2009, 32 patients with PTCL, NOS reviewed for the study. Median patient age was 57 (range 34–78) years. Median ALC at the time of diagnosis was 1.54 (range 0.41–12.64×109/L). Patients were divided two groups according to ALC count 1.0 ×109/L. Ten patients (31%) had lower ALC at diagnosis. Median follow up duration was 299 days (range 11–2164 days). Overall response rate was 61.5% (16 of 26 patients) and complete response (CR) rate was 42% (11 of 26 patients). Only two patients reached CR in low ALC group.There was no significant difference in overall response rate because of small number of patients. Superior overall survival was observed with an ALC 1.0 × 109/L (N = 22) versus an ALC < 1.0 × 109/L (N=10) (median OS: not reached vs 242 days, OS rates at 5 years, 57% vs 0%, p =0.016, respectively). Multivariate analysis demonstrated ALC to be an independent prognostic indicator for OS (Hazard Ratio 3.5, 95% confidence intervals 1.2–10.2; p<0.019) when compared to the International prognostic index (IPI) and Prognostic Index for PTCLU (PIT). This study suggested that low ALC is an independent prognostic factor for survival in patients with PTCL, NOS. Disclosures: No relevant conflicts of interest to declare.

Monocytosis As Prognostic Factor in Aggressive, Non-Primary Cutaneous Peripheral T-Cell Lymphoma: A Study of 251 Cases

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1608-1608
Author(s):  
Brady E Beltran ◽  
Erick Cotacallapa ◽  
Jorge J Castillo
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Worse Prognosis

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.

scholarly journals The Neutrophil-to-Lymphocyte Ratio Is Prognostic in Patients with Early Stage Peripheral T-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5346-5346
Author(s):  
Brady E Beltran ◽  
Denise Castro ◽  
Rodrigo Motta ◽  
Sally Paredes ◽  
Jose M Malaga ◽  
...  
Keyword(s):  
T Cell ◽  
Prognostic Factor ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Early Stage ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Neutrophil To Lymphocyte Ratio ◽  
Peripheral T Cell Lymphoma ◽  
Lymphocyte Ratio

Abstract Introduction: Peripheral T-cell lymphoma (PTCL) encompasses a group of rare and aggressive lymphomas. PTCL, unspecified (PTCLU) is the most common subtype of PTCL, and carries a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCLU (PIT) scoring systems are powerful risk-stratification tools in patients with PTCL. The neutrophil-to-lymphocyte ratio (NLR) has shown to be prognostic in patients with advanced stage PTCLU (Beltran Leuk Lymphoma 2016). The aim of this study was to evaluate whether the NLR is a prognostic factor in patients with early stage PTCLU. Methods: We included patients with a pathological diagnosis of PTCLU who were diagnosed and treated at our institution between 2001-2016. We excluded cases with stage 3 or 4 disease. IRB approval was obtained prior to research. Pathological samples were reviewed by hematopathologists to confirm the diagnosis. Pertinent clinicopathological data were collected through chart review, and are presented using descriptive statistics. The NLR was calculated by dividing the neutrophil by the lymphocyte count, and dichotomized in NLR>=4 and NLR<4. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate Cox models were fitted to evaluate hazard ratios (HR) for overall survival (OS). Results: 48 patients with a diagnosis of early stage PTCL were included in this analysis. Histologically, 40 patients (83%) were PTCL, unspecified, 7 (15%) were anaplastic large cell lymphoma, and 1 (2%) was enteropathy-associated T-cell lymphoma. The median age at diagnosis was 60 years (range 18-83 years) with a slight male predominance (82%). Clinically, 49% of patients were 60 or older, 34% presented with ECOG>1, 36% with elevated LDH, and 65% with extranodal disease; 44% had stage II and 56% had stage I disease. No patient had bone marrow involvement. 30% of patients presented with high/high-intermediate IPI score and 34% with high/high-intermediate PIT score. 27% of patients had a NLR >=4. There were no differences in age, LDH levels, extranodal involvement and stage between NLR>=4 and NLR<4. There was a trend towards worse ECOG performance status in NLR>=4 patients (p=0.06). The 3- and 5-year OS rates were 67% (95% CI 50-80%) and 52% (95% CI 29-71%), respectively. High/high-intermediate IPI score was associated with a worse outcome (HR 4.9, 95% CI 1.7-14.2; p=0.004), as well as high-high-intermediate PIT score (HR 3.9, 95% CI 1.2-12.7; p=0.03). According to NLR, NLR>=4 patients had a higher risk of death (HR 9.9, 95% CO 3.2-30.1; p<0.001). In a multivariate analysis adjusting for IPI and PIT scores, NLR>=4 was the only independent factor associated with a worse survival (HR 6.2, 95% CI 1.9-20.9; p=0.003). Conclusion: The NLR appears as a novel and easy to use prognostic factor for OS in previously untreated patients with early-stage PTCL. Our findings support the need for validation of the NLR in larger retrospective or prospective studies in patients with PTCL. Disclosures Castillo: Otsuka: Consultancy; Pharmacyclics: Honoraria; Abbvie: Research Funding; Millennium: Research Funding; Janssen: Honoraria; Biogen: Consultancy.

Prognostic Factors in Aggressive, Non-Primary Cutaneous Peripheral T-Cell Lymphoma in Peru: A Study of 227 Cases.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5021-5021
Author(s):  
Brady Beltran ◽  
Domingo Morales ◽  
Pilar Quinones ◽  
Carlos Desposorio ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
T Cell ◽  
Clinical Characteristics ◽  
Who Classification ◽  
Median Overall Survival ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma

Abstract Abstract 5021 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 Peruvian population has a higher incidence of PTCL, akin to the Asian population. The goal of this study is to therefore investigate the clinical characteristics and prognostic factors in patients with PTCL in a reference center in Peru. Methods A total of 227 cases of aggressive, non-primary cutaneous PTCL diagnosed between January 1997 and December 2008 were reviewed, reappraised according to their morphological, immunological and clinical characteristics, and reclassified according to the new WHO classification of lymphoid neoplasms. Kaplan-Meier method was used to estimate survival curves, which were compared using the log-rank test. The multivariate analysis was performed using the Cox proportional-hazard regression test. Results The mean age at diagnosis was 57 years (range 14 – 92 years) with a male-to-female ratio of 1:1. According to the new WHO classification of lymphoid neoplasms, 97 cases (43%) were classified as adult T-cell leukemia/lymphoma (ATLL), 84 cases (37%) as PTCL, unspecified (PTCLU), 28 cases (12%) as anaplastic large cell lymphoma (ALCL), 10 cases (4%) as extranodal NK/T lymphoma, nasal type, 4 cases (2%) as angioimmunoblastic lymphoma and 3 cases (1%) were diagnosed with more rare PTCL subtypes. Fifteen percent were stage I, 12% stage II, 16% stage III and 56% stage IV. Distribution based on the International Prognostic Index (IPI) score was: low 24%, low-intermediate 24.5%, intermediate-high 26% and high 25.5%. B symptoms were present in 64% of patients. The median overall survival (OS) for the whole group was 8.4 months, the 2-year OS was 34% and the 5-year OS was 27%. ATLL patients showed a median overall survival of 6.1 months, PTCL of 11.4 months, ALCL of 12.4 months and extranodal NK/T cell lymphoma of 7.8 months. The IPI score, the Prognostic Index for PTCLU (PIT) score and the presence of B symptoms showed statistical significance in both the univariate and the multivariate survival analysis (p=0.001, p=0.005 and p=0.005, respectively). Conclusions The distribution of PTCL subtypes in Peru is comparable to the series of patients reported in Asian countries. ATLL and PTCL-U are the most frequent aggressive, non-primary cutaneous PTCL subtypes found. PTCL tends to present with advanced stages and has a poor prognosis, with a 5-year OS of less than 30%. In the multivariate analysis, the IPI score, the PIT score and presence of B symptoms were independent prognostic factors for survival in PTCL. Disclosures No relevant conflicts of interest to declare.

Prognostic Value of Platelet Count in Patients with Peripheral T Cell Lymphoma

2019 ◽  
Vol 141 (3) ◽  
pp. 176-186 ◽  
Author(s):  
Mihong Choi ◽  
Jeong-Ok Lee ◽  
Jongheon Jung ◽  
Ji Yun Lee ◽  
Eunyoung Lee ◽  
...  
Keyword(s):  
Platelet Count ◽  
T Cell ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Poor Prognostic Factor

Background: Peripheral T cell lymphoma (PTCL) is a heterogeneous entity with poor survival. We evaluated the neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and platelet count as new prognostic factors for PTCL. Patients and Methods: We retrospectively analyzed 77 patients with PTCL initially treated with anthracycline-based chemotherapy. Survival curves were compared between groups with different initial NLR (iNLR), end-point NLR (eNLR), initial ALC, and platelet counts. Cox regression was used to analyze the risk factor for survival. Results: Patients with a higher eNLR (≥3), lymphopenia (< 1,000/μL), and thrombocytopenia (< 150 K/μL) had an inferior progression-free survival (PFS) and overall survival (OS) compared to their counterparts, while a higher iNLR (≥3) was predictive of a shorter OS but not PFS. Among these, thrombocytopenia was an independent poor prognostic factor for both PFS and OS, with a hazard ratio of 2.42 (p = 0.012) for PFS and 4.21 (p = 0.006) for OS. The presence of thrombocytopenia further stratified patients with a worse prognosis within overlapping risk-groups by the prognostic index for PTCL. Conclusions: Our study showed that thrombocytopenia at diagnosis was an independent prognostic factor for survival in patients with PTCL.

NK/T Cell Versus Peripheral T Cell Lymphoma: Significant Differences in Clinical Characteristics and Survival.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4600-4600
Author(s):  
Soon-Thye Lim ◽  
Fei Gao ◽  
Lay-Cheng Lim ◽  
Richard Quek ◽  
Daryl Lim ◽  
...  
Keyword(s):  
T Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Advanced Stage ◽  
Peripheral T Cell Lymphoma ◽  
Nk T Cell

Abstract Background: To compare the clinico-pathologic characteristics and prognosis of Natural Killer/T cell lymphoma (NK/TL) with peripheral T cell lymphoma (PTCL). Methods: A total of 556 resident patients (pts) with lymphoma were treated in the departments of medical oncology and hematology in an Asian institution from 2000 to 2005. Of these pts, 71 (12.8%) had NK/TL or PTCL and were included in this analysis. Pathology was centrally reviewed and classified according to the WHO classification. Results: NK/TL and PTCL comprised of 4.7% (26/556) and 7.9% (45/556) of all cases. Of the PTCL cases, histology was PTCL-NOS in 21, anaplastic large cell in 12 (5 were ALK-1 positive) and angioimmunoblastic T cell in 8 pts. Subcutaneous panniculitis T cell and γ/δ T cell lymphoma accounted for one case each. There were no significant differences between the two groups of pts in terms of sex, performance status, extranodal involvement and LDH level at presentation. However, more patients with NK/TL presented with stage I/II disease (65% vs. 31%, p=0.003). Among pts with NK/TL, 17 (65%) received CHOP-based chemotherapy, 4 received radiation alone and 5 received palliative chemotherapy. In the PTCL group, 39 (87%) received CHOP-based chemotherapy, 2 received radiation alone and 3 received palliative treatment only. Compared to PTCL, NK/TL was associated with a significantly inferior rate of complete remission (27% vs. 58%, p=0.01) and inferior overall survival (5 vs. 28.4 mos, p=0.001). Although age &gt; 60, ECOG ≥ 2, elevated LDH, advanced stage, IPI ≥ 2 and NK/T cell histology were each associated with decreased survival on univariate analysis, only NK/T cell histology and advanced stage were independently associated with decreased survival (see table 1). Conclusions: Contrary to expectation, the incidence of PTCL based on WHO classification in this Asian series is not higher than that reported in Western series. Compared to PTCL, the NK/T subtype is associated with a paricularly inferior prognosis and overrides the prognostic significance of IPI. These data suggest that NK/TL should be considered as a seperate entity and should not be considered together with other subtypes of T cell lymphoma in clinical trials. Table 1. NK/TL vs. PTCL: Univariate and Multivariate Analyses Univariate Analysis Multivariate Analysis Median (yr) P Hazard Ratio 95% CI P Male vs. Female 1.03 vs. Not reached 0.06 0.62 0.28 to 1.40 0.25 Age&lt;60 vs. ≥ 60 2.37 vs. 0.51 0.01 1.41 0.70 to 2.83 0.33 ECOG 0/1 vs. ≥ 2 1.99 vs. 0.36 0.002 1.52 0.63 to 3.65 0.354 LDH normal vs. High Not reached vs. 0.75 0.03 1.29 0.53 to 3.13 0.57 Stage I/II vs. III/IV 1.99 vs. 1.41 0.16 2.91 1.17 to 7.2 0.02 IPI 0/1 vs. ≥ 2 Not Reached vs. 0.42 0.002 2.22 0.82 to 5.99 0.12 PTCL vs. NK/TL 2.37 vs. 0.42 0.001 5.8 2.36 to 14.24 &lt;0.001

Lymphopenia Predicts Survival in Peripheral T-Cell Lymphoma, Unspecified.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1930-1930
Author(s):  
Brady Beltran ◽  
Domingo Morales ◽  
Pilar Quinones ◽  
Carlos Desposorio ◽  
Eduardo Sotomayor ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
T Cell ◽  
Prognostic Factor ◽  
Lymphocyte Count ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Independent Prognostic Factor ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma

Abstract Abstract 1930 Poster Board I-953 Background: Lymphopenia is an independent prognostic factor for survival for different hematological malignancies like follicular lymphoma, Hodgkin lymphoma and diffuse large B-cell lymphoma. The role of lymphopenia at diagnosis on survival in peripheral T-cell lymphoma, unspecified (PTCLU) is not known. Methods: Eighty seven patients with a diagnosis of PTCLU were evaluated at the Edgardo Rebagliati Martins Hospital in Lima, Peru from October 1997 until April 2008. The primary objective of the study was to assess the role of lymphopenia at diagnosis in survival in cases with PTCLU. Lymphocyte count at diagnosis was obtained from the standard complete blood cell count (CBC). Lymphopenia was defined as a lymphocyte count of less than 1 × 109/L. Kaplan-Meier survival estimates and the log-rank test were performed for univariate survival analyses and Cox proportion-hazard regression test was performed for the multivariate analysis. Results: Eighty four patients with a histological diagnosis of PTCLU were included in this study. The median follow-up was 13.4 months (range 1–68 months). The sample population included 54% males and 46% females with a median age of 57 years (range 18–87 years). The median number of lymphocytes at diagnosis was 1.3 × 109/L (range 0.06–5.2 × 109/L). Lymphopenia was present in 37% of cases. In the univariate analysis, lymphopenia was identified as a poor factor for survival (median OS 59 vs. 1 month; p<0.0001). In the multivariate analysis, lymphopenia was compared to the Prognostic Index for PTCLU (PIT) and it remained as an independent predictor for survival (Hazard Ratio 4.8, 95% confidence intervals 2.2–10.6; p<0.0001). Conclusion: This study demonstrates that lymphopenia is an independent prognostic factor for survival in patients with PTCLU, suggesting that the host immune system might play a preponderant role in survival in this group of patients. Disclosures: No relevant conflicts of interest to declare.

Safe and Effective Treatment of Patients with Peripheral T-Cell Lymphoma (PTCL) with the Novel HDAC Inhibitor, Belinostat, in Combination with CHOP: Results of the Bel-CHOP Phase 1 Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 253-253 ◽  
Author(s):  
Patrick B. Johnston ◽  
Amanda F. Cashen ◽  
Petros G. Nikolinakos ◽  
Anne W Beaven ◽  
Stefan Klaus Barta ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Anaplastic Lymphoma ◽  
Not Otherwise Specified ◽  
Baseline Characteristics ◽  
Grade 3

Abstract Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas associated with poor prognosis and repeated recurrence for most subtypes. Currently, anthracycline-based therapies such as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or CHOP-like therapies are recommended as the first-line treatment for PTCL, but the prognosis remains poor with most patients relapsing within 5 years. Thus, improved treatment strategies are still needed. Belinostat is a potent, pan-histone deacetylase inhibitor that was recently approved in the United States for the treatment of patients with relapsed or refractory PTCL (R/R PTCL). Approval was based on results from the pivotal Phase 2 BELIEF study (O'Connor et al, JCO, 2015) of belinostat in R/R PTCL, which demonstrated durable clinical benefit (objective response rate [ORR] 25.8%) and tolerability. Since belinostat (Bel) and each of the components of the CHOP regimen target different aspects of the cell cycle with different mechanisms of action, there is potential for a synergistic effect of a Bel-CHOP combination treatment regimen for patients with PTCL. Methods: Patients with PTCL received CHOP in association with 1000 mg/m2 of belinostat on various schedules, repeated every 21-days for up to 6 cycles. The cohort schema followed a traditional "3+3" dose escalation design. The objective of Part A of the study was to determine the Maximum Tolerated Dose (MTD) of the Bel-CHOP combination. Once the MTD was determined, at least 10 more patients were to be treated in the Expansion Phase (Part B). Belinostat was to be administered as a 1000 mg/m2 IV infusion once daily for up to 5 days, depending on the assigned cohort (Fig 1). The starting cohort was Cohort 3 (CHOP + 1000 mg/m2 of daily belinostat on Days 1-3). Patients received primary prophylaxis with growth factor (G-CSF) support. Dose-limiting toxicities (DLT) were considered during the 1st cycle and included: non-hematological toxicity Grades 3-4, platelet count &lt; 25 X 109/L at any time or ANC &lt; 0.5 X 109/L lasting more than 7 days despite G-CSF administration. The primary endpoint of the study was the determination of the MTD of the Bel-CHOP combination. Secondary endpoints included safety, tolerability and ORR (complete response [CR] + partial response [PR]) and pharmacokinetics. Results: A total of 23 patients were enrolled in the study, 11 of which were treated in Part A. One patient in Part A was deemed inevaluable because the patient died due to disease progression before completing Cycle 1. The MTD was determined to be 1000 mg/m2 on Days 1-5 (Cohort 5); 12 more patients were then treated at this dose level (Part B). The only DLT experienced in the study was in Cohort 3 (Grade 3 Nausea and Vomiting). At the time of this abstract, 18/23 patients (78%) have completed all 6 cycles of Bel-CHOP, with 87% completing at least 4 cycles. Ten patients (43%) had at least one serious adverse event (SAE) and 18 (78%) had at least one Grade 3 or 4 adverse event (AE). The most frequent Grade 3/4 AEs were hematological in nature: neutrophil count decreased (26%), anemia (22%), neutropenia (17%) and white blood cell count decreased (17%). The ORR for the18 patients that have completed an End of Study Visit is 89% (16/18), with the vast majority achieving a CR [72% (n=13)], and 17% (n=3) a PR. Progressive disease was reported in 2 patients. Conclusions: These results demonstrate that the combination of belinostat with CHOP (Bel-CHOP) is well tolerated, with all components of CHOP and belinostat being given at their standard therapeutic doses. The rates of AEs were consistent with those typically reported with CHOP alone, and clinical activity was demonstrated with a response rate of 89% based on 18 evaluable patients. Thus, Bel-CHOP is a promising new regimen in PTCL that will be further tested in a Phase 3 randomized trial. Table. Table. Figure 1. Summary of Demographic and Baseline Characteristics AITL= angioimmunoblastic T-cell lymphoma; ALCL =anaplastic large-cell lymphoma; ALK = anaplastic lymphoma kinase; NOS = not otherwise specified Figure 1. Summary of Demographic and Baseline Characteristics. / AITL= angioimmunoblastic T-cell lymphoma; ALCL =anaplastic large-cell lymphoma; ALK = anaplastic lymphoma kinase; NOS = not otherwise specified Disclosures Barta: Seattle Genetics: Research Funding. Bhat:Spectrum Pharmaceuticals, Inc: Employment. Song:Spectrum Pharmaceutical, Inc: Employment. Choi:Apectrum Pharmaceuticals, Inc: Employment. Allen:Spectrum Pharmaceuticals, Inc: Employment. Foss:Spectrum Pharmaceuticals; Celgene: Seattle Genetics: Infinity; Millenium: Consultancy, Honoraria, Research Funding, Speakers Bureau.

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