Myeloablative Chemotherapy for T-Cell Lymphoma: a Case for Autologous Stem Cell Transplantatin (Auto) in First Remission.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1141-1141 ◽  
Author(s):  
Issa F Khouri ◽  
Adriana Lopez ◽  
Grace-Julia Okoroji ◽  
Martin Korbling ◽  
Gloria McCormick ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Cox Model ◽  
Performance Status ◽  
Autologous Transplantation ◽  
T Cell Lymphoma ◽  
Cancer Center ◽  
P Value ◽  
Significant Difference ◽  
First Remission

Abstract In order to determine the long-term impact of AUTO in patients (pts) with T-cell lymphoma, we examined the outcome of 79 pts transplanted at the MD Anderson Cancer Center, in first partial or complete remission (CR) (AUTO1, n=20) or for relapsed / refractory disease (AUTO2, n=59) between 06/91 and 05/08. <<<PATIENTS>>> Median age (range) at transplantation was 49 (22–65) and 51 (16–77) for the AUTO1 and AUTO2 groups respectively (p=0.35); other baseline characteristics including gender, stage, B-symptoms, LDH, IPI, PET/Gallium status, history of marrow involvement, and performance status at transplantation were similar. There was a statistically significant difference between AUTO1 and AUTO2 with respect to histology {peripheral t-cell, angioimmunoblatic, and anaplastic/large cell were present in 80%, 5%, 15%, respectively in AUTO1, and 42%, 10%, and 45%, respectively in AUTO2 (p=0.02); one pt in AUTO2 had small lymphocytic and one had hepatosplenic T cell lymphoma}. Statistically significant differences were also noted with respect to B2-microglobulin (P=0.02; favoring AUTO1), number of prior chemotherapy regimens received {median 1 vs 3 for AUTO1 and AUTO2, respectively (p <0.001)}, disease status at transplantation {18% of AUTO2 had stable or progressive disease at transplant vs 0% in AUTO1 (P < 0.001)}, and # of CD34+cellsx10 6/Kg infused {median 9 vs 5 for AUTO1 and AUTO2, respectively}. Most pts in both group received BEAM as conditioning. Median follow-up time in months was 64 (95%CI, 31–87), and 47(95%CI29–121) for AUTO1 and AUTO, respectively. Median overall survival (OS) was 43.5 months (95%CI:30–70 for AUTO2 and the median OS was not reached for AUTO1 (P=0.01)(Figure). The median progression-free survival (PFS) was 16 months (95%CI:8–56) and 95 months (95%CI:6.94-NA) for the pts in the AUTO2 and AUTO1 groups, respectively (P=0.06). Univariate Cox models for OS showed that AUTO2 vs AUTO1 (HR 3.4, P=0.02), high LDH level (HR 2.6. P=0.01), PET/Gallium+ (HR 2.8, P=0.01), IPI2–4 (HR 3.4, P=0.002), marrow involvement (HR 6.3, P=0.02), and marrow vs peripheral blood as source of graft (HR 2.1, P=0.048) were important determinants of outcome. The univariate Cox model for PFS showed that only AUTO2 vs AUTO1, hi LDH, IPI and PET/gallium were statistically significant. A multivariate analysis that included the covariates with the lowest P value showed that AUTO2 vs AUTO1 remained the only important factor for OS (HR 4.79, P=0.035) while PET/ Gallium status at transplantation was the most important determinant of PFS (HR 3.13, P=0.006). <<<CONCLUSION>>> Autologous transplantation has the potential to cure a proportion of pts with t-cell lymphoma if performed during the first remission. Alternative strategies are needed for pts transplanted beyond first remission especially if they continue to have avid functional imaging at transplantation. Figure Figure

First-line therapy of T-cell lymphoma: Allogeneic or autologous transplantation for consolidation—Final results of the AATT study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7503-7503 ◽  
Author(s):  
Norbert Shmitz ◽  
Lorenz Truemper ◽  
Marita Ziepert ◽  
Kamal Bouabdallah ◽  
Guillaume Cartron ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
Observation Time ◽  
T Cell Lymphoma ◽  
Unrelated Donor ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

7503 Background: In patients (pts) with peripheral T-cell lymphoma (PTCL) results of first-line therapy remain poor; guidelines recommend consolidation with autologous transplantation (autoSCT) in transplant-eligible pts. AATT (Autologous or Allogeneic Transplantation in T-cell lymphoma) sought to improve first-line therapy and compared alloSCT with autoSCT. Methods: This was a prospective randomized trial comparing autoSCT with alloSCT in younger pts (18-60 yrs) with newly diagnosed PTCL who had achieved CR, PR, or SD after 4 courses of CHOEP and 1 course of DHAP. Pts were to receive BEAM followed by autoSCT or myeloablative conditioning (fludarabine, busulfan, cyclophosphamide) followed by alloSCT from a matched related or unrelated donor. Primary endpoint was 3-year event-free survival (EFS). The study was stopped prematurely after a pre-planned interim analysis (JCO 33, 2015, suppl 8507a). Results: 103 pts randomized upfront to autoSCT (n=54) or alloSCT (n=49) formed the full analysis set. Median age was 50 years, 63% were male. 36 pts (35%) could not proceed to transplantation mostly due to early progression. Median observation time for EFS was 42 months. 3-year EFS and overall survival (OS) did not significantly differ between alloSCT and autoSCT (EFS: 43% (95% CI29-57%) vs. 38% (25-52%), p=0.58, OS: 57% (43-71%) vs. 70% (57-82%) (p=0.41). Comparing pts who actually received autoSCT (n=41) or alloSCT (n=26) EFS, PFS, and OS also showed no significant difference. No patient relapsed but eight pts (31%) died of treatment-related mortality (TRM) after alloSCT compared to 13 relapses (36%) but no TRM observed after autoSCT. Comparison of pts with aaIPI 2/3 vs. 0/1 showed significant differences for all endpoints. Conclusions: AlloSCT or autoSCT given to consolidate response in pts with PTCL showed no significant survival differences. While exerting a strong GvL-effect alloSCT resulted in substantial TRM. For younger pts with PTCL autoSCT remains the preferred consolidation, in particular, because pts. relapsing after autoSCT can be successfully salvaged with alloSCT. Clinical trial information: 2007-001052-39.

Long-term survival of the nasal NK/T cell lymphoma

2008 ◽  
Vol 149 (17) ◽  
pp. 801-805
Author(s):  
Péter Rajnics ◽  
László Krenács ◽  
András Kenéz ◽  
Zoltán Járay ◽  
Enikő Bagdi ◽  
...  
Keyword(s):  
T Cell ◽  
Treatment Guidelines ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Diagnostic Procedures ◽  
T Cell Lymphoma ◽  
Term Survival ◽  
Barr Virus ◽  
Significant Difference ◽  
Nk T Cell

The nasal NK/T cell lymphoma is a rare, extranodal non-Hodgkin lymphoma in western civilizations, which has poor prognosis. The Epstein–Barr virus can be detected in tumor cells in nearly all cases. There are no definite treatment guidelines in our days. There is no significant difference in survival between radiotherapy and chemotherapy according to Asian studies. In this case study we show our diagnostic procedures, our treatment options and we present the summary of this illness based on the data found in the literature.

scholarly journals Outcomes of GDPT (gemcitabine, cisplatin, prednisone, thalidomide) versus CHOP in newly diagnosed peripheral T-cell lymphoma patients

2020 ◽  
Vol 12 ◽  
pp. 175883592092382 ◽  
Author(s):  
Yuanyuan Sun ◽  
Ling Li ◽  
Xin Li ◽  
Lei Zhang ◽  
Xinhua Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
The Other ◽  
Newly Diagnosed ◽  
Peripheral T Cell Lymphoma ◽  
Angioimmunoblastic T Cell Lymphoma ◽  
Significant Difference ◽  
Gene Expression Levels

Aim: To compare the outcomes of GDPT [gemcitabine (G), cisplatin (D), prednisone (P), thalidomide (T)] versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL (peripheral T-cell lymphoma). Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT (77 cases) and CHOP (76 cases) groups. Patients in each group were further divided into four subgroups: PTCL, not otherwise specified (PTCL-NOS); anaplastic large cell lymphoma (ALCL), angioimmunoblastic T cell lymphoma (AITL), and other types subgroup, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3, and ERCC1, patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, progression-free survival (PFS), and overall survival (OS) were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The overall response rate (ORR) of the GDPT group was better than that of the CHOP group (66.3% versus 50.0%, p = 0.042), as was the complete remission (CR) rate (42.9% versus 27.6%, p = 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% versus 53.0% for PFS, p = 0.035; 66.8% versus 53.6% for OS, p = 0.039). In the GDPT group, the difference in CR between the four subgroups was statistically significant ( p = 0.046). In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant ( p < 0.001 and p = 0.005, respectively). There were also statistically significant differences in CR between patients treated with CHOP and GDPT in the PTCL-NOS subgroup, AITL subgroup, and the other types subgroup ( p = 0.015; p = 0.003; p = 0.005, respectively). The data also showed a significant difference in OS among the four subgroups within the GDPT group ( p = 0.001). The OS of AITL was shorter than that of the other three subgroups. Four subgroups of CHOP showed a significant difference in PFS ( p = 0.019). There was no statistical association between responses and the gene expression levels of RRM1, ERCC1, TUBB3, and TOP2A. Conclusion: The GDPT group had better response rates and prolonged patient PFS and OS. As a promising new regimen, GDPT is expected to become the first-line therapy for PTCL. New agents should be applied to patients who do not achieve good responses with previous treatment, such as those diagnosed with angioimmunoblastic T cell lymphoma. Trial registration: This open randomized prospective clinical trial was registered at ClinicalTrials.gov (NCT01664975).

Clinical Characteristics of T-Cell Lymphoma Associated Hemophagocytic Syndrome: Comparison of T-Cell Lymphoma with and without Hemophagocytic Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3576-3576
Author(s):  
Hongyan Tong ◽  
Yanling Ren ◽  
Feng Xiao ◽  
Wenyuan Mai ◽  
Haitao Meng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Median Survival ◽  
Clinical Characteristics ◽  
Hemophagocytic Syndrome ◽  
Cell Lymphoma ◽  
Initial Therapy ◽  
T Cell Lymphoma ◽  
Β2 Microglobulin ◽  
Significant Difference

Abstract T-cell lymphoma associated hemophagocytic syndrome (T-LAHS) has been regularly reported in Asia countries and is considered with extremely poor prognosis. The rate of definite diagnosis during early stage is low and the therapeutic outcome has been disappointed. We therefore compared T-cell lymphoma patients with and without hemophagocytic syndrome (HPS) in order to have a better understanding of the clinical characteristics of T-LAHS. One hundred and thirteen patients (66 men and 47 women, age from 12 to 80 years with the median age of 42) with aggressive T-cell lymphoma admitted to our department between January 2000 and December 2005 were included in this study, while 28 of them were with T-LAHS. The patients were divided into LAHS group and no-LAHS group. The clinical data including clinical manifestations and laboratory findings were compared between the two groups by using Chi-square test. The method of Kaplan and Meier was used to analyze overall survival (OS). The results showed that LAHS occured in about 1/4 of all the patients with T-cell lymphoma, which were all aggressive type. The elevated rates of lactate dehydrogenase (LDH) and ferritin were much higher in LAHS group than in no-LAHS group. β2-microglobulin and ovarian cancer antigen (CA125) were also elevated in both groups, but there was no significant difference. The rate of hypo-fibrinogen and liver dysfunction were higher in LAHS group than that in no-LAHS group. The rate of bone marrow infiltration in LAHS group is remarkably higher than that in no-LAHS group (57% vs 32%, p&lt;0.05). The median survival was 40 days (16 days - 22 months) in the LAHS group, and the median survival of 11 patients accepted chemotherapy more than 2 courses was 6 months. By contrast, the 2-year survival for no-LAHS group was 43%. There was significant difference between the two groups. Three patients undergoing plasmapheresis as initial therapy had survived for 3–6 months. These results indicate that high suspicion is required for early diagnosis of T-LAHS. In patients with fever, hepatosplenomegaly and cytopenia, simultaneously with serum markers such as LDH, ferritin, TG, CA125, and β2-microglobulin constantly increasing, T-LAHS should be considered. For patients without extranodal invasion or enlargement of lymph nodes, repeating biopsy of multiple sites of bone marrow may help improving the diagnosis rate. As for treatment, other more intensive regimens were not superior to CHOP regimen. While the overall outcome of treatment is still unsatisfied, plasmapheresis as initial therapy is worth considering.

Late Relapses Characterize Autologous Transplantation (ASCT) in First Complete Remission (CR) for Peripheral T-Cell Lymphoma (PTCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5110-5110 ◽  
Author(s):  
Tarun Kewalramani ◽  
Steve Horwitz ◽  
Andrew D. Zelenetz ◽  
Stephen D. Nimer ◽  
Craig H. Moskowitz
Keyword(s):  
T Cell ◽  
Median Time ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
T Cell Lymphoma ◽  
Time To Progression

With the exception of ALK-positive anaplastic large cell lymphoma (ALCL), standard-dose chemotherapy is curative in a minority of patients (pts) with PTCL, and most pts have progressive disease less than 2 years from completing treatment. Several studies suggest that ASCT in 1st CR significantly improves the short-term outcome of pts with PTCL, but its long-term efficacy is not known. To address this, we assessed the outcome of sequential patients who underwent ASCT in 1st CR (n=15). Histologic subtypes were PTCL, unspecified, in 6 pts, angioimmunoblastic T-cell lymphoma in 5 pts, ALK-negative ALCL in 3 pts and hepatosplenic gamma delta T-cell lymphoma in 1 pt. Induction chemotherapy was CHOP (n=2) or CHOP-ICE hybrid (n=12) in 93% of pts. The age-adjusted IPI (AAIPI) was 2–3 in 9 of 14 assessable patients (64%), and 11 pts (73%) had stage III–IV disease. The conditioning regimen consisted of BEAM or CBV in 10 pts and TBI/Cy/VP-16 in 5 pts. All patients received peripheral blood progenitor cells for hematopoietic support. The median follow-up of all patients is 24 months (range 4.5–70). Five pts (33%) have progressed, with a median time to progression of 50 months (range 10–70). Four of the 5 pts who progressed did so more than 2 years from ASCT; they comprise 57% of patients with more than 2-years of follow-up. Four of 5 patients with progressive disease have died, with a median time from progression to death of 1 month (0.6–14.6). In this small series the AAIPI was not predictive of PFS or OS. While our results confirm the that ASCT in 1st CR significantly delays the time to progression, they suggest that it may not be curative in the majority of patients. If confirmed in ongoing larger prospective studies, this observation warrants trials of post-ASCT maintenance treatment and, for younger patients, trials of allogeneic transplantation in 1st CR or sequential ASCT followed by allogeneic transplantation. Figure Figure

A Retrospective Comparison of Autologous Vs. Allogeneic Transplantation for Peripheral T-Cell Lymphoma: A Single Institution Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4392-4392
Author(s):  
Frederick Lansigan ◽  
Stuart Seropian ◽  
Dennis Cooper ◽  
Francine Foss
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Unrelated Donor ◽  
T Cell Lymphomas ◽  
First Remission

Abstract Peripheral T-cell Lymphomas (PTCL) are a heterogenous group of malignanices that represent 10–15% of non-Hodgkin lymphoma (NHL). This group has a worse prognosis with conventional chemotherapy compared to B-cell lymphomas. Both autologous (AutoSCT) and allogeneic stem cell transplantation (AlloSCT) have been used as consolidation in first remission and at relapse, but the role of transplantation has not been clearly defined. We report a retrospective analysis of 42 patients with PTCL who underwent AutoSCT (24) or AlloSCT (18) between 8/1997 and 12/2007. The AlloSCT group consisted of 4 PTCL unspecified (PTCLu), 3 angioimmunoblastic T-cell lymphomas (AITL), 2 panniculitic T-cell lymphomas, 2 cutaneous T-cell lymphomas (CTCL) with large cell transformation, 2 NK-cell lymphomas, 2 anaplastic large cell lymphomas (ALCL, 1 Alk+, 1 Alk unknown), 1 hepatosplenic T-cell lymphoma, 1 enteropathic T-cell lymphoma, and 1 refractory CTCL. The AutoSCT group consisted of 6 PTCLu, 12 ALCL (5 Alk+, 5 Alk−, 2 Alk unknown), 4 AITL, 1 CTCL with transformation, and 1 T-lymphoblastic lymphoma. The median age of the AlloSCT and AutoSCT groups was 51 (range 29–72) and 52 years (range 19–67), respectively. The median number of prior treatments of the AlloSCT and AutoSCT groups were 3 (range 1 to 5) and 1 (range 1 to 5), respectively. Within the AlloSCT group there were 14 matched-related donor transplants, and 4 matched-unrelated donor transplants; 7 were ablative and 11 were reduced-intensity transplants; the AlloSCT conditioning regimens varied. The AutoSCT group predominantly received BEAM as their conditioning regimen. Median time from diagnosis to AlloSCT or AutoSCT was 18.4 (range 6.9 to 109) and 7.5 (range 3.9 to 25) months, respectively. Median follow-up times for the AlloSCT and AutoSCT groups were 28.6 and 23.5 months, respectively. The day 100 transplant-related mortality rates in the AlloSCT and AutoSCT groups were 11% and 0%, respectively. Within the AlloSCT group the relapse and non-relapse mortalities were 11% and 33%, respectively. In the AutoSCT group, the relapse mortality was 33%. The 1- and 2-year overall survival (OS) rates were similar within the AlloSCT and AutoSCT groups (78% vs 74%, and 67% vs 60%, respectively). The 1- and 2-year progression-free survival (PFS) rates for the AlloSCT vs AutoSCT groups were 68% vs 52%, and 53% vs 45%, respectively (p = 0.28). Within the AutoSCT group, 14 patients (58%) were transplanted in first complete remission (CR1), and 10 (42%) in second complete remission (CR2), beyond CR2, or partial remission (PR). Patients in CR1 had significantly better PFS (57 vs 17 months, p=0.007) and OS (76 vs 29 months, p=0.004) than those in CR2, PR2, or beyond. Within the AlloSCT group, there was a trend toward poorer OS in 6 patients (33%) who had prior AutoSCT (32 vs 60 months, p=0.15). One patient (6%) was transplanted in CR1, and is still alive. We conclude that outcomes for AutoSCT are best in CR1. For patients with resistant or relapsed disease, AlloSCT should be strongly considered rather than AutoSCT. Prior AutoSCT may affect the outcome of AlloSCT. These results suggest that a prospective randomized trial comparing AutoSCT and AlloSCT for aggressive PTCL in first remission is warranted.

Allogeneic Stem Cell Transplantation Results in a Low Relapse Rate in Patients with Peripheral T-Cell Lymphoma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 974-974
Author(s):  
Maike Nickelsen ◽  
Carmen Canals ◽  
Charalampia Kyriakou ◽  
Norbert Schmitz ◽  
Agnes Buzyn ◽  
...  
Keyword(s):  
Stem Cell ◽  
Relative Risk ◽  
T Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Chronic Gvhd ◽  
T Cell Lymphoma ◽  
Reduced Intensity Conditioning ◽  
Peripheral T Cell Lymphoma ◽  
Reduced Intensity

Abstract Patients (pts) suffering from mature (peripheral) T-cell lymphoma are known to have a poor outcome compared to pts with aggressive B-cell lymphoma when receiving conventional therapies. However, case reports and single centre experiences show promising results of allogeneic stem cell transplantation (allo SCT) for these pts. We here present a retrospective analysis of 103 pts with mature T-cell lymphoma who received an HLA-identical allo SCT in EBMT centres between 2000 and 2005. Histological subtypes of the patients were anaplastic large cell lymphoma (n=25; 4 anaplastic lymphoma kinase [ALK] positive, 11 ALK negative, 10 ALK unknown), peripheral T-cell lymphoma unspecified (n=51), angioimmunoblastic T-cell lymphoma (n=18) and aggressive T-cell lymphoma unspecified (n=9). Patients with primary cutaneous T-cell lymphoma or T-lymphoblastic lymphoma were excluded. Median follow up for surviving patients was 40 months (6–98), median age at allo SCT 42 years (18–68) and median time to allo SCT 17 months (3–233). 39 pts had failed a prior autologous SCT; 68 pts had chemosensitive disease at allo SCT (of these 15 in CR1) and 30 pts had chemorefractory or untested relapsed or progressive disease. Donors were HLA identical siblings for 73 and matched unrelated donors for 30 pts; 82 pts received peripheral blood stem cells. 54 pts were treated with reduced intensity conditioning before SCT. The cumulative incidence (CI) of acute graft versus host disease (GvHD) 100 days after SCT was 52% and had no effect on non-relapse mortality (NRM) or relapse rate (RR). 34 of 74 evaluable pts experienced chronic GvHD (14 limited, 20 extensive), CI 46% at 2 years. Introducing chronic GvHD as a time dependent covariate, this factor was associated with a higher NRM (p<0.001) and a lower RR (statistically not significant), resulting in a lower progression free survival (PFS) (p=0.001). For all patients CI of NRM and RR at 3 years were 36.7% and 24.9%, respectively, resulting in 41.4% PFS and 46.9% OS. Median time to relapse / progression was 4 (1–18) months. In multivariate COX analysis for PFS refractory disease (relative risk 3.4, p=0.001), prior failed auto SCT (relative risk 2.6, p=0.001) and poor performance status at SCT (relative risk 2.5, p=0.04) were significant adverse factors. Additionally, there were trends for T-cell depleted grafts (p=0.1), CMV status other than negative-negative (p=0.1) and reduced intensity conditioning (p=0.2) to be adverse factors. A subgroup of 39 good risk pts (good performance status, chemosensitive disease, no prior autologous SCT) had a PFS of 59%. This retrospective analysis on allo SCT in peripheral T-cell lymphoma shows an encouraging low RR but efforts have to be made to reduce NRM. Prospective studies are warranted to further define pts who will profit from an early allo SCT.

Bortezomib (BTZ) and Panobinostat (PAN) Combination Is Effective in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) or NK/T-Cell Lymphoma (NKL) and Maintenance Treatment May Be Essential for Sustained Response

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3669-3669
Author(s):  
Daryl Tan ◽  
William YK Hwang ◽  
Colin Phipps Diong ◽  
Wee Lee Goh ◽  
Lionel K.Y See ◽  
...  
Keyword(s):  
T Cell ◽  
Stable Disease ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Response Rate ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Objective Response ◽  
T Cell Lymphoma

Abstract Abstract 3669 Background: Relapsed/refractory PTCL and NKL after conventional chemotherapy carry a poor prognosis and there is currently no proven salvage treatment available. Numerous preclinical studies have demonstrated synergistic interactions between proteasome and histone deacetylase (HDAC) inhibitors. Inhibition of HDAC6 by PAN abrogates BTZ-induced protective aggreosome formation and accentuates BTZ induced endoplasmic reticulum stress, leading to further apoptosis. Primary end point of this ongoing phase II multi-center open-label clinical study (NCT00901147) is the objective response rate (ORR) according to the Revised Response Criteria (2007) among eligible patients (pts) treated with this novel combination of BTZ and PAN. Secondary end points include the evaluation of the progression-free survival (PFS) and the assessment of the safety and tolerability of the combination. Methods: Pts with histologically confirmed PTCL or NKL who failed or were refractory to 1 prior systemic therapy, and had measurable disease and ECOG performance status 0–2 were eligible. Pts were accrued according to a 2-stage Gehan design. Pts receive thrice weekly oral PAN (20 mg) and twice weekly BTZ (IV 1.3 mg/m2), both for 2 of 3 weeks for up to 8 cycles. Preliminary response data were available for all 11 pts recruited for stage 1 of the study. A response rate of >25% will allow the study to proceed to stage 2. Results: Among pts enrolled, histologies included: angioimmunoblastic T-cell lymphoma (AITL) n=4, PTCL (unspecified) n=4, ALK+ Anaplastic large cell lymphoma n=1 and NKL, nasal type n=2. The median age was 52 (35–72) years, and 70% were male. The ORR was 54.5% with 18% attaining a complete response. Four pts (36%) had a partial response, and stable disease was noted in 2 (18%). Pts received a median of 2 prior therapies (range 1–3); 27% received an autogous stem cell transplantation (SCT). Common treatment-related grade 3/4 adverse events included thrombocytopenia (36%), neutropenia (27%), diarrhoea (18%) and fatigue (9%). Peripheral neuropathy of any grade was observed in 35%. Among pts who responded or had stable disease, the median PFS was 6 months and disease progression occurred at a median of 2.5 months after stopping trial drugs. Two deaths have occurred: 1 due to progressive disease and 1 associated with an unrelated cardiac event. 3 pts successfully underwent subsequent allogeneic SCT. Conclusions: The study regimen shows activity across T/NK-cell lymphomas and ORR greatly exceeds the predefined threshold of 25% allowing, together with early tolerability data, continuation of study enrolment in stage 2. The early progression of the disease after stopping trial drugs albeit the high initial ORR suggests that the novel combination provides a tonic suppression of tumor proliferation and ongoing treatment will be beneficial for pts without option for subsequent alternative treatment like SCT. An extended phase of maintenance treatment will be incorporated into stage 2 of the study to allow pts to optimally benefit from the combination. Our interim findings may have implications on the design of future studies seeking proteasome and HDAC inhibition in PTCL or NKL. Ongoing correlative studies are designed to determine if the study regimen is more active in diseases with up-regulation of NF-kappa B activity or transcription factors/co-regulators known to be modified by acetylation. Disclosures: Tan: Novartis: Research Funding; Janssen: Equity Ownership, Honoraria, Research Funding. Goh:Novartis: Honoraria, Research Funding; Jansen: Honoraria, Research Funding.

Alternating non-cross-resistant multiagent chemotherapy (ANCRC) and high-dose chemotherapy followed by autologous stem cell support (HDC-ASCS) in first remission to improve outcome in patients with T-cell lymphoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18538-e18538
Author(s):  
Potjana Jitawatanarat ◽  
Richa Dawar ◽  
Kaweesak Chittawatanarat ◽  
Nicolas Batty ◽  
Myron Stefan Czuczman ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Final Analysis ◽  
High Dose Chemotherapy ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Front Line ◽  
First Remission ◽  
The Impact

e18538 Background: T-cell lymphomas represent a challenge for the practicing oncologist as evidence-based medicine is limited and the ORR to chemotherapy, PFS and OS rates are inferior when compared to B-cell lymphoma. CHOP offers limited activity, and there is a growing consensus that alternative regimens should be tested. We studied the impact of ANCRC or HDC-ASCS vs. CHOP in outcome of T-cell lymphoma. Methods: We retrospectively analyzed differences between the ORR, PFS and OS of T-cell lymphoma patients excluding ALCL treated with CHOP or HyperCVAD regimen alternating with HDAM in the front-line setting following by observation or HDC-ASCS. Pre-treatment demographic, clinical, and pathological characteristics were collected. Differences in outcomes were analyzed using a Cox proportional analysis. Results: ALCL, PTCL-NOS and AITL were the most common subtypes. After excluding ALCL (N=29), a total of 49 patients were included in the final analysis; 23 pts treated with CHOP; 12 pts with HyperCVAD/HDAM and 14 pts treated with other induction regimens. After induction therapy, 12 patients underwent HDC-ASCS in first remission. There were no differences in demographic and clinical characteristics between groups analyzed. There was a higher ORR and PFS among patients treated with hyperCVAD/HDAM (83.3%) vs. pts treated with CHOP (62%). However it did not improved OS when compared to CHOP. The use of HDC-ASCS in first remission was associated with improved OS. The median OS for pts observed after front-line chemotherapy was 32 months and 59 months for pts that received HDC-ASCS [Hazard ratio 0.54 (95% CI 0.16-1.83) (p=0.32)]. Conclusions: Our data suggest that hyperCVAD/HDAM results in higher ORR and PFS in T-cell lymphoma than CHOP. More importantly, the use of HDC-ASCS in first remission appears to improve the OS of non-ALCL T-cell lymphoma patients. ANCRC regimens incorporating novel agents follow by HDC-ASCS in first remission is emerging as an attractive therapeutic intervention for a selected group of T-cell lymphoma patients been evaluated in ongoing clinical trials.

Outcomes of GDPT (gemcitabine, cisplatin, prednisone,thalidomide) versus CHOP in newly diagnosed peripheral T-cell lymphoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8018-8018
Author(s):  
Ling Li ◽  
Yuanyuan Sun ◽  
Xin Li ◽  
Lei Zhang ◽  
Xinhua Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
The Other ◽  
Newly Diagnosed ◽  
Peripheral T Cell Lymphoma ◽  
Significant Difference ◽  
Gene Expression Levels

8018 Background: Peripheral T-cell lymphoma(PTCL) is highly heterogeneous invasive NHL.There is no consensus standard treatment for it now. So outcomes of GDPT versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in treating newly diagnosed PTCL were compared. Methods: An open-label prospective clinical trial with 153 newly diagnosed PTCL patients conducted between January 2010 and December 2018 was designed. Patients were randomly assigned to the GDPT group (77 cases) and CHOP group (76 cases). Patients in each group were further divided into four subgroups: PTCL-NOS, ALCL, AITL, and an other types, in accordance with pathological patterns. Based on expression of RRM1, TOP2A, TUBB3 and ERCC1, patients were divided into groups with high and low gene expression levels. Clinical characteristics, side effects, efficacy, PFS and OS were compared. Results: There were no significant differences in the basic clinical features or side effects between the GDPT and CHOP groups. The ORR of the GDPT group was better than that of the CHOP group (66.3%vs. 50.0%, P= 0.042), as was the CR rate (42.9% vs. 27.6%, P= 0.049). Patients in the GDPT group had a longer PFS and OS than the CHOP group. The 4-year PFS and OS rates in the GDPT group were both superior to those in the CHOP group (63.6% vs. 53.0% for PFS, P= 0.035; 66.8% vs. 53.6% for OS, P= 0.039).In the GDPT group, the difference in CR between the four subgroups was statistically significant (P = 0.046).In the CHOP group, differences in both CR and ORR among the four subgroups were statistically significant ( P= < 0.001 and P= 0.005, respectively).There were also statistically significant differences in CR between patients treated with CHOP and GDPT in the PTCL-NOS subgroup, AITL subgroup, and the other types subgroup( P= 0.015; P= 0.003; P= 0.005, respectively).The data also showed a significant difference in OS among the four subgroups within the GDPT group ( P= 0.001).The OS of AITL was shorter than that of the other three subgroups. Four subgroups of CHOP showed a significant difference in PFS ( P= 0.019). There was no statistical association between responses and the gene expression levels of RRM1, ERCC1, TUBB3 and TOP2A. Conclusions: The GDPT group had better response rates and prolonged the patients’ PFS and OS. As a promising new regimen, GDPT is expected to become the first-line therapy for PTCL. New agents should be applied to patients who do not achieve good responses with previous treatment, such as those diagnosed with angioimmunoblastic T cell lymphoma. Clinical trial information: NCT01664975 .

Sign in / Sign up

Export Citation Format

Share Document