Bexarotene Is Highly Active in the Treatment of Subcutaneous Panniculitis-Like T-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3344-3344 ◽  
Author(s):  
Ana M. Molina ◽  
Ranjana Advani ◽  
Sunil Reddy ◽  
Richard Hoppe ◽  
Jonathan W. Friedberg ◽  
...  
Keyword(s):  
T Cell ◽  
Combination Chemotherapy ◽  
T Cell Receptors ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Single Agent ◽  
Response To Therapy ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Cell Receptors

Abstract Background: Subcutaneous Panniculitis-like T-cell lymphoma (SPTCL) is a rare, often aggressive T-cell lymphoma. Recently it has been appreciated that there are two clinical courses, whereby some patients have rapidly progressive disease and others have a chronic course. The likelihood of an aggressive course may be dependent on the T-cell receptor phenotype expressed by the tumor, with γ/δ expression portending a worse outcome than α/β expression. In the WHO-EORTC classification γ/δ expressing cases of SPTCL are provisionally renamed as Primary Cutaneous γ/δ T-cell lymphoma. Although most reported cases have been treated with combination chemotherapy, there are no prospective trials for the treatment of SPTCL. With chemotherapy, only a minority of patients have durable remissions; the majority have either primarily refractory disease or relapses. Bexarotene is an oral retinoid used for the treatment of mycosis fungoides and other T cell lymphomas. Patients and methods: We treated eight SPTCL patients with bexarotene. There were four women and four men, with a median age of 56 years (range 23–80). All patients presented with disseminated subcutaneous nodules, Stage IV, but without extracutaneous involvement. Three patients presented with pancytopenia, without bone marrow involvement, suggestive of hemophagocytic syndrome. Four patients had an elevated LDH and four had ECOG PS > 2. Five patients received bexarotene as primary treatment. Three patients had progression of disease after previous combination chemotherapy. Doses of bexarotene ranged from 100mg/m2 – 450 mg/m2. All patients received at least one month of therapy. Results: Overall 5/8 (63%) patients responded. Two patients progressed at one and three months. One of these patients could only tolerate 100mg/m2. One patient had stable disease for four months. Two patients had partial responses (PR) lasting 10 and 18 months. One of the PR patients was given chemotherapy to induce a remission prior to a planned allogeneic stem cell transplant. They progressed on CHOP and ICE and then responded again to bexarotene. Three patients achieved a complete response (CR). Two remain in CR at 14 and 26 months on bexarotene. The other patient had a CR lasting 33 months. Bexarotene was then discontinued due to hypertriglyceridemia, and the patient developed new lesions within three months. As expected with bexarotene, toxicities of treatment were limited to hypertriglycerides and hypothyroidism. IPI was not predictive of response to therapy. Both patients with documented γ/δ T-cell receptors achieved a PR. Conclusion: Bexarotene showed a high response rate in SPTCL, which characteristically responds poorly to chemotherapy. These responses included patients with both γ/δ and α/β T-cell receptors. Given bexarotene’s favorable toxicity profile and demonstrated activity, it represents an excellent treatment option for patients with this rare T-cell lymphoma. Further study is required to determine whether bexarotene is best used as a single agent, or as part of combination or sequential therapies.

scholarly journals Epidemiology and Clinicopathology of Hepatosplenic T-Cell Lymphoma (HSTCL): Analysis of a Pooled Database

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-28
Author(s):  
Philip A Haddad ◽  
Dalia Hammoud ◽  
Kevin M. Gallagher
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
T Cell ◽  
Combination Chemotherapy ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
The Impact

Introduction: HSTCL is a rare and rapidly progressive extranodal T-cell lymphoma. It accounts to for 1-2% of all T/NK cell lymphomas. Afflicting adolescents and younger adults, HSTCL commonly presents with constitutional symptoms, cytopenias, and hepatosplenomegaly. Up to a third of all the reported cases arise within a clinical context of immunosuppression. This analysis was conducted to update and expand our existing knowledge of this rare disease. Methods: In order to study the demographic characteristics, cytogenetic and molecular signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 360 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathology factors on overall survival (OS). Results: A total of 360 patients with confirmed HSTCL were identified. The median age was 30 (0.8-86) years with a peak incidence between ages 13 and 26. There is male predominance with M:F ratio of 2.6 in the whole group, 6 in the immunosuppressed, 2.2 in γδ, and 1.2 αβ. HSTCL with TCRαβ tended to be more CD5+, CD8+, and CD57+. More than 90% presented with constitutional symptoms and had bone marrow involvement. Median overall survival of the whole group was 12 months. The median duration of symptoms to diagnosis is 2 months. The median time from immunosuppression to diagnosis is 5.3 years. Sex, age, jaundice, autoimmune hemolytic anemia, hemophagocytosis, and bone marrow involvement did not affect OS. Furthermore, i7 and/or +8 and TCR type did not impact OS. Compared to no treatment, combination chemotherapy and auto and allo stem cell transplant (SCT) were statistically superior with a median OS of 1, 9, 34, and 30 months respectively. While OS of combination chemotherapy was inferior to that of SCT, there was no significant difference between auto and allo SCT. Immunosuppression adversely impacted OS in the whole group (HR:0.40, p<0.0001) and among the SCT subgroup (HR:0.38, p=0.06). There was no difference between immunosuppression with and without TNFα inhibitors. The quality of response prior to transplant also seemed to impact outcome though it did not reach statistical significance (p=0.07) with OS of 15, 30, and 44 months for none/transient, response less than CR, and CR respectively. Splenectomy improved survival in the whole group (HR:0.66; 95%CI 0.47-0.93). Further analysis revealed that splenectomy impacted survival in the context of combination chemotherapy but not SCT. Conclusions: This study presents an updated epidemiologic and clinicopathologic data from a pooled cohort of patients with HSTCL. It identifies the impact of immunosuppression, quality of response, treatment modalities as well as splenectomy on OS. Disclosures No relevant conflicts of interest to declare.

A case of cutaneous T-cell lymphoma expressing γδ T-cell receptors

1993 ◽  
Vol 28 (2) ◽  
pp. 355-360 ◽  
Author(s):  
Mayumi Fujita ◽  
Yoshiki Miyachi ◽  
Fukumi Furukawa ◽  
Eiko Toichi ◽  
Ikuko Furukawa ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Γδ T Cell ◽  
Cell Receptors

Update of the NCI multiinstitutional phase II trial of romidepsin, FK228, for patients with cutaneous or peripheral T-cell lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8027-8027 ◽  
Author(s):  
R. Piekarz ◽  
R. Frye ◽  
J. Wright ◽  
W. Figg ◽  
S. Allen ◽  
...  
Keyword(s):  
T Cell ◽  
Histone Deacetylase Inhibitors ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Overall Response ◽  
Prior Therapy

8027 Background: The histone deacetylase inhibitors (HDIs) are a class of differentiating agents undergoing clinical testing. Like other HDIs, romidepsin (FK228) modulates expression of genes involved in cell cycle regulation and markers of differentiation in cancer cell lines, leading to induction of differentiation or apoptosis. Romidepsin has demonstrated clinical activity in patients with T-cell lymphoma. Methods: Patients with CTCL (42) or PTCL (36) were enrolled in the NCI multi-institutional trial and assigned to cohorts based on extent of prior therapy and pathology. Romidepsin is administered on days 1, 8, and 15 of a 28 d cycle with a starting dose of 14mg/m2. Responses for patients with PTCL are measured using Cheson criteria, and CTCL using RECIST criteria. Results: Cohort one, composed of 27 patients who had previously received no more than 2 prior cytotoxic regimens of chemotherapy, has completed enrollment. Responses observed include 3 patients with CR and 7 patients with partial responses, yielding an overall response rate of 37%. Of note, responses were observed independent of stage of disease. Among 18 patients with stage IV disease, 6 patients had a complete or partial response, including 3 patients with Sézary syndrome. When including patients with greater than 2 prior cytotoxic regimens, the overall response rate was 31%. A replicate arm has been opened with the goal of confirming the response rate observed in the first cohort. Response data have not been evaluated from this arm at this time. Responses observed in 36 patients with refractory or relapsed PTCL includes 3 patients with CR and 8 patients with partial responses, comprising an overall response rate of 30%. Responses were observed independent of prior therapy, with some patients having undergone prior stem-cell transplant. Molecular endpoint analysis was performed on peripheral mononuclear cells (PBMNCs) and tumor biopsies from treated patients evaluating histone acetylation and changes in gene expression. Conclusions: Romidepsin as a single agent appears to have significant single agent activity in patients with CTCL and PTCL. Combination therapy with romidepsin may increase efficacy and should be pursued. This protocol remains open to accrual. No significant financial relationships to disclose.

scholarly journals Romidepsin Induces Durable Responses in Patients with Relapsed or Refractory Angioimmunoblastic T-Cell Lymphoma (AITL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1742-1742 ◽  
Author(s):  
Barbara Pro ◽  
Steven M. Horwitz ◽  
H. Miles Prince ◽  
Francine M. Foss ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
T Cell ◽  
Systemic Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Single Agent ◽  
T Cell Lymphoma ◽  
Prior Systemic Therapy ◽  
Line Of Therapy

Abstract Background: AITL is a common subtype of peripheral T-cell lymphoma (PTCL) that typically presents with lymphadenopathy and extranodal disease and is associated with frequent infections due to immune dysregulation. Patients with AITL generally have a poor prognosis, even with aggressive chemotherapy. Romidepsin is a structurally unique, potent, bicyclic, class 1 selective histone deacetylase inhibitor approved by the US Food and Drug Administration for the treatment of patients with PTCL who have received at least 1 prior therapy and patients with cutaneous T-cell lymphoma who have received at least 1 prior systemic therapy. A phase 2, single-arm, open-label registration study (GPI-06-0002) demonstrated durable clinical benefit and long-term tolerability of romidepsin in patients with relapsed or refractory PTCL. Here, we present updated data for patients with AITL from GPI-06-0002. Methods: Patients with histologically confirmed PTCL (N = 130) who experienced failure with or were refractory to ≥ 1 prior systemic therapy received romidepsin 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days for up to 6 cycles; treatment could be extended for patients with stable disease (SD) or response. The protocol was amended to allow for (but not mandate) maintenance dosing of twice per cycle for patients treated for ≥ 12 cycles; dosing could be further reduced to once per cycle at ≥ 24 cycles in patients who had received maintenance dosing for ≥ 6 months. The primary endpoint was the rate of confirmed/unconfirmed complete response (CR/CRu) as determined by an independent review committee based on International Working Group criteria. Secondary endpoints included objective response rate (ORR: CR/CRu + partial response [PR]), duration of response (DOR), and time to progression; progression-free survival and overall survival (OS) were also assessed. Disease response was assessed every 2 treatment cycles. The analysis herein is focused on updated data (median follow-up, 22.3 months) in patients with AITL. Results: Of 27 patients with AITL, most had advanced disease (96% stage III/IV; 44% with bone marrow involvement; 52% with elevated lactate dehydrogenase) and heavy pretreatment (median, 2 [range, 1-8] prior therapies) and 37% were refractory to their last line of therapy. The ORR for patients with AITL was 33% (9 of 27 patients), with most responders achieving CR/CRu (6 of 27 patients; 22%). Most responses were noted at the first response assessment, with a median time to response of 52 days. Furthermore, an additional 8 patients with AITL achieved SD (30%), 3 of whom had disease stabilization for ≥ 90 days. The median DOR has not been reached, with the longest response ongoing at 56 months (Figure). Five patients with AITL and DOR of ≥ 12 months with romidepsin had either 1 (n = 2) or 2 (n = 3) prior therapies, and 3 of the 5 were refractory to their last line of therapy (CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone], GVD [gemcitabine, vinorelbine, doxorubicin], or pralatrexate). All 5 responding patients who remained on treatment for ≥ 12 cycles received maintenance dosing of twice per cycle. Dosing for the 3 patients with the most durable responses was also later amended to 1 dose per cycle. For all patients with AITL treated with romidepsin, the median OS was 18 months (range, 2-58 months). Grade 3/4 infections (all types pooled, regardless of relationship to study drug) were reported in 6 patients (22%), and no discontinuations due to infection occurred. Conclusions: Single-agent romidepsin induced rapid, complete, and durable responses in some patients with relapsed/refractory AITL, with several responses ongoing for > 3 years. Patients with long-term responses to romidepsin received maintenance dosing. These results support the use of romidepsin in relapsed/refractory AITL. Figure. Patients With AITL Who Achieved a Response to Romidepsin Figure. Patients With AITL Who Achieved a Response to Romidepsin Disclosures Pro: Celgene: Honoraria. Horwitz:Bristol Myers Squibb,: Consultancy; Amgen: Consultancy; Spectrum: Research Funding; Seattle Genetics: Consultancy, Research Funding; Kiowa Kirin: Research Funding; Infinity: Research Funding; Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Jannsen: Consultancy. Prince:Celgene: Honoraria, Research Funding. Foss:Celgene: Consultancy, Research Funding, Speakers Bureau. Sokol:Celgene: Consultancy. Morschhauser:Spectrum: Honoraria; Bayer: Honoraria; Mundipharma: Honoraria; Genentech: Honoraria; Gilead: Honoraria. Pinter-Brown:Celgene: Consultancy. Padmanabhan Iyer:Janssen Biotech, Inc.: Honoraria; Celgene: Speakers Bureau; Houston Methodist Cancer Center: Employment. Shustov:Celgene: Consultancy, Honoraria, Research Funding. Balser:Celgene: Consultancy. Coiffier:Celgene: Honoraria.

Gemcitabine Is An Active Agent in the Treatment of T Cell Non Hodgkin Lymphomas.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4771-4771
Author(s):  
Ahmad Jajeh
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Dose Range ◽  
Single Agent ◽  
Active Agent ◽  
T Cell Lymphoma ◽  
World Health ◽  
High Dose ◽  
Cell Transplant

Abstract Abstract 4771 Approximately 12- 15% of non- Hodgkin lynphoma NHL are caused by malignant Tcell lymphocytes. The success of the treatment in the aggressive form has lagged behind that of B -Cell in term of poor resonse and durability. Peripheral T-Cell lymphoma PTCL and cutaneous T-Cell lymphoma CTCL are two major charachterized classifiction in the World Health Organization based on their morphology, growth patern and genetics. Stem cell transplant and high dose chemotherapy have been associated with long term response rate of 45%. However this treatment is not well tolerated and not feasible for many patients. Other theraputic options include cytotoxic drugs CHOP,CVP regimen, purine analogues, Denileukin diftitox, Histone deacetylation inhibitors and novel antifolates drugs. In this abstract we will show our experience with gemcitabin an active antimetabolite as a single agent or in combination with other active drugs. Eight patients with PTCL, five with visceral stage of mycosis fundoides( one patient with HIV infection), two with refractory anaplastic Ki positive NHL and one with angioimmunoblastic type. All patients failed a minimum two lines of therapy. Mean age 58 years( range 28-75). Eight blacks, two whites, four hispanics and one asian. Meduim cycles given are four. The dose range 800-1000 mg/M2, given weekly x3 every 28 days cycle. Overall response rate is 85%. Complete response rate CR in eight patients ( three PTCL, three mycosis fungoides and two anaplastic large cell NHL). Partial response PR in four and stable disease in one. Median duration of response is nine months, range six to two years. Median time for response is six weeks. In conclusion:Gemcitabine is an active drug in T-Cell lymphomas particularly when used in combination with other active agents. Maintenance dosing or retreatment with this drug should be investigated. Disclosures: No relevant conflicts of interest to declare.

Clinicopathologic Characteristics of HIV-Associated Peripheral T-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3924-3924
Author(s):  
Jorge Castillo ◽  
Brady Beltran ◽  
Jaime Collins ◽  
Jose L Diez-Martin ◽  
Francisco Hernandez-Ilizaliturri ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Median Survival ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
The United States ◽  
Response To Therapy ◽  
T Cell Lymphoma ◽  
Cd4 Count

Abstract Abstract 3924 Poster Board III-860 Introduction The incidence of lymphomas is increased in HIV-infected individuals. Most of the cases are B-cell subtypes of non-Hodgkin lymphoma. Although the incidence of mature or peripheral T-cell lymphomas (PTCL) seems to be increased in HIV-positive cases, clinicopathological data is lacking. The objective of this study is to describe the characteristics of non-cutaneous PTCL in HIV-infected individuals and identify potential prognostic factors. Methods Institutions within and outside of the United States were invited to submit original data on cases of HIV-associated PTCL. Data on each case included country of origin, age, sex, ethnicity, CD4 count, use of highly active antiretroviral therapy (HAART), B symptoms, lymphoma subtype according to the WHO classification of lymphoid neoplasms, expression of ALK, EBV and Ki-67, T-cell gene rearrangement, number of extranodal sites, bone marrow involvement, clinical stage, performance status, lactate dehydrogenase (LDH) levels, frontline therapy, response, use of stem cell transplantation (HSCT), final outcome, survival in months and cause of death; these will be presented using descriptive statistics. Univariate analyses were performed using Kaplan-Meier survival estimates compared using the log-rank test. Cox proportional-hazard regression test was used for the multivariate analysis. P-values of less than 0.05 were considered significant. Results Thus far, data on 24 cases have been obtained from 7 institutions. From these cases, 13 (54%) are from South America, 5 (21%) from Europe, 3 (12.5%) from North America and 3 (12.5%) from Asia. Thirteen cases (54%) are Hispanic, 5 (21%) are Caucasian, 3 (12.5%) are Black and 3 (12.5%) are Asian. Median age is 39 years (range 26 to 58 years) and the male-to-female ratio is 7:1. Sixteen cases (70%) presented with B symptoms. Median CD4 count is 129 cells/mm3 (range 4 to 305 cells/mm3). Twelve cases (63%) reported use of HAART. Fourteen cases (58%) are PTCL, unspecified (PTCLU), 4 cases (17%) anaplastic large cell lymphoma (ALCL), 4 cases (17%) of NK/T-cell lymphoma (NKTCL) and 2 cases (8%) angioimmunoblastic lymphoma (AITL). All ALCL cases were ALK-negative; EBV was expressed in 50% of NKTCL cases but in none of the AITL cases. Four of 15 cases (27%) had involvement of more than 2 extranodal sites, 3 of 11 cases (27%) had bone marrow involvement, 19 of 24 cases (79%) presented with advanced stage, 5 of 12 cases (42%) had an elevated LDH level and 8 of 24 cases (33%) had a performance status higher than 2. Thirteen of 24 cases (54%) were treated with chemotherapy alone from which 8 cases (62%) received CHOP therapy; six of 24 cases (25%) did not receive any therapy. Nine of 14 cases (65%) responded to therapy (29% CR and 36% PR); 35% of cases did not respond to therapy. Five cases of 14 (36%) underwent HSCT; 4 cases (29%) in the frontline and 1 case (7%) in the salvage setting. At the time of this report, 63% of cases have died; 53% due to infectious complications and 40% due to lymphoma progression. The median survival for the group was 10 months. The median survival for treated (n=19) and untreated cases (n=5) were 10.5 and 1 month, respectively (p=0.005). Conclusions HIV-associated PTCL tends to affect younger men with CD4 counts of less than 200 cells/mm3. PTCLU is the most common subtype reported in HIV-infected individuals. HIV-associated ALCL cases do not appear to express ALK. The survival of treated HIV-associated PTCL cases is short at 10.5 months despite a 65% initial response to therapy. Accumulation of data continues. Disclosures: No relevant conflicts of interest to declare.

Pralatrexate Is Effective In Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL) with Prior Ifosfamide, Carboplatin, and Etoposide (ICE)-Based Regimens

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1753-1753 ◽  
Author(s):  
Andre Goy ◽  
Barbara Pro ◽  
Kerry Joanne Savage ◽  
Nancy L. Bartlett ◽  
Mary Jo Lechowicz ◽  
...  
Keyword(s):  
T Cell ◽  
Combination Chemotherapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
The United States ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Second Line ◽  
Peripheral T Cell Lymphoma ◽  
Line Therapy

Abstract Abstract 1753 Background: Peripheral T-cell lymphoma (PTCL) is a group of aggressive T- and NK-cell lymphomas with a poor prognosis, with most patients progressing within 6 to 12 months after first-line therapy. Despite a paucity of data in PTCL, combination chemotherapy such as ifosfamide/carboplatin/etoposide (ICE)-based regimens (eg, ICE, rituximab-ICE [RICE] and dexamethasome-ICE [DICE]), are often used in the salvage setting. These regimens can induce responses allowing some patients to proceed to a stem cell transplant (SCT), yet most patients relapse quickly (Horwitz et al, Blood. 2005;(106:a2679; Zelenetz et al Annals Oncol. 2003;14:i5-i10.). Pralatrexate (FOLOTYN®), a rationally-designed folate analog, was granted accelerated approval in the United States for the treatment of relapsed or refractory PTCL, based on results of the pivotal study, PROPEL (Pralatrexate in Patients with Relapsed Or Refractory Peripheral T-cell Lymphoma). The present exploratory analysis of PROPEL data was conducted to assess the efficacy of pralatrexate postfailure of ICE-based regimens. Methods: Of the 109 patients enrolled in PROPEL and evaluable for efficacy, a subset of 20 patients had received an ICE-based regimen as their second-line therapy and progressed at some point prior to treatment with pralatrexate (30 mg/m2 weekly for 6 of 7 week cycles). Results: The median age of the 20 patients with a prior ICE-based regimen was 45 years. A summary of pralatrexate efficacy data is presented in the table below. Pralatrexate demonstrated ORR of 40% in ICE-pretreated patients (n=20). Nine of the 20 patients received ICE-based regimens as their most recent therapy prior to pralatrexate. Of these, 2 patients did not respond to these aggressive combination chemotherapies, but did respond to pralatrexate (1 CR and 1 PR). Two of the 20 patients achieved a CR on pralatrexate and proceeded to SCT; DoR to pralatrexate in these patients was censored (at 1.3 and 4.9 months). However, these 2 patients remain in CR and the current disease-free period (DoR: pralatrexate + transplant) is 10.9 and 30.8 months. The most common grade 3 adverse events (AEs) were anemia (8 patients) and mucositis (5 patients), and grade 4 AEs was thrombocytopenia (6 patients). Five patients discontinued treatment with pralatrexate due to AEs. From a safety perspective, this compares favorably with ICE-based regimens, recognized for their intensity and their need for hospitalization for administration (Hertzberg et al, Ann Oncol. 2003;14[suppl 1] i11-i16). The PROPEL study also collected information on response to therapies administered prior to study entry. In the 20 patients included in the analysis, the ORR to prior ICE-based regimens was 25% with 3 patients achieving CR (15%) and 2 PR (10%). An additional 3 patients had SD (15%), 7 had PD (35%), and 5 patients had nonassessable response. The median duration on treatment for responders to ICE-based regimens was <1 month, in contrast with pralatrexate's long DoR (median 16.2 months according to investigators’ assessment). Conclusions Pralatrexate was highly active in patients with PTCL who received prior ICE-based chemotherapy, with an ORR of 40% including CRs leading to SCT in some patients. Of note, is the long duration of pralatrexate responses in marked contrast to the short response duration of the combination chemotherapy regimens. Taken together, the efficacy of single-agent pralatrexate compared favorably with ICE-based regimens, a finding that is consistent with other exploratory analyses, showing that pralatrexate can reverse the characteristic progressive resistance of PTCL patients to second-line chemotherapy, and that pralatrexate is an effective second-line treatment for patients with PTCL. Disclosures: Goy: Allos Therapeutics, Inc.: Consultancy, Honoraria. Pro:Allos Therapeutics, Inc. : Research Funding. Savage:Allos Therapeutics, Inc.: Consultancy, Honoraria. Lechowicz:Allos Therapeutics, Inc.: Consultancy; Celgene Corporation: Consultancy. Jacobsen:Allos Therapeutics, Inc.: Consultancy. Fruchtman:Allos Therapeutics, Inc.: Employment. O'Connor:Allos Therapeutics, Inc.: Research Funding.

scholarly journals Clinicopathologic Determinants of Survival in Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma (MEITL): Analysis of a Pooled Database

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-28
Author(s):  
Philip A Haddad ◽  
Neelakanta Dadi
Keyword(s):  
Weight Loss ◽  
T Cell ◽  
Surgical Resection ◽  
Combination Chemotherapy ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Anatomic Site ◽  
Duration Of Symptoms

Introduction: MEITL is a rare and rapidly progressive extranodal T-cell lymphoma that arises from the intestinal intraepithelial T lymphocytes. Established in the 2016 WHO classification, this entity was carved out of what was previously known as type 2 enteropathy-associated T-cell lymphoma. MEITL usually affects the young-old and is not associated with celiac disease. We conducted this analysis to explore the clinicopathologic determinants of survival in this newly established T-cell entity. Methods: In order to study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 116 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 116 patients with confirmed MEITL were identified. The median age was 59.5 years with a peak incidence between ages 56 and 68. There was a male predominance with M:F ratio of 2. The jejunum was the most commonly involved site (71%). Median OS of the whole group was 11 months. The most common presentations were abdominal pain, followed by perforation, diarrhea, and weight loss. The majority presented at stages I&II (78%). The median duration of symptoms prior to diagnosis was 4 months. Compared to no treatment, combination chemotherapy and stem cell transplant (SCT) were statistically superior with a median OS of 2, 9, and 34 months respectively (p=0.0005). Further analysis revealed that surgical resection imparted a survival advantage on its own and in conjunction with combination chemotherapy and SCT. When surgical resection was incorporated in the analysis, median OS amounted to 2, 5, 7, 11, 13, 24 months for no treatment, surgery alone, chemotherapy, surgery+chemotherapy, SCT, and surgery+SCT respectively (p=0.0015). The quality of response to treatment also seemed to impact the outcome (p=0.0005) with median OS of 6, 36, and 60 months for none/transient, PR, and CR respectively. OS was not impacted by sex, presentation with obstruction or perforation, or anatomic site involvement. While older age, weight loss, and TCRγδ seemed to negatively impact OS, they did not reach statistical significance. Conclusions: This study presents an updated clinicopathologic data from a pooled cohort of patients with MEITL. It identifies quality of response, treatment modalities as well as surgical resection as major determinants of OS in this rare disease. Disclosures No relevant conflicts of interest to declare.

Final Report Of a Phase II Clinical Trial Of Lenalidomide Monotherapy For T-Cell Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4376-4376 ◽  
Author(s):  
Ethan Toumishey ◽  
Angeli Prasad ◽  
Gregory S. Dueck ◽  
Neil Chua ◽  
Daygen Finch ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cell ◽  
Median Time ◽  
Combination Chemotherapy ◽  
Cell Lymphoma ◽  
Previous Treatment ◽  
T Cell Lymphoma ◽  
Final Report ◽  
Cell Transplant ◽  
T Cell Lymphomas

Abstract Background Patients with T-cell lymphomas face a poorer prognosis when compared to patients with B-cell lymphomas. New therapeutic approaches need to be developed in order to improve outcomes for these patients. We report the final results of a phase 2 multicenter clinical trial evaluating lenalidomide monotherapy in T-cell lymphomas. Methods Forty patients with relapsed and refractory T-cell lymphomas other than mycosis fungoides, as well as patients with untreated T-cell lymphoma who were not candidates for combination chemotherapy, were prescribed oral lenalidomide (25mg daily) on days 1 to 21 of each 28 day cycle, with standardized dose reductions for toxicity. Treatment continued until disease progression, death or unacceptable toxicity. The primary endpoint was overall response rate, and secondary endpoints were complete and partial response rates, progression-free and overall survival (PFS, OS), and safety. We also determined duration of response (DoR). Results Forty patients were enrolled in the study; one was subsequently deemed ineligible. In the 39 eligible patients, the median age was 65. ECOG PS was 0-1 (n=29), 2 (n=8), and 3 (n=2). The histology of the studied cases included peripheral T-cell unspecified (PTCL-u, n=14), angioimmunoblastic (n=9), anaplastic large cell (n=10), enteropathic T-cell (n=2), Hepatosplenic gamma/delta (n=2), and lymphoblastic T-cell lymphoma (n=2). The number of prior therapies was 0 (n=8), 1 (n=14), 2 (n=8), 3 (n=6), 4 (n=2), and 5 (n=1). Five patients had previous autologous stem cell transplant. Eleven patients were refractory to their previous treatment. The median time from diagnosis until the start of treatment was 14 months (range, 1-204 months). The median time from completion of prior therapy to the start of lenalidomide was 5 months (range, 1-48 months). The ORR was 10/39 (26%); 3 (8%) were complete responses and 7 were partial responses. Responses occurred in anaplastic, angioimmunoblastic, and PTCL-u histologies. Three additional patients had SD ≥5 cycles. The median OS was 12 months (range<1-69+ months), median PFS was 4 months (range,<1-50+ months) and the median DoR was 13 months (range 2-37+ months), including 5 responses lasting greater than 1 year. The most common grade 4 adverse event was thrombocytopenia (21%) while pain NOS (21%) and neutropenia (13%) were the most commonly reported grade 3 adverse events. Among the patients who had relapsed/refractory peripheral T-cell lymphoma (n=29) the ORR was 24%, median OS was 12 months, median PFS was 4 months, and median DoR was 5 months (range, 2-37+ months). The ORR of the subpopulation of previously untreated patients who were not eligible for combined chemotherapy (n=8) was 43%, median OS was 22 months (range,<1-38+ months), median PFS was 2 months (range,<1-38+ months), and median DoR was 21 months (range 5-28+ months). Discussion In T-cell lymphomas, oral lenalidomide monotherapy demonstrated clinically relevant efficacy. The toxicity profile in T-cell lymphoma is manageable and consistent with prior studies involving lenalidomide. Lenalidomide also showed promise for patients who are not eligible for combination chemotherapy. The results with lenalidomide in relapsed/refractory patients are comparable to those seen with other available monotherapies for this disease. Several durable (>1 year) responses were seen, but the proportion of durable responses was low. Future development of lenalidomide therapy for T-cell lymphomas should include efforts to identify the subset of patients most likely to benefit, and the development of rational drug combinations. Disclosures: Off Label Use: Lenalidomide was prescribed to treat T-cell lymphoma. Stewart:Celgene: Honoraria. van der Jagt:Millenium: Consultancy; Roche: Consultancy; Celgene: Consultancy. Reiman:Celgene: Consultancy; Celgene: Research Funding.

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