scholarly journals Clinical Spectrum, Evolution and Management of Autoimmune Cytopenia Associated with Angioimmunoblastic T-Cell Lymphoma: A Retrospective, Multicenter Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1816-1816
Author(s):  
Etienne Crickx ◽  
Radjiv Goulabchand ◽  
Claire Fieschi ◽  
Lionel Galicier ◽  
Paul Coppo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
T Cell ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Control Group ◽  
Autoimmune Cytopenia ◽  
Retrospective Multicenter Study ◽  
Smooth Muscle Antibodies

Abstract Introduction Angioimmunoblastic T-cell lymphomas (AITL) are frequently associated with immune system activation such as hypergammaglobulinemia, positive direct antiglobulin test, anti-smooth muscle antibodies and clinical autoimmunity. Autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) have been reported, but to date, there is no specific study focusing on autoimmune cytopenia (AIC) in AITL. We sought to determine the clinical characteristics, evolution and response to treatment of AITL presenting with autoimmune cytopenia, including ITP, AIHA, auto-immune neutropenia (AIN) and pure red cell aplasia (PRCA) in a large cohort of patients from the multicentric T-cell lymphoma consortium (TENOMIC). Patients and methods We conducted a retrospective, multicenter study of patients diagnosed with AITL between 2001 and 2015 and presenting with at least one AIC (i.e. AHAI and/or ITP and/or AIN and/or PRCA, defined according to the international criteria). Patients were retrospectively selected from a cohort of 293 patients with AITL from a multicentric T-cell lymphoma consortium (TENOMIC). Medical charts were collected using a standardized from. Patients with AIC were matched for age and sex to control patients (5/1 ratio) diagnosed with AITL without AIC from the cohort. Results 28 patients were included, with a mean age of 63 years (range 39 - 83), and 50% were females. There were 41 AIC (AIHA, n=21 (including 5 cold agglutinin diseases), ITP, n=12, PRCA, n=7, AIN, n=1). Among them, 17 patients had only one AIC, 7 had both ITP and AIHA (Evan's syndrome) and 4 had PCRA associated with another AIC. One hundred and thirty six control patients were included (mean age 64 years (range 35 - 84), 49% female). Clinical characteristics of AITL at diagnosis showed more stage IV disease in AIC patients versus control patients (86% vs 66%, P= 0.0442), as well as more bone marrow (71% vs 34%, P=0.0005) and splenic (61% vs 19%, P< 0.0001) involvement. Immune activation markers such as anti-smooth muscle antibodies (71% vs 0.9%, P< 0.0001), gammaglobulins titers (27 g/l vs 18 g/l, P= 0.0019), and EBV replication (89% vs 61%, P= 0.0232), were significantly increased in AIC patients versus control patients. AIC were mainly concomitant with AITL diagnosis (83%). Only 2 patients had AIC before AITL diagnosis (2 and 8 months), and 4 patients developed AIC during the disease course (median 14 months (8 - 114)). Mean hemoglobin level at AIHA and PRCA diagnosis were 7.1 g/dl and 5.3 g/dl, and red blood cell transfusions were required in 52% and 86% of patients, respectively. Mean platelet count was 35 x 109/L at ITP diagnosis, and 42% of patients had bleeding manifestations, although no life threatening bleeding manifestation was observed. First line treatments of AIC included corticosteroids (88%), chemotherapy for AITL (71%), intravenous immunoglobulin (27%), or other treatments (12%), and were effective in all patients except for two patients who presented with refractory ITP. Ten patients had a relapse of AIC (5 ITP, 4 AIHA, 3 PRCA) with a median time to relapse of 4 months (1 - 18)). All AIC relapses were associated with AITL relapse. Only 3 patients had active AIC while AITL was considered in remission, including one patient who developed ITP after autologous stem cell transplantation. Sixty-four percent versus 66% of patients experienced AITL relapse in AIC and control group, respectively (P=1). Median overall survival (OS) and median progression free survival (PFS) were 77 and 12 months in the AIC group, and 41 and 12 months in the control group, respectively (P=ns). Conclusion In summary, AITL associated with AIC had more advanced disease with increased immune activation compared to our control group, although it did not impact OS and PFS. AIC were mainly inaugural and responded well to chemotherapy. Interestingly, all AIC relapses were associated with AITL relapse. These findings are of interest for management of AITL patients presenting with AIC. Disclosures Casasnovas: Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; ROCHE: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Leblond:Roche: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Michel:Amgen: Honoraria; Novartis: Honoraria. Dupuis:janssen: Honoraria; ABBVIE: Membership on an entity's Board of Directors or advisory committees.

scholarly journals EFS12 Is a Powerful Predictive Tool for Outcomes in Stage I Aggressive Non Hodgkin Lymphoma: A Report from Nationwide Registry in a Resource Limited Country Thai Lymphoma Study Group

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2128-2128
Author(s):  
Kitsada Wudhikarn ◽  
Udomsak Bunworasate ◽  
Jakrawadee Julamanee ◽  
Arnuparp Lekhakula ◽  
Archrob Khuhapinant ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Non Hodgkin Lymphoma ◽  
Resource Limited ◽  
Lymphoma Study Group

Introduction: Stage I disease represents a minor subset of aggressive Non-Hodgkin Lymphoma (NHL) accounting around 10%. Overall prognosis is generally good but varied upon different histologic subtypes and topographic presentation. Herein, we describe an implication of event free survival at 12 months (EFS12) as a predictor for outcomes of stage I aggressive NHL including real-world data on clinical characteristics and treatment patterns of stage I aggressive NHL in a resource-limited country. Patients and methods: Thai lymphoma study group conducted the lymphoma registry which prospectively enrolled and systematically followed newly diagnosed lymphoma patients between 2007 and 2014 from 13 nationwide major University hospitals. We abstracted data of stage I aggressive NHL patients from the registry and obtained additional information from medical record. Clinical characteristics, treatment patterns and survival outcomes were described. EFS12 was a binary endpoint defined as whether patients developed events at 12 months after treatment initiation. Overall survival (OS) was defined as duration from a specific time-point either at the time of diagnosis, at EFS12 time-point to or at the event to death from any causes. Logistic regression model was used to evaluate the association between clinical characteristics and EFS12. Cox regression with EFS12 as a time-dependent co-variate and other clinical parameters were applied to evaluate association between EFS12 and OS. Results: Of 4,371 newly diagnosed lymphomas, there was a total of 636 stage I lymphoma patients (6.86%) including 590 NHL (519 B cell, 71 T/NK cell) and 46 HL. Among 590 stage 1 NHL, 435 were considered patients (356 diffuse large B cell lymphoma (DLBCL) and 8 Burkitt lymphoma (BL), 19 peripheral T cell lymphoma not otherwise specified (PTCL-NOS), 7 angioimmunoblastic T cell lymphoma (AITL), 11 anaplastic large cell lymphoma (ALCL), 1 other PTCL subtypes and 33 extranodal NK T cell lymphoma (ENKTL)). Table 1 summarizes baseline characteristics and treatment data of stage I aggressive NHL. At the time of analysis 61 patients relapsed and 146 patients had died. Major causes of death included infection related events (n=37, 25.3%), non-infectious related complication (n=21, 14.4%) and disease progression (n=60, 41.1%) respectively. With a median follow up of 47.3 months, both median event free survival (EFS) and overall survival (OS) were not reached with corresponding 4 years EFS and 4 years OS of 79.0% and 68.9% respectively (Figure 1A). Four-years OS of patients with aggressive B cell NHL, PTCL and ENKTL was 70.2%, 75.5% and 48.0% respectively. A total of 328 patients achieved EFS12 (No event within the first 12 months after first line treatment initiation). Patients who achieved EFS12 had significant better OS than patients who failed to achieve EFS12 (4-years OS 89.1% vs 7.1%, Hazard ratio 25.9, 95% Confidence Interval 17.7-37.9, P<0.001) (Figure 1C, 1D). Non-relapsed mortality and cumulative incidence of relapse was 15.1% and 19.0% respectively (Figure 1B). By using multivariable cox regression analysis, factors associated with favorable survival outcomes included absence of B symptoms, complete remission from therapy and achieving EFS12 (Table 2). Conclusion: Stage I disease represented a small proportion of aggressive NHL. Natural history and prognosis were highly varied depending upon histology. EFS12 was a power prognostic factor for stage I aggressive NHL and could be used as a clinical tool to stratify patients. Optimal treatment is to be defined to improve outcome and meanwhile minimize toxicities for stage I aggressive NHL patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Impact of Comorbidities on Outcomes of Peripheral T Cell Lymphoma in Elderly Patients: An International Retrospective Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Monica Mead ◽  
Henrik Cederleuf ◽  
Thomas Relander ◽  
Mats Jerkeman ◽  
Fredrik Ellin ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Cause Of Death ◽  
Research Funding ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Rank Test ◽  
Peripheral T Cell Lymphoma ◽  
Cutaneous Lymphomas ◽  
Ann Arbor

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

Long-Term Outcomes of Patients with Peripheral T-Cell Lymphoma after Autologous Hematopoietic Cell Transplantation

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Olivier Veilleux ◽  
Francisco Socola ◽  
Sally Arai ◽  
Robert Lowsky ◽  
Judith A Shizuru ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Study Cohort ◽  
Private Company ◽  
Autologous Transplant ◽  
Support Research

Introduction: Patients with T-cell lymphoma have variable clinical manifestations and outcomes depending on the histology and their response to therapies. However, the overall outcomes are not as good as their B-cell lymphoma counterpart with induction chemotherapy alone. Therefore, autologous transplant is often used as consolidation in first remission or at relapse because of the poor outcomes with conventional therapy. We have reported previously on Stanford experience of these patients who underwent autologous transplant before 2007 (BBMT 2008, 14:741). Here, we reported a retrospective review of patients in the modern era (2008-2018) with emphasis on the impact of pre-transplant disease status on outcomes and post-transplant relapse management. Method: Between July 1, 2008 and July 31, 2018, 102 consecutive patients with T-cell lymphoma received high dose chemotherapy/autologous hematopoietic cell rescue at Stanford and constitute the study cohort (Figure 1). This study cohort was selected for adequate follow-up (&gt;2 years) after transplant. Progression free survival (PFS) and overall survival (OS) was estimated from the date of transplant using the Kaplan-Meier method. PFS and OS were compared between groups with different pre-transplant disease status based on response to the last pre-transplant therapies (CR1 vs. PR1 vs. CR2). Result: This study cohort included patients with peripheral T-cell lymphoma, non-specified (n=21), angioimmunoblastic T-cell lymphoma (n=50), ALK-negative anaplastic large-cell lymphoma (n=14), ALK-positive anaplastic large-cell lymphoma (n=5), extranodal NK/T cell lymphoma (n=9), enteropathy-type T-cell lymphoma (n=1), adult T-cell leukemia/lymphoma (n=1) and hepatosplenic T-cell lymphoma (n=1). It had a male/female ratio of 61/41, and a median age of 58 years (range 23-71). At diagnosis the majority of the patients had stage III/IV disease (70%) and B symptoms (56%). The median time from diagnosis to transplant was 8.1 months (range 4-176). The majority of patients were in first complete remission (CR1, n=79) at the time of transplant, while others were in PR1 (n=11) or in CR2 (n=12) from last pre-transplant therapies. Ninety-one (89%) patients received high dose cyclophosphamide/carmustine/etoposide(CBV) and 11 patients received high dose carmustine/etoposide/cytarabine/melphalan (BEAM) prior to autograft infusion. Median follow-up post-transplant was 36.8 months (range 0.7-130) for the entire cohort. The estimated 3-year PFS and OS were 60% (95% CI 49-68%) and 75% (95% CI 65-82%), respectively (Figure 2A). Patients who were in CR1 had significantly better median PFS compared to patients in PR1 or CR2 (7.04 vs 1.19 years, p=0.039; 7.04 vs 0.48 years p=0.004, Figure 2B). The estimated 3-year PFS were 67% (95% CI 55-76%), 36% (95% CI 11-63%), and 29% (95% CI 8-56%) for the CR1, PR1 and CR2 groups respectively. Patients who were in CR1 also had significantly better median OS compared to patients in PR1 or CR2 (not reached vs 2.30 years, p=0.018; not reached vs 3.76 years p=0.045, Figure 2C).The estimated 3-year OS were 82% (95% CI 71-89%), 44% (95% CI 14-70%), and 53% (95% CI 21-78%) for the CR1, PR1 and CR2 groups respectively. In this cohort, there were no significant differences in either PFS or OS between different histology. Forty patients experienced disease relapse after transplant. The majority (n=28, 70%) of these patients received additional therapies including chemotherapy (n=13), brentuximab vedotin (n=12), HDAC inhibitor (n=7), and radiation (n=3) with a median systemic therapy of 2 (range 1-5). Thirteen patients eventually underwent allogeneic hematopoietic cell transplantation. The median OS after post-transplant relapse was 21.3 months (Figure 3). Both brentuximab vedotin and allogeneic transplant seemed to provide prolonged survival for these relapsed patients, with estimated 2-year post-relapse OS were 75% (95% CI 13-96%) and 63% (95% CI 28-84%) for the two groups respectively. Conclusion: Autologous transplant remains to be a good option as consolidation for patients with T-cell lymphoma, mostly in patients with first complete remission. While close to 40% of the patients experienced relapse after autologous transplant, additional therapies such as brentuximab vedotin or/and allogeneic transplant can provide long-term benefit for these patients. Disclosures Shizuru: Jasper Therapeutics, Inc: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Shiraz:Kite, a Gilead Company: Research Funding; ORCA BioSystems: Research Funding. Muffly:Servier: Research Funding; Amgen: Consultancy; Adaptive: Research Funding. Sidana:Janssen: Consultancy. Meyer:Orca Bio: Research Funding. Rezvani:Pharmacyclics: Research Funding. Miklos:Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Allogene Therapeutics Inc.: Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding; Adaptive Biotech: Consultancy, Other: Travel support, Research Funding. Negrin:Magenta Therapeutics: Consultancy, Current equity holder in publicly-traded company; Biosource: Current equity holder in private company; Amgen: Consultancy; BioEclipse Therapeutics: Current equity holder in private company; UpToDate: Honoraria; KUUR Therapeutics: Consultancy.

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.

Pralatrexate Is Active in Cutaneous T-Cell Lymphoma (CTCL): Results of a Multicenter, Dose-Finding Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 919-919
Author(s):  
Steven M. Horwitz ◽  
Madeleine Duvic ◽  
Youn Kim ◽  
Jasmine M Zain ◽  
Mary Jo Lechowicz ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Dose Reduction ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Single Agent ◽  
Optimal Dose ◽  
T Cell Lymphoma ◽  
Grade 3

Abstract Abstract 919 Background: Pralatrexate enters cancer cells via the reduced folate carrier-1 (RFC-1) and is efficiently polyglutamated by folylpolyglutamyl synthetase (FPGS), leading to high intracellular retention. In a Phase 1/2 study of patients with hematologic malignancies, pralatrexate demonstrated activity in aggressive T-cell lymphoma with a maximum tolerated dose (MTD) of 30 mg/m2 once weekly for 6 of 7 weeks. The generally indolent course of CTCL may be better treated at lower doses in a maintenance fashion if a lower incidence and severity of adverse events can be achieved while preserving activity. PDX-010 is an open-label, single-agent, multicenter, Phase 1 dose-reduction trial in patients with relapsed or refractory CTCL. The primary objective is to identify an optimal dose and schedule of pralatrexate for these patients. Methods: Eligibility included mycosis fungoides (MF), Sézary syndrome (SS), and primary cutaneous anaplastic large cell lymphoma (ALCL); with disease progression after at least 1 prior systemic therapy. The pralatrexate dose and schedule started at 30 mg/m2 by IV push on 3 of 4 weeks and subsequent cohorts received reduced doses (20, 15, 10 mg/m2) and/or schedules (3/4 or 2/3 weeks) of pralatrexate based on tolerability. All patients received supplementation with vitamin B12 1 mg intramuscularly every 8-10 weeks and folic acid 1 mg orally once daily. As we sought a well tolerated regimen the definition of DLTs to trigger dose reduction included toxicities such as grade ≥ 3 neutropenia, grade ≥ 2 thrombocytopenia, febrile neutropenia, grade ≥ 2 mucositis/stomatitis, and any toxicity leading to dose omission or reduction in cycle 1. If DLT occurred and a response was seen, the following cohort was opened at the next lower dose or next less frequent schedule. Response was evaluated by modified severity-weighted adjustment tool (SWAT) every 2 cycles for 6 months and then every 4 cycles. For patients with lymph node involvement, scans were completed at baseline and upon clinical response or end of treatment, whichever occurred first. Results: Thirty-one patients received pralatrexate, with 18 (58%) men and median age of 57 yrs (range, 30-81). Patients had received a median of 6 prior therapies (range, 1-25). Cohorts at the following doses/schedules were enrolled: 30 mg/m2 x 3/4 weeks (n=2), 20 mg/m2 x 3/4 weeks (n=3), 20 mg/m2 x 2/3 weeks (n=7), 15 mg/m2 x 3/4 weeks (n=6), 15 mg/m2 x 2/3 weeks (n=3), and 10 mg/m2 x 3/4 weeks (n=10). Patients received pralatrexate for a median of 72 days (range, 7-491+); 4 patients received >10 cycles of treatment. The most common treatment-related adverse events (all grades) were mucositis (18 patients [58%]), nausea (14 patients [45%]), fatigue (14 patients [45%]), pyrexia (7 patients [23%]), vomiting (6 patients [19%]), anemia (6 patients [19%]), and edema (5 patients [16%]). Grade 3-4 treatment-related toxicities in >1 patient each were mucositis (4 patients [13%]) and anemia (2 patients [6%]). Mucositis was dose limiting (≥ grade 2) in 8 patients (26%). A total of 11 responses were observed, including 2 complete responses and 9 partial responses. In the 18 patients who received pralatrexate at a dose intensity of 15 mg/m2 x 3/4 weeks or greater, the objective response rate was 56% (10/18 patients). This appeared to be the threshold dose for substantial activity in CTCL, below which the incidence of responses decreased in this dose de-escalation trial. Conclusion: Pralatrexate shows impressive activity in the treatment of relapsed CTCL. The optimal dose and schedule that provided activity with tolerability for CTCL was determined to be pralatrexate 15 mg/m2 weekly on 3 of 4 weeks. This cohort is being expanded to better assess efficacy and durability. Disclosures: Horwitz: Allos Therapeutics, Inc: Consultancy, Research Funding. Duvic:Allos Therapeutics, Inc.: Research Funding. Lechowicz:Allos Therapeutics, Inc.: Consultancy. Fruchtman:Allos Therapeutics, Inc.: Employment.

Final Results From a Pivotal, Multicenter, International, Open-Label, Phase 2 Study of Romidepsin In Progressive or Relapsed Peripheral T-Cell Lymphoma (PTCL) Following Prior Systemic Therapy

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 114-114 ◽  
Author(s):  
Bertrand Coiffier ◽  
Barbara Pro ◽  
H. Miles Prince ◽  
Francine M Foss ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
T Cell ◽  
Board Of Directors ◽  
Systemic Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Open Label ◽  
Advisory Committees ◽  
Prior Systemic Therapy

Abstract Abstract 114 Background: Romidepsin is a potent HDAC inhibitor approved by the FDA for patients (pts) with cutaneous T-cell lymphoma who have received at least 1 prior systemic therapy. Durable clinical benefit and tolerability of romidepsin in pts with recurrent or refractory PTCL have been previously observed in a phase 2 trial conducted by the National Cancer Institute. The aim of this phase 2, single-arm, open-label registration study was to evaluate the activity of romidepsin in a larger number of pts with progressive or relapsed PTCL. Methods: Pts with histologically confirmed PTCL (PTCL NOS, angioimmunoblastic T-cell lymphoma, ALCL [ALK-1 negative], other subtypes) who failed or were refractory to ≥ 1 prior systemic therapy, and had measurable disease and ECOG performance status 0–2 were eligible. Exclusions included inadequate bone marrow or other organ function and significant cardiovascular abnormalities. Pts received romidepsin 14 mg/m2 as a 4-h IV infusion on days 1, 8, and 15 every 28 days for up to 6 cycles; treatment could be extended for stable disease (SD) or response. The primary endpoint was rate of complete response (CR + CRu) as evaluated by a central Independent Review Committee (IRC) using International Working Criteria for non-Hodgkin's lymphoma. IRC assessment consisted of a 2-step process, with initial radiographic review of images (CT, MRI) followed by an overall clinical assessment based on the radiology evaluations, photographs, and relevant clinical parameters. Secondary endpoints included objective response rate (ORR): CR + CRu + partial response (PR), investigator-assessed responses, duration of response, time to response, and safety. Results: 131 pts from 48 US, European, and Australian sites were enrolled and received at least 1 dose of romidepsin (as-treated population); 130 patients had histologically confirmed PTCL by central review. Mean age of all pts was 59.4 y (range, 20–83) and median time since diagnosis was 1.25 y (range, 0–17). Median number of prior systemic therapies was 2 (range, 1–8). 21 pts (16%) had failed a prior stem cell transplant. Responses assessed by the IRC are noted in the table below. Longest duration of response is 26+ mo and 16 (94%) of the 17 pts with a CR had not progressed as of the data cutoff (March 31, 2010). Investigator-assessed responses included 21 pts (16%) with CR + CRu, 18 pts (14%) with PR for an ORR of 30%. Currently, 13 pts continue to receive treatment (range, 10–36 cycles). Adverse events (AEs) were reported in 126 of 131 pts (96%). AEs reported in ≥ 20% of pts were nausea (59%), fatigue (41%), vomiting (38%), thrombocytopenia (38%), diarrhea (35%), pyrexia (34%), neutropenia (30%), anorexia (28%), constipation (28%), anemia (23%), and dysgeusia (21%). AEs ≥ grade 3 were reported for 86 pts (66%), with the most common (≥ 5%) being pneumonia (5%), pyrexia (5%), sepsis (5%), and vomiting (5%). 60 pts (46%) had at least 1 serious AE: the most frequently reported (≥ 5%) were pyrexia (7%), pneumonia (5%), vomiting (5%), and sepsis (5%). 22 pts (17%) withdrew due to AEs. 8 pts (6%) died within 30 days of the last dose of romidepsin; 1 death, due to sepsis, was assessed as possibly related to treatment. Conclusions: Complete and durable responses were observed with single agent romidepsin in pts with relapsed PTCL. These data support the therapeutic potential for romidepsin in relapsed PTCL and suggest that romidepsin is a strong candidate for inclusion in future novel regimens for these diseases. As of the data cutoff (March 31, 2010), the median duration of follow-up for CR is 8.2 mo. Disclosures: Coiffier: Gloucester: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Off Label Use: Romidepsin is indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. Romidepsin is not currently approved for the treatment of peripheral T-cell lymphoma (PTCL). Pro:Celgene: Research Funding. Prince:Celgene: Consultancy, Honoraria, Research Funding. Foss:Celgene: Consultancy; Eisai: Consultancy, Speakers Bureau; Merck: Speakers Bureau; Allos: Consultancy, Speakers Bureau; Cephalon: Speakers Bureau. Sokol:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Caballero:Celgene: Membership on an entity's Board of Directors or advisory committees. Morschhauser:Roche: Consultancy, Honoraria; Bayer: Honoraria. Padmanabhan:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Shustov:Celgene: Research Funding. Nichols:Celgene: Employment. Carroll:Celgene: Employment. Balser:Gloucester Pharmaceutical: Consultancy. Horwitz:Celgene: Consultancy, Honoraria.

Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE): First Detailed Report of Primary Treatment

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1614-1614 ◽  
Author(s):  
Francine M. Foss ◽  
Kenneth R. Carson ◽  
Lauren Pinter-Brown ◽  
Steven M. Horwitz ◽  
Steven T. Rosen ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Board Of Directors ◽  
Initial Treatment ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Primary Treatment ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Advisory Committees

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

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