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 TP53 Mutations Identify High-Risk Peripheral T-Cell Lymphoma Patients Treated with CHOP-Based Chemotherapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1367-1367
Author(s):  
William T. Johnson ◽  
Nivetha Ganesan ◽  
Zachary D. Epstein-Peterson ◽  
Catherine Maccaro ◽  
Natasha Galasso ◽  
...  
Keyword(s):  
T Cell ◽  
Prospective Cohort ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Genetic Alterations ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Peripheral T Cell Lymphoma ◽  
Entire Cohort ◽  
Mutational Profiling

Abstract Introduction Mutational profiling in peripheral T-cell lymphoma (PTCL) is increasingly used to aid in diagnosis (Wang. Blood 2015), predicting response (Ghione. Blood Adv 2020), and prognosis (Watatani. Leukemia 2019). However, many analyses lack details of upfront treatment and survival outcomes. The Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) is a custom hybridization capture-based assay encompassing the protein-coding exons of &gt;400 targeted genes (Cheng. J Molec Diag 2015). Using the MSK-IMPACT data generated from a large TCL patient (pt) population (N=396), we sought alterations which may predict resistance to or high rates of relapse after CHOP-based chemotherapy. Methods PTCL pts with MSK-IMPACT were detected in the CBioPortal online platform. We included histologies treated with curative intent CHOP-based induction +/- autologous stem cell transplant (ASCT). This included PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), PTCL with a T-follicular helper phenotype (FH-TCL), ALK+ and ALK- anaplastic large cell lymphoma (ALCL), and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). Univariate analysis (UVA) for PFS and OS based on the presence of recurring genetic alterations was done using Cox proportional hazard regression analysis. Mutations (mut) assessed included TET2, DNMT3A, RHOA, IDH2, TP53, FAT1, STAT3, STAT5B, JAK1, SETD2, and copy number alterations (CNA) in TP53 and CDKN2A. Comparisons of survival curves were performed by log-rank test. As many pts were sequenced at relapse, to minimize bias, relevant findings were confirmed in the smaller set of pts sequenced at diagnosis and/or before relapse (prospective cohort). Results In total, 131 pts met inclusion criteria and had &gt;1 MSK-IMPACT. One pt with a 49-gene panel was also included (N=132). The prospective cohort had 73 (55%) pts. Histologies were PTCL-NOS (N=36, 27%), AITL (N=62, 47%), FH-TCL (N=9, 7%), ALK-ALCL (N=15, 11%), ALK+ALCL (N=6, 5%), and MEITL (N=4, 3%). Regimens were CHOP + etoposide (N=59, 45%), CHOP (N=40, 30%), brentuximab + CHP (N=15, 11%), other CHOP-based (N=18, 14%). The most frequent mut were TET2 (N=69, 52%), RHOA (N=40, 30%), DNMT3A (N=25, 19%), TP53 (N=21, 16%), and IDH2 (N=15, 11%), and for CNA were losses of TP53 (N=9, 7%) and CDKN2A (N=9, 7%). TET2 mut were most frequent in AITL (N=51, 82%), FH-TCL (N=6, 67%), and PTCL-NOS (N=10, 28%). RHOA mut were found in 2 cases of PTCL-NOS (6%) with the rest in AITL (N=33, 53%) and FH-TCL (N=5, 56%). DNMT3A mut were most frequent in AITL (N=19, 31%) and FH-TCL (N=4, 44%). IDH2 mut were exclusive to AITL (N=14, 23%) and FH-TCL (N=1, 11%). TP53 mut were found in all histologies: ALK-ALCL (N=5, 33%), PTCL-NOS (N=10, 28%), FH-TCL (N=2, 22%), AITL (N=2, 3%), and in one case each of ALK+ALCL (17%) and MEITL (25%). The 24-month PFS was 28% for the entire cohort, and 42% for the prospective cohort. On UVA for genetic alterations, only TP53 mut (P=0.0011) and TP53 deletions (P=0.009) associated with inferior PFS. On MVA, only TP53 mut remained significant (HR 2.0 [95% CI 1.1-3.5] P=0.02). No alteration associated with inferior OS. For the entire cohort, median PFS was 4.5 mos for TP53 mut (N=21) vs. 10.5 mos for TP53 wild-type (WT) (N=111) (log-rank P=0.0008). This was similar in the prospective cohort with a median PFS of 4.1 vs. 19.7 mos (log-rank P=0.02) (Figure 1). Compared to TP53 WT, TP53 mut were more likely to have PTCL-NOS (P=0.03), concurrent deletions of TP53 (P=0.0005), and a higher median number of alterations (P=0.01). There were no differences in age, stage, marrow disease, or IPI/PIT scores between TP53 mut and TP53 WT pts. There was a trend towards fewer CR (P=0.054) in TP53 mut. There were no differences in ITT with ASCT between the groups (P=0.5). This was similar in the prospective cohort (P=0.4). Six total (29%) TP53 mut received ASCT, and PFS was similar to ASCT in TP53 WT (median 18.2 vs. 19.7 mos, P=0.5), but 5/6 (83%) ultimately relapsed. Conclusions TP53 mut correlated with lower rates of CR, higher rates of relapse, and shorter PFS in this dataset of PTCL treated with CHOP-based chemotherapy. OS was not different compared to TP53 WT tumors. The confounding impact of histology and other prognostic factors as well as the lack of uniform prospective mutational profiling in this retrospective series precludes definitive conclusions and requires prospective confirmation. Figure 1 Figure 1. Disclosures Sauter: Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy; Kite/Gilead: Consultancy; Celgene: Consultancy, Research Funding; Gamida Cell: Consultancy; GSK: Consultancy; Bristol-Myers Squibb: Research Funding. Khan: Seattle Genetics: Research Funding. Moskowitz: ADC Therapeutics: Research Funding; Beigene: Research Funding; Seattle Genetics: Consultancy, Research Funding; Miragen: Research Funding; Bristol-Myers Squibb: Research Funding; Merck: Consultancy, Research Funding; Janpix Ltd.: Consultancy; Imbrium Therapeutics L.P./Purdue: Consultancy; Takeda: Consultancy; Incyte: Research Funding. Dogan: Seattle Genetics: Consultancy; Roche: Consultancy, Research Funding; Peer View: Honoraria; EUSA Pharma: Consultancy; Takeda: Consultancy, Research Funding; Physicians' Education Resource: Honoraria. Horwitz: ADC Therapeutics: Consultancy, Research Funding; Acrotech Biopharma: Consultancy; Affimed: Research Funding; Aileron: Research Funding; Celgene: Research Funding; C4 Therapeutics: Consultancy; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kyowa Hakko Kirin: Consultancy, Research Funding; Janssen: Consultancy; Kura Oncology: Consultancy; Millennium /Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Trillium Therapeutics: Consultancy, Research Funding; SecuraBio: Consultancy, Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Tubulis: Consultancy; Vividion Therapeutics: Consultancy; Verastem: Research Funding.

Stem Cell Transplant (SCT) and Pralatrexate Therapy: Outcome of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma Who Received SCT Prior to or Following Pralatrexate Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3420-3420
Author(s):  
Leslie Popplewell ◽  
Barbara Pro ◽  
Eric Jacobsen ◽  
Steven M. Horwitz ◽  
Adam Boyd ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Peripheral T Cell Lymphoma ◽  
Additional Therapy

Abstract Abstract 3420 Poster Board III-308 Background Stem cell transplant (SCT) may be offered as a curative approach in patients with chemotherapy-sensitive peripheral T-cell lymphoma (PTCL). Thus, new agents with the ability to induce a response for relapsed or refractory patients are important to identify. This analysis evaluated SCT use before or after pralatrexate, a new anti-folate, as monotherapy in the PROPEL study. Methods Patients with relapsed or refractory PTCL received pralatrexate 30 mg/m2 by IV push once weekly for 6 weeks in 7-week cycles with vitamin B12 and folic acid supplementation in PROPEL. Eligibility criteria included histologic confirmation of PTCL by central review, disease progression after ≥ 1 prior treatment, and ECOG performance status £ 2. Response was assessed centrally using the International Workshop Criteria. Patients who had received prior allogeneic SCT were not permitted to enroll. Patients with prior autologous SCT were eligible if they had not relapsed within 75 days of SCT. There were no restrictions on SCT after completing study treatment. Subsequent post-pralatrexate therapies were recorded during follow up until patient death, loss to follow-up, or data cutoff. Results One-hundred and nine patients in the PROPEL trial were evaluable for response. Eighteen (16%) had received autologous SCT previously, including 8 (7%) patients for whom SCT was the most recent therapy prior to study enrollment. The overall response rate (ORR: complete response [CR/CRu] or partial response [PR]) was 33% (6/18), including 2 CRs, for patients with a prior autologous SCT at any time prior to receiving pralatrexate and 63% (5/8), including 2 CRs, for those patients whose most recent therapy was autologous SCT. Patients were followed from initiation of pralatrexate for a median of 10.5 months (range, 1.0-24.0). Of the 109 patients who were evaluable for response, 6 (6%) patients went on to SCT (2 autologous SCT, 4 allogeneic SCT) as their initial subsequent therapy after responding to pralatrexate according to investigator assessment of response. Four of these patients were still in response by central review at the time they started SCT. At the time of data cutoff, no additional therapy was administered to any of these 4 patients post SCT. The other 2 patients had PRs by investigator review and progressive disease by central review at the time SCT was started; neither of these patients had additional therapy documented after SCT. All 6 patients were alive at the time of last contact. Conclusions The PROPEL trial showed that pralatrexate as a single agent had activity, including CRs, in patients who relapsed following an autologous SCT. The PROPEL trial also demonstrated that patients with relapsed or refractory PTCL can proceed to subsequent SCT after achieving a response with pralatrexate, permitting these patients a transplant option and potential cure. Disclosures Pro: Allos Therapeutics, Inc.: Research Funding. Jacobsen:Allos Therapeutics, Inc.: Consultancy. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding. Boyd:Allos Therapeutics, Inc.: Employment. Fruchtman:Allos Therapeutics, Inc.: Employment.

Pralatrexate Is Effective as Second-Line Treatment Following Cyclophosphamide/Doxorubicin/Vincristine/Prednisone (CHOP) Failure In Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4882-4882 ◽  
Author(s):  
Andrei Shustov ◽  
Barbara Pro ◽  
Christian Gisselbrecht ◽  
Leslie Popplewell ◽  
Nancy L. Bartlett ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Line Treatment ◽  
Second Line ◽  
Peripheral T Cell Lymphoma ◽  
Duration Of Response

Abstract Abstract 4882 Background: The most common therapy for first-line treatment of peripheral T-cell lymphoma (PTCL) is cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP). However, most patients progress within 6 to 12 months and there is no standard of care for second-line treatment. Despite a paucity of data in PTCL, B-cell lymphoma salvage regimens are regularly employed as a second-line treatment for PTCL. Pralatrexate was granted accelerated approval in the United States for the treatment of patients with relapsed or refractory PTCL, based on the results of the pivotal study, PROPEL (Pralatrexate in Patients with Relapsed Or Refractory Peripheral T-cell Lymphoma). All patients in PROPEL had received at least 1 prior therapy for PTCL, with a median of 3 prior systemic therapies (range 1 to 12). The objective response rate (ORR) was 29% (by central review) and 39% (by investigator assessment), with a median duration of response (DoR) of 8.1 months (by investigator) and 10.1 months (by central review). The present analysis was conducted to assess the efficacy of pralatrexate as a second-line treatment post-CHOP. Methods: Of the 109 patients who were treated with pralatrexate and evaluable for efficacy in the PROPEL study, a subset of 15 patients received pralatrexate (30 mg/m2 intravenously weekly for 6 of 7 week cycles) as their second-line treatment post-CHOP. Results: The demographics and disease characteristics of the 15 patients treated with pralatrexate in the second-line setting post-CHOP were reflective of the overall PROPEL patient population. Nine of 15 patients (60%) were male. Median age was 60 years. Eleven of the 15 patients had a prior response to CHOP (7 CR and 4 PR). The additional 4 patients had 1 SD and 3 PD, respectively. A summary of pralatrexate efficacy as second-line treatment post-CHOP is presented in the table below. CR=complete response; CRu=complete response unconfirmed; PR=progressive disease; SD=stable disease; PD=progressive disease; DoR=duration of response; PFS=progression-free survival; OS=overall survival. The 15 patients treated in second-line post-CHOP received a median of 16 doses of pralatrexate, for a median of 134 days. Only 1 patient had a grade 4 adverse event (AE) (sepsis) and the only grade 3 AEs to occur in >1 patient were thrombocytopenia (4 patients), and mucosal inflammation (3 patients). Two patients discontinued treatment with pralatrexate due to AEs. Two of the 15 patients remained on treatment (time on treatment = 12.9 and 18.5 months) and in response as of the data cut-off (August 2009), and their DoR data were censored. An additional 2 patients proceeded to stem cell transplant (SCT) after response to pralatrexate, and thus were censored for DoR (at 2.3 and 3.3 months). These 2 patients remain in CR and their current disease-free period (DoR: pralatrexate + SCT) is 20.1 and 21.7 months. The PROPEL study also collected information on response to therapies administered prior to study entry. Of note, 33 patients received combination chemotherapy as their second-line systemic treatment post-CHOP (ICE and DHAP being the most common regimens): the ORR for combination therapy was 33% and the median duration on treatment for responders was 4 months, which is substantially shorter compared with the DoR to pralatrexate (median 12.5 months, per investigators assessment). Conclusions: Pralatrexate administered as second-line treatment (post-CHOP) to patients with PTCL demonstrated high activity with durable responses, including CRs leading in some patients to SCT. Pralatrexate efficacy and safety profile compared favorably with combination chemotherapy in this disease setting. Taken together, this data suggests that pralatrexate is a highly effective, single-agent, second-line therapeutic option for patients with PTCL, including those who are candidates for bone marrow transplantation. Disclosures: Shustov: Allos Therapeutics, Inc.: Honoraria, Research Funding. Pro: Allos Therapeutics, Inc.: Research Funding. Gisselbrecht: Allos Therapeutics, Inc.: Research Funding. Lechowicz: Allos Therapeutics, Inc.: Consultancy; Celgene Corporation: Consultancy. Zain: Allos Therapeutics, Inc.: Speakers Bureau. Furman: Allos Therapeutics, Inc.: Research Funding. Fruchtman: Allos Therapeutics, Inc.: Employment. Horwitz: Allos Therapeutics, Inc.: Consultancy, Research Funding. O'Connor: Allos Therapeutics, Inc.: Research Funding.

scholarly journals Role of Single Agent and Combination Chemotherapy Strategies in Relapsed/Refractory Peripheral T-Cell Lymphoma: Results from the Complete Registry

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2926-2926 ◽  
Author(s):  
Robert Stuver ◽  
Niloufer Khan ◽  
Marc Schwartz ◽  
Mark Acosta ◽  
Massimo Federico ◽  
...  
Keyword(s):  
T Cell ◽  
Combination Therapy ◽  
Combination Chemotherapy ◽  
Initial Treatment ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Single Agent ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Multiagent Chemotherapy

Abstract Introduction: Patients with aggressive peripheral T-cell lymphoma (PTCL) often undergo induction with anthracycline-based chemotherapy followed by autologous stem cell transplantation in fit patients. Up to 40% of patients have primary refractory disease, and even for those who respond to induction, 5-year overall survival (OS) is 32% with the exception of ALCL. This results in a significant number of patients who need treatment in the relapsed and refractory (R/R) setting. While there is no standard approach for this group, multiagent chemotherapy regimens are often used, particularly in those who may be transplant candidates. Several novel single agents have shown activity in R/R PTCL and can often be given in a more continuous fashion than combination chemotherapy. In order to explore the potential benefits of single agents in comparison to combination chemotherapy in R/R PTCL, we examined treatment outcomes in a prospectively enrolled cohort of PTCL patients. Methods: Patients were enrolled in the Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE), a multinational prospective cohort of 500 newly diagnosed PTCL patients. Demographics, treatments, and outcomes were recorded until death or for at least 5 years. Analysis was restricted to 6 subtypes of PTCL: PTCL-NOS, AITL, ALCL, EATL, NKT, HSTCL. Primary refractory was defined as lack of a complete response (CR) to initial treatment. Relapsed was defined as a CR to initial treatment with progression at a later date. Patients in whom initial treatment was ≤4 days, unreported, or began >30 days before or after informed consent were excluded. Single agents were pralatrexate, romidepsin, brentuximab vedotin (BV), bendamustine, alisertib, denileukin diftitox, and lenalidomide. Combinations were any multiagent chemotherapy regimen excluding the above agents. Results: Of 462 patients with locked records, 57 met the above eligibility criteria and had treatment and followup data available for analysis. As first treatment in R/R disease, 26 patients received combination therapy (by subtype: PTCL-NOS [10], AITL [6], ALCL [3], EATL [1], NKT [5], HSTCL [1]) and 31 received single agents (by subtype: PTCL-NOS [13], AITL [5], ALCL [7], EATL [2], NKT [2], HSTCL [2]). The most common combination regimens had an ifosfamide-, gemcitabine-, or platinum-based backbone. Single agents used were: BV (12), romidepsin (8), pralatrexate (5), alisertib (3), bendamustine (1), denileukin diftitox (1), and lenalidomide (1). The objective response rate (ORR) for single agents was higher than for combination therapy (59% [17/29] vs. 46% [12/26], P=0.36), as was the CR rate (41% [12/29] vs. 19% [5/26], P=0.02). In those with R/R ALCL who received BV, ORR was 83% (5/6) and CR was 67% (4/6). Given these expected high response rates of BV in R/R ALCL, a subtype analysis excluding ALCL patients who received BV (ALCL-BV) was conducted and showed similar ORR between single and combination therapy (52% [12/23] vs. 46% [12/26], P=0.26), though CR still favored single agents (35% [8/23] vs. 19% [5/26], P=0.07). Excluding the ALCL-BV group, CRs were observed with BV (3/6), romidepsin (2/8), pralatrexate (1/5), bendamustine (1/1), and alisertib (1/3). Median progression-free survival (PFS) favored single over combination therapy (11.2 vs. 6.7 months, P=0.02). PFS in the ALCL-BV group was comparable at 11 months. Stem-cell transplantation occurred more frequently after single agent use than combination therapy (25% [8/31] vs. 7% [2/26]). Conclusion: Our analysis confirms the unmet need for better therapies in R/R PTCL. This data shows a trend towards increased CR and PFS with single agents in comparison to combination therapy, while maintaining the potential to bridge to transplantation. It is unclear whether the differences were driven by reduced toxicity and longer treatment duration with single agents, increased efficacy from BV in CD30-expressing cancers, or patient factors that led to therapy selection. However, despite the small size and exploratory nature of this analysis, single agents do not appear inferior to combination therapy with respect to disease control or ability to bridge to transplant with intent to cure. Our data can serve as a foundation for larger datasets or randomized trials which are needed to identify the truly superior strategy. In the meantime, the optimal approach for R/R PTCL remains unclear. Disclosures Schwartz: MS Biostatistics, LLC: Employment. Acosta:Spectrum: Employment. Pro:Seattle Genetics: Consultancy, Other: Travel expenses, Research Funding; kiowa: Honoraria; portola: Honoraria; Takeda Pharmaceuticals: Honoraria, Other: Travel expenses. Shustov:Seattle Genetics: Research Funding. Horwitz:Aileron Therapeutics: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Mundipharma: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Spectrum: Research Funding; Trillium: Consultancy; Corvus: Consultancy; Forty Seven: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Innate Pharma: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Portola: Consultancy; Kyowa-Hakka-Kirin: Consultancy, Research Funding. Foss:Seattle genetics: Consultancy; Miragen: Consultancy, Speakers Bureau; Mallinkrodt: Consultancy; Spectrum: Consultancy.

The Survival Outcome of the Patients with Relapsed/Refractory PTCL-NOS and AITL

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3984-3984
Author(s):  
Dai Chihara ◽  
Michelle A. Fanale ◽  
Mansoor Noorani ◽  
Jason R Westin ◽  
Loretta Nastoupil ◽  
...  
Keyword(s):  
T Cell ◽  
Salvage Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Survival Outcome ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Purpose: We assessed the survival outcome of patients with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) who experienced disease progression or relapse after first line and subsequent therapy. We sought to evaluate the impact of recently approved drugs (pralatrexate and romidepsin) in these patients. Patients and Methods: A total of 321 patients (180 PTCL-NOS, 141 AITL) initially diagnosed between 1999 and 2014 were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) after the progression/relapse following first-line chemotherapy (PFS1 and OS1), after first salvage therapy (PFS2 and OSP2) and after second salvage therapy (PFS3 and OS3) were calculated. Outcome was separately analyzed according to the histopathologic subtype focusing on the use of new drugs. Results: The median age of the patients was 60 (range: 20-83). With a median follow up of 52 months, 240 patients (135 PTCL-NOS, 105 AITL) experienced progression/relapse after the first-line therapy, of whom 17 were post upfront stem cell transplant (SCT). A total of 54 patients received pralatrexate (n=41) and/or romidepsin (n=26); in 1st salvage in 9 and 17 patients, and after 2nd salvage in 17, 24 patients, respectively (13 patients received both). Thirty-three and 28 patients eventually underwent autologous and allogeneic SCT after salvage chemotherapy, respectively. Three patients received both auto and allogeneic SCT. In patients with PTCL-NOS, the median PFS1, PFS2 and PFS3 were 8.4, 3.1 and 2.5 months, respectively (Figure). The median OS1, OS2 and OS3 were 28.5, 10.9 and 7.0 months, respectively. In patients with AITL, the median PFS1, PFS2 and PFS3 were 13.1, 10.9 and 2.4 months, respectively (Figure). The median OS1, OS2 and OS3 were 47.7, 15.1 and 8.1 months, respectively. Use of pralatrexate or romidepsin at the 1st or after 2nd salvage therapy were not associated with longer PFS2 or PFS3, but, the patients who received pralatrexate at some point during therapy had significantly longer OS than who did not in patients with PTCL-NOS (median OS2: 8.5 vs 31.1 months), which however should be interpreted with caution as use of pralatrexate may be the consequence, not the cause, of longer survival. Multivariate analysis adjusting baseline PIT risk factors and the duration of the response to first line therapy revealed that use of romidepsin at any time during the treatment was associated with significantly longer OS2 in patients with PTCL-NOS (HR: 0.51, 95%CI: 0.28-0.93). Use of pralatrexate or romidepsin after relapse were not associated with longer PFS or OS in the patients with AITL. Summary: Survival outcome for relapsed/refractory patients with relapsed/refractory PTCL-NOS and AITL remains poor. However, newer targetes agents may have potential to prolong survival in relapsed/refractory patients with PTCL-NOS. Caution is needed, however, in interpretation of this result due to the retrospective nature of the analysis. Further analyses are urgently needed to investigate the role of the use of newer agents at earlier lines of therapy to improve the survival outcome. Figure 1. Figure 1. Disclosures Westin: Spectrum: Research Funding. Nastoupil:Janssen: Research Funding; TG Therapeutics: Research Funding; AbbVie: Research Funding; Genentech: Honoraria; Celgene: Honoraria. Wang:Celgene: Research Funding.

Primary T-Cell Lymphoma of The Testis Presenting In A Young Adult

2020 ◽  
Vol 2020 ◽  
Author(s):  
MOUNIA BENDARI ◽  
Wafaa Matrane ◽  
Maryam Qachouh ◽  
Asmaa Quessar ◽  
Nisrine Khoubila
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Clinical Stage ◽  
T Cell Lymphoma ◽  
Second Line ◽  
Peripheral T Cell Lymphoma ◽  
Not Otherwise Specified ◽  
Ann Arbor ◽  
Prophylactic Chemotherapy ◽  
Line Chemotherapy

We report the case of a 40-year-old male presented with a painless right testicular swelling. Right radical orchidectomy was performed. The pathological diagnosis was peripheral T-Cell lymphoma-not otherwise specified (PTCL-NOS). According to Ann Arbor staging, the initial clinical stage was IEa. Treating him with four courses of the CHOEP protocol and intrathecal prophylactic chemotherapy was unsuccessful; with the appearance of orbital infiltration and a loco-regional extension. Although the patient started a second line chemotherapy, he unfortunately succumbed to death.

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.

scholarly journals A randomized phase 3 trial of auto vs. allo transplantation as part of first-line therapy in poor-risk peripheral T-NHL

Blood ◽  
2020 ◽  
Author(s):  
Norbert Schmitz ◽  
Lorenz H Truemper ◽  
Krimo Bouabdallah ◽  
Marita Ziepert ◽  
Mathieu Leclerc ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Allogeneic Transplantation ◽  
T Cell Lymphoma ◽  
High Dose ◽  
First Line ◽  
High Dose Therapy ◽  
Peripheral T Cell Lymphoma ◽  
First Line Therapy ◽  
Line Therapy

Standard first-line therapy for younger patients with peripheral T-cell lymphoma consists of six courses of CHOP or CHOEP consolidated by high-dose therapy and autologous stem cell transplantation (AutoSCT). We hypothesized that consolidative allogeneic transplantation (AlloSCT) could improve outcome. 104 patients with nodal peripheral T-cell lymphoma except ALK+ ALCL, 18 to 60 years of age, all stages and IPI scores except stage 1 and aaIPI 0, were randomized to receive 4 x CHOEP and 1 x DHAP followed by high-dose therapy and AutoSCT or myeloablative conditioning and AlloSCT. The primary endpoint was event-free survival (EFS) at three years. After a median follow-up of 42 months, 3-year EFS of patients undergoing AlloSCT was 43% (95% confidence interval [CI]: 29%; 57%) as compared to 38% (95% CI: 25%; 52%) after AutoSCT. Overall survival at 3 years was 57% (95% CI: 43%; 71%) versus 70% (95% CI: 57%; 82%) after AlloSCT or AutoSCT, without significant differences between treatment arms. None of 21 responding patients proceeding to AlloSCT as opposed to 13 of 36 patients (36%) proceeding to AutoSCT relapsed. Eight of 26 patients (31%) and none of 41 patients died due to transplant-related toxicity after allogeneic and autologous transplantation, respectively. In younger patients with T-cell lymphoma standard chemotherapy consolidated by autologous or allogeneic transplantation results in comparable survival. The strong graft-versus-lymphoma effect after AlloSCT was counterbalanced by transplant-related mortality. CHO(E)P followed by AutoSCT remains the preferred treatment option for transplant-eligible patients. AlloSCT is the treatment of choice for relapsing patients also after AutoSCT.

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