scholarly journals Use of crizotinib for refractory ALK-positive lymphomas

2017 ◽  
Vol 89 (7) ◽  
pp. 51-56 ◽  
Author(s):  
L N Shelikhova ◽  
V V Fominykh ◽  
D S Abramov ◽  
N V Myakova ◽  
M A Maschan ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Cell Lymphoma ◽  
Large Cell ◽  
First Line ◽  
Hematopoietic Stem ◽  
First Line Therapy ◽  
Line Therapy ◽  
Positron Emission ◽  
Before And After ◽  
Alk Positive

Aim. To evaluate the safety and efficacy of crizotinib used in pediatric patients with relapsed or refractory ALK-positive anaplastic large-cell lymphoma (ALCL). Subjects and methods. The paper describes the experience with crizotinib used in 8 patients with refractory ALK-ALCL before and after allogeneic hematopoietic stem cell transplantation (HSCT). Results. All the 8 (100%) patients treated with crizotinib were recorded to have complete responses, including complete metabolic ones (tumor disappearance as evidenced by positron emission tomography (PET)/computed tomography. Conclusion. Low and manageable toxicity of crizotinib and complete PET-negative responses in patients with resistant ALK lymphomas favor the need to test the drug as first-line therapy, by possibly decreasing the intensification of chemotherapy.

Relapsed or Refractory Anaplastic Large-Cell Lymphoma in Children and Adolescents After Berlin-Frankfurt-Muenster (BFM)–Type First-Line Therapy: A BFM-Group Study

2011 ◽  
Vol 29 (22) ◽  
pp. 3065-3071 ◽  
Author(s):  
Willi Woessmann ◽  
Martin Zimmermann ◽  
Meike Lenhard ◽  
Birgit Burkhardt ◽  
Claudia Rossig ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
First Line ◽  
Hematopoietic Stem ◽  
First Line Therapy ◽  
Line Therapy ◽  
First Relapse ◽  
Large Cell Lymphoma

Purpose To evaluate risk factors for outcome in children and adolescents with relapse of anaplastic large-cell lymphoma (ALCL) after comparable first-line therapy. Patients and Methods We analyzed a population-based cohort of 74 children with relapsed ALCL after Berlin-Frankfurt-Muenster–type first-line therapy between April 1990 and December 2003. The recommended salvage strategy was reinduction chemotherapy followed by autologous hematopoietic stem-cell transplantation (SCT). Results With a median follow-up time of 8.4 years (range, 4.5 to 16.4 years), the 5-year overall survival (OS) rate after first relapse was 57% ± 6%. Survival correlated with time of relapse and clinically advanced dissemination. Five-year OS of 16 patients who experienced progression during first-line therapy was 25% ± 11% compared with 66% ± 6% for 58 patients with a later relapse (P = .002). Five-year OS of 11 patients with bone marrow or CNS involvement was 27% ± 13% compared with 62% ± 6% for 63 patients without involvement (P = .001). Five-year event-free survival (EFS) and OS of 39 children who received the recommended autologous SCT were 59% ± 8% and 77% ± 7%, respectively. EFS after autologous SCT was significantly associated with time to relapse (progression: n = 3; EFS, 0; later relapse: n = 36; EFS, 64% ± 8%; P = .014) and CD3 expression (CD3 negative: n = 25; EFS, 72% ± 9%; CD3 positive: n = 11; EFS, 18% ± 12%; P < .001), but not with site of relapse, conditioning regimen, or graft manipulation. No relapses occurred among 10 patients with relapsed CD3-positive ALCL treated with allogeneic SCT. Conclusion Reinduction chemotherapy followed by autologous SCT proved feasible and efficacious for patients with a first relapse of CD3-negative ALCL after first-line therapy. Patients with progression during first-line therapy or relapsed CD3-positive ALCL may benefit from allogeneic SCT.

scholarly journals Low miR-214-5p Expression Correlates With Aggressive Subtypes of Pediatric ALCL With Non-Common Histology

2021 ◽  
Vol 11 ◽  
Author(s):  
Piero Di Battista ◽  
Federica Lovisa ◽  
Enrico Gaffo ◽  
Ilaria Gallingani ◽  
Carlotta C. Damanti ◽  
...  
Keyword(s):  
Prognostic Markers ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Cure Rate ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Prognostic Stratification ◽  
Alk Positive

The unsatisfactory cure rate of relapsing ALK-positive Anaplastic Large-Cell Lymphoma (ALCL) of childhood calls for the identification of new prognostic markers. Here, the small RNA landscape of pediatric ALK-positive ALCL was defined by RNA sequencing. Overall, 121 miRNAs were significantly dysregulated in ALCL compared to non-neoplastic lymph nodes. The most up-regulated miRNA was miR-21-5p, whereas miR-19a-3p and miR-214-5p were reduced in ALCL. Characterization of miRNA expression in cases that relapsed after first line therapy disclosed a significant association between miR-214-5p down-regulation and aggressive non-common histology. Our results suggest that miR-214-5p level may help to refine the prognostic stratification of pediatric ALK-positive ALCL.

The Survival Outcome of the Patients with Relapsed/Refractory Anaplastic Large-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2738-2738 ◽  
Author(s):  
Dai Chihara ◽  
Michelle A. Fanale ◽  
Mansoor Noorani ◽  
Jason R Westin ◽  
Loretta Nastoupil ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Survival Outcome ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Large Cell Lymphoma

Abstract Purpose: We assessed the survival outcome of patients with anaplastic large cell lymphoma (ALCL) who experienced disease progression or relapse after first line and subsequent therapy. We sought to evaluate the impact of brentuximab vedotin (BV), and survival outcome of patients with ALCL who experienced progression after BV. Patients and Methods: A total of 176 patients (74 ALK+, 102 ALK-) 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 OS2) and after second salvage therapy (PFS3 and OS3) were calculated. Outcome was separately analyzed according to the ALK status focusing on the use of BV. Results: The median age of the patients was 50 (range: 18-89). With a median follow up of 64 months, 111 patients (38 ALK+, 73 ALK-) experienced progression/relapse after the first-line therapy, of which 4 ALK- patients were post upfront stem cell transplant (SCT). Thirty and 15 patients eventually underwent autologous and allogeneic SCT after salvage chemotherapy, respectively. The median PFS1 and OS1 in patients with ALK+ALCL and ALK-ALCL were 8.4 and 28.5 months, and 13.1 and 47.7 months, respectively. In patients with ALK+ALCL, the median PFS1, PFS2 and PFS3 were 53.6, 5.2 and 2.3 months, respectively. The median OS1, OS2 and OS3 were not reached, 47.3 and 6.1 months, respectively. In patients with ALK-ALCL, the median PFS1, PFS2 and PFS3 were 12.9, 3.0 and 2.0 months, respectively. The median OS1, OS2 and OS3 were 54.3, 10.8 and 5.8 months, respectively. Interestingly, there were no significant difference in PFS2 between ALK+ALCL and ALK-ALCL. However, OS2 was significantly longer in patients with ALK+ALCL, suggesting possibly continued chemosensitivity of recurrent ALK+ALCL. A total of 30 patients received BV in 1st salvage (15 patients) and after 2nd salvage (15 patients).The use of BV at 1st salvage was associated with significantly longer PFS2 and OS2 both in patients with ALK-ALCL but not with ALK+ALCL likely due to small number of cases. Mutivariate analysis adjusting baseline PIT risk factors and the duration of the response to first line therapy revealed that use of BV (at any point in the salvage setting) is significantly associated with longer OS2 (HR: 0.43, 95%CI: 0.23-0.80). Overall, 12 patients experienced relapse/progression after BV treatment. The median OS after BV failure was 1.4 months (95%CI: 0.5-9.5 months) (Figure). Summary: Survival outcome for relapsed/refractory patients with ALK+ and ALK- patients is improved with BV. However, survival outcome after BV failure is very poor. A new treatment strategies to consolidate or maintain the response after BV and to develop more safe and better therapeutic options are needed. Figure 1. Figure 1. Disclosures Fanale: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Westin:Spectrum: Research Funding. Nastoupil:Celgene: Honoraria; Genentech: Honoraria; AbbVie: Research Funding; Janssen: Research Funding; TG Therapeutics: Research Funding. Wang:Celgene: Research Funding.

Influence of Baseline Positron Emission Tomography in Metastatic Gastroesophageal Cancer on Survival and Response to Therapy

Oncology ◽  
2021 ◽  
pp. 1-6
Author(s):  
Ahmed Abdelhakeem ◽  
Madhavi Patnana ◽  
Xuemei Wang ◽  
Jane E. Rogers ◽  
Mariela Blum Murphy ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Response To Therapy ◽  
Emission Tomography ◽  
Gastroesophageal Cancer ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Positron Emission ◽  
Pet Ct ◽  
Metastatic Burden

<b><i>Background:</i></b> The value of baseline fluorodeoxyglucose-positron emission tomography-computed tomography (PET-CT) remains uncertain once gastroesophageal cancer is metastatic. We hypothesized that assessment of detailed PET-CT parameters (maximum standardized uptake value [SUVmax] and/or total lesion glycolysis [TLG]), and the extent of metastatic burden could aid prediction of probability of response or prognosticate. <b><i>Methods:</i></b> We retrospectively analyzed treatment-naive patients with stage 4 gastroesophageal cancer (December 2002–August 2017) who had initial PET-CT for cancer staging at MD Anderson Cancer Center. SUVmax and TLG were compared with treatment outcomes for the full cohort and subgroups based on metastatic burden (≤2 or &#x3e;2 metastatic sites). <b><i>Results:</i></b> We identified 129 patients with metastatic gastroesophageal cancer who underwent PET-CT before first-line therapy. The median follow-up time was 61 months. The median overall survival (OS) was 18.5 months; the first progression-free survival (PFS) was 5.5 months. SUVmax or TLG of the primary tumor or of all metastases combined had no influence on OS or PFS, whether the number of metastases was ≤2 or &#x3e;2. Overall response rates (ORRs) to first-line therapy were 48% and 45% for patients with ≤2 and &#x3e;2 metastases, respectively (nonsignificant). ORR did not differ based on low or high values of SUVmax or TLG. <b><i>Conclusions:</i></b> This is the first assessment of a unique set of PET-CT data and its association with outcomes in metastatic gastroesophageal cancer. In our large cohort of patients, detailed analyses of PET-CT (by SUVmax and/or TLG) did not discriminate any parameters examined. Thus, baseline PET-CT in untreated metastatic gastroesophageal cancer patients has limited or no utility.

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.

scholarly journals Valproate in combination with rituximab and CHOP as first-line therapy in diffuse large B-cell lymphoma (VALFRID)

2018 ◽  
Vol 2 (12) ◽  
pp. 1386-1392 ◽  
Author(s):  
Kristina Drott ◽  
Hans Hagberg ◽  
Karin Papworth ◽  
Thomas Relander ◽  
Mats Jerkeman
Keyword(s):  
Histone Deacetylase Inhibitor ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Promising Strategy ◽  
Line Therapy ◽  
Deacetylase Inhibitor ◽  
Key Points

Key Points This trial evaluates addition of the histone deacetylase inhibitor valproate to standard R-CHOP therapy in DLBCL. Addition of valproate to R-CHOP is a promising strategy in DLBCL, but auditory side effects warrant monitoring.

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