scholarly journals HIGH‐RISK MANTLE CELL LYMPHOMA IN THE LYMA TRIAL: A LYSA STUDY

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
M. Cheminant ◽  
B. Burroni ◽  
Y. Bris ◽  
L. Chartier ◽  
L. Oberic ◽  
...  
2019 ◽  
Vol 37 ◽  
pp. 242-242
Author(s):  
C.W. Eskelund ◽  
A. Kolstad ◽  
I. Glimelius ◽  
R. Räty ◽  
L.R. Gjerdrum ◽  
...  

2020 ◽  
Vol 4 (15) ◽  
pp. 3486-3494
Author(s):  
Diego Villa ◽  
Laurie H. Sehn ◽  
Kerry J. Savage ◽  
Cynthia L. Toze ◽  
Kevin Song ◽  
...  

Abstract Rituximab-containing chemotherapy regimens constitute standard first-line therapy for mantle cell lymphoma (MCL). Since June 2013, 190 patients ≥18 years of age with MCL in British Columbia have been treated with bendamustine and rituximab (BR). The overall response rate to BR was 88% (54% complete response). Of these, 61 of 89 patients (69%) aged ≤65 years received autologous stem cell transplantation and 141 of 190 patients (74%) from the entire cohort received maintenance rituximab. Twenty-three patients (12%) had progressive disease, associated with high risk per the Mantle Cell Lymphoma International Prognostic Index (MIPI), Ki-67 ≥50%, and blastoid/pleomorphic histology. Outcomes were compared with a historical cohort of 248 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; January 2003 to May 2013). Treatment with BR was associated with significant improvements in progression-free survival (PFS), but not overall survival (OS), compared with R-CHOP in the whole cohort (3-year PFS, 66% BR vs 51% R-CHOP, P = .003; 3-year OS, 73% BR vs 66% R-CHOP, P = .054) and in those >65 years of age (3-year PFS, 56% BR vs 35% R-CHOP, P = .001; 3-year OS, 64% BR vs 55% R-CHOP, P = .063). Outcomes in transplanted patients were not statistically significantly different compared with R-CHOP (3-year PFS, 85% BR vs 76% R-CHOP, P = .135; 3-year OS, 90% BR vs 88% R-CHOP, P = .305), although in multivariate analyses, treatment with BR was associated with improved PFS (hazard ratio, 0.40 [95% confidence interval, 0.17-0.94]; P = .036) but not OS. BR is an effective first-line option for most patients with MCL, however, outcomes are suboptimal for those with high-risk features and further studies integrating novel agents are warranted.


2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Jared Williams ◽  
Shingi Chiruka

Mantle cell lymphoma is a relatively rare type of mature B-cell non-Hodgkin’s lymphoma with an incidence of approximately 8 cases per million persons per year. In patients with mantle cell lymphoma, there are rare case reports of the potentially life-threatening consequences of splenic rupture and rituximab-induced acute thrombocytopenia (RIAT) occurring separately, but there are no reports of these occurring in the same patient. Whilst rare, they are important to be aware of as early detection may prevent fatal outcomes.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2681-2681 ◽  
Author(s):  
Anne W Beaven ◽  
David A. Rizzieri ◽  
Zachary Powell ◽  
Zhiguo Li ◽  
Peggy Alton ◽  
...  

Abstract Abstract 2681 Background: Despite recent advances, the 5 year overall survival for patients with high risk diffuse large B cell lymphoma (DLBCL) is approximately 50% and there is still no known cure for patients with mantle cell lymphoma (MCL). This phase II study of multimodal dose dense therapy evaluated 2 courses of dose intense chemotherapy followed by radioimmunotherapy (RIT) consolidation in patients with previously untreated, mantle cell or high/high intermediate (int) risk aggressive B cell lymphoma. Aim: To evaluate the efficacy and safety of dose intense/dose dense, multimodal chemo-immunotherapy combined with RIT. Methods: Patients with untreated MCL or high int/high risk DLBCL were enrolled. Treatment regimen involved 3 phases of therapy: induction 1, induction 2 and consolidation with RIT (Table 1). Induction 2 occurred approximately 5 weeks after induction 1 and RIT was given 12–24 weeks after rituximab was completed. Patients were evaluated after each treatment phase and those with stable disease (SD) or better and blood count recovery could proceed to the next phase of therapy. Results: Thirty nine patients (pts) with high/high int risk DLBCL (n=25) or MCL (n=14) were enrolled. The median age was 60 years (range 21–80). Toxicity: Common, anticipated toxicities in the induction phases were thrombocytopenia, neutropenia, nausea, fatigue, and anemia. During Ind1 (n=39), grade (gr) III mucositis occurred in 13 pts (33%) and febrile neutropenia (FN) in 31 (79%). Three pts did not proceed to Ind2 due to death (1 candidemia, 1 septic knee prosthesis, 1 from complications of colectomy for prolonged diverticulitis after count recovery) and 2 withdrew to pursue less intense chemotherapy. During Ind2 (n=34) gr III mucositis occurred in 12pts (35%) and FN in 24 (67%). Two pts had gr III/IV cerebellar toxicity that was disabling in 1 pt. Of the 34 pts who received the Ind2, 9 did not receive RIT due to progressive disease (PD) (4), prolonged cytopenias (4), or diagnosis of pancreatic cancer (1). Twenty five pts received RIT and 3 (12%) had FN, 20 (80%) had gr III/IV neutropenia, 23 (92%) had gr III/IV thrombocytopenia, 1 pt died from bacteremia. Two pts developed myelodysplasia 21 and 48 months after starting therapy. Response: Pts were evaluated for response after Ind1, Ind2 and RIT. 38/39 pts were evaluable for response, with 1 pt withdrawing prior to assessment. The pts who died prior to response evaluation were counted as non-responders. The best overall response rate (ORR) was 95% (36/38) with a complete response rate (CR) of 84% (32/38). See tables 2 and 3 for more detailed response data by phase of treatment and disease type. After a median follow up of 17.2 months, 30 pts (77%) are alive (see figure). The median overall survival for MCL has not been reached and is 36.5 months for DLBCL. Deaths were from Hodgkin lymphoma (1), infection (3), DLBCL (2), complications of surgery (1), MCL (2). The median progression free survival is 36.5 months with 11/14 (79%) MCL and 14/25 (56%) DLBCL pts alive and in continued CR. Conclusion: The combination of dose dense, dose intense chemotherapy, monoclonal antibody, and RIT demonstrates considerable efficacy, despite expected toxicity, in high risk DLBCL and MCL pts. The response rates seen in this study are higher than expected from standard R-CHOP in this pt population. Further follow up to determine impact on OS and long term complications will be required to confirm these promising outcomes. Disclosures: Beaven: Glaxo Smith Kline: Family Member Employed by GSK. Off Label Use: Tositumomab is approved for use in relapsed/refractory low grade CD20 positive NHL. It is not FDA approved for first line use in diffuse large B cell lymphoma or mantle cell lymphoma. Neither cytarabine nor etoposide are approved for use in non-Hodgkin lymphoma. Rizzieri:Glaxo Smith Kline: Speakers Bureau. Moore:Glaxo Smith Kline: Speakers Bureau.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4522-4522
Author(s):  
Ping Yang ◽  
Shuozi Liu ◽  
Jing Wang ◽  
Wei Zhang ◽  
Hui Liu ◽  
...  

Abstract Background Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, most MCL cases have a rapid evolution and an aggressive behavior with an unfavorable outcome. Clinical features in mantle cell lymphoma appeared regional characteristics and the epidemiology of MCL in Asia is not accurate documented. MCL treatment opinions are not uniform between country/region within Asia and China. At present, the large-scale Asian patient-specific data for the treatment of MCL are lacking. Aims To obtain 'real world' clinical characteristics,treatment patterns and prognosis factors of MCL patients in China and to address the knowledge gap in Chinese MCL patients. Methods Patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. The median follow-up times was 36.0 months. The data of total 805 patients with mantle cell lymphoma were collected, 112 patients with incomplete clinical data, no chemotherapy and missing follow-up data were excluded. Finally, 693 patients with complete clinical data, treatment information and survival follow-up data were included in this study.Fully detailed information of patients, disease characteristics, treatments and outcomes were collected. Fisher's exact test or Pearson's Chi-squared test were used to compare categorical variables.Survival analysis was performed by Kaplan-Meier. Results The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. 477 patients (68.8%) were younger than 65 years at diagnosis.Advanced stage of diseases were 90.0%. Extranodal organ involvement was 83.4% and the most frequently involved extranodal organs were bone marrow(46.2%), spleen(36.1%), gastrointestinal tract(24.8) and oropharynx(17.7%). Blastic/pleomorphic mantle cell lymphoma accounted for 12.8%, and non-nodular mantle cell lymphoma accounted for 3.3%. Ki-67 more than 30% was 57.7% and Ki-67 ≥ 50% was 26.1%. The intermediate /high risk group was 49.8% according to MIPI score. The first-line therapeutic schedule is not completely unified, the most frequently regimen was CHOP/CHOP-like±R (n=312,45.0%) ,then high-dose cytarabine (n=222,32.0%), VR-CAP(n=44,6.3%), BR(n=30,4.3%), R-EPOCH (n = 17, 2.5%), FC / FCM±R regimen (n = 13,1.9%),and 55 patients(7.9%) uesd chemo-free regimen including IR / R2 / IR2 .Only 80 patients (11.5%) received autologous hematopoietic stem cell transplantation as consolidation therapy after chemotherapy remission. The ORR rate was 85.0%with 46.6% CR and 38.4% PR in the initial treatment.During the follow-up to June 2021(2-204months), 222 patients(32.0%) had died. The 5-year PFS and OS was 30.9% and 65.0%respectively.In the multivariate Cox regression model, ki67 ≥ 50% (HR 1.27, 95%CI 1.01-1.60, p = 0.038) ,stageⅢ/Ⅳ (HR1.56, 95%CI 1.05-2.33, p = 0.029),high- intermediate/high risk group accouding to MIPI-c (HR1.56, 95%CI 1.05-2.33, p = 0.008),spleen involvment (HR1.35, 95%CI 1.08-1.69, p = 0.009),without maintenance treatment (HR0.71, 95%CI 0.56-0.88, p = 0.003) ,SD/PD in inital treatment (HR6.20, 95%CI4.71-8.14, p < 0.001) were independently associated with poorer PFS while ki67 ≥50% (HR 1.74, 95%CI 1.31-2.31, p< 0.001),B symtom (HR 1.52, 95%CI 1.15-2.00, p = 0.003), high-intermediate/high risk group accouding to MIPI-c (HR1.43, 95%CI 1.24-1.64, p < 0.001),without high-dose cytarabine (HR0.47, 95%CI 0.31-0.70 ,p < 0.001) ,without maintenance treatment (HR0.40, 95%CI 0.28-0.58,p < 0.001)and relapse/refractory state (HR 4.04, 95%CI 2.21-7.39, p < 0.001) were independently associated with poorer OS. Conclusions This study describes the characteristics of mantle cell lymphoma in Chinese population with younger onset age and a higher tumor proliferation index. High dose cytarabine treatment and maintenance treatment have shown survival benefits in real-world.Recurrence and refractory is an important factor affecting survival,the strategy of combining molecular biological characteristics with novel strategies may improve outcome in these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4480-4480
Author(s):  
Seah H. Lim ◽  
William V. Esler ◽  
Yana Zhang ◽  
Jian Zhang ◽  
Phillip O. Periman ◽  
...  

Abstract Although autologous stem cell transplant (ASCT) may benefit patients with relapsed or high risk non-Hodgkin’s lymphoma (NHL), many patients still relapse and die of their disease. Most relapses occur during the first three years after transplant. In an attempt to reduce disease relapses, we have applied a maintenance regimen to patients after ASCT for B-cell NHL. In this regimen, all patients received low dose rituximab infusion (375 mg/m2 for one day only) every three months starting D+100 for a total of 2 years or until disease relapse. We reasoned that rituxan infusion given for only one day every three months may be sufficient to prevent disease relapse during this post-transplant period when any residual tumor bulk is likely low. Fifteen patients (eight men, seven women) with high-risk B-cell lymphoma have been treated. Their diagnoses: advanced mantle cell lymphoma in first complete remission (CR1) (8), refractory advanced marginal zone lymphoma (2), refractory follicular large cell lymphoma (1), high risk T-cell rich B-cell NHL in CR1 (1), Stage IV diffuse large cell lymphoma in CR1 (1) and relapsed B-cell NHL in CR2 (2). The median age was 59 years (range 38–72 years). CR was achieved using R-CHOP (10) or R-DHAP/R-ICE (5) and autologous hematopoietic stem cells were harvested during hematopoietic recovery from the last course of chemo-immunotherapy. With a median follow-up of 46 months (range 12–66) for the group and 47 months (range 16–66) for patients with advanced mantle cell lymphoma, the projected 5.5 years relapse-free survival for the group is 100% and the overall survival 80%. Two patients with mantle cell lymphoma died, one due to metastatic breast cancer and another a stroke at 40 and 41 months respectively. Unlike patients who underwent ASCT without rituximab, in whom B-cell recovery occurred between 3–6 months, we observed severe delays in the immunoglobulin recoveries in these patients (Figure 1). With a median immunoglobulin follow-up of 28 months (range 6–64), none of the fifteen patients showed normalization of total IgG. Two patients achieved a normalized total IgA and two a normalized total IgM. This hypogammaglobulinemia persists beyond the rituxan maintenance period. The median time to attainment of 75% normal level of immunoglobulin is 36 months for IgG, 48 months for IgA and not reached for IgM. The severe immunoglobulin deficiencies may be clinically relevant. Six of fifteen patients developed recurrent upper respiratory tract infection. No fatal infection was observed among any of the patients. Our results, therefore, suggest that low dose rituximab administration every three months after ASCT for high-risk B-cell lymphoma may prevent lymphoma relapse. However, this is associated with severe and prolonged delays in immunoglobulin recovery beyond the rituxan maintenance period. Careful monitoring of the immunoglobulin recovery and intervention as appropriate should be done routinely in these patients. Figure Figure


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2722-2722
Author(s):  
Marta García-Recio ◽  
Antonio Gutierrez ◽  
Antonia Obrador-Hervia ◽  
Lucia García Mañó ◽  
Leyre Bento ◽  
...  

Abstract Introduction: Mantle cell lymphoma (MCL) is mostly incurable. The current standard therapy achieves a high rate of complete remission (CR), but the pattern of continuous relapses still marks this disease as a challenge. We previously reported the efficacy of GemOx-R, a combination regimen of gemcitabine, oxaliplatin and rituximab, in patients with refractory and relapsing MCL. Our aim is to confirm our previous results in a larger retrospective series and evaluate the efficacy of each component of GemOx-R in a panel of MCL cell lines and in patient-derived primary cells. Methods: Between 2003 and 2015, 30 patients with MCL were included in a retrospective study of treatment with GemOx-R from the University Hospital Son Espases: 10 cases frontline and 20 in the salvage setting. Frontline cohort was consolidated with radioimmunotherapy and received maintenance therapy with rituximab. The translational study was performed in established cell lines as well as primary MCL lines from patients by cell viability, cell cycle, apoptosis and western blot analysis. Drug synergy was determined by the isobologram and combination index methods. Results: This is a high risk series of patients: median age 70 years, 87% stage IV and 86% intermediate or high risk MIPI. Overall response rate and CRR was 80% and 60% in the frontline cohort as well as 85 % and 60% for salvage patients, respectively. Median progression-free survival was 28 months in the entire series: 66 and 22 months, respectively, for the two cohorts. Median overall survival was 34 months in the entire series: not reached and 20 months, respectively, for the two cohorts. Grade 3 and 4 toxicity was as follows: neutropenia (63%), anemia (34%) and thrombocytopenia (30%) as well as 24% of grade 1 and 2 neurotoxicity. Cell viability and apoptosis analysis showed that oxaliplatin is the most effective drug in this regimen in contrast to the poor responses induced by gemcitabine and rituximab. Oxaliplatin had a profound effect on cellular viability, consistent with the induction of caspase activityand the downregulation of pro-survival proteins. We further present synergistic efficacy of oxaliplatin combined with cytarabine in MCL cells. Conclusions: (1) GemOx-R shows excellent results in MCL both in the frontline and salvage settings considering the high risk patients included. (2) Oxaliplatin is the most effective drug in GemOx-R; (3) oxaliplatin has a robust in vitro activity comparable to that of cytarabine, and the combination of both oxaliplatin and cytarabine shows a significant synergism; (4) taken together, our findings suggest that oxaliplatin alone or combined with cytarabine could constitute a new or alternative backbone for promising new regimens in MCL. Disclosures No relevant conflicts of interest to declare.


2013 ◽  
Vol 31 (19) ◽  
pp. e312-e315 ◽  
Author(s):  
Friederike Hunstig ◽  
Jakob Hammersen ◽  
Christa Kunert ◽  
Iver Petersen ◽  
Hartmut Merz ◽  
...  

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