First Line Treatment with the R-VAD+C Regimen Followed by ASCT for Patients under 65 with a Mantle Cell Lymphoma (MCL). From the GOELAMS Group.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4694-4694
Author(s):  
Remy Gressin ◽  
Sylvie Caulet Maugendre ◽  
Ghandi Damaj ◽  
Noel-Jean Milpied ◽  
Delphine Senecal ◽  
...  
Keyword(s):  
Prognostic Index ◽  
Good Prognosis ◽  
Second Step ◽  
First Line ◽  
Minor Response ◽  
Mantle Cell ◽  
Good Sequence ◽  
A Minor

Abstract This protocol followed the first GOELAMS protocol (also presented at ASH 2006) for MCL pts testing the addition of Rituximab with the VAD+C regimen followed by ASCT. Thirty nine pts were included in this phase II prospective study opened between January 2003 and December 2005. Inclusion criteria: MCL by the WHO (common or blastoïd variants), under 65 years with PS under 3, who never received chemotherapy. Treatment: the first step consist of 4 courses of R-VAD+C regimen (J1, Rituximab 375 mg/sqm; J1 to J4, Vincristin 0,4 mg/D, Adriblastin 9 mg/D and Dexamethasone 40 mg/D; J20 to J29 Chlorambucil 12 mg/D) every 35 days. Evaluation after 4 cycles with the Cheson criterias. Responders (at least 50%) have been collected after a 4 g/sqm cyclophosphamide stimulation and an in vivo purge with rituximab (375). Then, the second step consisted on one R-VAD+C and one VAD+C regimens followed by the transplantation prepared by the myeloablative regimen including Alkeran 140 mg/sqm and 8 grays/4 fr TBI. Results: 38/39 pts are evaluable. 34 biopsies were reviewed and consisted of 26 common forms and 8 blastoïd variants. 4 other diagnosis were possible only on blood (n=3) or bone marrow (n=1) analysis. Treatment: 28/38 (74%) have had a response to the first 4 R-VAD+C, 6 progressed (16%) and 4 (10%) have had only a minor response under 50%. 17/38pts (44,5%) were in CR or CRu after 4 R-VAD+C courses and 11 (29%) in PR>50%. Among the 23 pts evaluated after the transplantation, 20 were in CR, two progressed and one have a PR>50%. Survival: With a median follow-up of 19 months, OS and PFS at 2 years are 80% and 50 % respectively. The PFS is significantly affected by the Goelams Index for MCL described recently from a cohort of patients studied in our previous protocol (see abstract ASH 2006). Conclusion The R-VAD+C regimen followed by PBSCT is a good sequence for the treatment in first line of MCL patients, especially for those with a good prognosis profile defined by the new Goelams prognostic index which would worth being tested on a larger cohort.

scholarly journals Radioimmunotherapy for Mantle Cell Lymphoma: 5-Year Follow-up of 90 Patients from the International RIT-Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5263-5263
Author(s):  
Karin Hohloch ◽  
Christine Windemuth-Kieselbach ◽  
Pier Luigi Zinzani ◽  
Roberto E. Cacchione ◽  
Wojciech Jurczak ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Primary Therapy ◽  
First Line ◽  
Advisory Committees ◽  
Mantle Cell

To assess the efficacy of radioimmunotherapy (RIT) with 90yttrium-ibrutinib-tiuxetan (90Y-IT) in mantle cell lymphoma, data from 90 patients registered in the RIT Network with a median follow-up (FU) of 5.5 years after RIT were evaluated. 90Y-IT was given as first-line therapy in 45 (50%) (consolidation 44 pts., primary therapy 1 pt.) and at relapse in 45 (50%) patients (consolidation 24 pts., recurrence 12 pts., therapy refractory 3 pts., conditioning 2 pts., other 4 pts.). As a first-line treatment, 30 patients (pts.) (67%) achieved CR, 10 pts. (22%) PR%., 1 pt. (2%) PD, and for 4 pts. (9%) no response data was available. At relapse, CR was achieved in 17 pts. (38%), PR in 6 pts. (13%), SD in 2 pts. (4%), and 6 pts. (13%) had PD, while the response was not documented for 14 pts. (31%). After a median FU of 5.5 years, median PFS for all patients was 2.11 (95%CI: 1.03-2.32) years, and median OS was 4.05 (95%CI 2.79-7.21) years. Eleven pts. (12.2%) developed second malignancy. In conclusion, this is the largest report of MCL pts. treated with 90Y-IT to date. 90Y-IT was most often used as consolidation after first- and second-line chemotherapy and may improve the results achieved using chemoimmunotherapy alone. However, the results are less encouraging compared to treatment with small molecules such as ibrutinib. Disclosures Zinzani: TG Therapeutics: Honoraria, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy. Jurczak:Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bayer: Research Funding; Gilead: Research Funding; MorphoSys: Research Funding; Incyte: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Truemper:Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding; Roche: Research Funding; Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy. Scholz:Janssen-Cilag: Consultancy; Hexal: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Pfizer: Speakers Bureau; Roche: Consultancy; GILEAD: Consultancy, Speakers Bureau; Daiichi Sankio: Consultancy. OffLabel Disclosure: Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin) is approved for treatment of patients with relapsed follicular lymphoma and as consolidation therapy after chemo(immuno)therapy of patients with follicular lymphoma.

First-line treatment with Bendamustine plus Rituximab for patients with indolent non-Hodgkin’s lymphoma or Mantle cell lymphoma: Real-world experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19540-e19540
Author(s):  
Rouslan Kotchetkov ◽  
David Susman ◽  
Lauren Gerard ◽  
Erica DiMaria ◽  
Derek Wayne Nay
Keyword(s):  
Adverse Events ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
First Line ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3

e19540 Background: Bendamustine plus rituximab (B+R) was established as a preferred first line therapy for patients with previously untreated indolent non-Hodgkin’s lymphoma based on the BRIGHT and STIL trials. However, only few reports on efficacy and safety data of this combination in the real-world setting are available to-date. Methods: We conducted a retrospective review of patients who received therapy with standard doses of B+R in our cancer center from June 2013 to January 2021. Patients with indolent non-Hodgkin’s lymphoma (iNHL) and mantle cell lymphoma (MCL) who received more than one cycle of B+R were evaluated. Results: Amongst a total of 201 patients 56% were males and 44% females. Median age at B+R initiation was 72 years (range 34-94). Follicular lymphoma (FL) (50.3%), marginal zone lymphoma (MZL) (19.4%), and lymphoplasmacytic lymphoma (LPL) (14.5%) were the most common iNHL. Stage 3 and 4 diseases represented 19.9% and 68.6% of patients. Extranodal disease was found in 35.8%. The proportion of patients with high risk disease was 48.5% for FL (FLIPI ≥3), 86.6% for LPL (WMISS score ≥2), and 80.5% for MCL (MIPI score ≥6.2). Prior history of secondary malignancy had 23.4% of patients; 11.4% patients had ECOG 3. Most common indications for B+R initiation were bulky symptomatic lymphadenopathy (69.1%), cytopenia (36.8%) and constitutional symptoms (36.8%). Fifty-eight percent of patients had more than one indication for therapy. Median number of B+R cycles delivered was 6 (range: 1-6), median dose of bendamustine was 90 mg/m2 (range 45-90). Full doses of treatment were given in 66.7% of patients, reduced in 33.3% with mean dose 78.3 mg/m2. A total of 50.8% completed 6 cycles with no delays, in 49.2% treatment was delayed (mean delay time 1.8 weeks). Overall response was 94.5%, with 77.6% complete and 16.9% partial remission. Median duration of follow-up was 35 months (range: 4-91). At the end of follow-up, event free survival (EFS) was 77.1% and overall survival (OS) was 79.6%. Six percent of patients relapsed, 8% developed secondary hematological malignancies, including 14 cases of aggressive B-cell lymphoma and 2 cases of MDS. 16.9% of patients required support with G-CSF. Grade 3-4 neutropenia was recorded in 22.4%, febrile neutropenia in 7.5%, grade 3-4 anemia in 7.9%, and grade 3-4 thrombocytopenia in 3.9% of patients. Rituximab-associated infusion reactions, skin rash, thrombophlebitis, and infection were the most common non-hematological adverse events. A total of 80.6% of patients proceeded to rituximab maintenance. Conclusions: B+R chemoimmunotherapy is feasible to administer in non-clinical trial setting. Despite more dose reduction as compared to STIL trial, B+R retained its efficacy with comparable EFS and OS. No new adverse events or increase in secondary malignancies were found.

scholarly journals Bendamustine and rituximab as induction therapy in both transplant-eligible and -ineligible patients with mantle cell lymphoma

2020 ◽  
Vol 4 (15) ◽  
pp. 3486-3494
Author(s):  
Diego Villa ◽  
Laurie H. Sehn ◽  
Kerry J. Savage ◽  
Cynthia L. Toze ◽  
Kevin Song ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
First Line ◽  
Ki 67 ◽  
Historical Cohort ◽  
Entire Cohort ◽  
Mantle Cell

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.

scholarly journals Prospective Long-Term Follow-up after First-Line Subcutaneous Cladribine Treatment in Patients with Hairy Cell Leukemia. a Study of the SAKK (Swiss Group for Clinical Cancer Research)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2875-2875
Author(s):  
Rudolf A. Benz ◽  
Kornelius Arn ◽  
Martin Andres ◽  
Thomas Pabst ◽  
Urban Novak ◽  
...  
Keyword(s):  
Overall Survival ◽  
Secondary Malignancies ◽  
Hairy Cell ◽  
First Line ◽  
Purine Analogues ◽  
Minor Response ◽  
Kaplan Meier ◽  
Long Term Follow Up

Abstract Introduction : Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with a very indolent clinical course and patients may survive for many decades. First-line treatment with purine analogues such as cladribine (Cld) is considered standard of care since it is very efficient and induces profound remissions. However, patients with HCL often relapse after purine analogues and repeated treatment may increase morbidity and mortality. Despite good clinical evidence of long term control of the disease by several mainly single center studies of patients treated with purine analogues, there is only one study analyzing mainly subcutaneous (sc) treated patients based on registry data. We therefore performed a pooled long-term follow-up analysis of our prospective multicenter studies treating patients with sc Cld focusing on survival, secondary malignancy and retreatment. Materials and Methods : The SAKK included patients treated for HCL in 4 studies between 1993 and 2005. Three studies focused on first-line regimens with sc Cld, whereas the fourth protocol focused on the effect of Rituximab monotherapy in patients pretreated with Cld. Classical morphologic, immunohistochemistry and flow cytometry criteria were used as inclusion criteria and response was assessed by established criteria. Treatment algorithms in the 4 studies were as follows: 1) 5 days of Cld 0.14mg/kg sc followed by max 2 cycles of 7 days of Cld 0.1mg/kg sc in case of minor response or no response (SAKK 32/93); 2) Single shot of Cld 0.25mg/kg sc followed by a maximum of 2 cycles of 0.14mg/kg sc for 5 day in case of minor response, no response or relapse (SAKK 32/95); 3) 5 consecutive days of Cld 0.14mg/kg sc versus the same dose in 5 weekly applications (SAKK 32/98); 4) Rituximab 375 mg/m2iv weekly for 4 weeks in relapsed patients (SAKK 31/98). SAKK 32/93 included 63, SAKK 32/95 74 and SAKK 32/98 100 patients. Of the 26 patients registered in 31/98 20 were already in SAKK 32/93, 32/95 and 32/98. Therefore, we also included the treatment information and follow-up data of these 20 patients. All patients were subject to life-long follow-up within the clinical trials. Further information including secondary malignancies and retreatments were obtained by sending out questionnaires to the treating physicians of the study patients. Of the 237 patients 4 patients were in two of the studies and 10 patients have been excluded because of non-classical HCL phenotype. Therefore, a total of 223 patients were included in the analysis. Overall survival and follow-up time were assessed by Kaplan-Meier and reverse Kaplan-Meier method, respectively. Results : The median age of patients at the time of diagnosis was 55 (range 21 to 96) years, 50 patients were female (22.4%) and 173 (77.6%) male. At the time of data analysis, the median follow-up time was 12.1 (95%-CI 10.0 to 14.0) years. A total of 129 (57.8%) patients had the last follow-up information more than two years prior to the data cut-off in May 2016, however, the available information of all patients was used for the sub-analyses including secondary malignancies or retreatment. By the cut-off date, 49 patients have died, 14 (28.6%) due to secondary malignancies and 7 (14.3%) due to HCL progression. Median overall survival from diagnosis was 31.6 (95%-CI 31.6 to 37.8) years. Retreatment was necessary in 53 (23.7%) patients after a mean of 6 (0.2 to 20.4) years and first retreatment was mainly Cld (64%), rituximab (19%) or Cld and rituximab (13%). 21 patients (9.4%) required more than one retreatment with a mean number of 1.57 (range 1 to 5) treatments. A total of 42 (18.8%) patients developed secondary malignancies with an average time to occurrence of 7.1 (range: 0.1 to 17.7) years. The majority of the secondary malignancies were of non-hematological origin (85.9%), most frequently skin cancer (31.0%), followed by prostate cancer (19.0%) and colorectal cancer (16.7%). Six patients (14.4%) developed hematological secondary malignancies with a predominance of B-lymphoid neoplasms. Conclusion : Long-term overall survival in HCL patients treated with sc Cld was excellent and comparable to studies using iv Cld. Despite the long follow-up, sc Cld had a curative potential and relapses requiring re-treatment were observed only in a minority of patients. Secondary malignancies were predominantly non-hematological. These data indicate that patients need to be followed carefully with a special focus on secondary malignancies. Disclosures Chalandon: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.

scholarly journals The Outcome of Mantle Cell Lymphoma patients after Treatment Failure and Prognostic value of Secondary Mantle Cell International Prognostic Index (sec MIPI)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4425-4425 ◽  
Author(s):  
Marek Trneny ◽  
Pavel Klener ◽  
David Belada ◽  
Heidi Mocikova ◽  
Vit Prochazka ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Failure ◽  
Prognostic Value ◽  
High Dose ◽  
Line Treatment ◽  
First Line ◽  
Single Drug ◽  
Mantle Cell ◽  
First Line Treatment

Abstract Background: MCL is a distinct lymphoma entity with improved outcome achieved by the introduction of rituximab, high dose Ara-C and autologous stem cell transplantation (ASCT) into the first line therapy. The outcome of the relapsed patients (pts) remain however poor and there is little data on the outcome after subsequent relapses and there is no information on secondary MIPI prognostic value. Aim: To analyze the outcome of the MCL patients after first line treatment failure and to evaluate the prognostic role of the sec MIPI which is MIPI calculated at the time of relapse/progression. Methods: This analysis is a part of the Lymphoma project in which consecutive lymphoma patients are registered since the year 1999. Altogether 519 newly diagnosed MCL patients were registered in 5 university centers and 9 regional departments between 1999 and 2011. Patients who were treated with rituximab as part of the first line treatment (n=388) were included into the analysis. The diagnoses were confirmed according to WHO classification in the reference pathology centers. The median follow up is 4.5 years. Results: The whole cohort consists of 261 males and 127 females (2.1:1) with median age 65 y (28-87), the majority of pts had advanced disease (CS IV in 81.6% pts), PS ECOG ≥ 2 in 23.6% pts, elevated LDH in 52.5% of pts. The MIPI risk profile was as follows: low risk 21.7%, intermediate risk 27.2% and high risk in 51.1%. All pts received rituximab as part of the induction, 48.7% pts received CHOP, 5.7% alternation of CHOP and HD Ara-C, 26.2% intensive induction with HD Ara-C, 10.3% CVP, 6.4% FC. High dose therapy with ASCT was performed in 23.9% of pts. The ORR was 89.0% with 63.8 CR/CRu, 6.3% had stable disease and 4.9% were primary progressive. The PFS and OS were 2.9 y and 5.5 y with significant impact of MIPI risk (p<0.0001) for both PFS and OS. There were observed 179 relapses/progressions (R/P) and 70 deaths not related to subsequent progression. The cohort of patients with 1st R/P consisted out of 125 males and 54 females (2.3:1) with median age 68 years (38-89). The sed MIPI at the time of 1st R/P was low in 12.7% pts, intermediate in 32.1% and high 59.8% pts. Rituximab was used in 69.5% of patients, DHAP or ESHAP was used in 25.1% cases, FC in 22.8% of cases, CHOP like regimen in 9.4%, HD Ara-C in 11.8%, only 4.7% were treated with targeted therapy temsirolimus or lenalidomide. Altogether 77.2% pts were treated with the polychemotherapy and 22.8 with monotherapy. ASCT and AlloSCT were performed in 5.5% and 8.7% pts resp. During follow up there were observed 74 deaths not related to subsequent progression and 53 2nd R/Ps. The median of 2nd PFS and 2nd OS from the date of 1st R/P was 1.0 and 1.3 years resp. The sec MIPI low vs. intermediate vs. high risk had significant prognostic impact on 2nd PFS: 5.8 vs 1.7 vs 0.9 years (p<0.0001) (fig 1) as well as on OS : 5.8 vs 3.4 vs 1.1 years (p<0.0001) (fig 2). The cohort of 53 pts with 2nd R/P had median age 68 (38-85) yers, male/female ratio was 1.4. Rituximab was used in 45.9% of treated patients and 48.3% of pts were treated with single drug. During follow up 11 pts developed 3rd R/P and other 30 pts died due to current progression, toxicity or in remission. The median of 3rd PFS from the time of 2nd R/P was 6.8 m and OS 7.4 months. Pts who were treated for 3rd R/P recieved rituximab in 50% of cases and the majority (81.2%) were treated with other single drug. The median of 4th PFS from 3rdR/P was 4.9 m and OS 5.5 months . Conclusions: Our analysis of relapsed MCL patients shows that 1: Median PFS from the Dg was 2.9 y but each subsequent relapse resulted in significantly shorter PFS median 12.1, 6.8 and 4.9 months resp. 2: The median OS from Dg was 5.5y but after each relapse it became shorter - 15.7 m, 7.4 m and 5.5 months resp. 3: The sec MIPI at the time of relapse discriminates the groups with significantly different prognosis. Disclosures No relevant conflicts of interest to declare.

BEVATEM: Phase II single-center study of bevacizumab in combination with temozolomide in patients (pts) with first-line metastatic uveal melanoma (MUM): First-step results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8546-8546
Author(s):  
Sophie Piperno-Neumann ◽  
Vincent Servois ◽  
Francois-Clement Bidard ◽  
Pascale Mariani ◽  
Corine Plancher ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Phase Ii ◽  
Liver Perfusion ◽  
Perfusion Ct ◽  
Age Related Macular Degeneration ◽  
Second Step ◽  
Antiangiogenic Agents ◽  
Treatment Schedule ◽  
First Line ◽  
Minor Response

8546 Background: Overall survival (OS) of MUM pts remains poor. In our retrospective series of 470 MUM pts, median OS was 13 months, ranging from 3 to 12 and 21 months for best supportive care, systemic treatment and surgery groups respectively, stressing the lack of effective therapies in this rare cancer. Targeting angiogenesis seems to be promising in uveal melanoma. Intravitreal application of antiangiogenic agents is used to treat neovascular ocular diseases such as age-related macular degeneration or proliferative diabetic retinopathy. Bevacizumab suppressed in vitro growth and in vivo hepatic establishment of micrometastases in experimental uveal melanoma. Preclinical data suggest a potential clinical benefit of the combination of dacarbazine and bevacizumab. Methods: Phase II study, modified 2-step Fleming plan; with expected 6-month progression-free survival (PFS) rates of 15% with chemotherapy and 40% with BEVATEM, 35 pts are to be recruited for a power of 94% (α and β risk 3 and 6%). After the first 17 pts, the study will be continued and another 18 pts will be enrolled in the second step if ≥3 evaluable pts show stable disease or response. Primary endpoint: 6-month PFS according to RECIST. Secondary objectives: response and survival rates, safety; liver perfusion CT for functional imaging of response; impact of VEGF-A gene polymorphisms on bevacizumab pharmacodynamics. Treatment schedule: Temozolomide 150mg/m2 d1-d7 and d15-d21 oral route, Bevacizumab 10 mg/kg d8 d22 IV infusion, 6 cycles (d1=d28) then Bevacizumab maintenance until toxicity or progression. Results: From May 2010 to January 2011, 17 pts were enrolled according to the first step of the study: 3/17 achieved disease control at 6 months, second step is on going with 26/35 pts already recruited. One patient with minor response in liver and lung metastases is under Bevacizumab maintenance for 12 months. Safety of BEVATEM is as good as expected. Liver perfusion CT study showed decrease in blood flow and blood volume before lesion size decrease in one stable patient. Conclusions: BEVATEM study in first line MUM pts is on going, showing promising results in the first step of 17 pts.

Autologous Stem-Cell Transplant with a Rituximab Purge and Maintenance vs. Standard Chemotherapy for Mantle Cell Lymphoma: Extended Follow-Up of a Matched Pair Analysis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3051-3051 ◽  
Author(s):  
Lisa Hicks ◽  
Joseph M. Connors ◽  
Joy Mangel ◽  
Rena Buckstein ◽  
Michael Crump ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Matched Pair ◽  
Conventional Chemotherapy ◽  
Mantle Cell ◽  
Historical Controls

Abstract Background: We previously reported that 20 patients with newly diagnosed, stage III/IV mantle cell lymphoma (MCL) treated prospectively with an in vivo rituximab purge, autologous stem-cell transplantation (ASCT) and rituximab maintenance experienced superior progression free survival (PFS) compared to 40 matched, historical controls treated with conventional chemotherapy. We now report extended follow-up from this trial. Methods: Eligible patients were treated with 4–6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) followed by high dose therapy (cyclophosphamide, carmustine and etoposide) and ASCT. Rituximab (375 mg/m2) was given once 5 days prior to stem cell collection (as an in vivo purge), and as two, 4-week maintenance courses 8 and 24 weeks after ASCT. Historical control patients matched for age, stage and gender were randomly selected from a lymphoma database maintained by the British Columbia Cancer Agency. Two control-patients were selected for every trial patient. All control patients were treated with either an anthracycline based-regimen, or a regimen containing fludarabine and cyclophosphamide. Results: Median follow-up is 5.3 years for the experimental cohort and 10.1 years for the control cohort. In the ASCT cohort, 8 patients have relapsed and 4 patients have died, 2 of progressive disease, 1 of a presumed cardiac event 7 months post-ASCT, and one of hepatitis B reactivation 11 months post-ASCT. Five-year OS and 5-year PFS were superior in MCL patients treated with ASCT+ rituximab compared to matched, historical MCL patients treated with conventional chemotherapy (5y OS 80% vs. 38%, P=0.0017; 5y PFS 72% vs. 19%, P=0.0001). One patient developed myelodysplastic syndrome 5.5 years after ASCT, and one patient was diagnosed with breast cancer 4.8 years after ASCT. Conclusions: With more than 5 years of follow-up MCL patients treated with ASCT plus rituximab continue to experience significantly improved OS and PFS compared to matched, historical controls. Overall Survival Overall Survival

Primary Treatment of Waldenstrom's Macroglobulinemia with Dexamethasone, Rituximab and Cyclophosphamide (DRC): Final Analysis of a Phase II Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 438-438 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Evdoxia Hadjiharissi ◽  
Marie-Christine Kyrtsonis ◽  
...  
Keyword(s):  
Median Time ◽  
Progressive Disease ◽  
Alkylating Agents ◽  
Primary Treatment ◽  
Line Treatment ◽  
Second Line ◽  
Time To Progression ◽  
Minor Response ◽  
A Minor

Abstract Abstract 438 Between November 2002 and April 2006, 72 patients with Waldenstrom's Macroglobulinemia (WM) were enrolled in this multicenter trial of primary treatment with DRC which consisted of dexamethasone 20mg IV followed by rituximab 375 mg/m2 IV on day 1 and oral cyclophosphamide 100 mg/m2 bid on days 1 to 5 (total dose 1000 mg/m2). DRC courses were repeated every 21 days for six courses and then patients without progressive disease were observed without treatment. Patient characteristics, toxicity and response data have been reported previously (Dimopoulos et al, J Clin Oncol 2007;25:3344): 83% of patients achieved a response including 7% complete, 67% partial and 9% minor responses. In June 2012 we updated this study (minimum follow-up >6 years) in order to assess time to progression, time to next treatment, type and response of second-line treatment, overall survival (OS) and cause-specific survival (CSS) in which deaths unrelated to WM or complications of treatment were censored. Second line treatment was administered to patients who experienced progressive disease and also met criteria for treatment requirement based on consensus recommendations (Kyle et al, Sem Oncol 2003;30:116). The median time to progression was 35 months (95% Confidence Interval: 22–48 months) and the median time to next treatment requirement was 51 months. Among several factors who were analyzed for their possible correlation with shorter time to progression, only lymphadenopathy was significant (p=0.028). Among 40 patients who received second line treatment, 28 patients were retreated with either rituximab alone (n=7) with DRC (n=11) or with rituximab combined with other agents (n=10) and 23 patients (82%) achieved a minor response or better. The remaining 12 patients were treated with alkylating agents (n=5), with nucleoside analogues (n=4) with bortezomib (n=2) or with high dose therapy (n=1) and 8 patients achieved a minor response or better. So far 35 (49%) patients have died including 15 patients from unrelated causes (4 lung cancer, 1 bladder cancer, 1 melanoma, 1 gastric cancer, 1 pancreatic cancer, 4 complicated of heart diseases, 2 stroke and 1 pancreatitis). One patient, who received further therapy with fludarabine, developed myelodysplastic syndrome and 2 patients developed diffuse large-B cell lymphoma (one after DRC and one after multiple treatments which included alkylating agents and fludarabine). The probability for 5-year OS and CSS is 62% and 78%, respectively while median OS and CSS is 95 and 104 months respectively (figure). Post progression survival was 82 months and median survival after second line therapy was 82 months. The International Prognostic Staging System (IPSS) is predictive for OS. The probability for 5-year OS is 100%, 67% and 48% for patients with low-, intermediate- and high- risk WM (p=0.005). We conclude that this long-term follow-up analysis of the original phase II study showed that the DRC regimen is associated with a significant median time to progression of about 3 years and that most patients who develop disease progression respond again to rituximab-based regimens. So far, this regimen has not been associated with development of secondary myelodysplasia. The DRC regimen represents an active and safe treatment choice for patient with symptomatic WM. Disclosures: No relevant conflicts of interest to declare.

Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma: A Retrospective Study of the Geltamo Group (1994-2011)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3980-3980
Author(s):  
Ana García-Noblejas ◽  
Eulogio Conde ◽  
Alejandro Martín ◽  
María Jesús Vidal ◽  
Rafael Rojas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Cell Lymphoma ◽  
Disease Status ◽  
Line Treatment ◽  
First Line ◽  
Kaplan Meier ◽  
Mantle Cell ◽  
First Line Treatment

Abstract INTRODUCTION Autologous stem cell transplantation (ASCT) is one of the current treatment options for first-line treatment of mantle cell lymphoma (MCL) in young and fit patients in first complete response (CR). Nevertheless its role in less than CR, after intensive chemotherapy schemas or as consolidation after salvage regimens has not been established. AIM To analyze the impact of patient and treatment characteristics on outcome of MCL patients treated with ASCT. METHODS Retrospective analysis of MCL patients treated with ASCT and registered in the GELTAMO database from 1994 to 2011. An outcome up-date was performed on December 2013. The study was approved by local ethical committees. Statistical analysis was performed using SPSS 15.0. RESULTS Two hundred and forty eight patients were registered from the GELTAMO database. Patients’characteristics : median age was 55 years old (range 21-70 y), 70% male. One hundred and fifty eight patients (68%) were transplanted in CR, 125 were in first CR (79% of all CR) and 33 in second or third CR (21%). Fifty two patients (22%) were transplanted in first partial response and 15 (6%) with chemosensitivity disease after relapse. Only 8 patients (3%) were transplanted with refractory disease. Response : forty-eight out of 75 patients (64%) without CR at ASCT converted to CR after transplant. Survival: Sixteen percent of patients were lost to follow-up one year after transplantation. Median follow-up for alive patients was 47 months (range 0-245 months). Progression free survival for patients transplanted in first CR was 45 months (CI95%: 33-56 months), for patients transplanted in first partial response (PR) was 28 months (CI95%: 15-21months) and for patients transplanted in other response was 19 months (CI95%: 12-26 months). In the whole series, median overall survival (OS) from transplantation was 69 months (CI95% 51-87 months) and for those patients transplanted in first CR was 98 months (CI95% 67-130 months). When patients without CR before transplant are analyzed separately, those who achieved CR after transplantation have better PFS (38 vs 10 months, p<0.001) and OS (74 vs 16 months, p<0.001) than others. Treatment related mortality was 4%. We analyzed the variables that could be associated with PFS and OS. We considered age (≤60 vs >60), ECOG (<2, ≥2), IPI (<2, ≥2), status at transplant (1st CR vs others), conditioning with TBI and HDAC in first line treatment. In univariate analysis, ECOG (p=0.04) and status at transplant (p=0.01) were the variables associated with PFS. For OS, the same variables resulted significant (p<0.001 and p=0.07, respectively) and also, HDAC emerged as significant variable associated with outcome. (p=0.05). In multivariate analysis, ECOG and status at transplant remained as independent prognostic factors for PFS while ECOG and HDAC in first line had impact for OS, see Table 1. Table 1. Variables identified as independent prognostic factors for PFS and OS in multivariate analysis. PFS OS p RR (95% CI) p RR ECOG 0.01 3.6 (1.3-9.9) 0.04 4.5 (1.6-12.5) Status at trasplant 0.03 1.4 (1-2) 0.09 (ns) ---- HDAC at 1st line 0.7 (ns) ---- 0.014 0.5 (0.3-0.8) Afterwards, a survival analysis for PFS and OS was performed according to have received high dose AraC (HDAC) in first line treatment or not and disease status (DS) before ASCT (Table 2). Table 2. Survival analysis according to have received HDAC in 1st line treatment and disease status (DS) before ASCT DS before ASCT N Firts line treatment N PFS (CI95%)(Kaplan Meier) p OS (CI95%)(Kaplan Meier) p 1st CR 125 No HDAC 52 37 (22-51) 0.13 64 (37-91) 0.01 HDAC 72 56 (33-78) No reached 1st PR 52 No HDAC 35 33 (3-63) 0.59 61 (0-126) 0.9 HDAC 17 27 (18-37) 69 (46-92) ≠1st CR/PR 51 No HDAC 46 20 (13-27) 0.16 35 (5-66) 0.9 HDAC 5 11 (7-16) No reached CONCLUSION This retrospective study reproduces previous results published about the role of ASCT in MCL: ASCT consolidation in first CR induces high survival rates with a median PFS of 45 months and median OS of 98 months. Patients without CR after ASCT had a significant inferior outcome. ECOG < 2 and status at transplantation are crucial for PFS and first line treatment with AraC improves significantly OS, particularly in patients with first CR. Disclosures No relevant conflicts of interest to declare.

scholarly journals Bendamustine and Rituximab As Induction Therapy in Both Transplant Eligible and Ineligible Patients with Mantle Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2814-2814
Author(s):  
Diego Villa ◽  
Laurie H Sehn ◽  
Kerry J Savage ◽  
Cynthia L Toze ◽  
Kevin Song ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Patient Preference ◽  
Systemic Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
First Line ◽  
Treatment Characteristics ◽  
Mantle Cell ◽  
Induction Regimen

Background Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma associated with poor outcomes. First-line treatment incorporates cytotoxic chemotherapy and rituximab, but there is no single standard of care regimen. In British Columbia (BC), between January 2003 and May 2013, R-CHOP was the preferred induction regimen. Based on results from the STIL-1 trial (Rummel et al, Lancet 2013) demonstrating improved CR rate and prolonged progression-free survival (PFS) of bendamustine and rituximab (BR) compared with R-CHOP, in June 2013, BR became the standard first-line therapy for all patients with MCL regardless of age. In both eras, fit patients generally ≤65 years of age responding to induction were eligible for high-dose BEAM and autologous stem cell transplantation (ASCT). Maintenance rituximab (MR) has been offered to responding patients post ASCT since 2004 and for transplant ineligible patients since 2012. The aim of this study was to assess the efficacy of BR as an induction regimen for MCL. Methods Patients with MCL treated with first-line BR were identified in the BC Cancer clinical and pathology databases as well as the Leukemia/BMT Program of BC transplant database. BR was initiated no later than December 2018. Treatment received was verified using the BC Cancer Provincial Pharmacy database, and clinical characteristics were verified using the BC Cancer Information System. Radiotherapy for localized disease, splenectomy, or a period of observation prior to systemic therapy were permitted. PFS and overall survival (OS) were calculated from the date of initiation of systemic therapy. In the subgroup of patients ≤65 years of age, results were compared to a historical cohort uniformly treated with R-CHOP. Baseline and treatment characteristics associated with PFS or OS (p<0.05) as well as the treatment variable (BR vs. R-CHOP) were included in Cox regression multivariate models using a backward likelihood ratio approach. Results A total of 190 BR-treated patients were identified. Table 1 shows clinical and treatment characteristics. Excluding 4 patients with an unknown response to BR, 101 (54%) patients achieved a complete response and 62 (33%) a partial response, for an 87% overall response rate. 23 (12%) patients progressed during or within 3 months after BR, and all had highly proliferative MCL (Ki-67 ≥30%) or blastoid/pleomorphic histology. Among the 89 BR-treated patients ≤65 years of age, 60 (67%) underwent ASCT and 29 (33%) did not (10 PD, 10 patient preference, 7 comorbidities, 2 pending). Among the 101 patients >65 years old, 9 underwent ASCT (age 66-71) and 92 did not. 63/69 patients received MR after ASCT, and 77/121 received MR after BR (without ASCT). Reasons for not receiving MR (6 after ASCT, 44 after BR) were 25 PD, 10 ASCT/BR toxicity, 7 pending, 3 patient preference, 3 early deaths, 2 physician preference. With a median follow-up of 2.4y (range 0.2 - 6.1) in living patients the 3y OS was 69.5% (95% CI 69.4-70.6) and 3y PFS 62.8% (95% CI 62.4-63.6). Baseline characteristics and outcomes were similar between patients ≤65y treated with BR vs. R-CHOP (Table 1, Figure 1A and 1B). 81/140 (58%) patients treated with R-CHOP underwent ASCT. In the subgroup of patients who underwent ASCT, outcomes calculated from the point of ASCT were not statistically different between BR vs. R-CHOP. In univariate analysis, age >65y, ECOG performance status >1, elevated LDH, blastoid/pleomorphic morphology, no ASCT, and no MR were associated with worse PFS and OS. In multivariate analysis including these variables as well as chemoimmunotherapy regimen, treatment with BR was not associated with PFS or OS. Conclusions In this population-based analysis, BR is an effective induction regimen for both transplant eligible and ineligible patients. ASCT is feasible in patients treated with BR induction. Even though BR was associated with a numerical improvement in PFS compared to R-CHOP in patients ≤65y, differences in PFS and OS were not statistically significant. Longer follow-up is necessary to fully understand the impact of BR in the frontline setting. We observed PD in 12% patients, suggesting that BR may not be an optimal induction regimen across all patients with MCL, particularly in those with aggressive or highly proliferative disease. Disclosures Villa: Roche, Abbvie, Celgene, Seattle Genetics, Lundbeck, AstraZeneca, Nanostring, Janssen, Gilead: Consultancy, Honoraria. Sehn:Morphosys: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Merck: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Janssen-Ortho: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria. Savage:BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Song:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Scott:Roche/Genentech: Research Funding; Celgene: Consultancy; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria.

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