Cost of treatment failure in patients with mantle cell lymphoma: results of a large U.S. observational study

2015 ◽  
Vol 15 ◽  
pp. S218
Author(s):  
Mekre Senbetta ◽  
Marie-Noëlle Robitaille ◽  
R Scott McKenzie ◽  
Patrick Lefebvre
Keyword(s):  
Observational Study ◽  
Treatment Failure ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Cost Of Treatment ◽  
Mantle Cell

Alternating Courses of 3x CHOP and 3x DHAP Plus Rituximab Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation (ASCT) Is Superior to 6 Courses CHOP Plus Rituximab Followed by Myeloablative Radiochemotherapy and ASCT In Mantle Cell Lymphoma: Results of the MCL Younger Trial of the European Mantle Cell Lymphoma Network (MCL net)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 110-110 ◽  
Author(s):  
Olivier Hermine ◽  
Eva Hoster ◽  
Jan Walewski ◽  
Vincent Ribrag ◽  
Nicole Brousse ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Mantle Cell Lymphoma ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
High Dose ◽  
Advisory Committees ◽  
Overall Response ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 110 Background: Mantle Cell Lymphoma (MCL) has been characterized by poor long term prognosis with a median survival of only 3 to 4 years. However, outcome has improved during the last decades. In its first randomized trial, the MCL net demonstrated that myeloablative consolidation followed by ASCT resulted in a significant prolongation of PFS in advanced stage MCL (Dreyling et al Blood 2005). Recent phase II studies suggested that the addition of rituximab to CHOP like chemotherapy and/or high dose ARA-C may significantly improve remission rates and PFS. A French phase II trial using sequential R-CHOP/R-DHAP followed by ASCT showed an overall response rate of 95% with a CR rate of 61% translating into a median EFS of 83 months and a 75% survival rate at 5 years (Delarue et al ASH 2008). Methods: To evaluate the potential superiority of a high dose ARA-C containing regimen, the MCL net initiated a randomized trial comparing 6 courses of CHOP plus Rituximab followed by myeloablative radiochemotherapy (12 Gray TBI, 2×60mg/kg Cyclophosphamide) and ASCT (control arm A) versus alternating courses of 3x CHOP and 3x DHAP plus Rituximab followed by a high dose ARA-C containing myeloablative regimen (10 Gray TBI, 4×1,5 g/m2 Ara-C, 140mg/m2 melphalan) and ASCT (experimental arm B). Patient eligibility criteria included previously untreated MCL stage II-IV up to the age of 65 years. Histological diagnosis was confirmed by a central pathology review board. The primary end point time to treatment failure (TTF) was monitored continuously by a sequential procedure based on a one sided triangular test. Stable disease after induction, progression or death from any causes, were considered as treatment failure. Sample size was calculated to detect a hazard ratio of 52% for arm B with a power of 95%. Randomization was stopped as soon as a significant difference was observed between the two arms. Results: From July 2004 to May 2010, 497 patients were randomized in 4 countries (Germany, France, Poland, Belgium). The 391 patients evaluable for the primary analysis (19 no MCL, 87 not yet documented) displayed similar characteristics in both treatment arms: median age 55 vs 56 years, male 78% vs 79%, stage IV 85% vs 79%, B symptoms 43% vs 33%, ECOG >2 5% vs 5%, elevated LDH 37% vs 38%, and MIPI low/int/high risk 61%/25%/14% vs 62%/23%/15%, respectively. After induction overall response was similarly high in both arms (A: 90% vs B: 94%; p=0.19) and CR rate and combined CR/CRu rate were significantly higher in arm B (26% vs 39%; p=0.012 and 41% vs 60%; p=0.0003). The number of patients transplanted was similar in both arms (72% vs 73%) and after transplantation overall response and CR rates were comparable in both arms (97% vs 97% and 63% vs 65%, respectively). After a median follow up of 27 months, patients in arm B experienced a significantly longer TTF (49 months vs NR; p=0.0384, hazard ratio 0.68) mainly due to a lower number of relapses after CR/CRu/PR (20% vs 10%), whereas the rate of ASCT-related deaths in remission was similar in both arms (3% vs 4%). Although CR rate after ASCT was comparable in both arms, remission duration (RD) after ASCT was superior in Arm B (48m vs NR; p=0.047). Interestingly, for patients in CR after ASCT, RD after ASCT was also presumably superior in arm B (51 months vs NR; p=0.077). At the time of analysis overall survival was similar in both arms with medians not reached and 79% vs. 80% survival rates at 3 years (p=0.74). Safety after induction was comparable in both arms except for an increased grade 3/4 hematological toxicity (Hb 8% vs 28%, WBC 48% vs 75%, platelets 9% vs 74%, respectively), an excess of renal toxicity (creatinine grade 1/2: 8% vs 38%, grade 3/4: none vs 2%), and more frequent grade 1/2 nausea and vomiting in arm B. Toxicities of both conditioning regimen were similar, except for higher grade 3/4 mucositis (43% vs. 61%) in Arm B, and higher grade 1/2 liver toxicity and constipation in Arm A. Conclusions: High dose ARA-C in addition to R-CHOP+ASCT increases significantly complete response rates and TTF without clinically relevant increase of toxicity. Therefore, induction regimen containing high dose ARA-C followed by ASCT should become the new standard of care of MCL patients up to 65 years. Disclosures: Walewski: Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Stilgenbauer:Amgen: Research Funding; Bayer: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Sanofi Aventis: Research Funding. Feugier:roche: Consultancy, Honoraria. Bosly:Roche: Membership on an entity's Board of Directors or advisory committees. Gisselbrecht:Roche: Research Funding.

scholarly journals Italian real life experience with ibrutinib: results of a large observational study on 77 relapsed/refractory mantle cell lymphoma

Oncotarget ◽  
2018 ◽  
Vol 9 (34) ◽  
pp. 23443-23450 ◽  
Author(s):  
Alessandro Broccoli ◽  
Beatrice Casadei ◽  
Alice Morigi ◽  
Federico Sottotetti ◽  
Manuel Gotti ◽  
...  
Keyword(s):  
Observational Study ◽  
Mantle Cell Lymphoma ◽  
Life Experience ◽  
Cell Lymphoma ◽  
Real Life ◽  
Mantle Cell ◽  
Large Observational Study

A Multicentre Phase II Trial Testing Gemcitabine in the Treatment of Patients with Newly Diagnosed, Relapsed or Chemotherapy Resistant Mantle Cell Lymphoma: SAKK 36/03.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4454-4454
Author(s):  
Felicitas Hitz ◽  
Giovanni Martinelli ◽  
Emanuele Zucca ◽  
Walter Mingrone ◽  
Roger Von Moos ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Treatment Failure ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Stage Iv ◽  
Response Duration ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Mantle Cell ◽  
Trial Treatment

Abstract Mantle cell lymphoma (MCL) has a very poor prognosis. Remissions are often incomplete and short with a median survival of less than 3 years and a 5 year survival of < 30%. Young patients are usually treated with intensive chemotherapy regimens or a stem cell transplant. In elderly, unfit patients aggressive treatments are not a realistic approach. This trial set out to assess Gemcitabine in the treatment of patients with newly diagnosed, relapsed or chemotherapy resistant MCL not fit enough for intensive chemotherapy regimens. The primary endpoint was the objective response. Eligibility criteria were a WHO performance status < 2, age ≥ 18 years, a histologically confirmed diagnosis of MCL along with at least one measurable lesion of diameter ≥ 11 mm, ≤ 2 previous lines of chemotherapy. Gemcitabine was given in doses of 1000mg/m2 as a 30 minute infusion on days 1 and 8 of each 3 week cycle for a total of 9 cycles. To prevent flu-like symptoms, one dose of steroids per Gemcitabine infusion was administered. Response duration was read as the time from trial registration to a relapse for patients reaching a remission on the trial therapy. Progression-free survival was defined as the time from trial registration to death or disease progression, treatment failure as early termination of the trial treatment. Patient enrollment began in Aug 2004. Stage I analysis concluded the trial treatment was not promising for further investigation, due to only 1 (10%) patient reaching a remission, and patient accrual stopped after the inclusion of 18 patients in March 2006. Median age at enrollment was 70 years. 66% of the patients were male. MCL was newly diagnosed in 50% of the patients and relapsed in the remainder. Ann Arbor stage IV rating was present in 15 patients, stage II in 1 patient and stage I in 2 patients. Bone marrow involvement was reported in 10 patients. Gastrointestinal tract involvement was reported in 4 patients. Involvement of > 1 extranodal organ was seen in 3 patients. One CR, 4 PRs, 8 SDs and 4 PDs were recorded as a best response. The patient achieving a CR was one of the patients presenting with a stage IV disease. Most myelotoxicities occurred during the first chemotherapy cycle. Neutropenia CTC grade 1 in 24 (19.8%), grade 2 in 35 (28.9%) and grade 3/4 was seen in 24 (19.8%) of the cycles. Thrombocytopenia CTC grade 1 was recorded in 55 (45.5%) cycles and grade 2/3 in 9 (7.7%) cycles. Three patients developed non-hematological serious adverse events, defined as an inpatient or prolonged hospitalisation or a life threatening illness related to the trial medication; dyspnea, glomerular microangiopathy with hemolytic uremic syndrome, and hyperglycemia. The median time-to-progression and response duration was 8.0 (95% confidence interval: 5.5 – 9.3) and 10.6 (95% confidence interval: 5.5 – 10.9) months respectively. The median time-to-treatment failure was not reached. We conclude that Gemcitabine is well tolerated and that it can stabilise MCL in elderly patients. However, Gemcitabine as a monotherapy has only limited activity in MCL patients in terms of treatment response. Further trials should therefore assess gemcitabine in frail patients with MCL.

scholarly journals PS1264 FRENCH IBRUTINIB OBSERVATIONAL STUDY (FIRE): REAL-WORLD STUDY OF IBRUTINIB TREATMENT FOR MANTLE CELL LYMPHOMA (MCL) IN FRANCE

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 578-579
Author(s):  
B. Slama ◽  
A. Delmer ◽  
G. Cartron ◽  
B. Anglaret ◽  
O. Fitoussi ◽  
...  
Keyword(s):  
Observational Study ◽  
Mantle Cell Lymphoma ◽  
Real World ◽  
Cell Lymphoma ◽  
Mantle Cell

A Multicenter Study Evaluating the Efficacy and Safety of Bendamustine in the Treatment of Mantle Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4940-4940
Author(s):  
Sean Warsch ◽  
Peter Hosein ◽  
Lauren S. Maeda ◽  
Ash A Alizadeh ◽  
Izidore S Lossos
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Mantle Cell Lymphoma ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Cancer Center ◽  
Time To Treatment ◽  
Mantle Cell ◽  
Time To Treatment Failure ◽  
Autologous Hsct

Abstract Abstract 4940 Background: Bendamustine has evolved as an increasingly used chemotherapeutic agent for diverse lymphomas in the United States (US) and Europe. It is an alkylating agent that was approved in the US for use as a first line therapy for chronic lymphocytic leukemia and relapsed indolent B-cell non-Hodgkin's Lymphoma (NHL) in 2008. However, the two pivotal studies that established bendamustine for this indication included only few patients with mantle cell lymphoma (MCL). The goal of this retrospective study was to evaluate efficacy of bendamustine in MCL. Patients and Methods: We retrospectively reviewed the records of all MCL patients who were treated with bendamustine at Jackson Memorial Hospital and the Sylvester Comprehensive Cancer Center (both in Miami, FL) and the Stanford Cancer Center (in Stanford, CA). The primary endpoint was overall response rate (ORR) and secondary endpoints were overall survival (OS), time to treatment failure (TTF), and safety. Results: Thirty MCL patients received bendamustine, 28 in combination with rituximab and 2 as monotherapy. Nineteen of these patients were treated at the University of Miami and 11 at Stanford. The median age at diagnosis was 58 years and 77% of the patients were male. The most common extranodal site of involvement at diagnosis was the bone marrow (57%), followed by the GI tract (33%). Most patients presented with advanced disease, with 69% and 28% of the patients having stage IV and III disease at diagnosis, respectively. Seven patients (23%) were diagnosed with the blastic variant of MCL. Five patients received bendamustine as initial therapy and 25 for relapsed disease. Five of these patients had relapsed MCL after an autologous HSCT The most common schedule was bendamustine 100mg/m2 on days one and two and rituximab 375mg/m2 on day one of a 28 day cycle, for a median of six cycles. Of the 30 patients, there were fifteen complete responses (CR) and ten partial responses (PR), for an ORR of 83% (95% confidence interval [CI] 70–97%). With a median follow-up of 8 months (range 0.3–29.5 months), the median overall survival (OS) was not reached; the one-year OS rate was 73%; the two year OS rate was 67%. When OS and time to treatment failure (TTF) were stratified by response (using a 2-month landmark as the starting point for analysis), patients achieving a CR had a significantly longer OS and TTF compared to patients who did not achieve a CR (log rank p < 0.001). The TTF and OS were significantly worse for patients with the blastic variant versus the diffuse variant. In 5 patients with relapse post autologous HSCT, bendamustine induced a CR in three and a PR in one other patient. The majority of serious adverse events associated with bendamustine were hematological. Grade 3 or 4 neutropenia, anemia, and thrombocytopenia occurred in 23%, 3%, and 20%, respectively. Common non-hematologic grade 1 or 2 toxicities were fatigue (27%), edema (20%), erythematous rash (20%), and nausea (13%). Two patients developed neurological sequelae during or after treatment with bendamustine. The first patient developed left sided weakness and dysmetria ten months after completing therapy. A brain biopsy revealed progressive multifocal leukoencephalopathy. A second patient developed ataxia and incontinence while on rituximab plus bendamustine therapy and expired before a definitive diagnosis could be established. Conclusions: Bendamustine appears to have a favorable profile as a second-line agent for patients with relapsed MCL. The response rate is at least comparable to other therapies, especially when examined in light of the toxicity profile seen with other regimens. This study supports the need for continued investigation of bendamustine as a therapy for MCL patients both in the frontline and relapsed settings in prospective clinical trials, some of which are presently ongoing. Disclosures: No relevant conflicts of interest to declare.

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