Combination Biologic Therapy Without Chemotherapy As Initial Treatment For Mantle Cell Lymphoma: Multi-Center Phase II Study Of Lenalidomide Plus Rituximab

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 247-247 ◽  
Author(s):  
Jia Ruan ◽  
Peter Martin ◽  
Bijal D. Shah ◽  
Stephen J. Schuster ◽  
Sonali M. Smith ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Initial Treatment ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Maintenance Phase ◽  
Progression Free Survival ◽  
Induction Phase ◽  
Mantle Cell ◽  
Progression Of Disease

Abstract Background Initial treatment for mantle cell lymphoma (MCL) is not standardized. Current conventional upfront chemoimmunotherapies are generally not curative and can be deferred in some patients. This presents an opportunity to evaluate novel therapeutic approaches in the first line setting. Lenalidomide, an immunomodulatory compound which targets both the tumor cells directly and the tumor microenvironment, has shown clinical efficacy either alone or in combination with rituximab in relapsed MCL. We report findings of the first study of a chemotherapy-free approach as initial treatment for MCL, using lenalidomide and rituximab as a combination biologic doublet. Methods The study protocol includes both an induction phase and a maintenance phase. During the induction phase, lenalidomide is administered at 20 mg daily on days 1-21 of a 28-day cycle for a total of 12 cycles, with dose escalation to 25 mg daily if tolerated. Standard dose rituximab is administered weekly x 4 during cycle 1, then once every other cycle, for a total of 9 doses. During the maintenance phase which starts with cycle 13, lenalidomide is administered at 15 mg daily on days 1-21 of a 28-day cycle, with rituximab maintenance once every other cycle until progression of disease. The primary objective was to evaluate overall response rate (ORR). Secondary objectives included safety analysis, progression-free survival, overall survival, and QOL assessment. Based on a Simon two-stage design comparing an ORR of ≥60% with treatment to an unacceptable ORR of ≤40% (alpha=10%, power=80%), 15 or more overall responses out of 28 enrolled patients were required to declare the treatment effective and worthy of further testing. Results From 7/2011 to 2/2013, 31 subjects with previously untreated MCL were enrolled at 4 centers, and the study met its accrual. At study entry, median age was 65 years (range 42-86), and the M:F ratio was 3:1. All patients had stage III/IV disease, 12 (39%) had elevated LDH, and 27 (87%) had bone marrow involvement. MIPI scores were evenly distributed between low-, intermediate-, and high-risk (36%, 32%, and 32% respectively). Ki67 index was <30% in 23 (74%) subjects. Treatment was generally well tolerated with expected side effects. Grade 3-4 hematologic toxicities included neutropenia (39%), thrombocytopenia (13%) and anemia (7%). Grade 3-4 non-hematologic toxicities included rash (23%), tumor flare (7%) and serum sickness associated with rituximab (7%). Grade 1-2 infections included URI (29%), UTI (10%), pneumonia (10%) and sinusitis (7%). One incidence each of DVT and PE were observed and resolved with treatment. As of July 2013 at a median follow-up of 12 months (range 5-23 months), 27 (87%) patients remain on study without evidence of disease progression, including 18 who have completed induction and now in the maintenance phase. Four patients went off study – one withdrew consent, two had progression of disease, and one could not tolerate tumor flare associated side effects. Thirty patients are evaluable for efficacy with at least one response assessment. The preliminary ORR for evaluable patients is 77% (95% CI = 57% to 89%) with 40% CR/CRu (95% CI = 23% to 59%), and may further improve with additional follow-up on continued treatment. Median time to objective response was 2.8 months, with CR typically confirmed between 6-12 months. Four patients (13%) have stable disease with ongoing clinical benefit at 5+, 6+, 12+ and 13+ months. Median progression-free survival and duration of response have not been reached. Neither MIPI score nor Ki67 index correlated with response. All patients have maintained or improved quality of life parameters during treatment by FACT-Lym analysis. Conclusions This study provides the first demonstration that a chemotherapy-free, combination biologic approach is feasible as initial therapy for mantle cell lymphoma. Lenalidomide up to 25 mg daily given 21 out of 28 days can be safely combined with rituximab as frontline therapy for MCL. Preliminary efficacy data on response rates are encouraging. More precise assessment of response rate and durability will require more follow-up with additional subjects. However, these data justify further evaluation of the lenalidomide + rituximab regimen both alone and as a platform for the integration of novel agents in combination approaches in MCL both in the upfront and relapsed settings. Disclosures: Ruan: Celgene: Consultancy, Research Funding, Speakers Bureau. Off Label Use: Lenalidomide in the frontline treatment of mantle cell lymphoma. Martin:Seattle Genetics: Consultancy, Speakers Bureau; Millennium: Research Funding; Genentech: Speakers Bureau; Celgene: Consultancy, Research Funding; Teva: Consultancy, Research Funding. Shah:Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Schuster:Celgene: Research Funding. Smith:Micromet: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; Allos: Consultancy; Genentech: Consultancy; Onyx: Consultancy. Furman:Celgene: Research Funding. Coleman:Celgene: Consultancy. Leonard:Celgene: Consultancy; Genentech: Consultancy.

Sustained Remission with the Combination Biologic Doublet of Lenalidomide Plus Rituximab As Initial Treatment for Mantle Cell Lymphoma: A Multi-Center Phase II Study Report

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 625-625 ◽  
Author(s):  
Jia Ruan ◽  
Peter Martin ◽  
Bijal D. Shah ◽  
Stephen J. Schuster ◽  
Sonali M. Smith ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Initial Treatment ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Maintenance Phase ◽  
Progression Free Survival ◽  
Induction Phase ◽  
Mantle Cell ◽  
Grade 3

Abstract BACKGROUND: Initial treatment for mantle cell lymphoma (MCL) is not standardized. Current conventional upfront chemoimmunotherapies are generally not curative. Lenalidomide, an immunomodulatory compound which targets both the tumor cells directly and the tumor microenvironment, has shown clinical efficacy either alone or in combination with rituximab in relapsed MCL. We report the mature findings of the first study of a chemotherapy-free approach as initial treatment for MCL, using lenalidomide and rituximab as a combination biologic doublet. METHODS: The study protocol includes both an induction phase and a maintenance phase. During the induction phase, lenalidomide is administered at 20 mg daily on days 1-21 of a 28-day cycle for a total of 12 cycles, with dose escalation to 25 mg daily if tolerated. Standard dose rituximab is administered weekly x 4 during cycle 1, then once every other cycle, for a total of 9 doses. During the maintenance phase which starts with cycle 13, lenalidomide is administered at 15 mg daily on days 1-21 of a 28-day cycle, with rituximab maintenance once every other cycle until progression of disease. The primary objective was to evaluate overall response rate (ORR). Secondary objectives included safety analysis, progression-free survival, overall survival, and QOL assessment. RESULTS: From 7/2011 to 4/2014, 38 subjects with previously untreated MCL were enrolled at 4 centers, and the study met its accrual. At study entry, median age was 65 years (range 42-86), and the M:F ratio was 2.5:1. All patients had stage III/IV disease, 14 (37%) had elevated LDH, and 34 (89%) had bone marrow involvement. MIPI scores were evenly distributed between low-, intermediate-, and high-risk (34%, 34%, and 32% respectively). Ki67 index was <30% in 26 (68%) subjects. Treatment was generally well tolerated with expected side effects. Grade 3-4 hematologic toxicities included neutropenia (47% in total, 42% with induction, 24% with maintenance), thrombocytopenia (13%) and anemia (8%). Grade 3-4 non-hematologic toxicities including rash (26%), tumor flare (11%), serum sickness associated with rituximab (8%) and fatigue (8%), were reported during induction phase only. Grade 1-2 infections including URI (34%), UTI (16%), sinusitis (11%) and bronchitis (8%) were reported during both induction and maintenance. One patient developed grade 3 cholangitis from cholecystitis requiring cholecystectomy. Secondary malignancy was reported in an 86 yo patient who developed melanoma in-situ and Merkel cell carcinoma following 18 month of therapy. As of July 2014 at a median follow-up of 24 months (range 3-35 months), 37 patients are alive, and 36 patients are evaluable for efficacy with at least one response assessment. Two patients were inevaluable – one withdrew consent, and one was intolerant of tumor flare. The ORR for all patients is 84.2% (95% CI = 68.7% to 94%) with 52.6% CR (95% CI = 35.8% to 69%). Median time to objective response was 2.8 months, with median time to CR achieved at 11 months. Thirty (79%) patients remain on study without evidence of disease progression, including 24 who have completed induction and are now in maintenance. During induction, 29% of patients tolerated dose escalation of lenalidomide to 25 mg from 20 mg, while 39% required dose reduction to 15 mg or less. Six evaluable patients had disease progression – 3 with primary refractory disease, 3 progressed following initial responses (1 CR with PFS of 18 months, 2 PRs with PFS at 14 and 25 months, respectively). Median progression-free survival and duration of response have not been reached. The 2-yr PFS rate is estimated at 83.9% (95% CI = 65.2% to 93.1%). Neither MIPI score nor Ki67 index correlated with response. Quality of life parameters were maintained or improved during treatment by FACT-Lym analysis. CONCLUSIONS: This study provides the first demonstration that a chemotherapy-free, combination biologic approach is feasible and active as initial therapy for mantle cell lymphoma. A high proportion of MCL patients can achieve durable remissions while maintaining quality of life with the frontline therapy of lenalidomide up to 25 mg daily given 21 out of 28 days combined with rituximab. These data justify further evaluation of the lenalidomide + rituximab regimen both alone and as a platform for the integration of novel agents in combination approaches in MCL, particularly in the upfront setting. (ClinicalTrials.gov - NCT01472562.) Disclosures Ruan: Celgene: Consultancy, Research Funding, Speakers Bureau. Off Label Use: Study of lenalidomide in the frontline setting for mantle cell lymphoma.. Martin:Janssen: Honoraria. Shah:Pharmacyclics: Speakers Bureau; SWOG: Consultancy; Celgene: Consultancy, Speakers Bureau; NCCN: Consultancy; Seattle Genetics, Inc.: Research Funding; Janssen: Speakers Bureau. Smith:Gilead: Consultancy; Genentech: Consultancy, DSMB for another compound, DSMB for another compound Other; Celgene: Consultancy, Research Funding. Furman:Genentech: Consultancy, Speakers Bureau; Celgene: Research Funding. Svoboda:Celgene: Research Funding. Leonard:Genentech: Consultancy; Celgene: Consultancy.

Updated Analysis of a Prospective Phase II Trial of R-MACLO-IVAM Followed by Maintenance for Mantle Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1622-1622
Author(s):  
Jose D Sandoval-Sus ◽  
Peter J Hosein ◽  
Deborah Goodman ◽  
Alexandra Stefanovic ◽  
Joseph D Rosenblatt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
Maintenance Phase ◽  
Induction Phase ◽  
Rituximab Maintenance ◽  
Mantle Cell

Abstract Abstract 1622 Background: Contemporary therapy for mantle cell lymphoma (MCL) in fit patients usually consists of an induction phase followed by autologous stem cell transplantation (SCT). We previously reported a phase II trial of intensive chemotherapy induction with R-MACLO-IVAM followed by thalidomide maintenance and demonstrated promising progression-free survival (PFS) and overall survival (OS) rates without SCT (Lossos et al, Leuk Lymph 2010). We subsequently modified the protocol to utilize rituximab maintenance instead of thalidomide. Herein we present updated results and follow-up for the patients treated on this trial. Methods: This was a prospective single-arm phase II trial conducted at the University of Miami with IRB approval. Eligible patients were chemotherapy-naïve and had a confirmed diagnosis of MCL using WHO criteria, age 18–75 years, ECOG PS 0–2, adequate organ function and no history of HIV or prior cancer. Pretreatment staging include CT and PET scans, endoscopy, colonoscopy and bone marrow biopsy. Cycle 1 consisted of R-MACLO (rituximab, methotrexate, doxorubicin, cyclophosphamide and vincristine) followed by G-CSF. When the ANC was >1.5×109/L, cycle 2 with R-IVAM (rituximab, ifosfamide, mesna, etoposide and cytarabine) was begun, followed by G-CSF, as previously reported. Fourteen days after ANC recovery from cycle 2, cycles 3 and 4 were given in identical fashion to 1 and 2. Four weeks after ANC recovery from cycle 4, patients were re-staged and responses were assessed by standard criteria. Patients who achieved complete responses (both radiologically and pathologically) were eligible for the maintenance phase. The first 22 patients were treated with thalidomide maintenance (target daily dose of 200mg); the protocol was subsequently modified to utilize rituximab maintenance at a dose of 375 mg/m2 IV weekly × 4 weeks, repeated every 6 months. Maintenance therapy was continued until MCL relapse or intolerable toxicity. OS was calculated from the date of diagnosis to the date of death or last follow up. PFS was calculated from date of diagnosis until the date of pathological evidence of recurrence or death. Data were summarized using descriptive statistics and survival was analyzed using the Kaplan-Meier method. Results: Between June 2004 and June 2012, 32 patients were enrolled, 22 on the first phase and 10 after the amendment to rituximab maintenance. All patients were evaluable for toxicity and 31 were evaluable for response. Median age was 56.5 years (range 39–73). All subjects had at least stage III disease with bone marrow involvement in 84% and gastrointestinal involvement in 38%. Distribution according to MIPI: low 28%; intermediate 38%; high 34%. All patients had diffuse variant except 2 with blastic variant. Twenty-eight patients completed all 4 cycles of therapy; treatment was stopped in 2 after 3 cycles, and in one after 2 cycles, and 1 died during cycle 1. Of the 31 patients completing 2 cycles of chemotherapy, 29 (94%) achieved a complete response (CR) and 2 had a partial response (PR). After a median follow-up of 54.9 months, the 5-year PFS was 69% (95% CI 51% – 82%) and the 5-year OS was 88% (95% CI 72% – 95%) [Fig 1 & 2]. Lower MIPI group (low vs intermediate vs high) was associated with longer PFS (log rank p = 0.007) and longer OS (log rank p = 0.036) [Fig 3 & 4]. Nine patients relapsed and 5 died; 1 died from sepsis on cycle 1; 1 died in CR at 38 months from non-small cell lung cancer diagnosed 19 months after MCL and the other 3 died from relapsed MCL after 22, 24 and 60 months respectively. Seven of the 9 patients who relapsed were treated with rituximab and bendamustine and one underwent an allogeneic SCT. Toxicities during the chemotherapy phase for the last 10 patients were similar to what was previously published for the first 22 patients, with the exception of lower renal toxicity since the dose of methotrexate was reduced to a total of 4.2 g/m2 instead of 6.7 g/m2 prior to the amendment. The toxicities during the thalidomide maintenance phase were similar to what was previously reported. For the 10 patients who received rituximab maintenance, there were no unexpected toxicities during the maintenance phase. Conclusions: R-MACLO-IVAM results in a high overall response rate (94% CR and 6% PR) and a low relapse rate after over 4.5 years of median follow-up. The median PFS and OS still have not been reached. These results compare favorably with regimens that include upfront SCT. Disclosures: No relevant conflicts of interest to declare.

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.

scholarly journals Ibrutinib-Lenalidomide-Rituximab in Patients with Relapsed/Refractory Mantle Cell Lymphoma: Final Results from the Nordic Lymphoma Group MCL6 (PHILEMON) Phase II Trial

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-36
Author(s):  
Mats Jerkeman ◽  
Martin Hutchings ◽  
Riikka Räty ◽  
Karin Fahl Wader ◽  
Anna Laurell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Research Funding ◽  
Tp53 Mutation ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
Molecular Remission ◽  
Mantle Cell ◽  
Grade 3

Introduction: In spite of improvements in treatment of mantle cell lymphoma (MCL), this is still considered an incurable lymphoma entity, and the majority of patients eventually relapse. Ibrutinib is a very active agent in MCL, but in vitro has been shown to partially antagonize the activity of rituximab, by suppression of NK cell activity and subsequent ADCC. Lenalidomide, on the other hand, improves rituximab-induced ADCC. In this multi-centre open-label phase II trial, we evaluated safety and efficacy of this triplet combination in patients with relapsed or refractory MCL. Methods: Patients with MCL, relapsing after or refractory to at least one rituximab-containing chemotherapy regimen, WHO PS 0-3, and measurable disease were eligible. The primary endpoint was maximal overall response rate (ORR) measured with CT and PET/CT. Minimal residual disease (MRD) monitoring by PCR was performed during follow-up, according to EuroMRD criteria. Ion Torrent sequencing of the most frequently mutated genes in MCL was performed on frozen tumor cells from bone marrow at time of relapse. Health-related quality of life was assessed by the EORTC-QLQ C30 questionnaire before and during treatment. Treatment schedule: Induction phase: Up to twelve 28-day cycles with: Lenalidomide 15 mg p o daily, days 1-21, Ibrutinib 560 mg p o days 1-28, Rituximab 375 mg/m2 i v day 1 in cycle 1, then 1400 mg s c (or 375 mg/m2i v) days 8, 15 and 22 in cycle 1, then day 1 in cycles 3, 5, 7, 9 and 11. Maintenance phase: For patients in CR, PR or SD, not in need of other treatment, given until progression, cycle duration 56 days. Ibrutinib: 560 mg p o days 1-56, 2. Rituximab 1400 mg s c (or 375 mg/m2i v) day 1 of each cycle. Results: Accrual of 50 pts was completed in June 2016, at 10 centres in Sweden, Norway, Denmark and Finland. The median age was 69.5 years, with a median MIPI score of 6.2. Patients had received a median of two previous regimens, four had progressed after single agent ibrutinib, and three had received prior allo-SCT. A TP53 mutation was detected in 11 of 49 evaluable cases (22%), 8 cases were of blastoid/pleomorphic histology, and 22 of 40 evaluable cases had a Ki67 &gt;30%. Treatment emergent-AEs of any grade in ≥20% of patients were rash (24%) and fatigue (20%). Five pts (10%) experienced rash grade 3, mainly during cycle 1. Hematological toxicity was generally of low grade, apart from grade 3-4 neutropenia in 5 patients. One patient died due to possible treatment-related toxicity (septic shock). In total, 27 patients achieved CR (54%) and 10 PR (20%). Among evaluable patients with a TP53 mutation, blastoid/pleomorphic histology or Ki67 &gt;30%, the CR rates were 7/11 (64%), 15/8 (62%) and 11/22 (50%), respectively. After a median follow-up of 40 months, the median PFS is 18 months (95% CI 6.5-28), and median OS 47 months (95% CI 30-64). Patients with a detectable TP53 mutation at relapse (n=11) had a median PFS of 13 months (95% CI 4.2-21), whereas pts without a TP53 mutation had a median PFS of 34 months (95% CI 8.3-60). Of the 28 patients evaluable for MRD at 6 months, 15/27 (56%) patients achieved molecular remission in blood and 12/28 (43%) in bone marrow. After 12 months, MRD-negativity in BM was 68% (13/19). Out of 4 patients with TP53-mutated MCL, 2 were MRD-negative in BM after 12 months, as well as 2 out of 4 patients with blastoid/pleomorphic histology. By self-reported HRQOL, a lower level of emotional functioning (EF), as well as a higher level of pain (PA) at baseline, was associated with inferior PFS. In addition, low EF was associated with inferior OS. By a Cox regression multivariable analysis, including MIPI, TP53, histology, Ki67, EF and PA, only MIPI was prognostic for PFS or OS with this regimen. Conclusions: The combination of ibrutinib, lenalidomide and rituximab has been shown to be an active and well tolerated regimen in this cohort of high risk R/R MCL, associated with a high rate of molecular remission. The activity in TP53 mutated MCL is lower than in unmutated disease, but this regimen may still serve as an option for a bridge to an allogeneic transplantation or CAR-T therapy in this category of patients. Disclosures Jerkeman: Roche: Research Funding; Abbvie: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Gilead: Research Funding. Hutchings:Genmab: Honoraria; Genmab: Consultancy; Takeda: Consultancy; Roche: Research Funding; Celgene: Research Funding; Daiichi: Research Funding; Sankyo: Research Funding; Genmab: Research Funding; Janssen: Research Funding; Novartis: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; Roche: Honoraria; Roche: Consultancy; Takeda: Honoraria.

High Remission Rates and Prolonged Progression Free Survival in Newly Diagnosed Patients with Mantle Cell Lymphoma Treated with R-MACLOIVAM-T

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3597-3597 ◽  
Author(s):  
Peter J Hosein ◽  
Daniel Morgensztern ◽  
Francine Coleman ◽  
Gail Walker ◽  
Maricer Escalon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Relapse Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Mantle Cell ◽  
Grade 3

Abstract Background: Mantle cell lymphoma (MCL) is an unfavorable subtype of B-cell non-Hodgkin lymphoma characterized by median progression-free survival (PFS) and median overall survival (OS) of only 1.5 and 3–4 years respectively. Although high-dose therapy and an autotransplant may prolong OS, it does not result in a long-term disease free survival. Therefore, there is a need for novel therapeutic approaches for this entity. Methods: We conducted a single-arm phase II study in subjects with newly-diagnosed MCL to assess efficacy and safety of a novel intensive regimen R-MACLO-IVAM-T, a modification of a protocol designed by Magrath et al (JCO1996;14:925). The study size of 22 patients was based on precision of a two-sided 95% confidence interval for the 18-month progression free survival rate. Eligible subjects had a confirmed diagnosis of MCL using WHO criteria, age 18–75 years, ECOG PS ≤ 2, adequate organ function and no history of HIV or prior cancer. Lymphoma extent at presentation was assessed by standard staging procedures as well as esophagogastroduodenoscopy and colonoscopy. Prior to initiating thalidomide maintenance, subjects were enrolled in the STEPS® program. Cycle 1 consisted of R-MACLO: rituximab 375 mg/m2 IV on day 1, doxorubicin 45 mg/m2 IV on day 1, cyclophosphamide 800 mg/m2 IV on day 1 and 200 mg/m2/day on days 2–5, vincristine 1.5 mg/m2 on days 1 and 8 capped to 2mg, methotrexate 1.2 g/m2 IV on day 10 over 1 hour followed by 5.52 g/m2 IV over 23 hours followed by leucovorin 36 hours later. G-CSF was begun on day 13. When the ANC was >1.5×109/L, cycle 2 with R-IVAM was begun: rituximab 375 mg/m2 IV day 1, cytarabine 2 g/m2 IV every 12 hours on days 1 and 2, etoposide, 60 mg/m2 on days 1–5 and ifosfamide 1.5 g/m2 on days 1–5 with mesna. Fourteen days after ANC recovery from cycle 2, cycles 3 and 4 were given in identical fashion to 1 and 2. Four weeks after ANC recovery from cycle 4, subjects were re-staged and responses were assessed by standard criteria. Subjects achieving CR at the end of therapy received thalidomide 200 mg/day until MCL relapse or intolerable toxicity. Results: Accrual started in 4/2004 and ended in 3/2008 when the planned 22 subjects were enrolled. All subjects were evaluable for toxicity and 21 were evaluable for response. Median age was 56.5 years (range 39–73). All subjects had at least stage 3 disease with bone marrow involvement in 19 and gastrointestinal involvement in 10. Distribution according to IPI: 0–1 factor, 3; 2 factors, 8; 3 factors, 8; and 4 factors, 3. Twenty subjects had diffuse variant and 2 had blastic variant. Nineteen subjects completed all 4 cycles of therapy; treatment was stopped in 2 subjects after 2 and 3 cycles respectively, and one subject died during the first cycle. Of the 21 subjects completing 2 cycles of therapy, 20 achieved CR and one PR. Two subjects relapsed at 9 and 33 months respectively, while 19 remain relapse free after median follow-up of 25 months (range 5–51). With a total follow-up of 545 months, the estimated relapse rate is 4.4 per 100 patients per year. There were two deaths: 1 from sepsis on cycle 1 day 8 and the other in CR at 38 months from non-small cell lung cancer diagnosed 19 months after MCL. Common severe toxicities were grade 3–4 neutropenia, thrombocytopenia and anemia in 33%, 19% and 17% of R-MACLO cycles and in 50%, 88% and 68% of R-IVAM cycles respectively. There were 14 bacteremias in 82 cycles, 12 of which were after R-IVAM therapy. Six episodes of reversible grade 1–2 renal toxicity occurred after methotrexate. The thalidomide maintenance dose was reduced in 6 subjects due to grade 3–4 neutropenia and reduced or stopped in 8 subjects because of grade 3–4 peripheral neuropathy. Patients remain under follow-up for relapse and survival. Conclusions: R-MACLO-IVAM-T results in a high overall response rate of 100% (95% CR and 5% PR) and a low relapse rate. At a median follow-up of 25 months, median PFS and OS were not reached. The 2-year actuarial PFS of 94% compares favorably with previously reported 2-year actuarial PFS of 40% and 67% for CHOP-like regimens without and with upfront bone marrow transplantation (Blood2005;105: 2677). The contribution of thalidomide maintenance to this outcome requires additional study. A multicenter clinical trial is suggested.

A Phase I/II Study of Lenalidomide in Combination with Rituximab in Relapsed/Refractory Mantle Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2719-2719 ◽  
Author(s):  
Luhua Wang ◽  
Luis Fayad ◽  
Fredrick B. Hagemeister ◽  
Sattva Neelapu ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Employment Equity ◽  
Mantle Cell ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 2719 Poster Board II-695 Background: Rituximab directly targets CD20 positive lymphoma cells while lenalidomide targets the microenvironment. This combination was proven effective in vitro and in vivo in mantle cell lymphoma (Wu et al, Clin Cancer Res 2008; Zhang et al, Am J Hematol 2009). Clinically, lenalidomide (Habermann et al, Br J Haematol 2009) and rituximab have single-agent activity in mantle cell lymphoma (MCL) and may be an effective combination. The goal of our study was to determine the maximum tolerated dose (MTD) in phase 1 and evaluate the efficacy and safety of lenalidomide plus rituximab in patients with relapsed/refractory MCL in phase 2. Methods: Patients with relapsed/refractory MCL received lenalidomide on days 1–21 of every 28-day cycle, and rituximab (375 mg/m2) weekly during cycle 1. Dose escalation was used to determine the MTD with lenalidomide (10 mg, 15 mg, 20 mg, and 25 mg). Dose-limiting toxicity (DLT) was defined as grade 3 or 4 non-hematologic, or grade 4 hematologic adverse events in cycle 1. Phase 2 has reached targeted enrolment with 45 patients treated at MTD. Kaplan-Meier method was used to estimate progression free survival rate and response duration. Median time to event in months with 95% confidence interval was calculated. Of 45 patients treated at the MTD, the median age was 66 (46–85), 91% were males. All patients had received prior rituximab and were enrolled regardless of prior rituximab sensitivity or resistance. Results: The median follow-up time for the censored observations was 11.4 months. Two DLTs occurred at 25 mg in phase 1 (hypercalcemia, non-neutropenic fever); therefore, the MTD was 20 mg. The grade 3–4 non-hematologic events included elevated AST, elevated ALT, fatigue, myalgia, tremors, ataxia, cough, deep vein thrombosis, dyspnea, edema (facial), infection, neuropathy sensory, rash, and respiratory failure. Grade 3–4 hematologic adverse events included neutropenia (37 events), neutropenic fever (4 events), and thrombocytopenia (16 events). There were no responses in patients treated at 10 mg or 15 mg. Thirty six patients (36) were evaluable for response. Nine (9) patients are too early in their treatment and are not yet eligible for response evaluation. Among the 36 evaluable patients, 11 (31%) patients achieved CR, 8 (22%) patients achieved PR, 3 (8%) patients had minor response, 6 (17%) patients had stable disease and 8 (22%) patients had progressive mantle cell lymphoma. The overall response rate (CR + PR) was 53%. Seventy eight (78%) patients achieved stable disease or better and benefited from oral Lenalidomide plus 4 doses of rituximab. The median time to response was 2 months (2–8), and the median duration of response for the 19 patients with CR or PR was 18 months (95% CI: 10.6, NA) (range1–30 months). The median progression free survival for all patients on phase 2 was 14 months (95% CI: 9.8, NA) (ranging from 1–32 months). Conclusion: Oral lenalidomide plus rituximab resulted in durable responses in relapsed/refractory MCL with a favourable toxicity profile. Disclosures: Wang: Celgene: Honoraria, Research Funding. Hagemeister:Celgene Corporation: Consultancy. Samaniego:Celgene Corporation: Research Funding. Yi:Celgene Corporation: Research Funding. Shah:Celgene Corporation: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Elan: Consultancy; Millennium: Research Funding, Speakers Bureau. Bell:Celgene Corporation: Employment, Equity Ownership. Knight:Celgene Corporation: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Zeldis:Celgene: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Updated Efficacy and Safety, and Exploratory Ki-67 Results For The MCL-001 Study Of Lenalidomide In Mantle Cell Lymphoma Patients Who Relapsed Or Were Refractory To Bortezomib

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3057-3057 ◽  
Author(s):  
Andre Goy ◽  
Michael E. Williams ◽  
Sevgi Kalayoglu Besisik ◽  
Johannes Drach ◽  
Radhakrishnan Ramchandren ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
High Dose ◽  
Efficacy And Safety ◽  
High Dose Therapy ◽  
Ki 67 ◽  
Mantle Cell ◽  
Heavily Pretreated

Abstract Introduction Patients with mantle cell lymphoma (MCL) typically respond to initial therapy and almost inevitably relapse with frequent chemoresistance over time and poor outcome. Multiple phase II studies have established the efficacy and safety of lenalidomide, an immunomodulatory agent with tumoricidal and antiproliferative properties, in relapsed/refractory MCL. The prospective phase II multicenter MCL-001 “EMERGE” study led to FDA approval of lenalidomide for patients with relapsed/refractory MCL after 2 prior treatments, that included bortezomib. The activity of lenalidomide was seen regardless of MIPI, number of prior therapies, prior high dose therapy, bulky disease or high tumor burden. One of the most established prognostic factors in MCL is the proliferation index Ki67 (MIB1), now confirmed both in standard and dose-intensive high-dose therapy strategies. We present here longer follow-up of efficacy and safety from the MCL-001 study in patients relapsed/refractory to bortezomib and the potential relationship between Ki-67 and efficacy outcomes. Methods Patients with heavily pretreated MCL, that included prior bortezomib, received lenalidomide 25 mg/day PO, days 1-21 in 28-day cycles until disease progression or intolerability. Primary study endpoints were overall response rate (ORR) and duration of response (DOR); secondary endpoints included complete response (CR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and safety. Response rates and time-to-event data were analyzed by independent central reviewers per modified IWG criteria and Kaplan-Meier estimates respectively (data cut-off March 20, 2013). Ki-67 was examined as an exploratory endpoint by immunohistochemistry for 81/134 patients (60%) either performed on biopsy samples for 24 patients, or based on the Ki-67 scores reported in local pathology reports for 57 patients. Results Median age for the enrolled intent-to-treat patient population (N=134) was 67 years (range, 43-83; 63% ≥65 years). The median number of previous therapies was 4 (range, 2-10; 78% received ≥3), 93% stage III/IV, and 72% were <6 months from last prior treatment. At a median follow-up of 13.2 months, the ORR was 28% (CR/CRu 8%), with a median DOR of 16.6 months (95% CI, 9.2-26.7; median not reached in patients with CR/CRu) by central review. Median TTR was 2.3 months (95% CI, 1.7-13.1), with a median time to CR/CRu of 4.1 months (95% CI, 1.9-13.2). Median PFS was 4.0 months (95% CI, 3.6-6.9), and median OS was 20.9 months (95% CI, 13.7-24.4). The average dose intensity of lenalidomide was 20 mg/day, for a median duration of 94.5 days (range, 1-1,256). Dose reductions or interruptions due to adverse events (AEs) occurred in 40% and 58% of patients, respectively. Neutropenia (44%), thrombocytopenia (28%), and anemia (11%) were the most common treatment-related grade 3/4 AEs. Ki-67 results were available in 81/134 patients, and efficacy data were categorized using 30% and 50% cut-off thresholds for Ki-67 expression (Table 1). Although patient numbers were limited, the ORR was similar in both lower and higher Ki-67 group, but those with lower Ki-67 levels demonstrated better CR rates, DOR and survival outcomes compared with patients with elevated Ki-67. Conclusions Single-agent lenalidomide in heavily pretreated patients with relapsed/refractory MCL post-bortezomib showed durable long-term efficacy with a consistent safety profile. Consistent with what is reported in the literature, high Ki-67 is associated with poor outcome in our cohort with shorter OS. Though based on retrospective evaluation and subsets of patients, the ORR to lenalidomide was similar in both low and high Ki-67 groups, suggesting lenalidomide can be active in patients expressing high levels of Ki67. Prospective studies are needed to confirm these findings. Disclosures: Goy: Celgene: Consultancy, Research Funding, Speakers Bureau. Off Label Use: This is a phase 2 clinical study of safety and efficacy for lenalidomide in patients with MCL. Williams:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Drach:Celgene: Honoraria. Ramchandren:Celgene: Research Funding. Zhang:Celgene: Employment. Cicero:Celgene: Employment. Fu:Celgene: Employment. Heise:Celgene: Employment, Equity Ownership. Witzig:Celgene: Research Funding.

scholarly journals Five-year follow-up of lenalidomide plus rituximab as initial treatment of mantle cell lymphoma

Blood ◽  
2018 ◽  
Vol 132 (19) ◽  
pp. 2016-2025 ◽  
Author(s):  
Jia Ruan ◽  
Peter Martin ◽  
Paul Christos ◽  
Leandro Cerchietti ◽  
Wayne Tam ◽  
...  
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Mantle Cell Lymphoma ◽  
Initial Treatment ◽  
Cell Lymphoma ◽  
Chronic Therapy ◽  
Key Points ◽  
Mantle Cell

Key Points Lenalidomide plus rituximab as induction and maintenance therapy for MCL can achieve durable MRD-negative complete remissions. Chronic therapy–associated adverse events are generally nonaccumulative and remain manageable.

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.

Nationwide Investigation of Patient Trajectories in Mantle Cell Lymphoma - Initial Data from the Swedish MCL Complete Project

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-4
Author(s):  
Mats Jerkeman ◽  
Thorgerdur Palsdottir ◽  
Ingrid Glimelius ◽  
Alexandra Albertsson-Lindblad ◽  
Caroline Weibull ◽  
...  
Keyword(s):  
Initial Data ◽  
Mantle Cell Lymphoma ◽  
Treatment Response ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Population Based ◽  
First Line ◽  
Mantle Cell ◽  
Early Progression

Background Mantle cell lymphoma (MCL) is a B-cell malignancy, with increasing incidence. It is currently not considered curable. Although a proportion of patients obtain prolonged remission after first line chemoimmunotherapy, most patients will experience several lines of therapy. Hitherto, population based data of the complete care trajectories for patients with MCL have not been available, limiting our knowledge to that from single centre experiences. Here, we present the initial data from a nationwide attempt to collect all available data from all patients diagnosed with MCL. Methods Patients with a primary diagnosis of MCL in 2006-2018 were identified in the Swedish Lymphoma Register and followed until March 6, 2020. The register contains information about clinical characteristics, prognostic factors, primary treatment, treatment response and relapse. Information on further lines of therapy, including treatment response and progression/relapse was extracted through medical chart review in all patients. Results In total, 1411 patients were diagnosed with MCL during the period 2006-2018. Currently, complete data are available for 445 (32%). The most frequently used first line regimens were R-bendamustine (n=131, 29%) and Nordic MCL2 (n=102, 21%). 31 patients (7%) were managed with an initial watch and wait strategy. 87 patients (19%) received consolidation with an autologous stem cell transplant, and 51 (11%) patients received rituximab maintenance. After a median follow-up of 49 months (IQR 25-81), 279 patients (63%) did not experience any relapse, and the median age for patients without relapse was higher compared to the relapse group (73 vs 70 years). 166 patients (37%) experienced a first relapse or progression. The most frequently used second line regimen was R-bendamustine (n=49, 30%). 102 (21%) and 51 (11%) experienced a second or third relapse/progression, respectively. The median PFS after 1st (PFS-1), 2nd, (PFS-2), 3rd (PFS-3) and 4th (PFS-4) lines of therapy were 40, 11, 6, and 4 months. Patients with early progression, defined as a PFS-1 &lt;24 months (POD24-1) had an inferior outcome (median OS of 23 vs. 101 months) compared to patients with a later relapse. Similarly, patients with a POD24-2 had an inferior outcome compared to patients with PFS-2 ³24 months (median OS 8.4 vs 61 months). Conclusion In this population-based series, mainly treated with conventional chemoimmunotherapy, 63% of patients diagnosed with MCL did not experience relapse/progression after a median follow-up of 40 months - due to death before relapse or continuous remission. In addition, PFS and OS continue to drop with successive lines of therapies. Early progression, both after 1st and after 2nd line therapy is associated with markedly impaired OS -identifying patient populations in need of novel treatment strategies. Figure 1 A. Progression-free survival (PFS) in 445 patients with mantle cell lymphoma (MCL) diagnosed in Sweden 2006-2018 according to first line regimen. B. Overall survival (OS) according to time to relapse (PFS -1 &lt; 24 months or &gt;24 months). Figure Disclosures Jerkeman: Abbvie: Research Funding; Celgene: Research Funding; Gilead: Research Funding; Janssen: Research Funding; Roche: Research Funding. Weibull:Janssen Cilag: Research Funding. Smedby:Celgene: Consultancy; Janssen: Research Funding; Takeda: Research Funding.

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