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

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 <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 < 24 months or >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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Radioimmunotherapy for Mantle Cell Lymphoma: 5-Year Follow-up of 90 Patients from the International RIT-Registry

Blood ◽

10.1182/blood-2019-124192 ◽

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.

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

Blood ◽

10.1182/blood-2019-124217 ◽

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

Blood ◽

10.1182/blood-2020-133298 ◽

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 >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 >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.

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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 ◽

10.1182/blood.v122.21.3057.3057 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3057-3057 ◽

Cited By ~ 2

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.

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

Blood ◽

10.1182/blood.v122.21.247.247 ◽

2013 ◽

Vol 122 (21) ◽

pp. 247-247 ◽

Cited By ~ 5

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.

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Treatment of Indolent Non-Hodgkin’s Lymphoma in Germany - Results of a Representative Population-Based Survey.

Blood ◽

10.1182/blood.v110.11.1353.1353 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1353-1353 ◽

Cited By ~ 2

Author(s):

Martin Dreyling ◽

Sebastian Fetscher ◽

P. Kornek ◽

Arnd Nusch ◽

Martin Kornacker ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Population Based ◽

Antifungal Drugs ◽

Lymphocytic Leukemia ◽

Indolent Lymphoma ◽

Therapeutic Approaches ◽

First Line ◽

Mantle Cell ◽

Population Based Survey

Abstract In advanced stage indolent lymphoma, therapeutic approaches may vary from watch and wait, antibody monotherapy, conventional chemotherapy or dose-intensified consolidation up to allogeneic strategies. In this nation-wide survey, representative hematological/oncological centers monitored current treatment strategies under routine conditions. 495 centers involved in the treatment of indolent lymphoma including university hospitals (UH), community hospitals (CH), and office-based hematologists (OBH) were contacted. 13% of identified centers provided information on 741 patients corresponding to 10% of the expected national prevalence. Detailed data on 576 unselected patients (median age 67 years, range 17 to 95) with treatment decision in the second and third quarter of 2006 (start, change or end of therapy) of 46 representative centers (2 UH, 25 CH, and 19 OBH) were included in this analysis. Data were verified by monitoring anonymized patients source data. Median age was 67 with hypertension (28%), coronary heart disease (14%), diabetes (11%), heart failure (8%), cardiac arrhythmia (7%) and renal impairment (7%) being the most frequent concomitant diseases at time of diagnosis. Histology included 39% follicular lymphoma, 26% chronic lymphocytic leukemia (CLL), 10% marginal zone, 9% mantle cell lymphoma, and 16% other histologies. Aim of initial therapy was curative in 35%, aiming at improved survival in 62% and palliation in 54% of patients. Radiation (10%), antibody monotherapy (4%), chemotherapy (33%) and combined immuno-chemotherapy (31%) were the most frequent approaches. Applied chemotherapies included CHOP (46%), fludarabine combinations (F/FC/FCM: 15%), chlorambucil (14%), CVP/COP (9%), Bendamustin (4%), with maintenance (12%) and autologous/allogeneic stem cell consolidation both in 3% of patients. In first relapse, complex regimen including immuno-chemotherapy (49%), maintenance therapy (16%), and autologous/allogeneic transplantation (14%/4%) were more frequently planned. As expected, significant differences were observed between follicular, mantle cell lymphoma and CLL. Interestingly, supportive measures including antibiotics (34%), erythrocyte transfusions (32%), G-CSF (22%), immunoglobulins (19%), antifungal drugs (13%), and erythropoietin (10%) were frequently applied already in first line therapy. Overall response was 83% (FL: 97%, MCL: 95%, CLL: 74%) with a 39% CR rate. Only 10% of first line patients were treated within studies (UH: 19%, CH: 5%, OBH: 13%). In this population-based survey, patient characteristics differed significantly from published study cohorts as did clinical strategies and therapeutic approaches. Thus, clinical studies more relevant to the treatment of medically compromised patients are urgently warranted.

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Lenalidomide, Bendamustine, and Rituximab As First-Line Therapy For Patients >65 Years With Mantle Cell Lymphoma: Preliminary Results From The Nordic Lymphoma Group MCL4 (LENA-BERIT) Phase I-II Trial

Blood ◽

10.1182/blood.v122.21.4377.4377 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4377-4377 ◽

Cited By ~ 9

Author(s):

Mats Jerkeman ◽

Alexandra Albertsson-Lindblad ◽

Arne Kolstad ◽

Anna Laurell ◽

Riikka Räty ◽

...

Keyword(s):

Phase I ◽

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

High Dose Chemotherapy ◽

High Dose ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Mantle Cell

Abstract Background Mantle cell lymphoma is a disease of the elderly, with a median age of 70 years. Younger patients may be treated with potentially curative treatment including high dose chemotherapy. For elderly patients, however, no standard therapy has been defined. In the current trial, we investigate if the addition of lenalidomide (LEN) to rituximab (R)+bendamustine (B) (B 90 mg/m2 D1-2 and R 375 mg/m2 D1) followed by maintenance with LEN for 7 months may enhance efficacy, with manageable toxicity, for the older population of MCL patients. Methods Eligibility criteria were age > 65 years, or ≤ 65 years, unable to tolerate high dose chemotherapy, with untreated mantle cell lymphoma, stage II-IV. BR was given for 6 cycles q4w. In the phase I part, the MTD of LEN was established as 10 mg days 1-14 during the induction phase, cycles 2-6. Prednisolone 20 mg days 1-14 was given during cycle 2. When LEN was initially given from cycle 1, we encountered unexpected grade III-IV toxicity in the form of cutaneous and allergic reactions. In the maintenance phase, LEN single therapy was given as follows: cycles 7-8 - 10 mg days 1-21, cycles 9-13 - 15 mg days 1-21. Results The trial was concluded June 1, 2013, after inclusion of 51 patients, of whom 24 were in the phase I part. The median age is 72 years. According to MIPI, 55% were high risk. Presently, 29 patients are evaluable for response after 6 cycles LBR. ORR is 28/29 (97%), CR+CRu 23 (79%). 17 out of 28 evaluable patients (61%) were MRD-negative after 6 cycles. After a median follow-up of 18 months, the median PFS has not been reached, and the estimated PFS at 2 years is 74%. Eight patients have died, 3 due disease progression, 3 due to treatment related toxicity, 1 of lung cancer in a heavy smoker, 1 of CMML. Overall survival at 2 years is 87%. Conclusions When omitted in cycle 1, lenalidomide in combination with R-bendamustine is feasible as first-line therapy in older patients with MCL, and is associated with a high response rate, also as assessed by MRD. The long term efficacy of this regimen remains to be established by longer follow-up. Disclosures: No relevant conflicts of interest to declare.

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Ofatumumab-Bendamustine As First Line Treatment for Elderly Patients with Mantle Cell Lymphoma: A Phase II Risk Adapted Design with Comprehensive Geriatric Assessment

Blood ◽

10.1182/blood.v124.21.1751.1751 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1751-1751

Author(s):

Carla Casulo ◽

Augustine Iannotta ◽

Jannelle Walkley ◽

Craig H. Moskowitz ◽

Alison J Moskowitz ◽

...

Keyword(s):

High Risk ◽

Mantle Cell Lymphoma ◽

Phase Ii ◽

Research Funding ◽

Cell Lymphoma ◽

Single Agent ◽

Line Treatment ◽

First Line ◽

Mantle Cell ◽

First Line Treatment

Abstract Introduction: Mantle cell lymphoma (MCL) is a heterogeneous disease and risk-stratification of patients (pts) for treatment is not performed routinely. For older pts ineligible for aggressive treatments, comprehensive geriatric assessments (CGA) are recommended but not routinely implemented into practice. Commonly used chemo-immunotherapeutic options result in low rates of complete remission (CR) (40%-50% bendamustine-rituximab; Rummel et al Lancet 2013; Flinn et al Blood 2014), with frequent relapses. Risk-stratification of older MCL pts through biological and clinical characteristics may improve treatment outcomes and reduce toxicity. Ofatumumab may have an advantage over rituximab given more efficient complement activation and complement dependent cytotoxicity. To test this we designed a phase II risk-stratified study of ofatumumab alone or in combination with bendamustine as first line treatment for elderly MCL with the goal of improved remission rates and extended survival. Methods: This was a single-institution phase II study. The primary objective was response. Eligible pts were 65 years of age or older with untreated MCL and/or ineligible for aggressive treatments such as high dose chemotherapy/autologous stem cell transplant. Patients were risk-stratified for therapy. Low risk pts with no GELF/NCCN criteria, low/intermediate risk MIPI, Ki-67 index < 30% and no blastic morphology received single agent ofatumumab weekly for 4 doses. High risk pts with GELF/NCCN criteria present, high risk MIPI, Ki-67 index > 30% or blastic morphology received ofatumumab and bendamustine (O-B) every 28 days for 6 cycles. A simon-two stage design was implemented requiring 6 of 12 pts to have a CR in the O-B arm to proceed. Pts receiving ofatumumab only were permitted to cross over to O-B for less than a partial response (PR) at restaging. Survival probability was estimated by the Kaplan-Meier method. CGA was performed prior to each cycle, and correlation to treatment toxicity was evaluated as a secondary endpoint. Results: Twenty pts in total were enrolled. Median age was 73 (range: 44-83). Seven pts (35%) were classified as low risk and received single agent ofatumumab. Thirteen pts (65%) were classified as high risk and received O-B. All patients in the O-B arm completed 6 cycles of treatment, all met GELF/NCCN criteria. Of these, 54% had high risk MIPI, 54% had Ki67 ≥30%. Among pts receiving single agent ofatumumab, 71% (5 pts) had < PR (stable disease), 1 had CR (14%), and 1 pt was not evaluable. Three pts with < PR crossed over to the O-B arm. Among 12/16 evaluable pts (3 too early, 1 withdrew) in the O-B arm; overall response rate was 92%; CR rate was 67%, PR rate 25%. One patient had stable disease (8%). After median follow-up of 1.8 years (range 0.1-2.6 years), overall survival in the entire group is 100%. Progression free survival at 2 yrs for the O-B arm is estimated at 68%. Both regimens were safe and well tolerated. Incidence of grade 3/4 serious adverse effects was 15% (3 of 22 patients), all in the O-B group. Baseline CGA identified patients as low (n=15) and medium risk (n=3) for grade 3/4 toxicity, with all three SAE (pneumonia, UTI, SVT) occurring in medium risk patients (p=0.001). Baseline timed-up and go showed a trend for anticipated toxicity for patients in the worst quartile (p=0.11). Conclusions: The combination of ofatumumab and bendamustine has promising activity in elderly pts with high risk MCL, with superior CR rates compared to historical chemo-immunotherapeutic regimens. Single agent ofatumumab had modest activity, but was safe in low risk pts and did not impact responses to chemoimmunotherapy. CGA assessment may help predict toxicity. Ofatumumab-bendamustine is effective as first line treatment for older pts with MCL and holds promise as a platform for combination with novel agents in prospective trials of untreated MCL. Figure 1 Figure 1. Disclosures Off Label Use: Ofatumumab is an anti CD20 monocloncal antibody not approved for use in mantle cell lymphoma. Moskowitz:Genentech: Research Funding; Merck: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding. Zelenetz:Foundation Medicine, Inc: Consultancy. Hamlin:Seattle Genetics, Inc.: Consultancy, Research Funding.

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Long-Term Clinical and Molecular Remissions in Patients with Mantle Cell Lymphoma (MCL) Following High-Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT)

Blood ◽

10.1182/blood-2019-122353 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2819-2819

Author(s):

Bernd Metzner ◽

Jochen Casper ◽

Koehne Claus-Henning ◽

Andrea Renzelmann ◽

Thomas H. Mueller ◽

...

Keyword(s):

Maintenance Therapy ◽

Mantle Cell Lymphoma ◽

Research Funding ◽

Cell Lymphoma ◽

Advisory Board ◽

Scientific Advisory Board ◽

Mantle Cell ◽

Scientific Advisory

Background:Long-term clinical and molecular remissions in patients with MCL following HDT and ASCT have been evaluated in only a few studies. Results are especially limited for remission duration over 5 years. So the curability of this disease remains an open question. Patients and methods:Altogether 61 patients with MCL were treated in our institution with ASCT from 1998 to April 2019 (50 1st-line ASCT, ten 2nd-line ASCT, one 3rd-line ASCT). The data were collected retrospectively in 29 and prospectively in 32 patients who participated in two clinical trials: the 1st-line therapy trials of the German Low Grade Lymphoma Study Group (GLSG, principal investigator W. Hiddemann [Dreyling M, Blood 2005] and the European Mantle Cell Lymphoma Network [Hermine O, Lancet 2016], respectively. The diagnosis was regularly approved by the reference pathology of the GLSG (W.K.). The induction therapy before 1st-line ASCT consisted of 6 courses CHOP (n=11), mostly combined with rituximab and followed by Dexa-BEAM, and 6 alternating courses of R-CHOP and R-DHAP (n=39), respectively. For the salvage treatment patients usually received three to four courses of the DHAP protocol or the ESHAP protocol, since 2001 also combined with rituximab.Stem cell apheresis was carried out in the Blood Transfusion Service following these protocols in remission. High-dose protocols: 1) total body irradiation with cyclophosphamide or melphalan and cytarabin (n=32) or 2) BEAM (n=29). Patients with partial remission after ASCT received a radiotherapy (RT) with 30-36 Gy in the field of persisting lymphoma, if possible (n=4). Since 09/2016 patients received a maintenance therapy with rituximab after ASCT (every 2 months, planned for 3 years, n=14). Further details are described in an earlier publication of our first 36 patients (Metzner B, Ann Hematol 2013). Response assessment was performed by careful clinical examination and by ultrasound, chest x-ray and partly CT at regular 3 - 12 monthly time points. In the case of long-term remission (≥ 5 years; n = 18), peripheral blood was regularly tested twice a year for minimal residual disease (MRD) by quantitative t(11;14) or allel specific IGH RQ-PCR and/or IGH-consensus PCR.Calculations were done using IBM SPSS Statistics Version 25. Data were analysed as of 01 July 2019. Results:With a median follow-up of 5 years (range 0.1-20) 10-year overall survival, progression-free survival (PFS) and freedom from progression (FFP) after 1st-line ASCT were 54%, 46% and 52%, respectively, after 2nd-line ASCT 42%, 20%and 20%, with a significant difference for PFS (p=0.045) and FFP (p=0.014) between 1st-line and 2nd-line cohort.Further prognostic factors (like sex, age, MIPI, bone marrow involvement, remission grade at ASCT: CR vs. PR, type of HDT: TBI vs. BEAM…) seemed to be without relevance (considering the small subgroups). Only one clinical relapse occurred after 5 years following ASCT in 1stor 2ndremission, respectively (one patient 6 years after 1st-line ASCT and another patient 7 years after 2nd-line ASCT and subsequent radiotherapy). So far, 18 patients experienced long-term remissions of at least 5 years (median 9 years, from 5 to 16 years). Fifteen of 17 tested patients were MRD negative at last follow-up, the two MRD positive patients (positive at a low level below the quantitative measuring range) had no clinical signs of relapse at last follow-up. None of these 18 patients had received rituximab maintenance therapy. None showed clinical criteria of "smoldering mantle cell lymphoma" at induction therapy. Treatment-related mortality at 100 days after ASCT was 1.6% (pneumonitis following TBI). One patient developed a secondary invasive malignancy in remission after ASCT (acute myeloid leukemia 4 years following TBI). Conclusion: Sustained long-term clinical and molecular remissions up to 16 years can be achieved following ASCT (without rituximab maintenance therapy), indicating the potential curative impact of 1st-line ASCT in MCL. The 2nd-line ASCT was obviously less effective. Disclosures Dreyling: Celgene: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: scientific advisory board, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: scientific advisory board, Research Funding, Speakers Bureau; Bayer: Consultancy, Other: scientific advisory board, Speakers Bureau; Gilead: Consultancy, Other: scientific advisory board, Speakers Bureau; Acerta: Other: scientific advisory board; Novartis: Other: scientific advisory board; Sandoz: Other: scientific advisory board. Klapper:Roche, Takeda, Amgen, Regeneron: Honoraria, Research Funding.

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CD5 Negative Mantle Cell Lymphoma: Clinicopathologic Correlations and Outcome in 58 Cases

Blood ◽

10.1182/blood.v128.22.2964.2964 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2964-2964

Author(s):

Annapurna Saksena ◽

Yuan Miao ◽

Pei Lin ◽

Michael Wang ◽

C. Cameron Yin ◽

...

Keyword(s):

B Cell ◽

Mantle Cell Lymphoma ◽

Board Of Directors ◽

Research Funding ◽

Cell Lymphoma ◽

P Value ◽

Clinicopathologic Features ◽

Advisory Committees ◽

Mantle Cell

Abstract Introduction: Mantle cell lymphoma (MCL) is a B-cell neoplasm that has a characteristic immunophenotype of being positive for CD5, B-cell antigens and cyclin D1. A small subset of cases of MCL can be negative for CD5, approximately 5% in the literature. The clinicopathologic features and prognosis of patients with CD5-negative MCL are poorly characterized. Here, we study a group of patients with CD5- MCL and compare them with a group patients with CD5+ MCL. Methods: From a total of 270 cases of MCL accessioned from 2004-2015, 58 CD5- cases (study group) and 212 CD5+ cases (control group) were identified. All cases of MCL were positive for cyclin D1 by immunohistochemistry and, in most patients, CCND1-IGH was shown FISH. Cases negative for CD5 were assessed by flow cytometry and/or immunohistochemistry. Fisher exact test was utilized to analyze differences between the CD5- and CD5+ groups. Patient survival was analyzed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional hazards model analyses for OS and PFS were performed (SPSS 22 software). A P-value of less than 0.05 was considered statistically significant. Results: The CD5- group included 39 men and 19 women with a median age of 66 years (range, 36- 88 years) at time of diagnosis. The CD5- and CD5+ groups shared overlapping clinicopathological features, but CD5- cases showed a lower percentage of men (P=0.006) than CD5+ cases. Treatment information was available for 50 patients. Twenty-nine (58%) patients were treated initially with R-Hyper CVAD therapy (rituximab, fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high dose methotrexate and cytarabine). Seventeen (34%) patients were treated initially with less aggressive therapy: 7 with R-CHOP; 8 had other rituximab-based chemotherapy regimens; 2 received rituximab as a single agent. Four patients (8%) were observed without therapy. After induction, 34 patients achieved complete remission (CR), 5 patients achieved partial remission (PR), 6 patients showed no response (NR) or progressive disease (PD), and 5 patients lost follow-up. Ten patients also underwent stem cell transplantation (SCT): 5 patients received allogeneic SCT, the other 5 autologous SCT. With a median follow-up of 45.7 months (range, 2.0-174.3 months), 13 of 56 (23.2%) patients died, 43 of 56 (76.8%) patients were alive at last follow-up, and the rest of 2 patients lost follow up. The induction chemotherapy regimens and CR and PR rate were not significantly different between the CD5- and CD5+ groups (p>0.05). Survival analysis showed patients with CD5- MCL had a tendency for longer OS (Figure 1A, P=0.078). Further analysis showed that lack of CD5 expression predicted a superior OS in a few subsets of MCL patients defined with 1) normal WBC count (p=0.049); 2) Stage I/II disease (p=0.046); 3) Low/intermediate MIPI (p=0.041) and 4) Ki67≥30% (at a borderline p value of 0.05). Patients with CD5- MCL also showed a significantly longer progression-free survival (PFS) (Figure 1B, P=0.01). Absence of CD5 expression was associated with a better PFS in MCL patients with advanced disease (stage III-IV) (P=0.035), a normal leukocyte count (P=0.018), a normal serum lactate dehydrogenase level (P=0.046), classical morphology (P=0.029), and low/intermediate MIPI (p=0.0004). Multivariate Cox regression analysis revealed that MIPI was the only independent prognostic factor for both OS and PFS (P=0.026 and P=0.001 respectively) and CR/PR also predict a better OS (P=0.004) in CD5- MCL patients. Conclusion: The clinicopathologic features were similar between patients with CD5- MCL and those with CD5+ MCL, except that less men in the CD5- MCL group. Lack of CD5 expression was associated with a favorable PFS in MCL patients. Recognizing this subgroup of CD5- MCL has not only a diagnostic significance, but also a prognostic significance. Figure Figure. Disclosures Wang: Acerta Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno Therapeutics: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharma: Research Funding; Asana BioSciences: Research Funding; BeiGene: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Onyx: Research Funding.

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