Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 753-753

Abstract: Background: Early progression of disease (POD) in patients (pts) with mantle cell lymphoma (MCL) following intensive frontline treatment has been associated with inferior survival (Dietrich et al Ann Oncol 2014 and Visco et al Br J Haematol 2019), but the optimal time point to define early POD and the predictive significance of early POD following less intensive frontline treatment is not well established. We compare outcomes after all frontline treatments in a large MCL cohort categorized by time to progression and describe outcomes by class of second line treatment for pts with primary refractory disease. Methods: Clinical and outcome data for MCL pts treated between 2000 and 2017 were collected from 12 US centers. Overall survival (OS), defined from time of 1st progression, and secondary progression free survival (PFS2), defined from 1st progression to 2nd progression or death, were estimated by Kaplan-Meier and compared by log-rank test. Univariable and multivariable analyses were performed using Cox proportional hazards models for OS. 95% confidence intervals were calculated for all estimates and displayed in square brackets. We defined intensive treatment as high dose cytarabine in frontline therapy and/or autologous stem cell transplant in 1st remission. Pts were categorized into three groups: (a) refractory disease to frontline therapy or POD within 6 months of frontline therapy was termed primary refractory (PRF); (b) POD between 6 to 24 months of therapy was termed POD24 and (c) POD beyond 24 months was termed POD & gt;24. Salvage therapy was categorized as chemoimmunotherapy (CIT) for pts treated with CIT alone, BTK inhibitor (BTKi) for pts treated with BTKi single agent or in combination, and lenalidomide / bortezomib for pts treated with one or both agent +/- anti-CD20 therapy. Results: Of 1,168 pts with MCL, 457 pts had relapsed and were included in this analysis. The median age was 62, 77% were male, and ECOG PS was 0/1 in 94%. Median follow-up was 2.6 years (yr) after first progression. The most common induction regimens were R-HyperCVAD (26%), R-CHOP (24%), bendamustine and rituximab (19%), and R-M-CHOP (10%). Frontline treatment was intensive in 54%. Sixty five pts (14%) were PRF, 153 (34%) had POD24, and 239 (53%) had POD & gt;24. Additional baseline characteristics and comparison between groups are summarized in Table 1. The median OS was 1.3 yr [0.9-2.4] for PRF pts, 3 yrs [2-6.8] for POD 24, and 8 yrs [6.2-not reached (NR)] for POD & gt;24 (p & lt;0.0001). Comparing median PFS2 by time to POD, median PFS2 was 1 yr [0.4-1.3] for PRF, 1 yr [0.8-1.4] for POD24 and 2.3 yrs [1.8-3.2] for POD & gt;24 pts (p & lt;0.0001). Among PRF pts, median OS was 0.9 yr [0.4-3] for intensive treatment pts versus 2.0 yrs [0.9-4.5] among less intensive treatment (p=0.33). Among POD24 pts, median PFS2 was 0.8 yr [0.5-1] following intensive vs 2 yrs [0.8-2.9] with less intensive treatment (p=0.0003); likewise OS was shorter after intensive vs less intensive treatment, median 2 yrs [1.1-3.4] vs 6.8 yrs [3.1-9.7] (p=0.05). Both PRF and POD24 were associated with inferior OS on univariable analysis (Table 2) and remained associated with inferior OS on multivariable analysis independent of MIPI score and B symptoms (sx); HR 7.7 [3.9-15.1] for PRF and HR 2.5 [1.4-4.5] for POD24, HR 2.5 [1.4-4.5] for high MIPI score, and HR 1.3 [0.8-2.2] for B sx. Among pts with PRF MCL, median PFS2 and OS were 1.2 [0.5-2.3] and 2.4 [0.7-4.5] yrs for BTKi (n=21), 0.5 [0.2-2.3] and 1.1 [0.5-NR] yrs for CIT (n=22), and 0.3 [0.1-0.6] and 1.9 [0.1-2] yrs for lenalidomide / bortezomib (n=8) as 2nd line therapy. Two pts with PRF MCL received no further therapy and both died within one month of POD. Conclusions: Time to relapse is predictive of outcome in pts with MCL and outcomes with current salvage therapies are poor for pts with relapse within 6 months of frontline therapy. Of currently available second line therapies, BTKi were associated with improved PFS2 in refractory pts. Outcomes are particularly poor for pts who receive intensive induction therapies yet still relapse early, representing a population at high risk for early mortality related to MCL. Novel treatment approaches should be evaluated in this population, including CAR-T cell therapy, and attempts to improve risk stratification at diagnosis and develop improved therapies for high-risk pts should continue. Disclosures Maddocks: Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Merck: Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees. Kolla:Amgen: Equity Ownership. Bachanova:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Research Funding; Novartis: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Celgene: Research Funding; GT Biopharma: Research Funding. Gerson:Abbvie: Consultancy; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Merck: Research Funding; Mundipharma: Honoraria; Bayer: Consultancy, Research Funding; Seattle Genetics: Honoraria, Research Funding; Takeda: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Mundipharma: Honoraria. Hill:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Martin:Karyopharm: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Teneobio: Consultancy. Danilov:Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Bristol-Meyers Squibb: Research Funding; Aptose Biosciences: Research Funding; Bayer Oncology: Consultancy, Research Funding; TG Therapeutics: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy; MEI: Research Funding; Janssen: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Takeda Oncology: Research Funding; AstraZeneca: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Grover:Seattle Genetics: Consultancy. Karmali:Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau. Ghosh:AstraZeneca: Honoraria, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; SGN: Consultancy, Honoraria, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Research Funding; Forty Seven Inc: Research Funding. Park:BMS: Consultancy, Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Hamadani:Pharmacyclics: Consultancy; Merck: Research Funding; Celgene: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Janssen: Consultancy; Otsuka: Research Funding; Medimmune: Consultancy, Research Funding; Takeda: Research Funding. Kahl:BeiGene: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy. Flowers:Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy; Denovo Biopharma: Consultancy; National Cancer Institute: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Bayer: Consultancy; AbbVie: Consultancy, Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Karyopharm: Consultancy; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy. Cohen:LAM Therapeutics: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Astra Zeneca: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; ASH: Research Funding; Lymphoma Research Foundation: Research Funding; Hutchison: Research Funding; UNUM: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-128415

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4153-4153

Abstract: Introduction: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent-behaving disease can safely defer treatment (Calzada et al, 2018). In this subgroup, a lack of evidence to support the decision-making behind the choice of therapy has led to a wide diversity in treatments. We evaluated the importance of treatment intensity in patients with MCL who defer initial therapy. Methods: We included patients ≥ 18 years old with MCL from 11 academic centers and defined the deferred subgroup as patients who started therapy ≥ 90 days after diagnosis. Patients who received high dose cytarabine as part of their induction or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy while all other approaches were non-intensive. We identified differences between the baseline characteristics of the two groups using Fisher's exact tests, chi-squared tests, and t-tests as appropriate. We calculated progression-free (PFS) and overall survival (OS) from the date of diagnosis using the Kaplan-Meier method and compared the two groups using the log-rank test. Univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Results: Of 968 identified patients with MCL, 233 did not initiate therapy within 90 days of diagnosis and were considered deferred. Deferred patients had a lower Ann Arbor stage (p 〈 0.001), Ki-67 (p 〈 0.001) and LDH (p=0.007) at diagnosis compared to patients undergoing immediate treatment. Within the deferred group, 80 patients received intensive therapy (including 59 who completed ASCT in first remission), 99 received non-intensive therapy, and the remaining 54 patients did not receive any documented treatment and were excluded from this analysis. The most common intensive regimens included R-HyperCVAD and R-CHOP, and the most common non-intensive regimens included R-bendamustine and R-CHOP without ASCT. There was no difference in time to treatment, ECOG performance status, ethnicity, Ann Arbor stage or presence of B-symptoms between the two groups. However, patients who received non-intensive therapy were older (p 〈 0.001), more likely to have a normal LDH (p=0.03), and more likely to be treated at the reporting academic center (p=0.008). There was no significant difference in OS (Figure 1A, p=0.7) or PFS (Figure 1B, p=0.16) between the deferred patients who subsequently received non-intensive vs. intensive therapy. Univariate analysis of PFS highlighted the significance of: LDH (HR 0.62, p= 0.04), lack of blastoid morphology (HR 0.53, p=0.032), treatment initiation at participating academic center (HR 0.43, p 〈 0.001), post-induction rituximab (HR 0.42, p=0.003), and higher baseline hemoglobin level (HR 0.90, p=0.038) as predictors of improved PFS. Multivariable analysis demonstrated that post-induction rituximab (HR 0.16, p=0.008) and treatment initiation at an academic center (HR= 0.17, p 〈 0.001) predicted improved PFS while pre-existing coronary artery disease (HR=5.28, p=0.015) was associated with decreased PFS. A univariate analysis found that lack of blastoid histology (HR 0.24, p 〈 0.001), normal LDH (HR 0.31, p 〈 0.001), increased baseline hemoglobin (HR 0.83, p=0.005), post-induction rituximab (HR 0.16, p=0.014), and treatment initiation at an academic center (HR 0.34, p=0.003) significantly improved OS. In a multiviariable analysis, lack of blastoid histology (HR 0.11, p 〈 0.001) predicted improved OS while pre-existing diabetes mellitus (HR 5.98, p=0.005) and age (HR 1.08, p=0.001) were significantly associated with inferior OS. Intensity of treatment was not significantly associated with PFS or OS in the univariate or multivariable models. Conclusions: Among this large group of MCL patients who deferred therapy, use of an intensive induction therapy did not improve OS or PFS compared to patients who received non-intensive treatments. Our findings suggest that other patient- and disease-related factors may affect PFS and OS in this patient subgroup. Prospective studies to evaluate tools incorporating these factors will be useful in identifying the optimal therapy approach for patients with MCL who have completed an initial period of observation. Disclosures Calzada: Seattle Genetics: Research Funding. Bachanova:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; GT Biopharma: Research Funding; Gamida Cell: Research Funding. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Merck, Takeda, Celgene, Seattle Genetics, Bayer: Research Funding. Danilov:Takeda Oncology: Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Astra Zeneca: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Bayer Oncology: Consultancy, Research Funding. Grover:Seattle Genetics: Consultancy. Karmali:Gilead: Speakers Bureau; AstraZeneca: Speakers Bureau. Hill:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Park:Rafael Pharma: Consultancy; BMS: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Speakers Bureau; BMS: Consultancy; Teva: Research Funding; Gilead: Speakers Bureau; Takeda: Research Funding; G1 Therapeutics: Consultancy; Teva: Consultancy. Blum:Novartis: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding; Morphosys: Research Funding. Hamadani:Cellerant: Consultancy; Celgene Corporation: Consultancy; MedImmune: Consultancy, Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Ostuka: Research Funding; Takeda: Research Funding; ADC Therapeutics: Research Funding; Merck: Research Funding; Janssen: Consultancy. Kahl:Genentech: Consultancy; Seattle Genetics: Consultancy; ADC Therapeutics: Research Funding. Flowers:Denovo Biopharma: Consultancy; Celgene: Research Funding; Spectrum: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Gilead: Research Funding; Pharmacyclics/ Janssen: Consultancy; BeiGene: Research Funding; Bayer: Consultancy; Pharmacyclics: Research Funding; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Abbvie: Research Funding; Gilead: Consultancy; Janssen Pharmaceutical: Research Funding; OptumRx: Consultancy; Genentech/Roche: Consultancy; Millennium/Takeda: Research Funding; Abbvie: Consultancy, Research Funding; Karyopharm: Consultancy; National Cancer Institute: Research Funding; Genentech/Roche: Research Funding; Acerta: Research Funding. Cohen:Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Takeda: Research Funding; BioInvent: Consultancy; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-117547

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: American Journal of Hematology, Wiley, Vol. 96, No. 11 ( 2021-11), p. 1374-1384

Abstract: Clinical outcomes and predictors of survival in patients with newly diagnosed mantle cell lymphoma (MCL) treated in the rituximab era (2000–2015) at 12 US academic centers were assessed to identify determinants of survival across age groups. Objectives were to characterize and compare practice patterns, outcomes and prognostic factors for survival in younger patients (age  〈  65) and older patients (age ≥ 65 years). Among 1162 patients included, 697 were younger and 465 were older. In younger patients, 2‐year progression free survival (PFS) and overall survival (OS) rates were 79% and 92% respectively; blastoid histology, ECOG ≥ 2, and lack of maintenance rituximab (MR) remained statistically relevant to poor OS on univariate analysis (UVA) and multivariate analysis (MVA). In older patients, 2‐year PFS and OS rates were 67% and 86% respectively; lack of maintenance rituximab remained significantly associated with inferior PFS and OS on UVA and MVA ( p   〈  0.001). Two‐year PFS rates were 79%, and 67% and 2‐year OS rates were 92% and 86% for ages 〈 65 and ≥ 65 respectively ( p   〈  0.001). First‐line high‐dose cytarabine exposure and/or MR lessened the negative impact of age on survival. Taken collectively, survival outcomes for older patients remain inferior to those of younger patients in the rituximab era. However, maintenance rituximab and potentially high‐dose cytarabine‐based induction can mitigate the negative impact of age on survival.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v96.11

DOI: 10.1002/ajh.26306

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 1492749-4

In: Blood Advances, American Society of Hematology, Vol. 5, No. 23 ( 2021-12-14), p. 5179-5189

Abstract: Although an expanding array of effective treatments has resulted in recent improvement in survival of patients with mantle cell lymphoma (MCL), outcomes remain heterogeneous, and identification of prognostic factors remains a priority. We assessed the prognostic impact of time to progression of disease (POD) after first-line therapy among 455 patients with relapsed MCL. Patients were categorized by duration of first remission as PRF/POD6, defined as progressive disease during induction or POD within 6 months of diagnosis (n = 65; 14%); POD6-24, defined as POD between 6 and 24 months after diagnosis (n = 153; 34%); and POD & gt;24, defined as POD & gt;24 months after diagnosis (n = 237; 53%). The median overall survival from POD (OS2) was 1.3 years (95% confidence interval [CI], 0.9-2.4) for patients with PRF/POD6, 3 years (95% CI, 2-6.8) for those with POD6-24, and 8 years (95% CI, 6.2-NR) for those with POD & gt;24. Median OS2 was inferior in patients with early POD (defined as PRF/POD6 or POD6-24) after both intensive and less intensive frontline treatment. The prognostic performance of time until POD was replicated in an independent cohort of 245 patients with relapsed MCL, with median OS2 of 0.3 years (95% CI, 0.1-0.5) for PRF/POD6, 0.8 years (95% CI, 0.6-0.9) for POD6-24, and 2.4 years (95% CI 2.1-2.7) for POD & gt;24. Early POD is associated with inferior OS2 in patients with relapsed MCL, identifying a high-risk population for future prospective studies.

Type of Medium: Online Resource

ISSN: 2473-9529 , 2473-9537

URL: Article

DOI: 10.1182/bloodadvances.2021004765

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 2876449-3

In: European Journal of Haematology, Wiley, Vol. 107, No. 3 ( 2021-09), p. 301-310

Abstract: While most patients with mantle cell lymphoma (MCL) receive therapy shortly after diagnosis, a subset of patients with indolent‐behaving disease can safely defer treatment. In this subgroup, we evaluated the importance of treatment intensity in patients with MCL who defer initial therapy. Methods Out of 1134 patients with MCL from 12 academic centers, we analyzed 219 patients who initiated therapy at least 90 days after diagnosis. Patients who received induction with high‐dose cytarabine and/or autologous stem cell transplantation (ASCT) in first remission were considered to have received intensive therapy (n = 88) while all other approaches were non‐intensive (n = 131). Results There was no difference in progression‐free (PFS; P  = .224) or overall survival (OS; P  = .167) in deferred patients who received non‐intensive vs. intensive therapy. Additionally, univariate and multivariate Cox proportional hazards models were performed for PFS and OS. Treatment at an academic center (HR 0.43, P  = .015) was associated with improved OS in both univariate and multivariate models, while intensity of treatment was not associated with improved OS in either model. Conclusions These results indicate that intensified initial treatment is not associated with improved survival after deferring initial therapy, although prospective studies are needed to determine which of these patients with MCL may benefit from intensive therapy.

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.v107.3

DOI: 10.1111/ejh.13649

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 2027114-1

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3997-3997

Abstract: Introduction: Time to treatment (TTT) is an important prognostic factor in patients with newly diagnosed diffuse large B-cell lymphoma (Maurer et al JCO 2018) where patients who initiate therapy quickly after diagnosis have an inferior event free survival compared to those who do not require such immediate treatment initiation. More recently, TTT has shown to be associated with adverse clinical factors and inferior outcomes in mantle cell lymphoma (MCL; Maurer, et al ASH, 2018). However, there is a paucity of data on the impact of TTT on overall survival (OS). We sought to validate these findings and to evaluate the impact of TTT on survival outcomes in newly diagnosed patients with MCL. Methods: We included patients from 12 medical centers in the United States with MCL diagnosed between January 1, 2000, and January 1, 2018, who had information on the TTT and initiated treatment within 60 days of diagnosis (to exclude patients whose treatment was purposefully deferred). TTT was defined as the time in days from first lymphoma diagnosis to initiation of therapy. Patients who received treatment within 14 days were categorized into short TTT group. We compared differences between the two groups (TTT 〈 =14 days vs TTT 〉 14 days and ≤ 60 days, longer TTT group) using chi-squared test, Fisher's exact tests, or ANOVA tests as appropriate. OS was defined as the time from diagnosis to death or last follow-up. Patients not experiencing an event were censored at their last known follow-up. OS was determined using the Kaplan-Meier method, and univariable and multivariable models were developed to identify predictors of OS. Results: Of 1,168 patients with newly diagnosed MCL, seven hundred fifty-five patients met the inclusion criteria and were included in this analysis, including 205 (27%) with short TTT and 550 (73%) with longer TTT. Median time to treatment was 7 days (range, 0-14) for the short TTT group vs 31 days for the longer TTT group (range, 15-60 days). The median age for the entire cohort was 63 years, 75% of patients were male, and 93% of patients had ECOG 0-1. The proportion of patients with stage 4 disease (93 vs 86%, p=0.015), elevated LDH (58 vs 39%, p 〈 0.001), 〉 3 cytogenetic abnormalities (29 vs 14%, p=0.005), B symptoms (47 vs 29%, p 〈 0.001) and high MIPI score (49 vs 27%, p 〈 0.001) was higher in short TTT group compared to longer TTT group. 65% received intensive induction therapy in the short TTT group relative to 57% in the longer TTT group (p=0.046) (Table). On univariable analysis, factors associated with inferior OS included, TTT 〈 =14 days (HR=1.66, 95%CI=1.23-2.27, p 〈 0.001), ECOG 〉 =2 (p 〈 0.001), stage IV disease (p=0.01), elevated LDH (p 〈 0.001), WBC 〉 10k (p=0.002), BM involvement (p 〈 0.001), splenomegaly (p 〈 0.001), ≥3 cytogenetic abnormalities (p 〈 0.001), non-intensive regimen (p=0.03), B symptoms (p 〈 0.001), and high MIPI score (p 〈 0.001). With a median follow-up of 3.4 years, the median OS was 8.8 years (95%CI=7-NA) for patients with short TTT group and 12.5 years (95% CI: 11.4-18.7) for patients with longer TTT group (Figure; p 〈 0.001). In the multivariable model including ECOG, LDH, intensive regimen and B symptoms, short TTT (HR=2, 95%CI=1.25-3.22; p=0.004), ECOG 〉 =2 (HR=2.25, 95%CI=1.22-4.14; p=0.009), elevated LDH (HR=1.81, 95%CI=1.16-2.85; p=0.01), and receipt of non-intensive regimen (HR=1.61, 95%CI=1.04-2.50; p=0.03) were significant predictors of OS while B symptoms was not. Conclusions: Short TTT for patients with newly diagnosed MCL is associated with aggressive disease features and inferior OS despite an increased likelihood of receiving intensive induction regimens. Further studies are needed to identify molecular determinants of such aggressive disease behavior that can be assessed quickly and utilized to initiate appropriate therapy in a timely manner. Ongoing front-line clinical trials in MCL should be developed in a way to facilitate enrollment of patients requiring urgent therapy, including potentially permitting a cycle of off-study treatment to manage symptoms while a patient is screened and enrolled. Disclosures Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Kolla:Amgen: Equity Ownership. Bachanova:GT Biopharma: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Gamida Cell: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Gerson:Seattle Genetics: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy. Barta:Mundipharma: Honoraria; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Danilov:Bristol-Meyers Squibb: Research Funding; Aptose Biosciences: Research Funding; Takeda Oncology: Research Funding; AstraZeneca: Consultancy, Research Funding; TG Therapeutics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Genentech: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; MEI: Research Funding; Janssen: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy. Grover:Seattle Genetics: Consultancy. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau. Hill:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Ghosh:Forty Seven Inc: Research Funding; AbbVie: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; T G Therapeutics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Astra Zeneca: Speakers Bureau; Genentech: Research Funding; Spectrum: Consultancy, Speakers Bureau. Park:Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; BMS: Consultancy, Research Funding. Hamadani:Pharmacyclics: Consultancy; Medimmune: Consultancy, Research Funding; Janssen: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Celgene: Consultancy; Otsuka: Research Funding; Merck: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding. Martin:I-MAB: Consultancy; Sandoz: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Teneobio: Consultancy. Kahl:AbbVie Inc, Acerta Pharma - A member of the AstraZeneca Group, AstraZeneca Pharmaceuticals LP, BeiGene, Celgene Corporation, Genentech, Pharmacyclics LLC, an AbbVie Company, Roche Laboratories Inc.: Consultancy. Flowers:V Foundation: Research Funding; National Cancer Institute: Research Funding; Millenium/Takeda: Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Karyopharm: Consultancy; Spectrum: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Optimum Rx: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Bayer: Consultancy. Cohen:Seattle Genetics, Inc.: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; Janssen Pharmaceuticals: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-128632

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 25, No. 3 ( 2019-03), p. S23-S24

Type of Medium: Online Resource

ISSN: 1083-8791

URL: Article

DOI: 10.1016/j.bbmt.2018.12.093

Language: English

Publisher: Elsevier BV

Publication Date: 2019

detail.hit.zdb_id: 3056525-X

detail.hit.zdb_id: 2057605-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e20064-e20064

Abstract: e20064 Background: Therapeutic intensity poses a challenge for older or medically unfit pts with untreated MCL. We assessed clinical outcomes and predictors of survival in older MCL pts treated in the rituximab era. Methods: We included pts ≥ 65 yrs of age with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to characterize practice patterns and survival outcomes in older pts and secondarily to assess predictive factors of survival. Results: Data were collected from 12 centers for 1168 pts. For 465 pts ≥ 65 yrs of age (median 70; range 65-100), variable denominators indicate missing data: 305 of 444 pts (69%) were male; 23 (8%), 110 (39%) and 148 (53%) of 281 pts had low, intermediate and high-risk MIPI respectively. Median time from diagnosis to first treatment was 31 days (range 0-2611 days). In 407 older pts with initial treatment data, 148 (36%) received BR, 65 (16%) a cytarabine containing regimen, 9 (2%) lenalidomide, and 92 (23%) other treatments that excluded BTK inhibitors (BTKi). 68 of 365 pts (19%) were enrolled on clinical trial for initial therapy, 88 of 369 pts (24%) received autologous transplant (AHCT) in first remission, and 155 of 351 pts (44%) received maintenance rituximab (MR). Median f/u was 2.7 yrs. 41 of 465 pts (9%) had primary refractory disease (POD6); 107 (23%) progressed within 24 months (POD24). Treatment data were available for 157 relapsing pts: 58 (37%) were treated with BTKi/BTKi combinations. PFS and OS rates were compared across young and older age cohorts: 2 yr PFS rates were 79%, 69%, and 66% and 2 yr OS rates were 92%, 87%, and 84% for age 〈 65, age 65-69, and age ≥ 70 respectively (p 〈 0.001). In the older cohort: on UVA, ECOG ≥2, BM involvement, blastoid histology, 〉 3 cytogenetic abnormalities and lack of MR were associated with inferior PFS and OS (p = 0.012 – 〈 0.001). POD6 and POD24 were associated with decreased OS (p 〈 0.001). AHCT in first remission did not impact PFS or OS. After MVA, MR remained significantly associated with improved PFS and OS (p 〈 0.001). 2 yr PFS rates were 81% and 58% and 2 yr OS rates were 96% and 80% with and without MR respectively (p 〈 0.001). Conclusions: In this large cohort of older pts in the rituximab era, survival outcomes remain inferior to younger pts. MR is associated with improved PFS and OS but AHCT does not yield better survival. A small number of pts received BTKi salvage therapy. As such, our data does not reliably reflect the potential advancements in survival achieved with the introduction of BTKis. Focused clinical trials are necessary to identify effective therapeutics in this population.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2020.38.15_suppl.e20064

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2020

detail.hit.zdb_id: 2005181-5

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 3483-3483

Abstract: Introduction: Mantle cell lymphoma (MCL) is a rare form of lymphoma with no current standard of care. As a result, clinical trials are critical to improving our understanding of the disease and its management. However, clinical trial participation is often limited due to lack of access to studies, restrictive eligibility criteria, and decisions by treating physicians or patients not to participate. We evaluated the rate of enrollment and outcomes associated with clinical trial participation of patients with MCL at 12 US Medical Centers. Methods: We included patients from 12 medical centers in the United States with MCL diagnosed between January 1, 2000, and January 1, 2018, who were ≥ 18 years old, received any induction therapy, and for whom it was known whether initial treatment was on a clinical trial (CT) or not. We compared differences between the two groups (CT vs not) using Fisher's Exact and Chi-square tests as appropriate. We defined overall survival (OS) as time from diagnosis to death. Patients not experiencing an event were censored at their last known follow-up. OS was determined using the Kaplan-Meier method, and univariate and multivariable models were developed to identify predictors of OS. Results: Eight hundred twelve patients were included in this analysis, including 164 (20%) patients who participated in a clinical trial during initial therapy. Rate of participation ranged from 4% to 36% across contributing sites. Median age for the entire cohort was 62 years, 572 (74%) of patients were male, and 95% of patients had ECOG 0-1. MCL International Prognostic Index (MIPI) risk score was high in 163 patients (31%), and 84% of patients had stage IV disease. Ki67 was & gt;30% in 169/225 (43%) patients with available data, and 19% of patients (65/271) had a complex karyotype with & gt; 3 chromosomal abnormalities. Four hundred sixteen (53%) of patients received an intensive induction regimen (defined as initial treatment with a high-dose cytarabine-containing regimen and/or receipt of autologous hematopoietic cell transplantation as consolidation), including 333 patients (43%) who underwent transplant consolidation. Patients with an increased lactate dehydrogenase (LDH) level (p & lt;0.001) and & gt; 3 cytogenetic abnormalities (p=0.015) were less likely to participate in clinical trials, but there was no significant difference in rates of participation based on MIPI (p=0.49) or ECOG performance status (p=0.22; Table). Patients treated on study were less likely to receive an intensive regimen compared to those treated off study (p=0.002). Median time to treatment from diagnosis was 35 days for patients enrolled on trial and 31 days for patients not enrolled on trial (p=0.83). With a median follow-up of 3.8 years, the median OS was 13.6 years (95% CI: 11.5-21.1) for patients not treated on a trial and not reached (95% CI: 9.9 - Not Reached) for patients treated on trial (Figure; p=0.036). In a multivariable model including clinical trial participation, MIPI, time to initial treatment, and receipt of an intensive induction regimen, only clinical trial participation (HR 0.54, 95%CI: 0.31-0.93; p=0.028) and high risk MIPI score (HR 4.24, 95% CI: 2.37-7.56; p & lt;0.001) were significant predictors of OS while receipt of an intensive regimen and time to initial treatment were not. Conclusions: Participation in a clinical trial is associated with improved OS among patients with untreated MCL, even when accounting for time to initial treatment and MIPI score. This study is unable to account for other factors that may predict trial participation including baseline comorbidities, socioeconomic status, social support, and distance to the treating center that are frequently factors that limit trial participation. However, these findings do suggest that enrollment on a clinical trial frequently leads to a successful outcome for patients in addition to providing answers to key clinical questions and should be considered for all eligible patients. Disclosures Cohen: Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; UNUM: Research Funding; LAM Therapeutics: Research Funding; Hutchison: Research Funding; Genentech, Inc.: Consultancy, Research Funding; ASH: Research Funding; Lymphoma Research Foundation: Research Funding; Astra Zeneca: Research Funding. Calzada:Seattle Genetics: Research Funding. Kolla:Amgen: Equity Ownership. Bachanova:Incyte: Research Funding; Novartis: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Research Funding; GT Biopharma: Research Funding; Celgene: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees. Gerson:Abbvie: Consultancy; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Barta:Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding. Danilov:MEI: Research Funding; Seattle Genetics: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Curis: Consultancy; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Celgene: Consultancy; Aptose Biosciences: Research Funding; Takeda Oncology: Research Funding; Bayer Oncology: Consultancy, Research Funding; Bristol-Meyers Squibb: Research Funding; Abbvie: Consultancy; Pharmacyclics: Consultancy. Grover:Seattle Genetics: Consultancy. Karmali:Astrazeneca: Speakers Bureau; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution. Hill:TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding. Ghosh:Spectrum: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Astra Zeneca: Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Forty Seven Inc: Research Funding; Genentech: Research Funding; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; T G Therapeutics: Consultancy, Research Funding; AbbVie: Consultancy, Speakers Bureau. Park:BMS: Consultancy, Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Hamadani:Otsuka: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Janssen: Consultancy; Merck: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy; Medimmune: Consultancy, Research Funding; Pharmacyclics: Consultancy. Martin:Karyopharm: Consultancy; I-MAB: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Sandoz: Consultancy; Teneobio: Consultancy. Flowers:Pharmacyclics/Janssen: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Millenium/Takeda: Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; BeiGene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Spectrum: Consultancy; Celgene: Consultancy, Research Funding. Kahl:BeiGene: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-128864

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1525-1525

Abstract: INTRODUCTION The optimal frontline treatment for mantle cell lymphoma (MCL) is not clearly defined. Bendamustine + rituximab (BR) is commonly used as initial therapy. The role of maintenance rituximab (MR) after BR is not agreed upon due to limited data supporting this practice, whereas MR improves overall survival (OS) after autologous stem cell transplant (ASCT) and after R-CHOP for elderly patients who do not receive ASCT. Preliminary results from a subgroup analysis of the randomized phase 3 MAINTAIN study revealed neither a progression-free survival (PFS) nor OS benefit for MR as compared to observation for MCL pts (Rummel, ASCO 2016). In follicular lymphoma patients, however, there does appear to be a PFS benefit to rituximab maintenance following BR. Given these disparate results, we sought additional data to evaluate the role of rituximab maintenance following BR in MCL METHODS MCL pts treated at 12 U.S. medical centers with frontline BR who achieved a complete response (CR) or partial response (PR) and who did not receive consolidative ASCT from 2011 - 2017 were included. Use of MR was based on individual physician/patient preferences. Baseline pt characteristics were compared using chi-squared test, Fisher's exact tests, or ANOVA. Descriptive statistics, comparisons, and OS using the Kaplan-Meier method were stratified by response status as determined by the treating site (complete response (CR) only, partial response (PR) only, and CR/PR). RESULTS Among 135 pts responding to frontline BR who did not complete subsequent ASCT, 80% achieved complete remission (CR) and 20% had a partial remission (PR). Median age was 70 (range 45 - 93) years and 66% were male. Baseline MIPI score was low (13%), intermediate (38%), or high (49%) among patients with available data (n = 92) and did not differ between treatment cohorts. Among responding patients, 78 (58%) received MR and 57 (40%) were observed. With a median follow up of 3.1 years, median OS was not reached for pts responding to BR (with CR or PR) who received MR vs. 6 years for those who received no maintenance (Figure Panel A, P = 0.0013). Use of MR vs. observation was associated with a significant improvement in OS for pts in PR at the end of induction therapy (Figure Panel B, median not reached vs. 1.7 years, P = 0.006), but there was no statistically significant OS difference for pts in CR (Figure Panel C, median not reached vs. 9.6 years, P = 0.2575). In multivariable analysis, MIPI score & lt;6.2 was associated with improved OS [Hazard Ratio (HR) 0.35 (95% confidence interval (CI) 0.12 - 1.02], P = 0.055) as was the use of MR [HR 0.28 (95% CI 0.10-0.79), P = 0.016] . CONCLUSIONS Whereas the MAINTAIN trial showed no PFS advantage to MR after BR for MCL pts, in this multi-center outcomes analysis across multiple US centers, the use of MR was associated with an improvement in OS in pts receiving frontline BR without consolidative ASCT. The survival benefit was only observed for pts in PR after induction therapy. Because of the potential for selection bias in the application of MR, further validation cohorts and prospective study are needed to clarify if there is benefit to maintenance therapy after BR-treated patients not undergoing ASCT as well as the potential for differential benefit of maintenance based on remission status Disclosures Hill: Takeda: Research Funding; Amgen: Research Funding; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Martin:Janssen: Consultancy; I-MAB: Consultancy; Celgene: Consultancy; Sandoz: Consultancy; Karyopharm: Consultancy; Teneobio: Consultancy. Calzada:Seattle Genetics: Research Funding. Kolla:Amgen: Equity Ownership. Bachanova:Gamida Cell: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; GT Biopharma: Research Funding; Novartis: Research Funding. Gerson:Abbvie: Consultancy; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Barta:Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Celgene: Research Funding; Merck: Research Funding; Mundipharma: Honoraria; Seattle Genetics: Honoraria, Research Funding; Celgene: Research Funding; Mundipharma: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Research Funding. Danilov:Curis: Consultancy; Bristol-Meyers Squibb: Research Funding; TG Therapeutics: Consultancy; Abbvie: Consultancy; Genentech: Consultancy, Research Funding; Bayer Oncology: Consultancy, Research Funding; Takeda Oncology: Research Funding; MEI: Research Funding; Pharmacyclics: Consultancy; Aptose Biosciences: Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; Seattle Genetics: Consultancy; AstraZeneca: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Celgene: Consultancy; Janssen: Consultancy. Grover:Seattle Genetics: Consultancy. Karmali:Takeda, BMS: Other: Research Funding to Institution; Astrazeneca: Speakers Bureau; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau. Ghosh:Celgene: Consultancy, Research Funding, Speakers Bureau; T G Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Speakers Bureau; Spectrum: Consultancy, Speakers Bureau; Astra Zeneca: Speakers Bureau; Forty Seven Inc: Research Funding; Genentech: Research Funding; Gilead/Kite: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Park:G1 Therapeutics: Consultancy; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; Teva: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Hamadani:Otsuka: Research Funding; Merck: Research Funding; Celgene: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Pharmacyclics: Consultancy; Medimmune: Consultancy, Research Funding; Takeda: Research Funding. Kahl:Seattle Genetics: Consultancy; BeiGene: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding. Flowers:Optimum Rx: Consultancy; Acerta: Research Funding; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; National Cancer Institute: Research Funding; TG Therapeutics: Research Funding; AbbVie: Consultancy, Research Funding; Bayer: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Millenium/Takeda: Research Funding; V Foundation: Research Funding; Karyopharm: Consultancy; BeiGene: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Denovo Biopharma: Consultancy. Cohen:Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; Genentech, Inc.: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-129404

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7