scholarly journals Long-Term Outcome of Conjunctival Extranodal Marginal Zone Lymphoma: A Large Single-Institution Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2435-2435
Author(s):  
Eduardo Saul ◽  
Juan Pablo Alderuccio ◽  
Isildinha M. Reis ◽  
Wei Zhao ◽  
Sunil G. Iyer ◽  
...  
Keyword(s):  
Family Member ◽  
Research Funding ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Competing Risk ◽  
Single Institution ◽  
Ann Arbor ◽  
Localized Disease ◽  
Frontline Therapy

Abstract Background The most common subtype of B-cell lymphomas presenting in the conjunctiva is extranodal marginal zone lymphoma (EMZL), accounting for ~80% of cases. Most patients (pts) present with localized disease, and radiation therapy (RT) is the preferred treatment strategy. We aimed to retrospectively analyze our single-institution experience to provide further insight into the characteristics and long-term outcomes of conjunctival EMZL. Methods We evaluated 72 pts diagnosed with conjunctival EMZL between 01/1995 and 12/2020 at the University of Miami. Pts' characteristics included age, sex, TNM-AJCC ocular lymphoma and Ann Arbor staging systems, MALT-IPI score, treatment (RT, chemotherapy, rituximab), and treatment response (complete response (CR), partial response, stable disease, progression of disease). Primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated using the Kaplan-Meier method, and compared using the log rank test and the univariable Cox regression analysis. We also performed a competing risk univariable analysis (UVA) assessing predictors of cumulative incidence of relapse/progression, with death without relapse as a competing risk, using the Fine and Gray regression analysis. Results Among all 72 pts, mean age was 59.9 yrs (7-93) with 38 (52.8%) being >60 yrs old, 46 (63.9%) were female, 56 (77.8%) had unilateral conjunctival disease, localized disease (T1N0M0 and Ann Arbor stage I) was present in 63 (87.5%), 6 (8.3%) had disseminated disease with more than 1 extranodal site involved, and 29 (40.3%) had a MALT-IPI of 1 or 2. After biopsy and surgical removal, 65 (90.2%) received additional treatment, while 6 (8.3%) were followed only, and in one case therapy information was not available . RT was the most common treatment (53 pts [73.6%], with 46 [86.8%] of those treated with ≥ 30 Gy). In two of these patients RT was combined with chemotherapy. Other treated pts received immunochemotherapy (12 [16.7%], including rituximab in 8). Five pts with stage II-IV disease received systemic therapy. CR was achieved in 63 (87.5%) after first line treatment, and no high-grade lymphoma transformation was seen. With a median follow up of 6.67 yrs (0.56-24.13), there were 14 relapses (19.4%). Among 53 pts treated with RT there were 8 relapses (15.1%), only one (1.9%) within the RT field. There were 23 progression events (31.9%, 14 relapses and 9 deaths without documented relapse), and a total of 14 deaths (19.4%). Mean PFS and OS were 6.69 yrs (0.49-20.37, SD 4.95) and 7.81 yrs (0.56-24.13, SD 5.40), respectively. The 10-yr PFS and OS were 68.4% (95%CI 52.8, 79.8%) and 89.4% (95%CI 77.4, 95.2%), respectively. Variables associated with shorter PFS in UVA Cox model were age > 60 yrs (HR=2.93, 95%CI 1.08, 7.95; p=0.035), high MALT-IPI (1-2) (HR=2.42, 95%CI 1.01, 5.78; p=0.048), and use of chemotherapy only (HR=2.73, 95%CI 1.13, 6.56; p=0.025). Variables associated with shorter OS included age >60 yrs (HR=9.07, 95%CI 1.17, 70.26; p=0.035) and high MALT-IPI (HR=6.19, 95%CI 1.35, 28.33; p=0.019). CR after frontline therapy was associated with longer PFS (HR=0.13, 95%CI 0.04, 0.45; p=0.001) but not OS. PFS of MALT-IPI 0 vs 1-2 was significantly longer (p=0.042), with 10-yr PFS 80.9% (95%CI 63.4%, 90.6%) vs 55.6% (95%CI 32.1%, 73.8%). Similarly, longer OS was observed in MALT-IPI 0 pts (p=0.0077; 10-yr OS 95.2% [95%CI 82.2%, 98.8%] vs 80.6% [95%CI 55.6%, 92.4%]) (Figure). A subset UVA Cox analysis of patients with Ann Arbor stage I showed longer PFS associated with CR after frontline therapy (HR 0.15, 95%CI 0.04, 0.58; p=0.006) with no significant association with age >60 yrs, high MALT-IPI or use of chemotherapy. Variables associated with shorter OS were age >60 yrs (HR 8.01, 95%CI 1.00, 63.98; p=0.05) and high MALT-IPI (HR 13.41, 95%CI 1.67, 107.99; p=0.015), similarly to the primary analysis. On univariable Fine and Gray regression models with death without relapse/progression as a competing risk, RT (SHR=0.33, 95%CI 0.12, 0.96; p=0.041) and CR-post frontline therapy (SHR=0.11, 95%CI 0.03, 0.36; p<0.001) were associated with lower risk of relapse. Conversely, chemotherapy (SHR=3.47, 95%CI 1.20, 10.0; p=0.022) was associated with higher risk of relapse. Conclusion Patients with conjunctival EMZL exhibit excellent long-term survival, and RT remains the most effective frontline therapy. MALT-IPI appropriately identifies patients at risk for treatment failure. Figure 1 Figure 1. Disclosures Alderuccio: ADC Therapeutics: Consultancy, Research Funding; Oncinfo / OncLive: Honoraria; Puma Biotechnology: Other: Family member; Inovio Pharmaceuticals: Other: Family member; Agios Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member. Lossos: Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy; NCI: Research Funding; Stanford University: Patents & Royalties; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment.

scholarly journals Splenic Marginal Zone Lymphoma: A U.S Population-Based Survival Analysis (1997-2016)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4014-4014
Author(s):  
Jorge Florindez ◽  
Juan Pablo Alderuccio ◽  
Izidore S. Lossos
Keyword(s):  
Family Member ◽  
Survival Data ◽  
Marginal Zone ◽  
Stage Iv ◽  
Population Based ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Seer Database ◽  
Advisory Committees ◽  
Ann Arbor

INTRODUCTION: Splenic marginal zone lymphoma (SMZL) is a rare and indolent form of NHL with no standard treatment due to scarcity of clinical trials. Watch and wait approach, single agent rituximab or with chemotherapy and splenectomy are valid treatment approaches. No population-based studies examining the impact of chemotherapy and splenectomy on survival of SMZL patients are available. Thus, we decided to compare survival outcomes by clinical factors in SMZL patients deposited in the SEER database, emphasizing in the role of splenectomy on survival outcomes. METHODS: Retrospective analysis of SMZL cases in the SEER database from 1997 to 2016.SEER collects cancer incidence and survival data from population-based cancer registries covering 34% of the U.S. population. PATIENTS: SEER database was queried for SMZL patients at all ages from 1997 to 2016. Cases without histologic confirmation or no survival data were excluded. Demographic and clinical variables (age, sex, race, ethnicity, B-symptoms, Ann-Arbor stage, DLBCL transformation, first malignancy, chemotherapy with or without rituximab, splenectomy and radiotherapy) were summarized by descriptive statistics. Logistic regression used to determine variables associated with splenectomy. Overall survival (OS) and Cancer-specific survival (CSS) were the major end-points, estimated by Kaplan-Meier method. Cox regression used to calculate Hazard Ratios. RESULTS: 2212 patients met inclusion criteria, with a median age of 68yo (25-96). Patient characteristics were a follows: males (n=1152, 52.1%); whites (n=1991, 90.0%), blacks (112, 5.1%); Non-Hispanics (n=2049, 92.6%); B-symptoms (n=461, 20.8%); first malignancy (n=1754, 79.3%); Ann-Arbor Stage I (429, 19.4%), Stage IV (n=1351, 61.1%); DLBCL transformation (n=84, 3.8%). Adjusted Odds ratio (aOR) were used to compare splenectomy versus non-splenectomy treated patients: ≥60yo (aOR 0.49;0.40-0.62), males (aOR 0.77;0.64-0.93). Median survival of all the patients was 120 months (95%CI:111-132); On univariate analysis: shorter OS was significantly associated with age ≥60(HR 3.55;2.87-4.38) and non-first malignancy(HR 1.6;1.36-1.88), while shorter CSS was significantly associated with age ≥60(HR 1.76;1.33-2.34), B-symptoms (HR 1.93;1.44-2.60), Stage IV (HR 1.62;1.15-2.28), DLBCL transformation (HR 2.27;1.55-3.33) and treatment with chemotherapy (HR 1.54;1.22-1.94). On multivariate analysis, shorter OS was significantly associated with age ≥60(HR 3.52;2.83-4.37), male sex (HR 1.15;1.00-1.33), B-symptoms (HR 1.23;1.01-1.51) and non-first malignancy (HR 1.42;1.20-1.67). Shorter CSS was significantly associated with age ≥60(HR 2.15;1.61-2.87), Hispanic ethnicity (HR 1.44;1.00-2.07), B-symptoms (HR 1.77;1.30-2.39), DLBCL transformation (HR 2.03;1.38-2.99) and treatment with chemotherapy (HR 1.38;1.07-1.77). Ann Arbor staging and splenectomy were not associated with OS or CSS. CONCLUSIONS: Older age, Hispanic ethnicity, B-symptoms, DLBCL transformation, and treatment with chemotherapy were associated with poor lymphoma-specific survival. Although, age<60 and female gender were associated higher odds to undergo splenectomy, splenectomy had no impact on the risk of lymphoma-related death or OS. This retrospective study demonstrates that chemotherapy treatment (excluding rituximab) was associated with inferior outcomes in SMZL, while advanced Ann-Arbor stage was not associated with shorter survival as is observed in other indolent lymphomas that commonly present at advanced stage. Table Disclosures Alderuccio: Targeted Oncology: Honoraria; Foundation Medicine: Other: Immediate family member; Agios: Other: Immediate family member; Puma Biotechnology: Other: Immediate family member; OncLive: Consultancy; Inovio Pharmaceuticals: Other: Immediate family member. Lossos:NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Janssen Scientific: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Omission of Staging Bone Marrow Biopsy Does Not Affect Outcomes in Patients with Stage I Extranodal Marginal Zone Lymphoma (EMZL) Treated with Radiation Therapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2829-2829
Author(s):  
Juan Pablo Alderuccio ◽  
Derek Isrow ◽  
Isildinha M. Reis ◽  
Sunil Iyer ◽  
Jessica Meshman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Radiation Therapy ◽  
Family Member ◽  
Board Of Directors ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Stage I ◽  
Competing Risk ◽  
Advisory Committees ◽  
Significant Difference

INTRODUCTION: Patients with stage I localized extranodal marginal zone lymphoma (EMZL) treated with radiation therapy (RT) have excellent outcomes. Negative bone marrow (BM) biopsy at diagnosis is key to confirm early stage disease. However, BM biopsy is not performed in some patients for various reasons such as comorbidities, patient refusal or physician decision. The aim of this study was to assess the effects of BM status (negative vs. not done) on disease recurrence/progression and survival in EMZL patients presenting with otherwise localized disease by imaging and treated with RT. METHODS: From January 1995 to January 2019, we identified 188 patients with stage I EMZL treated with frontline RT at the University of Miami Health Care System. All patients had biopsy proven EMZL and scans (CT, MRI, and/or PET-CT) at the time of diagnosis. Medical records were reviewed and pertinent information gathered. Relapse/progression was subclassified based on disease location: inside, outside, or inside and outside of the radiation field (RF). The competing risk method and the Gray's test were used in analysis of incidence rates of type of relapse/progression and lymphoma-specific death. The Kaplan-Meier method and the log-rank test were used in analyses of progression-free survival (PFS) and overall survival (OS). RESULTS: Among 188 patients included in this study, 104 (55.3%) were ≤60 years and 135 (71.8%) <70 years. 117 (62.2%) females and 98 (52.1%) non-Hispanic Whites. EMZL location was as follows: Orbit 118 (62.8%), gastric 19 (10.1%), head & neck 14 (7.4%), dural 13 (6.9%), skin 12 (6.4%), and other 12 (6.4%). Most patients had a negative staging BM biopsy (148, 78.7%); however, in 40 (21.3%) patients BM biopsy was not performed. Patients without BM biopsy at diagnosis were mainly >60 years (26, 65%). Radiation doses broadly varied but most patients (176, 93.6%) received ≥30 Gy. 183 patients (97.3%) achieved complete response (CR) following RT with 2 (1.1%) achieving partial response (PR), 2 (1.1%) stable disease and 1 (0.5%) demonstrating disease progression. Among 176 patients receiving ≥30 Gy RT, 173 (98.2%) achieved CR. With a median follow-up of 6.2 years (range 0.3-22.3 years) the 10 years-PFS was 64.4% (95%CI:54.9%-72.5%). No difference in PFS was observed by location of disease or BM biopsy (negative vs. not done). Patients treated with ≥30Gy had statistically significantly longer PFS compared to patients treated with <30Gy, whether or not BM biopsy was done. There were 52 progression events, including 5 inside RF (4 relapses/1 progression), 6 inside & outside (5 relapses/1 progression), 25 outside alone (24 relapses/1 progression), and 16 non-lymphoma deaths. Taking into account non-lymphoma death as a competing risk, the 5-year incidence of lymphoma relapse/progression was 2.9% (95%CI:1.1-6.3%) inside RF, 3.4% (95%CI:1.2-7.3%) inside & outside RF and 9.8% (5.8-15.0%) outside RF. Importantly, there was no higher cumulative incidence of each type of relapse/progression relative to RF (inside p=0.2490, inside & outside p=0.1617, and outside alone p=0.3070) in patients without vs. negative staging BM biopsy. There were 23 deaths, 7 attributed to lymphoma. The 10-year OS was 83.3% (95%CI:75.0-89.0%), and there was no difference in OS by EMZL location. Patients without staging BM biopsy had shorter OS (p=0.0062). However, when lymphoma-specific death was analyzed (non-lymphoma death as competing risk) the estimated 10-year cumulative incidence of lymphoma-specific death was 5.3% (2.3%-10.2%) and there was a non-statistically significant difference between patients with and without staging BM biopsy (p=0.5201). The cumulative 10-years incidence of non-lymphoma specific death (lymphoma death as competing risk) was 11.4% (95% CI:6.3%-18.2%). There was a statistically significant difference by BM biopsy status (p=0.0107), with patients without staging BM biopsy having higher incidence of non-lymphoma death compared to negative BM biopsy patients (10-yr rate 26.7% vs 7.9%, respectively), likely due to coexistent comorbidities. CONCLUSION: In this large cohort of patients with stage I EMZL treated with RT we demonstrate for the first time that omission of BM biopsy at diagnosis does not affect lymphoma-specific survival or the incidence of disease relapse/progression overall or by relapse location type, suggesting that diagnostic BM biopsy may not be necessary. Disclosures Alderuccio: Foundation Medicine: Other: Immediate family member; Inovio Pharmaceuticals: Other: Immediate family member; Targeted Oncology: Honoraria; Agios: Other: Immediate family member; Puma Biotechnology: Other: Immediate family member; OncLive: Consultancy. Lossos:NIH: Research Funding; Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Outcomes of Primary and Secondary Transformed B-Cell Lymphomas

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3894-3894
Author(s):  
Sedat Demirdas ◽  
Lewin Eisele ◽  
Jörg Hense ◽  
Ulrich Dührsen ◽  
Andreas Hüttmann
Keyword(s):  
Radiation Therapy ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Research Funding ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Aggressive Lymphoma ◽  
B Cell Lymphomas ◽  
Ann Arbor ◽  
Extranodal Disease

Abstract Introduction: Transformed B-cell lymphomas (t-BCL) harbor features of indolent and aggressive disease and it is assumed that transformation conveys an unfavorable prognosis. Because of the ambiguous pathological findings these lymphomas are rarely included into clinical trials. As a result, there is a lack of information about t-BCL patients' short-term and long-term outcomes although very recently a large retrospective analysis detailed the outcomes of transformed follicular lymphoma (t-FL) (Blood June 23, 2015; DOI 10.1182/blood-2015-01-621375). t-BCLs can be separated into a primary type, i.e. transformation at the time of diagnosis, and a secondary type, i.e. transformation after a previous diagnosis of indolent BCL. The present study reports the outcome of patients with t-BCL and also includes indolent lymphomas other than FL. Methods: This is a retrospective, single center analysis of patients with t-BCL seen at the Dept. of Hematology and the Dept. of Medical Oncology at the University Hospital Essen between 1999 and 2015. The departments' archives were screened for patients with primary or secondary t-BCL. A lymphoma was considered transformed when the diagnosis of indolent lymphoma (FL grade 1, 2, 3A; extranodal marginal zone lymphoma (EMZL), nodal marginal zone lymphoma (NMZL), splenic marginal zone lymphoma (SMZL), small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)) preceded a diffuse large B-cell lymphoma (DLBCL) or other aggressive lymphoma or was simultaneously present. Lymphomas were classified according to WHO 2008 terminology whenever possible. FL with simultaneous grade 3A and grade 3B portions were classified as primary t-BCL. Central pathology review was not performed. Demographic parameters, treatment history, response and outcome data were collected. Survival analyses were performed using the Kaplan-Meier method. The log rank test was used to calculate survival differences, p values > 0,05 were considered statistically significant. Multivariable Cox regression analysis was used where appropriate. The ethics committee of the faculty of medicine, University of Duisburg-Essen, approved this study (14-5497-BO). Results: 92 patients treated between 1999 and 2015 were identified. 47 (51 %) were female. 38 (41%) suffered from primary and 54 (59%) from secondary t-BCL. Median age at transformation was 60 years (30-87). For secondary t-BCL, time to transformation spanned 2-275 months with a median of 40.5. The treatment approach influenced time to transformation: 33.3 (median) months for observation only (n=20) and 66 months (median) for chemotherapy or rituximab-chemotherapy (n=20; p=0.02). After radiation therapy (n=10) median time to transformation was 32 months. 4 patients received chemotherapy and radiation therapy. FL grade1-3 was diagnosed in 67 patients (73%). Other diagnoses included EMZL (n=9), LPL (n=5), NMZL (n=3) SLL (n=3), SMZL (n=2) and other low-grade lymphomas (n=3). Histology at transformation was DLBCL in 86 patients. FL grade 3B, Burkitt-like lymphoma and aggressive lymphoma, unclassified, were diagnosed in 2 patients each. In primary t-BCL Ann Arbor stages III or IV were found in 25 patients (63 %), extranodal disease was present in 13 (34%), and 7 (18%) suffered from B symptoms. In secondary t-BCL Ann Arbor stages III or IV were found in 41 patients (66 %), extranodal disease was present in 12 (22%), and 11 (20%) suffered from B symptoms. Follicular Lymphoma International Prognostic Index high risk categories at time of transformation were evaluable for 42/67 FL patients and more frequent in secondary t-FL (n=33 (79%)) than in primary t-BCL (n=9 (21%)). Treatment of primary vs secondary t-BCL included CHOP (5/5), R-CHOP (29/23), R-ASHAP (0/10), Burkitt-type protocol (1/2), R-GemOx (0/2), R-ICE (0/2), radiation only (6/0), BEAM + ASCT (0/8), and other regimens. Overall survival (OS) at 5 years was dependent on remission status after first treatment of transformation with 86% for patients in CR, 66% for PR (CR vs PR p=n.s.) and 6% [CI=4.6-38.3] for PD (CR vs PD: p<0.0001) (Figure; 82 evaluable patients). 5-year OS for primary t-BCL was 73.3% and 47.6% for secondary t-BCL, respectively (p=0.0018) (Figure; 92 evaluable patients). Conclusion: In this study primary t-BCL had a favorable outcome when compared with secondary t-BCL. The assumed adverse prognostic impact of transformation may not hold true for primary t-BCL. Figure 1. Figure 1. Disclosures Dührsen: Alexion Pharmaceuticals: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Hüttmann:Roche: Research Funding; Amgen: Consultancy, Research Funding; Gilead: Consultancy; Takeda: Consultancy, Other: Travel support; Celgene: Other: Travel support, Speakers Bureau.

scholarly journals Rituximab monotherapy for splenic marginal zone lymphoma with villous lymphocytes: report on long-term disease control for two patients with recurrence after splenectomy

2010 ◽  
Vol 128 (6) ◽  
pp. 375-377 ◽  
Author(s):  
Márcio Debiasi ◽  
Marluce Hehnemann ◽  
Bernardo Garicochea
Keyword(s):  
Randomized Clinical Trials ◽  
Marginal Zone ◽  
Treatment Guidelines ◽  
Case Reports ◽  
Specific Treatment ◽  
Marginal Zone Lymphoma ◽  
Splenic Marginal Zone Lymphoma ◽  
Purine Analogues ◽  
Relapsed Lymphoma

CONTEXT: Splenic marginal zone lymphoma (SMZL) is a lymphoproliferative B-cell disorder that has a favorable prognosis, with estimated overall five-year survival of 70%. The majority of symptomatic patients undergo splenectomy, while a few receive first-line chemotherapy, especially with purine analogues. There are no specific treatment guidelines for patients for whom splenectomy fails to provide a cure. It is still unclear whether these patients should undergo cytotoxic chemotherapy, considering they have now a relapsed lymphoma (which is theoretically more aggressive), or whether they should be spared from treatments of greater toxicity, given that their disease usually develops with a more indolent course, even when it recurs. CASE REPORT: Here, we present two patients whose disease recurred after splenectomy and for whom rituximab monotherapy provided satisfactory treatment. From these cases, it can be suggested that postponement of cytotoxic treatments may be possible in at least some situations. It needs to be emphasized that the evidence to support this approach is based only on case reports, since there are no randomized clinical trials on this subject.

scholarly journals Results of a Phase I Trial of Lenalidomide, Rituximab (R2) and Ixazomib for Frontline Treatment of High Risk Follicular and Indolent Non-Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Brian T. Hill ◽  
Deepa Jagadeesh ◽  
Alex V. Mejia Garcia ◽  
Robert M. Dean ◽  
Omer N. Koc ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Board Of Directors ◽  
Research Funding ◽  
Marginal Zone ◽  
Proteasome Inhibitors ◽  
Marginal Zone Lymphoma ◽  
Aggressive Lymphoma ◽  
Advisory Committees ◽  
Frontline Treatment

INTRODUCTION: Lenalidomide and Rituximab (R2) is an effective frontline treatment regimen for patients (pts) with indolent B-cell lymphoma including follicular lymphoma (FL). Recent phase III data from the RELEVANCE trial comparing R2 to traditional chemoimmunotherapy showed that this regimen is generally well-tolerated and has favorable clinical efficacy [61% overall response, 53% CR rate, 77% 3-year progression free survival (PFS) (Morschhauser, et al)]. Proteasome inhibitors such as bortezomib disrupt NF-KB signaling and have shown clinical activity in indolent NHL. Although randomized trials have failed to demonstrate clinical benefit of adding bortezomib to standard chemoimmunotherapy regimen bendamustine + rituximab (BR) for frontline treatment of FL, the addition of proteasome inhibitors to lenalidomide is a mainstay of treatment for plasma cell neoplasms due to synergistic antitumor effect. The oral proteasome inhibitor ixazomib has less potential for dose-limiting neuropathy than bortezomib, making it an attractive option to incorporate into the R2 regimen. We sought to investigate the safety and efficacy of the addition of ixazomib to R2 for FL and indolent B-cell NHL through a phase I clinical trial of this combination for patients with high risk disease. METHODS: Adult (age ≥ 18) pts with untreated FL or other indolent lymphoma, adequate organ function and performance status were enrolled. To be enrolled, FL patients were required to have stage 2, 3 or 4 disease, with high tumor burden by GELF criteria and/or FLIPI score of 3-5. During 3 x 3 dose escalation, ixazomib was given at a dose of 2 mg (n=3), 3 mg (n=3) or 4 mg (n=12) PO on days 1, 8, and 15 with lenalidomide 20 mg PO on days 1-21 every 28 days. Rituximab was administered at standard dosing on days 1,8,15,21 for cycle 1, once every 28 days for cycles 2-6 and then once every 2 months for cycles 7-12. Treatment was continued for 12 cycles and no maintenance therapy was specified per protocol. All pts received low dose aspirin for venous thromboembolism prophylaxis and acyclovir for prevention of VZV reactivation. Response assessments by CT were performed after cycle 3 and 6 and by PET/CT at the end-of-treatment (cycle 12). RESULTS: 20 pts were enrolled and 18 were eligible for treatment [15 FL (14 grade 1-2, 1 grade 3A), 2 splenic marginal zone lymphoma and 1 nodal marginal zone lymphoma].The median age of treated pts was 61 (range 40-83) years old. 55% of patients were female. Stage at diagnosis was II (n =2), III (n = 4) and IV (n = 12). For FL pts, FLIPI scores at enrollment were low (n=2), intermediate (n = 5) and high risk (n=8) and FLIPI-2 scores were low (n=3), intermediate (n = 2) and high risk (n=10). There were no dose limiting toxicities during 3 x 3 dose escalation. Grade (G) 1/2 and G3/4 treatment-related hematologic adverse events (AEs) included neutropenia (6%, 28%), thrombocytopenia (16.7%, 5.6%) and anemia (16.7%, 0%). The most common treatment-related AEs included nausea/vomiting (44% G1, 11% G2), diarrhea, (50% G1, 22% G2, 5% G3), rash (33% G1, 6% G2, 11%G3), peripheral neuropathy (22% G1, 6% G2), myalgia/arthralgia (17% G1, 17% G2), and infection (33% G2, 17% G3). There was one pulmonary embolism and no cases of febrile neutropenia. As of June, 2020, median follow-up among living pts was 21 months. 4 pts discontinued treatment due to disease progression; 2 with transformation to aggressive lymphoma. Of the transformed cases, one subject died on study due to progression disease and one developed CNS disease on study treatment but proceeded to autologous stem cell transplant. The best overall response rate was 61.2% [55.6% CR, 5.6% PR): 22.2% had stable disease and 16.7% had disease progression. 18-month Kaplan-Meier estimates of PFS and overall survival were 71% and 94%, respectively (Figure). CONCLUSION: R2 can safely be combined with at the target dose of 4 mg of ixazomib for treatment-naïve indolent NHL patients. Non-hematologic AEs were generally consistent with known toxicity of each component of therapy. CR rate and PFS were was similar to the outcomes reported in the RELEVANCE trial despite enrolling high risk patient. R2 may serve as backbone for future studies of novel treatment combinations for high risk FL after thorough evaluation for occult transformation to aggressive lymphoma. Disclosures Hill: Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding. Jagadeesh:MEI Pharma: Research Funding; Regeneron: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Debiopharm Group: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees. Caimi:Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding; Genentech: Research Funding. Smith:Takeda: Research Funding; Celgene: Research Funding. OffLabel Disclosure: Ixazomib is off-label for treatment of NHL

Long-term outcomes of frontline 90Y-ibritumomab tiuxetan in marginal zone lymphoma

2020 ◽  
Vol 61 (13) ◽  
pp. 3234-3238
Author(s):  
Izidore S. Lossos ◽  
Isildinha M. Reis ◽  
Joseph D. Rosenblatt ◽  
Juan Pablo Alderuccio
Keyword(s):  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Long Term Outcomes ◽  
Ibritumomab Tiuxetan

scholarly journals Risk Factors for Transformation to Higher-Grade Lymphoma and Its Impact on Survival in a Large Cohort of Patients With Marginal Zone Lymphoma From a Single Institution

2018 ◽  
Vol 36 (34) ◽  
pp. 3370-3380 ◽  
Author(s):  
Juan Pablo Alderuccio ◽  
Wei Zhao ◽  
Amrita Desai ◽  
Nicolas Gallastegui ◽  
Jeremy Ramdial ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lactate Dehydrogenase ◽  
Follicular Lymphoma ◽  
Lymphoid Tissue ◽  
Initial Treatment ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Competing Risk ◽  
Elevated Lactate ◽  
Elevated Lactate Dehydrogenase

Purpose Given the paucity of data on higher-grade transformation (HGT) to aggressive lymphoma in patients with marginal zone lymphoma (MZL), we report on a large cohort of patients, identify risk factors, and determine HGT impact on overall survival (OS). Methods We analyzed 453 patients with biopsy-proven MZL seen at our institution between 1995 and 2016. Kaplan-Meier, Cox proportional hazards regression, and competing risk methods were used in analyses of time-to-event outcomes. Results Thirty-four patients (7.5%) had biopsy-proven HGT to diffuse large B-cell lymphoma, including seven (21%) diagnosed at the time of initial MZL diagnosis. Among 27 incident patients, median time to HGT was 29 months (range, 1.3 to 135 months). Higher risk of HGT was observed in those with nodal/splenic MZL (subdistribution hazard ratio [SHR], 2.60; P = .023). On multivariable competing risk analysis, elevated lactate dehydrogenase (SHR, 2.71), more than four nodal sites (SHR, 2.97), and failure to achieve complete remission (CR) after initial treatment (SHR, 3.76) conveyed significantly higher risk for HGT ( P < .02). International Prognostic Index (IPI), Follicular Lymphoma IPI, and Mucosa-Associated Lymphoid Tissue Lymphoma IPI were only significant predictors of HGT univariably. Patients with HGT had shorter OS (5-year rate, 65% v 86%; P < .001). Patients who presented with HGT within 12 months since MZL diagnosis had shorter OS than those with HGT at MZL diagnosis combined with those with HGT more than 12 months later (4-year rate, 43% v 81%, P < .001). Non-CR and higher scores of IPI, Follicular Lymphoma IPI, and Mucosa-Associated Lymphoid Tissue Lymphoma IPI were the main significant predictors for shorter progression-free survival and OS. Conclusion Failure to achieve CR after initial treatment, elevated lactate dehydrogenase, and more than four nodal sites at the time of MZL diagnosis are the main predictors of increased risk of HGT. Patients with HGT have shorter OS.

scholarly journals Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis

2020 ◽  
Vol 4 (22) ◽  
pp. 5773-5784
Author(s):  
Ariela Noy ◽  
Sven de Vos ◽  
Morton Coleman ◽  
Peter Martin ◽  
Christopher R. Flowers ◽  
...  
Keyword(s):  
B Cell ◽  
Marginal Zone ◽  
Single Agent ◽  
Final Analysis ◽  
Marginal Zone Lymphoma ◽  
Safety And Efficacy ◽  
Pathway Gene ◽  
Biomarker Analysis

Abstract Advanced marginal zone lymphoma (MZL) is an incurable B-cell malignancy dependent on B-cell receptor signaling. The phase 2 PCYC-1121 study demonstrated the safety and efficacy of single-agent ibrutinib 560 mg/d in 63 patients with relapsed/refractory MZL treated with prior rituximab (RTX) or rituximab-based chemoimmunotherapy (RTX-CIT). We report the final analysis of PCYC-1121 with median follow-up of 33.1 months (range: 1.4-44.6). Overall response rate (ORR) was 58%; median duration of response (DOR) was 27.6 months (95% confidence interval [CI]: 12.1 to not estimable [NE]); median progression-free survival (PFS) was 15.7 months (95% CI: 12.2-30.4); and median overall survival (OS) was not reached (95% CI: NE to NE). Patients with prior RTX treatment had better outcomes (ORR: 81%; median DOR: not reached [95% CI: 12.2 to NE]; median PFS: 30.4 months [95% CI: 22.1 to NE]; median OS: not reached [95% CI: 30.3 to NE]) vs those with prior RTX-CIT treatment (ORR: 51%; DOR: 12.4 months [95% CI: 2.8 to NE]; PFS: 13.8 months [95% CI: 8.3-22.5]; OS: not reached [95% CI: NE to NE]). ORRs were 63%, 47%, and 62% for extranodal, nodal, and splenic subtypes, respectively. With up to 45 months of ibrutinib treatment, the safety profile remained consistent with prior reports. The most common grade ≥3 event was anemia (16%). Exploratory biomarker analysis showed NF-κB pathway gene mutations correlated with outcomes. Final analysis of PCYC-1121 demonstrated long-term safety and efficacy of ibrutinib in patients with relapsed/refractory MZL, regardless of prior treatment or MZL subtype. This trial was registered at www.clinicaltrials.gov as #NCT01980628.

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