scholarly journals Novel Prognostic Markers in Previously Treated Chronic Lymphocytic Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4688-4688
Author(s):  
Cindy M Pabon ◽  
Danielle M. Brander ◽  
Tiffany Stewart ◽  
J. Brice Weinberg
Keyword(s):  
High Risk ◽  
Research Funding ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Small Sample ◽  
Novel Agents ◽  
The Novel ◽  
Clin Pathol ◽  
Progression Of Disease ◽  
Btk Inhibitors

Abstract Background: We need new biomarkers that manage CLL patients receiving novel chemotherapeutic agent treatments. In our earlier pilot study, we reported an association of inferior outcomes in those with higher IgM density, or those with IgG isotype expression, not explained by traditional markers such as unmutated IGHV or TP53 aberrations (Brander, et al., ASH abstract 118, 2011). The International Prognostic Index for CLL (CLL-IPI) was developed to provide CLL risk stratification, but this tool was largely studied in those treated conventionally (Lancet Oncol 17:779-790, 2016). Here we report studies of CLL cell IgM expression and outcomes in CLL patients treated with novel agents. We hypothesized that high IgM expression is associated with poor progression free survival (PFS) in patients treated with novel agents. Methods: We studied samples from 906 Duke University CLL patients. Fifty seven of 906 patients had received ibrutinib, acalabrutinib, and/or venetoclax. We classified CLL cell IgM expression surface isotype as low (<30%), moderate (31-60%), or high (>60%), and noted presence of class switching to IgG. We collected the following: social and geographical demographics, IGHV mutation status, CLL-IPI score, Rai staging, beta-2-microglobulin, FISH, cytogenetics, and treatment response per iwCLL definitions. PFS was defined as time from initiation of treatment with novel agents to progression of disease or death. Results: Of 57 CLL patients, 42 were alive at the time of followup. Median time for followup was 62 months for patients on BTK-inhibitors and 32 months for those on the Bcl-inhibitor venetoclax. Social demographics were similar across all treatment groups. Deaths were noted in each group (2/7 acalabrutinib, 13/45 ibrutinib, 6/13 venetoclax), with progression of disease as the leading cause. Many patients were not treatment naïve before starting novel agents. Specifically, 14/19 patients most recently on venetoclax had been exposed to a novel inhibitor. PFS did not correlate with surface IgM expression and outcomes for those treated with BTK inhibitors or venetoclax. Previously, approximately 25% of CLL patients with TP53 mut/del17p relapsed within 24 months of initiating traditional chemoimmunotherapeutics. Our TP53 mut/del17p group treated with BTK inhibitors had improved PFS (p=0.005) (Figure 1). Similarly, by univariate cox regression, we found statistically significant PFS in patients with high risk mutations treated with BTK inhibitors (p=0.042). There was no statistically significant correlation between CLL-IPI score and PFS, nor high IgM expression density and PFS for those treated with BTK inhibitors. Conclusions: We hypothesized that higher IgM expression density is associated with reduced PFS in patients treated with the novel agents. This was not identified in our study of 57 patients who had been treated with ibrutinib, acalabrutinib, or venetoclax. There was significantly shorter PFS for patients treated with BTK-inhibitors and TP53 mutand/or del17p compared to those without these genomic changes (p=0.005). This is consistent with prior studies. Historically, approximately 25% of CLL patients with TP53 mut/del17p relapsed within 24 months of initiating traditional chemoimmunotherapeutic agents. Our TP53 mut/del17p group treated with BTK inhibitors had improved PFS compared to the historical outcomes with a PFS of 66.5 months despite being a relapsed/refractory group. Our data supports prior studies identifying this as a high-risk subgroup of patients in need of investigational agent treatments (Catherwood MA, et al, J Clin Pathol, 72:343-346, 2019; and Gordon MJ, et al. Clin Cancer Res, In press, 2021). While the CLL-IPI score generally helps with prognostication of CLL patients, it was not significantly superior in our analyses in these patients. Other retrospective studies have also identified the limitations of the CLL-IPI score in the era of novel agents. Our work is limited by a small sample size of patients treated with the novel agents and by the retrospective nature of the study. With larger cohorts and longer followup, our future prospective studies will help clarify the role of surface immunoglobulin expression relative to CLL biology, and patient outcomes while receiving novel treatments. Figure 1 Figure 1. Disclosures Brander: BeiGene: Research Funding; Juno Therapeutics/Celgene/Bristol Myers Squibb: Research Funding; AstraZeneca: Research Funding; Verastem: Consultancy; Genentech: Consultancy, Research Funding; ArQule: Research Funding; Ascentage: Research Funding; DTRM: Research Funding; ArQule/Merck: Consultancy; LOXO: Research Funding; MEI Pharma: Research Funding; Novartis: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Pfizer: Consultancy, Other: Biosimilars outcomes research panel; TG Therapeutics: Consultancy, Research Funding; AbbVie: Consultancy, Other: informCLL registry steering committee, Research Funding; NCCN: Other: panel member.

scholarly journals Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study

2015 ◽  
Vol 33 (23) ◽  
pp. 2516-2522 ◽  
Author(s):  
Carla Casulo ◽  
Michelle Byrtek ◽  
Keith L. Dawson ◽  
Xiaolei Zhou ◽  
Charles M. Farber ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Reference Group ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Hazard Ratio ◽  
First Line ◽  
Progression Of Disease ◽  
Validation Set ◽  
Poor Outcomes

Purpose Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death. Patients and Methods In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility. Results Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index–adjusted hazard ratio, 19.8). Conclusion In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials.

scholarly journals Evaluating upfront high-dose consolidation after R-CHOP for follicular lymphoma by clinical and genetic risk models

2020 ◽  
Vol 4 (18) ◽  
pp. 4451-4462
Author(s):  
Stefan Alig ◽  
Vindi Jurinovic ◽  
Mohammad Shahrokh Esfahani ◽  
Sarah Haebe ◽  
Verena Passerini ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Statistical Significance ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Risk Scores ◽  
High Dose ◽  
Risk Models ◽  
Progression Of Disease ◽  
Risk Patients

Abstract High-dose therapy and autologous stem cell transplantation (HDT/ASCT) is an effective salvage treatment for eligible patients with follicular lymphoma (FL) and early progression of disease (POD). Since the introduction of rituximab, HDT/ASCT is no longer recommended in first remission. We here explored whether consolidative HDT/ASCT improved survival in defined subgroups of previously untreated patients. We report survival analyses of 431 patients who received frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for advanced FL, and were randomized to receive consolidative HDT/ASCT. We performed targeted genotyping of 157 diagnostic biopsies, and calculated genotype-based risk scores. HDT/ASCT improved failure-free survival (FFS; hazard ratio [HR], 0.8, P = .07; as-treated: HR, 0.7, P = .04), but not overall survival (OS; HR, 1.3, P = .27; as-treated: HR, 1.4, P = .13). High-risk cohorts identified by FL International Prognostic Index (FLIPI), and the clinicogenetic risk models m7-FLIPI and POD within 24 months–prognostic index (POD24-PI) comprised 27%, 18%, and 22% of patients. HDT/ASCT did not significantly prolong FFS in high-risk patients as defined by FLIPI (HR, 0.9; P = .56), m7-FLIPI (HR, 0.9; P = .91), and POD24-PI (HR, 0.8; P = .60). Similarly, OS was not significantly improved. Finally, we used a machine-learning approach to predict benefit from HDT/ASCT by genotypes. Patients predicted to benefit from HDT/ASCT had longer FFS with HDT/ASCT (HR, 0.4; P = .03), but OS did not reach statistical significance. Thus, consolidative HDT/ASCT after frontline R-CHOP did not improve OS in unselected FL patients and subgroups selected by genotype-based risk models.

scholarly journals Molecular profiling and management of mantle cell lymphoma

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 30-40 ◽  
Author(s):  
Jia Ruan
Keyword(s):  
Cell Cycle ◽  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Molecular Profiling ◽  
Novel Agents ◽  
High Dose ◽  
Mantle Cell

Abstract Mantle cell lymphoma (MCL) is a distinct subtype of B-cell non-Hodgkin lymphoma characterized by the t(11;14)(q13;q32) translocation leading to cyclin D1 overexpression and cell cycle dysregulation. Molecular profiling with gene expression and deep sequencing analyses has identified genomic and epigenomic alterations in pathways regulating the cell cycle, DNA damage response, proliferation, and survival, which contribute to disease progression with important prognostic and therapeutic implications. Clinically, the nonnodal MCL subset is notable for leukemic presentation, indolent behavior, and association with hypermutated IGHV and lack of SOX11 expression, which differentiates it from the conventional nodal MCL. In addition to the Mantle Cell Lymphoma International Prognostic Index score and proliferative gene signatures, 17p/TP53 and 9p/CDKN2A alterations, and genomic complexity have emerged as clinically useful biomarkers of high-risk disease associated with aggressive disease behavior, resistance to chemotherapy, and poor overall survival. Although intensive chemoimmunotherapy regimens that incorporate high-dose cytarabine and stem cell transplantation have improved survival in young and fit MCL patients, the introduction of Bruton tyrosine kinase inhibitors and other novel agents has made effective outpatient-based treatment accessible to nearly all MCL patients. Optimizing combinations of novel agents in the relapsed setting and moving novel agents to the first-line setting have the potential to fundamentally change the MCL therapeutic landscape for the better, especially for patients ineligible for chemotherapy or those with high-risk mutations that are resistant to chemotherapy.

Real-world (RW) treatment (tx) patterns and outcomes of 3,455 previously untreated mantle cell lymphoma (MCL) patients (pts) in U.S. routine clinical practice.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7504-7504
Author(s):  
Peter Martin ◽  
Michael Wang ◽  
Anita Kumar ◽  
Keqin Qi ◽  
Katherine Daly ◽  
...  
Keyword(s):  
High Risk ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Community Setting ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Non Hodgkin Lymphoma ◽  
Community Oncology ◽  
Mantle Cell ◽  
Ecog Ps

7504 Background: MCL is a non-Hodgkin lymphoma with heterogeneous biology and outcomes. We characterized RW tx patterns and outcomes of MCL pts to identify factors associated with outcomes in the US. Methods: This retrospective study included adult MCL pts diagnosed Jan 2011-Nov 2020 in the nationwide Flatiron Health EHR-derived deidentified database. Pt characteristics, tx patterns, time to next tx (rwTTNT, defined as start of first-line [1L] tx to subsequent tx or death) and rwOS were evaluated. Results: 3455 pts were included, 85.3% from a community oncology setting. In 2946 (85.2%) pts with documented 1L MCL tx, median age was 69.5 y (range 27.7-85.3); 9.5% had blastoid/pleomorphic MCL. 262 (39.6%) and 235 (35.6%) of 661 pts with available MCL international prognostic index (MIPI) had intermediate and high risk, respectively. 150/1253 pts (12.0%) with available ECOG PS had PS ≥ 2. Chemoimmunotherapy was the most common 1L tx, including BR in 1223 (41.5%), R-CHOP in 512 (17.4%) and cytarabine (ara-C)-containing tx in 414 (14.1%). 667 pts received R maintenance (MR). In 1036 pts < 65 y, 243 pts received 1L stem cell transplant (SCT), mainly autologous. In 1L-treated pts, with median follow-up of survivors of 45.3 mos (range 0.03-117.2), median rwTTNT was 24 mos; 36-mo rwOS was 67%. The Table shows tx received and outcomes by age and SCT status. MVA analyses showed age ≥ 65 y, ECOG PS ≥ 2, LDH/ULN ≥ 1, WBC ≥ 10 × 109/L, bulky disease (≥ 5 cm) and blastoid/pleomorphic morphology were associated with shorter rwTTNT and rwOS; MR was independently associated with longer rwTTNT and rwOS. In pts < 65 y who were alive and did not initiate subsequent tx within 6 mos of 1L tx (“SCT-eligible”), 36-mo rwTTNT and rwOS were similar between pts treated with vs without SCT: 65% vs 59% and 86% vs 85%, respectively. Conclusions: In this large RW cohort of primarily community-based US practices, median 1L rwTTNT for MCL pts was ̃ 2 y. BR was the most commonly used 1L tx. SCT was uncommon even in pts < 65 y, suggesting RW considerations may influence SCT eligibility and availability. Also, SCT was not clearly associated with rwOS. As with other reports, older age and high-risk disease features were predictive of worse outcome in RW, while MR appeared to be associated with better outcomes. Outcomes across the board appear worse than prospective trials, suggesting a need to focus on developing tx that can be delivered effectively in the community setting.[Table: see text]

scholarly journals Follicular lymphoma: are we ready for a risk-adapted approach?

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 358-364 ◽  
Author(s):  
Brad S. Kahl
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Randomized Clinical Trials ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Predictive Biomarkers ◽  
Western Hemisphere ◽  
Ongoing Research ◽  
High Risk Patients ◽  
Risk Patients

Abstract Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab after randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Yet, the disease is biologically and clinically heterogeneous with wide variations in outcomes for individual patients. The ability to accurately risk-stratify patients and then tailor therapy to the individual is an area of ongoing research. Historically, tumor grade, tumor burden, and the FL international prognostic index (version 1 and version 2) have been used to distinguish low-risk from high-risk patients. Biologic factors such as mutations in key genes can identify patients at high risk for poor outcomes to first-line therapy (mutational status of 7 genes [EZH2, ARID1A, MEF2B, EP300, FOX01, CREBBP, and CARD11] with Follicular Lymphoma International Prognostic Index). More recently, the quality of the response to initial therapy, as measured by either PET imaging or by remission duration, has been show to identify individuals at high risk. However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation.

scholarly journals A Novel Prognostic Index for Patients with EBV-DLBCL NOS: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1436-1436
Author(s):  
Brady E Beltran ◽  
Denisse Castro ◽  
Luis Villela ◽  
Efreen Montaño Figueroa ◽  
Ana Florencia Ramirez-Ibarguen ◽  
...  
Keyword(s):  
Latin American ◽  
Research Funding ◽  
Cox Regression ◽  
International Prognostic Index ◽  
Eastern Cooperative Oncology Group ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
World Health ◽  
Serum Lactate Dehydrogenase ◽  
Latin American Countries

Abstract Introduction: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is a newly recognized entity by the World Health Organization. EBV+ DLBCL, NOS is commonly encountered in Latin American countries and carries a dismal prognosis. Current prognostic models such as the Oyama and the International Prognostic Index (IPI) score have limited prognostic value in this patient population. Therefore, we aim to evaluate the ability of these models to risk stratify patients and propose a novel prognostic model in the largest cohort of Latin American patients with EBV+ DLBCL, NOS. Methods: This retrospective cohort study included patients ≥18 years from six Latin American countries diagnosed and treated at tertiary centers from 2010 to 2020. Hematopathologists at each institution reviewed pathological samples to confirm the diagnosis of EBV+ DLBCL, NOS. We collected clinicopathological data by reviewing the medical records of the patients. The primary endpoint was overall survival (OS), defined as the time from the date of diagnosis until death from any cause or last visit. The secondary endpoint, progression-free survival (PFS), was defined as the time from diagnosis until death, progression, or last visit. Our novel model (Grupo de Estudio Latinomericano de Linfoproliferativos [GELL] Score) includes the Eastern Cooperative Oncology Group (ECOG) performance status ≥2, extranodal involvement &gt;1, serum albumin &lt;3.5 g/dL, serum lactate dehydrogenase (LDH) above the upper limit of normal, and platelet-to-lymphocyte ratio &gt;455. We assigned a value of 1 to each of the abovementioned elements in the score and classified the patients as low (0 points), intermediate (1-2 points), and high (3-5) risk. OS and PFS probabilities were computed with the Kaplan-Meier method and compared with the log-rank test. We used Cox regression to evaluate the proportional hazard ratios (HR) of each score for our study outcomes. The C-index was employed to measure discrimination of each model. We used cross-validation to evaluate the model performance. Results: A total of 154 patients with EBV+ DLBCL, NOS were included in this analysis. The median age at diagnosis was 58 years (range 19-86 years) with a slight male predominance (53%). EBER was positive in all cases (range 1-100%). Clinically, 39% presented ECOG ≥2, 57% had B symptoms, 50% had an extranodal disease as a primary tumor, and 71% had Ann Arbor stage III/IV. Fifty-one percent of the patients had an elevated LDH level, and 43% had albumin &lt;3.5 g/dL. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen was administered in 79% of individuals as first-line treatment. The overall response rate was 80% (62% complete response and 18% partial response). With a median follow-up of 61 months, the 5-year OS and PFS rates were 61% and 47%, respectively. The 5-year OS rates of patients with low, intermediate, and high-risk disease according to the GELL score was 90%, 59%, and 33%, respectively (Fig 1A). The 5-year PFS rates were 82%, 39%, and 23%, respectively (Fig 2A). Table 1 shows the Cox regression and the discrimination analysis for each of the scores. The GELL score has the highest discriminatory index for OS and PFS compared to the IPI, Revised-IPI, National Comprehensive Cancer Network-IPI, and the Oyama score (Figure 1 and 2). Conclusions: This study proposes a novel score for risk stratification of patients with EBV+ DLBCL, NOS. The GELL score appears to better discriminate OS and PFS than previous scores. Our results should be validated in an independent prospective cohort. Figure 1 Figure 1. Disclosures Ramirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

scholarly journals Integration of cell of origin into the clinical CNS International Prognostic Index improves CNS relapse prediction in DLBCL

Blood ◽  
2019 ◽  
Vol 133 (9) ◽  
pp. 919-926 ◽  
Author(s):  
Magdalena Klanova ◽  
Laurie H. Sehn ◽  
Isabelle Bence-Bruckler ◽  
Federica Cavallo ◽  
Jie Jin ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Cns Relapse ◽  
Relapse Prediction ◽  
Expression Status ◽  
Dual Expression

Abstract Central nervous system (CNS) relapse carries a poor prognosis in diffuse large B-cell lymphoma (DLBCL). Integrating biomarkers into the CNS–International Prognostic Index (CNS-IPI) risk model may improve identification of patients at high risk for developing secondary CNS disease. CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study. Cell of origin (COO) was assessed using gene-expression profiling. BCL2 and MYC protein expression was analyzed by immunohistochemistry. The impact of CNS-IPI, COO, and BCL2/MYC dual-expression status on CNS relapse was assessed using a multivariate Cox regression model (data available in n = 1418, n = 933, and n = 688, respectively). High CNS-IPI score (hazard ratio [HR], 4.0; 95% confidence interval [CI], 1.3-12.3; P = .02) and activated B-cell‒like (ABC) (HR, 5.2; 95% CI, 2.1-12.9; P = .0004) or unclassified COO subtypes (HR, 4.2; 95% CI, 1.5-11.7; P = .006) were independently associated with CNS relapse. BCL2/MYC dual-expression status did not impact CNS relapse risk. Three risk subgroups were identified based on the presence of high CNS-IPI score and/or ABC/unclassified COO (CNS-IPI-C model): low risk (no risk factors, n = 450 [48.2%]), intermediate risk (1 factor, n = 408 [43.7%]), and high risk (both factors, n = 75 [8.0%]). Two-year CNS relapse rates were 0.5%, 4.4%, and 15.2% in the respective risk subgroups. Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk for developing CNS relapse. The study was registered at www.clinicaltrials.gov as #NCT01287741.

scholarly journals Bendamustine and rituximab as induction therapy in both transplant-eligible and -ineligible patients with mantle cell lymphoma

2020 ◽  
Vol 4 (15) ◽  
pp. 3486-3494
Author(s):  
Diego Villa ◽  
Laurie H. Sehn ◽  
Kerry J. Savage ◽  
Cynthia L. Toze ◽  
Kevin Song ◽  
...  
Keyword(s):  
High Risk ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
First Line ◽  
Ki 67 ◽  
Historical Cohort ◽  
Entire Cohort ◽  
Mantle Cell

Abstract Rituximab-containing chemotherapy regimens constitute standard first-line therapy for mantle cell lymphoma (MCL). Since June 2013, 190 patients ≥18 years of age with MCL in British Columbia have been treated with bendamustine and rituximab (BR). The overall response rate to BR was 88% (54% complete response). Of these, 61 of 89 patients (69%) aged ≤65 years received autologous stem cell transplantation and 141 of 190 patients (74%) from the entire cohort received maintenance rituximab. Twenty-three patients (12%) had progressive disease, associated with high risk per the Mantle Cell Lymphoma International Prognostic Index (MIPI), Ki-67 ≥50%, and blastoid/pleomorphic histology. Outcomes were compared with a historical cohort of 248 patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; January 2003 to May 2013). Treatment with BR was associated with significant improvements in progression-free survival (PFS), but not overall survival (OS), compared with R-CHOP in the whole cohort (3-year PFS, 66% BR vs 51% R-CHOP, P = .003; 3-year OS, 73% BR vs 66% R-CHOP, P = .054) and in those &gt;65 years of age (3-year PFS, 56% BR vs 35% R-CHOP, P = .001; 3-year OS, 64% BR vs 55% R-CHOP, P = .063). Outcomes in transplanted patients were not statistically significantly different compared with R-CHOP (3-year PFS, 85% BR vs 76% R-CHOP, P = .135; 3-year OS, 90% BR vs 88% R-CHOP, P = .305), although in multivariate analyses, treatment with BR was associated with improved PFS (hazard ratio, 0.40 [95% confidence interval, 0.17-0.94]; P = .036) but not OS. BR is an effective first-line option for most patients with MCL, however, outcomes are suboptimal for those with high-risk features and further studies integrating novel agents are warranted.

The Follicular Lymphoma International Prognostic Index (FLIPI) Predicts Treatment Outcome in Patients with Advanced Stage Follicular Lymphoma Treated Front-Line with Rituximab and the Combination of Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 925-925 ◽  
Author(s):  
Christian Buske ◽  
Eva Hoster ◽  
Martin Dreyling ◽  
Joerg Hasford ◽  
Michael Unterhalt ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Relative Risk ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Risk Group ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Intermediate Risk ◽  
Advanced Stage ◽  
Front Line

Abstract Background: The Follicular Lymphoma International Prognostic Index (FLIPI) has been developed to predict prognosis and to allow risk adapted treatment decisions in patients with follicular lymphoma (FL) before the widely use of Rituximab. However, the addition of Rituximab to standard induction chemotherapy with its long-term beneficial effects has profoundly changed the treatment outcome in patients with advanced stage FL and has become the new standard in the first line therapy of this disease. Therefore, we addressed the question, whether the prognostic value of the FLIPI could be reconfirmed in patients with advanced stage FL treated initially with a rituximab/chemotherapy combination. Methods: The FLIPI index was tested in patients treated with Rituximab and CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone, R-CHOP) in a prospective multicenter phase 3 trial of the GLSG using the time to treatment failure (TTF) as target parameter. Results: 362 Patients treated with R-CHOP were evaluable for TTF. Of the 338 patients evaluable for all FLIPI risk factors, 14% of patients were classified as low, 41% as intermediate and 45% as high risk. After a median follow-up time of 20 months, patients with low risk and intermediate risk FLIPI had almost identical TTF (2-years TTF 92% vs 90%, 95% C.I., 83% to 100% and 84% to 96%, respectively). In contrast, the TTF was significantly shorter in the high risk FLIPI group (2-years TTF 67%, 95% C.I., 58% to 76%) as compared to the combined low/intermediate risk FLIPI group (relative risk 3.0, 95% C.I., 1.7 to 5.1; p &lt; 0.0001). In addition, responding patients with high risk FLIPI had a significantly shorter progression free survival as compared to the low/intermediate risk group (relative risk 3.3, 95% C.I., 1.8 to 6.0; p &lt; 0.0001). When postremission treatment was taken into account, the FLIPI separated the high risk group from the low/intermediate risk group in 65 patients treated with autologous stem cell transplantation (relative risk 6.0, 95% C.I., 1.4 to 25.2) as well as in 242 patients who had received IFN-α maintenance or no postremission therapy (relative risk 3.2, 95% C.I., 1.8 to 5.8). As the FLIPI was able to separate the high from the low/intermediate risk group in patients with advanced follicular lymphoma treated initially with Rituximab and CHOP we next performed a multivariate analysis to determine the impact of the individual parameters incorporated in the FLIPI on the TTF. The serum LDH level greater than the upper normal limit (relative risk 2.6, 95% C.I., 1.5 to 4.5) and the hemoglobin level below 12 g/dl (relative risk 2.5, 95% C.I., 1.4 to 4.3) were independently associated with a shorter TTF in these patients, whereas the age and the number of nodal areas were not discriminant. Conclusion: Taken together, these data indicate that the FLIPI is a valid prognostic index for identifying high-risk patients in FL, also after front-line combined immuno-chemotherapy. The index will remain an important tool to adjust treatment decisions in individual patients according their risk profile and to design clinical trials for the different risk groups in the era of antibody-based therapy.

The Addition of Rituximab to CHOP Chemotherapy Improves Response Rate, Failure-Free Survival and Overall Survival for Follicular Grade 3 Lymphoma Compared to CHOP Alone

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1289-1289 ◽  
Author(s):  
Michael J. Overman ◽  
Lei Feng ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Mark Hess ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Response Rate ◽  
International Prognostic Index ◽  
High Risk Patient ◽  
Prognostic Index ◽  
Cancer Center ◽  
Free Survival ◽  
Historical Comparison ◽  
Grade 3

Abstract Background: FL3 is a subcategory of follicular lymphomas that is challenging in that it behaves aggressively like large cell lymphomas. If treated with CHOP, however it has a clinical course of relapse and treatment failure similar to grade 1–2 follicular lymphoma. We looked at the outcome of FL3 patients treated with RCHOP, combining rituximab with CHOP. There are no large study reports of this regimen’s results in FL3 to our knowledge. Patients and Methods: We retrospectively reviewed the records of 45 patients with follicular grade 3 lymphoma who were treated with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) at The University of Texas MD Anderson Cancer Center (UTMDACC). Response rate (RR), failure-free survival (FFS), and overall survival (OS) were estimated and a historical comparison to 111 CHOP only treated patients was made. Results: The International Prognostic Index (IPI) distribution was: 47% Low, 36% Low-Intermediate, 13% High-intermediate, and 4% High-risk. The complete response rate was 96%. Forty-four out of 45 patients are still alive. Median follow-up is 3.5 years. The 3-year FFS rate according to IPI was 80% (95% CI: 64% to 100%) in low risk, 81% in low-intermediate (95% CI 64% to 100%), and was 50% (95% CI: 25% to 100%) in high-intermediate/high-risk patient group. The addition of rituximab to CHOP improved both 5-year FFS, 71% (95% CI: 58% to 87%) compared to 44% of CHOP alone (95% CI: 36% to 55%) with p-value of 0.019 and 5-year OS, 98% (95% CI: 93% to 100%) compared to 75% (95% CI: 67% to 84) with p-valule of 0.0034. The addition of rituximab to CHOP improve the FFS compared to CHOP alone when subgroups of IPI were analyzed and compared (p=.002) Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival. Poor risk patients continue to demonstrate a high rate of failure despite the use of rituximab.

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