scholarly journals Time for an individualized approach to first-line management of follicular lymphoma

Haematologica ◽  
2022 ◽  
Vol 107 (1) ◽  
pp. 7-18 ◽  
Author(s):  
Guillaume Cartron ◽  
Judith Trotman
Keyword(s):  
Follicular Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
Disease Response ◽  
First Line Therapy ◽  
Histological Transformation ◽  
Early Progression ◽  
Individualized Approach ◽  
Survival Expectations ◽  
Indolent Disease

Follicular lymphoma is a heterogeneous B-cell lymphoma both in presentation and at progression. For most patients it is a chronic, relapsing indolent disease with overall survival expectations now potentially beyond 20 years. However, in a significant minority (~20%) who experience early progression or histological transformation after treatment, the disease no longer has an indolent behavior. This review looks at the development of prognostic indices, staging and therapies for follicular lymphoma, identifying where the data can, and cannot, guide the multidisciplinary team to determine an individualized approach to first-line therapy. A nuanced patient- and disease-specific approach is necessary to maximize disease response and survival while minimizing therapeutic toxicity.

Clinical utility of interim CT scans in patients receiving bendamustine and rituximab for first line treatment of follicular lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19565-e19565
Author(s):  
Farheen Manji ◽  
Sita Bhella ◽  
Anca A. Prica ◽  
Robert Kridel ◽  
Vishal Kukreti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Patient Characteristics ◽  
Complete Response ◽  
Rank Test ◽  
First Line ◽  
Disease Response ◽  
First Line Therapy ◽  
Computed Tomography Scanning

e19565 Background: Interim imaging with computed tomography scanning (CT) has been performed during most clinical trials of chemoimmunotherapy in patients with follicular lymphoma (FL) receiving first line systemic therapy. Based on this, interim imaging is commonly performed, but there is little evidence of its utility in clinical practice. Methods: The objective of this study was to retrospectively review outcomes of interim CTs (iCT) in adult patients with biopsy proven FL (grade 1-3a, 3b excluded) who received first line therapy with bendamustine and rituximab (BR) at Princess Margaret Cancer Centre from January 1 2013- December 31 2018. Baseline patient characteristics at diagnosis and treatment were retrieved from a prospectively populated database, and results of interim, end of treatment and end of maintenance therapy (if applicable) imaging were assessed. Disease response was assessed using Lugano response criteria as partial response (PR), complete response (CR), stable disease (SD) or progressive disease (PD). Descriptive statistics and Kaplan Meier Survival functions with a log rank test were used to analyze the data. The study was approved by the Princess Margaret Research Ethics Board. Results: A total of 108 patients were identified: mean age at diagnosis 61 years (IQR 52.4-69.5), 83% with stage III/IV disease, 27.8% bulky ( > 10cm) and median FLIPI score 2. Median follow up was 55.9 months (6.6-100.1 months). Of them, 101 patients (93.5%) had interim imaging done between cycle 2 and cycle 5 , most commonly CT scan (n = 98, 97.0%). The majority of iCTs showed a PR (n = 81, 80.1%), with a minority showing a CR (n = 11, 10.9%) and SD (n = 2, 1.9%). Seven patients had PD noted on iCT. Four patients had a second malignancy identified on biopsy of lesions found on iCT (thymoma, poorly differentiated carcinoma, lung adenocarcinoma and spindle cell tumour), 2 of whom were symptomatic at the time of iCT. Three patients had biopsy proven transformation to diffuse large B cell lymphoma (DLBCL); 2 were symptomatic at the time of iCT and only 1 had asymptomatic PD. The 3 year progression free survival (PFS) for all patients was 87.55%. Patients with a PR on iCT had similar 3 year PFS compared to those with CR (87.25% vs 90.00%, p = .52) as well as overall survival (94.80% vs 88.89%, p = .88). Conclusions: In this cohort, iCT was not useful for identifying patients with asymptomatic early progression of FL during treatment with BR. The majority of patients receiving systemic treatment for FL have at least a PR to BR on iCT, which is not associated with inferior PFS or OS compared to those with CR. Patients with symptomatic or asymptomatic PD during treatment warrant biopsy to identify histologic transformation or other malignancies. The rate of second cancers identified on iCT will be further explored in a cohort of FL patients treated with R-CVP and R-CHOP.

Rituximab Fails to Reduce Histologic Transformation (HT) Rate of Follicular Lymphoma (FL) to Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 837-837 ◽  
Author(s):  
Ariel E Marciscano ◽  
Neel Gupta ◽  
Zhigang Zhang ◽  
Julie Teruya-Feldstein ◽  
Ariela Noy
Keyword(s):  
Follicular Lymphoma ◽  
Lower Risk ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma

Abstract Background: Histologic Transformation (HT) of indolent follicular lymphoma to aggressive lymphoma is a critical and sometimes fatal event in a patient’s disease course. It is unclear if rituximab influences HT. We have previously shown that single agent rituximab is used earlier in the disease course than traditional chemotherapy likely due to rituximab’s high therapeutic index (Cohler et al., ASH 2007). Others have shown rituximab also improves the complete response rate, disease free and overall survival of follicular lymphoma when used as a single agent and in combination with chemotherapy. Theoretically, this could reduce the disease burden over a patient’s lifetime and consequently the transformation rate. Methods: We retrospectively screened 3500 patients and identified 584 eligible patients at Memorial Sloan Kettering Cancer Center (MSKCC) with newly diagnosed, treatment naïve, indolent follicular lymphoma. We compared two cohorts of rituximab usage: 1998– 2000 and 2001–2006. In the former, patients received rituximab predominantly in the relapsed setting. In the latter, patients liberally received rituximab even as single agent first line therapy. Histologic transformation to diffuse large B cell lymphoma (DLBCL) was the primary study endpoint. All therapy was recorded. Results: Median follow-up time was 92 months for the 1998–2000 cohort and 41 months for the 2001–2006 cohort. Patients in the latter cohort received rituximab both earlier in the course of follow up and more often as a first line therapy. The median time from diagnosis to first rituximab was 21 months vs. 2 months, respectively. Rituximab was given alone or in combination as first line systemic therapy to 36% of the 1998–2000 cohort, but to 93% of the 2001–2006 cohort. The comparative risks of transformation between the two cohorts were not statistically significant (P-value = 0.41 by log rank comparison). The cumulative incidence of transformation 36 months after diagnosis was 8.1% for the 1998– 2000 cohort and 4.4% for the 2001–2006 cohort. Furthermore, patients receiving rituximab first line, either single agent or in combination, compared to patients receiving rituximab as salvage therapy, showed essentially no difference in risk of histologic transformation. (P-value = 0.68) Surprisingly, patients never receiving rituximab had a significantly lower risk of transformation than those who received rituximab at any point (p-value = 0.0095), however, these rituximab naïve patients had lower risk FLIPI scores accounting for the difference (p-value = 0.15). Notably, 173/584 patients never received systemic therapy, and 102 of these were expectantly monitored without any local therapy, such as radiotherapy or therapeutic surgery). None of these 102 patients had transformation within the first 36-months of follow up. Finally, we confirm Ginè et al.’s earlier finding that a higher risk FLIPI score confers a higher risk of transformation. (Annals of Oncology, 2006) For each unit increase of FLIPI risk score (e.g., 3 à 4), the probability of histologic transformation at any time point increases 1.72 fold. Moreover, high-risk FLIPI patients (3–5 risk factors) have a 3.3-fold increase in risk of HT (p-value <0.0001). Conclusions: Patients diagnosed with FL in 2001–2006 received rituximab earlier in their disease and more frequently than those diagnosed in 1998–2000. However, in contrast to our hypothesis, this did not translate to a lower risk of transformation for the 2001– 2006 cohort. The 36-month risk of transformation was lower in patients with lower FLIPI scores. This data supports the clinical decision to expectantly monitor low-risk FLIPI patients.

scholarly journals Incidence, Risk Factors and Prognosis of Transformation in Follicular Lymphoma: a Multicentre Retrospective Analysis of 1763 Patients from the Geltamo Spanish Lymphoma Cooperative Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3944-3944 ◽  
Author(s):  
Sara Alonso* ◽  
Miguel Alcoceba* ◽  
Laura Magnano ◽  
Marcio Andrade ◽  
María García-Álvarez ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Follicular Lymphoma ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Prognostic Impact ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract INTRODUCTION Follicular lymphoma (FL) may, over time, transform into an aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). Transformed follicular lymphomas (tFL) have a worse prognosis due to poorer response to treatment than primary DLBCL. The incidence of transformation is estimated in ~3% per year, although it varies largely between different studies (24%-70% overall). These differences are mainly due to different criteria to define tFL, to lack of evidence of tFL by biopsy, absence of clonality studies discarding secondary de novo NHL, studies performed in the pre-Rituximab era, or different follow-up times among studies. With all this pitfalls, the actual incidence of transformation remains an open question. The aim of the present study is to analyse the incidence and prognostic impact of transformation in patients with FL in a large retrospective series of the Spanish group of Lymphomas (GELTAMO). PATIENTS&METHODS A total of 1763 patients from 19 Spanish centres diagnosed of FL between 2000 and 2011 were recruited in the study. Data were obtained from the database of centres willing to participate in this study. True tFL (FL to DLBCL) were recorded. From the original cohort, FL IIIb, composite FL+DLBCL, discordant FL (FL in bone marrow and DLBCL in adenopathy or viceversa), and downgrading tFL (DLBCL at diagnosis and relapse of FL) were excluded. Patients with inadequate follow-up were not considered. Therefore, 1611 patients (grade I, II, and IIIa) were finally included. This study was approved by the Salamanca University Hospital Ethic Committee. RESULTS One hundred and ten patients (median follow up of 6 years) were transformed to DLBCL. Cumulative incidence of transformation at 5, 10, and 15 years was of 5%, 9%, and 14%, respectively. With a median follow up of 75.9 months (2 to 179), median time to transformation was 66 months, ranged 1-179. Considering survival from diagnosis of FL, tFL patients had a shorter OS than non-transformed (19% vs. 69%, p<0,0001). Most of the tFL patients (92%) have previously received treatment for FL, 63% of them with Rituximab. Median number of treatment lines before transformation was 2 (1-7). Factors influencing risk of tFL in the multivariate analysis included non-response to first line therapy (PR, p<0.001, HR:2,5 95% CI:1.5-4.2; others, p<0.0001, HR: 8,1 95% CI: 4.1-16.0), and FLIPI>2 (p=0.002, HR: 2,1 95% CI: 1.3-3.4). In the multivariate analysis, factors predicting decreased OS after transformation included non-achievement of CR after first line therapy (p<0,001, HR:4.3 95% CI:2-9.1), and elevated LDH at the moment of transformation (p=0,003, HR:3 95% CI:1.5-6.3). We analyzed separately the role of autologous stem cell transplantation (ASCT) in transformed FL patients. Patients that received ASCT were significantly younger (<70 years) p<0,001, had a better performance status (ECOG <2) (p=0,008) and had achieved a better response (CR) (p<0,001) than those who did not receive ASCT. All of them in our series were treated with rituximab based regimens at transformation. When we analyzed those patients that were eligible for ASCT (younger than 70), patients that received ASCT showed a better OS after transformation than those who did not (51% vs 26% at 5 years, p=0,004). Interestingly, patients who achieve CR to first line therapy at transformation did not beneficiate of ASCT (54% vs 66% at 5 years, p=0,8) while those who do not achieve CR did (50% vs 16% at 5 years, p=0,008). CONCLUSIONS In this series, one of the largest reported in the rituximab era, high risk FLIPI (>=2) and non-response to FL first line therapy were associated with a higher risk of transformation.Only non-response to transformed FL treatment therapy and a high LDH at transformation were associated with a worse OS after transformation in the multivariate analysis. Autologous transplantation in transformed patients could have a benefit in terms of OS after transformation, but after the introduction of immunochemotherapy strategies, perhaps patients responding to treatment after transformation do not beneficiate from this strategy. *Equal contribution; ‡Equal senior contribution Disclosures Sancho: CELLTRION, Inc.: Research Funding.

scholarly journals Impact of Treatment Sequencing on Outcomes and Costs in Relapsed Follicular or Other Low Grade B-Cell Non-Hodgkin Lymphoma - Results of an Evidence-Based Budget Impact Model

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Ali McBride ◽  
Daniel O. Persky
Keyword(s):  
Follicular Lymphoma ◽  
Low Grade ◽  
Second Line ◽  
Treatment Sequence ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Duration Of Response ◽  
Budget Impact Model

Introduction: The choice of initial therapy in follicular lymphoma can be a key determinant in future therapy, as irreversible toxicities with first line regimens can impact the patient's ability to tolerate future treatment. Minimizing drug exposure will result in less frequent occurrence of significant adverse events and associated treatment costs. In the era of COVID-19 pandemic, there is additional benefit to minimizing the number of patient visits and hospital admissions. Limited information exists related to the outcomes and associated costs of existing treatment sequences. Additionally, treatment administration at different types of clinical sites results in varied reimbursement models, making informed evaluation of clinical and financial evidence challenging. Methods: The current study applies a budget impact model methodology in order to describe the associated impact of treatment selection and sequencing on outcomes and costs in the treatment of relapsed or refractory low-grade follicular lymphoma in first line therapy followed by Consolidation and also in first line therapy to second line therapy. Key model inputs included: Number of treatment cycles, number of days a treatment was received, duration of response (DOR), rate of side effects and associated costs, and total treatment costs, including drugs, medical treatment, laboratory testing and adverse event costs. Treatment outcomes were based on the published literature that summarized the overall response rate, median DOR, and toxicity. Treatment regimen costs were evaluated based on payer pricing, Wholesale Acquisition Cost (WAC), Average Selling Price (ASP) and Average Wholesale Price (AWP) and modified to adjust for weight-based dosing and negotiate payer reimbursement rates. Associated medical costs for medical treatment and supportive care were estimated using current Medicare fee schedule rates. Included were seven options for first line therapy of follicular lymphoma from 2020 NCCN Guidelines - (Bendamustine + rituximab (BR); Bendamustine + Obinutuzumab (OB); CHOP rituximab (RCHOP); CHOP + Obinutuzumab (OCHOP); CVP+ rituximab (RCVP); CVP + Obinutuzumab (OCVP); Lenalidomide + rituximab (R2)), followed by three for Consolidation (Rituximab maintenance (RM); Obinutuzumab maintenance (O); Radioimmunotherapy (RIT with 90 Y-ibritumomab tiuxetan (Y90-IT, Zevalin)) and three Second Line therapy options (RIT; Lenalidomide only; Lenalidomide + Obinutuzumab (LO)). Results: The treatment sequence of first line BR followed by Consolidation with RIT Y90 (Zevalin) had the longest predicted DOR (2586 days). The associated treatment sequence costs were $212,485 for BR followed by Y90-IT, compared with $233, 388 for BR followed by rituximab maintenance, which had a predicted DOR of 2478 days. The predicted DOR for treatment sequences starting with OCHOP, OCVP and RCHOP and followed by RIT with Y90-IT was approximately 1000 days less than BR followed by Y90-IT for a cost difference of $4,421, $12,914 and $25,826, respectively. The treatment sequence of first line BR followed by Second Line RIT Y90-IT had the second longest predicted DOR of 2586 days at costs of $212,485, compared to 2778 days for BR followed by LO, at a total sequence costs of $796,695. Conclusion: The use of Y90-IT in Consolidation or Second Line treatment demonstrated desired patient outcomes at one of the lowest cost profiles. Additionally, Y90-IT administration can be completed in only two clinic visits, reducing patient travel and contact, improving safety in an era of COVID-19 precautionary measures and reducing cost. Figure 1. Duration of Response and Total Sequence Costs for Twelve First Line to Consolidation and First Line to Second Line Treatment Regimens. Disclosures McBride: Merck: Speakers Bureau; Coherus BioSciences: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; MorphoSys: Consultancy; Sandoz: Consultancy.

Multimodality Therapies and Optimal Schedule of Antibodies: Rituximab in Lymphoma as an Example

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 321-328 ◽  
Author(s):  
Michele Ghielmini
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Optimal Schedule ◽  
B Cell Lymphoma ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
Clinical Challenge ◽  
Indolent Disease ◽  
Agent Treatment

Abstract Rituximab was the first humanized antibody widely used on patients, so research on its optimal use was a clinical challenge. Many studies have been performed to optimize its dose and schedule, and more are ongoing. The dose of 375 mg/m2 has become standard, mainly because it shows activity and has little associated toxicity. The combination of rituximab with chemotherapy has been shown to prolong remission in all types of lymphomas, and in patients with diffuse large B-cell lymphoma it can improve survival. As a single agent, particularly when the treatment is prolonged over several months, results are similar to chemotherapy but with fewer side effects. Finally, used as maintenance therapy it can prolong the duration of chemotherapy-obtained remissions. Based on available data, the administration of 375 mg/m2 before each chemotherapy cycle can be recommended for first line treatment of patients with curable B-cell lymphomas and for patients with high-risk indolent lymphoma who are rituximab-naïve. Single-agent treatment at a prolonged schedule is recommended for cases of indolent disease not in need of urgent response and for patients who are unlikely to tolerate chemotherapy.

scholarly journals Valproate in combination with rituximab and CHOP as first-line therapy in diffuse large B-cell lymphoma (VALFRID)

2018 ◽  
Vol 2 (12) ◽  
pp. 1386-1392 ◽  
Author(s):  
Kristina Drott ◽  
Hans Hagberg ◽  
Karin Papworth ◽  
Thomas Relander ◽  
Mats Jerkeman
Keyword(s):  
Histone Deacetylase Inhibitor ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Promising Strategy ◽  
Line Therapy ◽  
Deacetylase Inhibitor ◽  
Key Points

Key Points This trial evaluates addition of the histone deacetylase inhibitor valproate to standard R-CHOP therapy in DLBCL. Addition of valproate to R-CHOP is a promising strategy in DLBCL, but auditory side effects warrant monitoring.

scholarly journals Lenalidomide in follicular lymphoma

Blood ◽  
2020 ◽  
Vol 135 (24) ◽  
pp. 2133-2136 ◽  
Author(s):  
Christopher R. Flowers ◽  
John P. Leonard ◽  
Nathan H. Fowler
Keyword(s):  
United States ◽  
Follicular Lymphoma ◽  
Single Agent ◽  
The United States ◽  
First Line ◽  
Safety And Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Immunomodulatory Drug

Abstract Lenalidomide is an immunomodulatory drug approved in the United States for use with rituximab in patients with relapsed/refractory follicular lymphoma. We reviewed data from trials addressing the safety and efficacy of lenalidomide alone and in combination with rituximab as a first-line therapy and as a treatment of patients with relapsed/refractory follicular lymphoma. Lenalidomide-rituximab has been demonstrated to be an effective chemotherapy-free therapy that improves upon single-agent rituximab and may become an alternative to chemoimmunotherapy.

Sign in / Sign up

Export Citation Format

Share Document