-
Blood Advances Aug 2023The combination of rituximab, bendamustine, and low-dose cytarabine (R-BAC) has been studied in a phase 2 prospective multicenter study from Fondazione Italiana Linfomi...
The combination of rituximab, bendamustine, and low-dose cytarabine (R-BAC) has been studied in a phase 2 prospective multicenter study from Fondazione Italiana Linfomi (RBAC500). In 57 previously untreated elderly patients with mantle cell lymphoma (MCL), R-BAC was associated with a complete remission rate of 91% and 2-year progression-free survival (PFS) of 81% (95% confidence interval [CI], 68-89). Here, we report the long-term survival outcomes, late toxicities, and results of minimal residual disease (MRD) evaluation. After a median follow-up of 86 months (range, 57-107 months), the median overall survival (OS) and PFS were not reached. The 7-year PFS and OS rates were 55% (95% CI, 41-67), and 63% (95% CI, 49-74), respectively. Patients who responded (n = 53) had a 7-year PFS of 59% (95% CI, 44-71), with no relapse or progression registered after the sixth year. In the multivariate analysis, blastoid/pleomorphic morphology was the strongest adverse predictive factor for PFS (P = .04). Patients with an end of treatment negative MRD had better, but not significant, outcomes for both PFS and OS than patients with MRD-positive (P = 0.148 and P = 0.162, respectively). There was no signal of late toxicity or an increase in secondary malignancies during the prolonged follow-up. In conclusion, R-BAC, which was not followed by maintenance therapy, showed sustained efficacy over time in older patients with MCL. Survival outcomes compare favorably with those of other immunochemotherapy regimens (with or without maintenance), including combinations of BTK inhibitors upfront. This study was registered with EudraCT as 2011-005739-23 and at www.clinicaltrials.gov as #NCT01662050.
Topics: Humans; Adult; Aged; Rituximab; Lymphoma, Mantle-Cell; Bendamustine Hydrochloride; Follow-Up Studies; Cytarabine; Prospective Studies; Neoplasm Recurrence, Local
PubMed: 37171620
DOI: 10.1182/bloodadvances.2023009744 -
Leukemia & Lymphoma 2016Bendamustine has achieved widespread international regulatory approval and is a standard agent for the treatment for chronic lymphocytic leukemia (CLL), indolent... (Review)
Review
Bendamustine has achieved widespread international regulatory approval and is a standard agent for the treatment for chronic lymphocytic leukemia (CLL), indolent non-Hodgkin lymphoma and multiple myeloma. Since approval, the number of indications for bendamustine has expanded to include aggressive non-Hodgkin lymphoma and Hodgkin lymphoma and novel targeted therapies, based on new bendamustine regimens/combinations, are being developed against CLL and lymphomas. In 2010, an international panel of bendamustine experts met and published a set of recommendations on the safe and effective use of bendamustine in patients suffering from hematologic disorders. In 2014, this panel met again to update these recommendations since the clarification of issues including optimal dosing and management of bendamustine-related toxicities. The aim of this report is to communicate the latest consensus on the use of bendamustine, permitting the expansion of its safe and effective administration, particularly in new combination therapies.
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Consensus Development Conferences as Topic; Disease Management; Disease Progression; Drug Resistance; Hematologic Diseases; Hematologic Neoplasms; Humans; Recurrence; Retreatment
PubMed: 26592922
DOI: 10.3109/10428194.2015.1099647 -
Expert Opinion on Pharmacotherapy Jul 2012Chronic lymphocytic leukemia (CLL) often has an extended disease course. With a median age at diagnosis of 72 years, newer treatment options with less toxicity than... (Review)
Review
INTRODUCTION
Chronic lymphocytic leukemia (CLL) often has an extended disease course. With a median age at diagnosis of 72 years, newer treatment options with less toxicity than standard nucleoside analogue-based regimens are needed. Historically, few therapy options are available once CLL has become refractory to nucleoside analogues. Bendamustine has emerged as a feasible therapy for older and less fit CLL patients, with clinical efficacy in previously untreated and refractory CLL.
AREAS COVERED
This paper reviews several of the pivotal clinical trials that established the clinical activity of bendamustine in previously untreated and relapsed/refractory CLL. The toxicity profile of bendamustine, primarily myelosuppression and infections, is reviewed and compared across different CLL populations. A review of the clinical data focuses on potential explanations for differences in response rates and duration of remission reported across studies and how this may impact the development of therapies for CLL.
EXPERT OPINION
Bendamustine is a valuable new agent for the management of CLL. Ongoing clinical trials are comparing bendamustine with standard CLL regimens in untreated disease, and investigating bendamustine combinations with novel targeted therapies and monoclonal antibodies. These studies will help to define the optimal role for bendamustine in CLL management.
Topics: Antineoplastic Agents, Alkylating; Bendamustine Hydrochloride; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Nitrogen Mustard Compounds
PubMed: 22663160
DOI: 10.1517/14656566.2012.693163 -
Hematology. American Society of... Dec 2017Most people with mantle cell lymphoma (MCL) present with diffuse adenopathy and benefit from early initiation of rituximab and high-dose cytarabine- or... (Review)
Review
Most people with mantle cell lymphoma (MCL) present with diffuse adenopathy and benefit from early initiation of rituximab and high-dose cytarabine- or bendamustine-based therapies. Some patients, however, present with primarily nonnodal disease that can follow either an indolent or a rapidly progressive, treatment-resistant clinical course. Rarely, patients present with explosive disease that can be challenging to manage and often involves the central nervous system. New agents with improved therapeutic indices facilitate treatment while maintaining quality of life, but also present new complications at the time of treatment failure. Although uncommon presentations are not new to clinicians who treat MCL, the increasing clarity of underlying biology and prognostic implications may help us develop more specialized treatment strategies.
Topics: Bendamustine Hydrochloride; Central Nervous System Neoplasms; Cytarabine; Humans; Lymphoma, Mantle-Cell; Rituximab
PubMed: 29222271
DOI: 10.1182/asheducation-2017.1.304 -
Expert Review of Hematology May 2023Extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue is an indolent lymphoma originating from marginal zone B-cells and associated with chronic... (Review)
Review
INTRODUCTION
Extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue is an indolent lymphoma originating from marginal zone B-cells and associated with chronic inflammation. EMZL demonstrates distinct genomic alterations according to the primary extranodal site of disease but commonly affects signaling pathways including NF-ĸB, B-cell receptor, and NOTCH. Treatment with radiation therapy is commonly implemented in localized diseases, and multiple agents are available for patients with advanced-stage diseases in need of therapy. Bendamustine with rituximab is a frontline platform associated with high efficacy.
AREAS COVERED
Clinical features, diagnosis, genomics, models enabling risk stratification, treatment options, and future directions.
EXPERT OPINION
The lack of consistent genotyping profile in EMZL precludes the development of tissue and circulatory biomarkers for the diagnosis, risk stratification, and monitoring of minimal residual disease. Furthermore, the biological heterogeneity observed in extranodal sites associated with overall limited genomic data prevents the testing of druggable pathways aiming for a personalized treatment approach. Future clinical trials should focus on EMZL considering the unique clinical characteristics in the eligibility criteria and response assessment to better inform efficacy of novel agents and delineate sequences of therapies.
Topics: Humans; Prognosis; Lymphoma, B-Cell, Marginal Zone; Rituximab; Bendamustine Hydrochloride
PubMed: 37086394
DOI: 10.1080/17474086.2023.2206557 -
Frontiers in Immunology 2023Classical Hodgkin lymphoma (cHL) is the most common pediatric lymphoma. Approximately 10% of patients develop refractory or recurrent disease. These patients are treated...
INTRODUCTION
Classical Hodgkin lymphoma (cHL) is the most common pediatric lymphoma. Approximately 10% of patients develop refractory or recurrent disease. These patients are treated with intensive chemotherapy followed by consolidation with radiotherapy or high-dose chemotherapy and autologous stem cell reinfusion. Although this treatment is effective, it comes at the cost of severe long-term adverse events, such as reduced fertility and an increased risk of secondary cancers. Recently, promising results of inducing remission with the immune checkpoint inhibitor nivolumab (targeting PD-1) and the anti-CD30 antibody-drug conjugate Brentuximab vedotin (BV) +/- bendamustine were published.
METHODS
Here we describe a cohort of 10 relapsed and refractory pediatric cHL patients treated with nivolumab + BV +/- bendamustine to induce remission prior to consolidation with standard treatment.
RESULTS AND DISCUSSION
All patients achieved complete remission prior to consolidation treatment and are in ongoing complete remission with a median follow-up of 25 months (range: 12 to 42 months) after end-of-treatment. Only one adverse event of CTCAE grade 3 or higher due to nivolumab + BV was identified. Based on these results we conclude that immunotherapy with nivolumab + BV +/- bendamustine is an effective and safe treatment to induce remission in pediatric R/R cHL patients prior to standard consolidation treatment. We propose to evaluate this treatment further to study putative long-term toxicity and the possibility to reduce the intensity of consolidation treatment.
Topics: Humans; Child; Hodgkin Disease; Nivolumab; Brentuximab Vedotin; Bendamustine Hydrochloride; Treatment Outcome
PubMed: 37583696
DOI: 10.3389/fimmu.2023.1229558 -
Blood Advances Feb 2024Lymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of...
Lymphodepletion (LD) is an integral component of chimeric antigen receptor T-cell (CART) immunotherapies. In this study, we compared the safety and efficacy of bendamustine (Benda) to standard fludarabine/cyclophosphamide (Flu/Cy) LD before CD19-directed, CD28-costimulated CART axicabtagene ciloleucel (axi-cel) for patients with large B-cell lymphoma (LBCL) and follicular lymphoma (FL). We analyzed 59 patients diagnosed with LBCL (n = 48) and FL (n = 11) consecutively treated with axi-cel at the University of Pennsylvania. We also analyzed serum samples for cytokine levels and metabolomic changes before and after LD. Flu/Cy and Benda demonstrated similar efficacy, with complete remission rates of 51.4% and 50.0% (P = .981), respectively, and similar progression-free and overall survivals. Any-grade cytokine-release syndrome occurred in 91.9% of patients receiving Flu/Cy vs 72.7% of patients receiving Benda (P = .048); any-grade neurotoxicity after Flu/Cy occurred in 45.9% of patients and after Benda in 18.2% of patients (P = .031). In addition, Flu/Cy was associated with a higher incidence of grade ≥3 neutropenia (100% vs 54.5%; P < .001), infections (78.4% vs 27.3%; P < .001), and neutropenic fever (78.4% vs 13.6%; P < .001). These results were confirmed both in patients with LBCL and those with FL. Mechanistically, patients with Flu/Cy had a greater increase in inflammatory cytokines associated with neurotoxicity and reduced levels of metabolites critical for redox balance and biosynthesis. This study suggests that Benda LD may be a safe alternative to Flu/Cy for CD28-based CART CD19-directed immunotherapy with similar efficacy and reduced toxicities. Benda is associated with reduced levels of inflammatory cytokines and increased anabolic metabolites.
Topics: Humans; Bendamustine Hydrochloride; Cytokines; CD28 Antigens; Immunotherapy, Adoptive; Lymphoma, Follicular; Cyclophosphamide; Biological Products
PubMed: 38113468
DOI: 10.1182/bloodadvances.2023011492 -
Hematology. American Society of... Dec 2016It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in... (Review)
Review
It is an unprecedented time for the treatment of patients with chronic lymphocytic leukemia (CLL) with the recent approval of several targeted agents for use in frontline, relapsed, refractory, and high-risk disease. Traditionally, frontline management of CLL has been a combination of chemotherapy (fludarabine, cyclophosphamide, bendamustine, or chlorambucil) with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab). The current landscape is rapidly evolving with the advent of therapies that demonstrate selective inhibition of important pathways necessary for CLL proliferation and survival. Despite considerable progress, much is still unknown and optimal treatment selection and sequence is still debatable. None of the new agents have been compared against each other and the impact of adding an additional agent to monotherapy is not yet fully elucidated. In routine clinical practice, the choice of therapy is based on nonrandomized comparisons, presence of comorbidities, and toxicity considerations. These recently approved drugs (ibrutinib, idelalisib, and venetoclax) are reporting excellent outcomes, including patients with high-risk disease such as 17p deletion (17p-) or TP53 mutations (TP53mut). Ibrutinib and venetoclax have been approved for use in 17p- patients (frontline and relapsed, respectively). Ibrutinib is currently moving into the frontline space given recent regulatory approvals. This review will summarize and interpret the limited therapeutic sequencing data available, highlighting the need for additional studies to optimize combination strategies and treatments after failure or discontinuation of these novel agents.
Topics: Alanine; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Cell Proliferation; Chlorambucil; Chromosome Deletion; Chromosomes, Human, Pair 17; Cyclophosphamide; DNA Mutational Analysis; Disease-Free Survival; High-Throughput Nucleotide Sequencing; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Rituximab; Smith-Magenis Syndrome; Tumor Suppressor Protein p53
PubMed: 27913471
DOI: 10.1182/asheducation-2016.1.128 -
International Journal of Cancer May 2023Bendamustine and rituximab (BR) is a preferred first-line therapy for indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL); however, few reports on BR... (Observational Study)
Observational Study
Bendamustine and rituximab is well-tolerated and efficient in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study.
Bendamustine and rituximab (BR) is a preferred first-line therapy for indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL); however, few reports on BR performance in elderly patients are available to date. We compared safety and efficacy of BR in patients ≥70 years (elderly) vs <70 years (younger) treated at our institution. Among 201 patients, 113 were elderly (median age: 77 years), including 38 patients ≥80 years, and 88 were younger (median age: 62 years). Elderly patients had more bone marrow involvement by lymphoma, anemia, ECOG status 3 and high-risk disease follicular lymphoma (P < .05 for all). Fifty-four percent of elderly received full dose of bendamustine vs 79.5% of younger patients. More elderly patients (54%) vs younger (43.2%) experienced treatment delay. Less elderly proceeded to rituximab maintenance. Overall, the number of adverse events per patient and transformed B-Cell lymphoma/secondary malignancies were similar between groups. Elderly patients had less febrile neutropenia, rituximab-associated infusion reactions, but more herpes zoster reactivation. There were more deaths in the elderly (37.2%) vs younger (10.2%) groups (P < .001), mainly due to non-lymphoma-related causes. With median follow-up of 42 months [4.0-97.0] disease-free survival for the elderly was similar to younger patients. There was no difference between patients <80 and ≥80 years (P = .274). In conclusion, the real-world elderly patients have more advanced disease and higher ECOG status. BR is well-tolerated; elderly patients had lower incidence of febrile neutropenia. Dose reduction and treatment delays are common, but BR efficacy was not affected even in very old patients (≥80 years).
Topics: Humans; Adult; Aged; Middle Aged; Rituximab; Lymphoma, Mantle-Cell; Bendamustine Hydrochloride; Lymphoma, Non-Hodgkin; Febrile Neutropenia; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36545885
DOI: 10.1002/ijc.34412 -
Swiss Medical Weekly 2018Over the last few years, there have been many changes in the management of patients with follicular lymphoma, resulting in improvements in progression-free survival and... (Review)
Review
Over the last few years, there have been many changes in the management of patients with follicular lymphoma, resulting in improvements in progression-free survival and quality of life. In addition to established regimens such as radiotherapy and immunochemotherapy, new treatment options are on the horizon. Furthermore, even the use of established chemotherapy agents has evolved, with new combinations moving to the forefront of the current treatment strategy. Nevertheless, there remains an unmet need for patients who have early relapses, those who are not responsive to anti-CD20 treatment regimens and for those in whom minimal residual disease persists even after immunochemotherapy. This review provides a summary of current developments in the diagnosis, treatment and management of follicular lymphoma, focusing on the clinical issues from a Swiss perspective.
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Combined Modality Therapy; Disease Management; Humans; Immunotherapy; Lymphoma, Follicular; Neoplasm Grading; Positron Emission Tomography Computed Tomography; Quality of Life; Recurrence; Rituximab; Survival Rate
PubMed: 30044476
DOI: 10.4414/smw.2018.14635