This is the second article in a 4part series on bendamustine. Hodgkin lymphoma nhl and chronic lymphocytic leukemia cll. Final results from the phase iiib green safety study with a focus on. In the german chronic lymphocytic leukemia study group, it was demonstrated that 90.
The following information is not intended to endorse any particular medication. November 29, 2012 please note that sections pertaining to the use of bendamustine. For treating some types of blood cancers such as nonhodgkins lymphoma nhl and chronic lymphocytic leukemia cll. The safety of bendamustine in patients with chronic lymphocytic leukemia or nonhodgkin lymphoma and concomitant renal impairment. Food and drug administration fda oncology center of excellence. This article discusses the efficacy of bendamustine for patients with chronic lymphocytic leukemia cll and nonhodgkin lymphoma nhl in the registration studies cited in the us product labeling. Bendamustine in chronic lymphocytic leukemia and refractory. Bendamustine for the firstline treatment of chronic. Chronic lymphocytic leukemia cll, the most common form of leukemia in europe and.
Optimal use of bendamustine in chronic lymphocytic. Evaluation of bendamustine in combination with fludarabine. Chronic lymphocytic leukemia small lymphocytic lymphoma overview lymphoma is the most common blood cancer. While the previous article discussed the efficacy of bendamustine for patients with chronic lymphocytic leukemia cll and nonhodgkin lymphoma nhl in the registration studies cited in the us product labeling, this article discusses its safety. Pdf efficacy of bendamustine and rituximab as first salvage. Venetoclaxrituximab in relapsed or refractory chronic. Bendamustine was administered at a dose of 90 mgm2 on days 1 and 2 combined. Patients with chronic lymphocytic leukaemia cll have a median of 2 comorbidities thurmes et al, 2008, which compromise overall and. Microabstractwe performed a singlecenter retrospective study on 459 chronic lymphocytic leukemia patients diagnosed since 2000 to assess the prognostic and predictive role of immunoglobulin heavy chain ighv mutational status and load. Although this is an effective treatment, it results in untoward toxicity. Rituximab plus bendamustine or chlorambucil for chronic. Bendamustine plus alemtuzumab for refractory chronic. Listing a study does not mean it has been evaluated by the u.
This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less toxic combination consisting of bendamustine and rituximab. Lymphoma occurs when cells of the immune system called lymphocytes, a type of white blood cell, grow and multiply uncontrollably. Given the indolent nature of the disease, symptomatic patients. Prognostic and predictive effect of ighv mutational status. In vitro studies have demonstrated synergistic proapoptotic effects of bendamustine and the cd20 antibody rituximab br in primary cll cells. Bendamustine is an alkylating agent approved for the treatment of chronic lymphocytic leukemia cll and bcell nonhodgkin lymphoma. Bendamustine and rituximab in combination with copanlisib. Chronic lymphocytic leukemia cll and small lymphocytic lymphoma sll represent different clinical manifestations of a common lymphoproliferative disorder. In 2008, bendamustine was approved by united states food and drug association for the treatment of chronic lymphocytic leukemia and rituximab resistant indolent lymphoma.
Chronic lymphocytic leukemia cll bendeka bendamustine hydrochloride injection is indicated for the treatment of patients with chronic lymphocytic leukemia. Guideline for the treatment of chronic lymphocytic leukaemia. The sequential application of bendamustine and obinutuzumab combined with venetoclax caused no unexpected or cumulative toxicities. Chronic lymphocytic leukemia treatment algorithm 2018 blood. Efficacy relative to first line therapies other than chlorambucil has not been established. Appropriate use of bendamustine in firstline therapy of chronic. The approval of bendamustine was based on results from an unpublished, comparative, phase 3 trial 02clliii of 301 treatmentnaive patients with binet stage b or c cll. The two main forms of lymphoma are hodgkin lymphoma hl and nonhodgkin lymphoma nhl. Unfortunately, cll is considered incurable with the chemotherapeutic agents available today. For over 40 years, bendamustine was used in the former german democratic republic as monotherapy in the treatment of nonhodgkin lymphoma nhl, chronic lymphocytic leukemia cll, multiple myeloma mm, hodgkin lymphoma hl, breast cancer, and smallcell. The high proportion of patients who achieved overall responses, both treatmentnaive and relapsed or refractory patients irrespective of physical fitness and genetic risk factors, compare favourably to established chronic lymphocytic leukaemia therapies. The expanding role of bendamustine in chronic lymphocytic. On november 21, 2019, the brutons tyrosine kinase btk inhibitor acalabrutinib was approved for the treatment of adults with chronic lymphocytic leukemia cll or small lymphocytic lymphoma sll.
Bendamustine demonstrated clinical activity in pretreated hematological malignancies due to its unique mechanism of action distinct from standard alkylating agents. Phase iii randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia wolfgang u. First, it was used solely in the gdr for the treatment of cll, indolent nonhodgkins lymphoma and multiple myeloma. Chronic lymphocytic leukemia cll is the most common leukemia in the. The estimated percentage of patients with progressionfree survival at 2 years was 74, 87, and 88 percent for bendamustine plus rituximab, ibrutinib alone hazard ratio for progression or death, 0. When most of the cancer cells are located in the bloodstream and. Bendamustine therapy in chronic lymphocytic leukemia. This study assesses its efficacy in patients with chronic lymphocytic leukemia pre. Bfr bendamustine, fludarabine, and rituximab allogeneic. Oct 02, 2014 in this phase 12 study, we tested the safety and efficacy of escalating doses of bendamustine 70, 90, 110, and mgm 2 per day for 3 days, coupled with our historical fixed doses of fludarabine and rituximab bfr, as a nonmyeloablative allogeneic conditioning regimen for patients with relapsed lymphoma n 41 and chronic lymphocytic. The treatment landscape for patients with chronic lymphocytic leukemia cll has changed considerably with the introduction of very effective oral targeted therapies such as ibrutinib, idelalisib. Efficacy of bendamustine in chronic lymphocytic leukemia. Bendamustine for patients with indolent b cell lymphoproliferative malignancies including chronic lymphocytic leukaemia an updated meta.
Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia cll and bcell nonhodgkin lymphoma. Fixed duration of venetoclaxrituximab in relapsedrefractory. Bendamustine and its role in the treatment of unfit patients. More recently combination therapy with bendamustine rituximab has been shown to be highly effective in cll and should be considered one of the standard regimens offered to patients. Positive efficacy achieved with bendamustine debulking. This is the third article in a 4part series on bendamustine. Patients and methods in all, 117 patients, age 34 to 78 years, 46. Acute promyelocytic leukemia vyxeos daunorubicin cytarabine jazz pharmaceutical jump start program 18555899367. Rituximab and bendamustine have demonstrated activity in non. Mable investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabineineligible patients with chronic lymphocytic leukemia. The disease typically occurs in elderly patients and has a highly variable clinical course. The safety of bendamustine in patients with chronic. Bendamustine followed by obinutuzumab and venetoclax in. As the most prevalent form of adult leukemia, chronic lymphocytic leukemia cll affects thousands of patients each year.
Leukemic transformation is initiated by specific genomic alterations that. Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib. Generally, a peripheral blood lymphocyte count 5000 x 10 9 lymphocytesliter is defined as the threshold to separate cll from sll. Knowing the subtype of your disease is important because your treatment approach may be based on your subtype. Jul 30, 2019 chronic lymphocytic leukemia is characterized by the clonal proliferation and accumulation of mature, typically cd5. Safety of bendamustine in chronic lymphocytic leukemia and. Chronic lymphocytic leukemia cll and small lymphocytic lymphoma sll are forms of nhl that arise from b lymphocytes. The ontario renal network advises the ontario government on chronic kidney disease and is a division of cco. Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia. Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progressionfree survival than bendamustine plus rituximab. The novel twodrug combination of bendamustine plus rituximab had shown promise for the firstline treatment for chronic lymphocytic leukemia cll, and it is less toxic than the standard three.
Knauf, toshko lissichkov, ali aldaoud, anna liberati, javier loscertales, raoul herbrecht. Cancers free fulltext transcriptional modulation by. In this phase 12 study, we tested the safety and efficacy of escalating doses of bendamustine. Copanlisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bendamustine plus rituximab in chronic lymphocytic leukemia. Chronic lymphocytic leukemia cll is the commonest leukemia in western countries. Bendamustine for treatment of chronic lymphocytic leukemia ncbi. Chronic lymphocytic leukemia small lymphocytic lymphoma 2017 update john m pagel, md, phd swedish cancer institute seattle, washington. Computerized and manual consistency checks were performed by the data. We evaluated the activities of ide in comparison to bendamusine ben, a commonly used alkylating agent, in primary cll cells ex vivo. Despite its acceptable shortterm toxicity profile, longterm toxicities are less well established. This multicenter, investigatorinitiated phaseii study evaluates a sequential treatment with two cycles of bendamustine.
Pdf bendamustine in combination with ofatumumab in relapsed. Giving bendamustine and rituximab with copanlisib may work better than bendamustine and rituximab alone in treating chronic lymphocytic leukemia or small lymphocytic lymphoma. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. Bendamustine in chronic lymphocytic leukemia and non. Myelosuppression, graftversushost disease gvhd, and relapse remain major causes of morbidity after stem cell transplantation for relapsed lymphoma. Bendamustine versus fludarabine in chronic lymphocytic. Chronic lymphocytic leukemia cll is the most common form of adult leukemia, estimated to comprise over one third of all new leukemia cases. Bendamustine offers a therapeutic option for treatment of chronic lymphocytic leukemia cll with clinical activity and a toxicity profile that will allow for treatment of a broad range of patients. Most patients with chronic lymphocytic leukemia cll will require therapy at some point during their disease course, and typically receive chemoimmunotherapy as initial treatment 1. Efficacy of bendamustine and rituximab as first salvage treatment in. Chronic lymphocytic leukemia cll, or bcell chronic lymphocytic leukemia, is the most common type of human leukemia. Chronic lymphocytic leukemia cll and small lymphocytic lymphoma sll. Aug 25, 2011 bendamustine demonstrated clinical activity in pretreated hematological malignancies due to its unique mechanism of action distinct from standard alkylating agents.
Bendamustine combines alkylating properties with purine analogue properties making it an effective drug in chronic lymphocytic leukemia where agents that affect these pathways have proven useful. The introduction of targeted agents has revolutionized the treatment of chronic lymphocytic leukemia but only few patients achieve complete remissions and minimal residual disease negativity with ibrutinib monotherapy. Bendamustine, followed by ofatumumab and ibrutinib in. Preclinical studies indicate that bendamustine and rituximab. The fludarabine and cyclophosphamide couplet has become the backbone of the chronic lymphocytic leukemia cll standard of care. Bendamustine debulking followed by ofatumumab and ibrutinib demonstrated an overall response rate of 92% in patients with chronic lymphocytic leukemia, meeting the primary end point of the phase ii cll2bio trial, and was welltolerated with no new safety signals. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia.
Extended followup of patients treated with bendamustine. Unmutated ighv patients had the shortest progressionfree survival pfs and overall survival p bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia. The combination of bendamustine treanda and rituximab rituxan induced a 12month progressionfree survival pfs of 78. Bendamustine in chronic lymphocytic leukemia and nonhodgkin. Bendamustine for treatment of chronic lymphocytic leukemia.
Apr 27, 2018 green nct01905943 is a nonrandomized, openlabel phase iiib study investigating obinutuzumab alone or plus chemotherapy in chronic lymphocytic leukemia cll. Polatuzumab vedotin plus bendamustine with rituximab in relapsedrefractory diffuse large bcell lymphoma. Bendamustine for patients with indolent b cell lymphoproliferative. Bendamustine and rituximab br is one of the most widely adopted cit. Ambedkar institute rotary cancer hospital aims, new delhi, india. Ruppert, nyla heerema, weiqiang zhao, allison m booth, wei ding, nancy l. Safety and efficacy of bendamustine and rituximab br regimen in indian chronic lymphocytic leukemia patients a gogia medical oncologu, b. Firstline chemoimmunotherapy with bendamustine and. Rituximab plus bendamustine vs standard therapy for cll.
The lifetime risk for developing cll is 1 in 216 men and women. Bendamustine treanda for chronic lymphocytic leukemia. Phase iii randomized study of bendamustine compared with. For over 40 years, bendamustine was used in the former german democratic republic as monotherapy in the treatment of nonhodgkin lymphoma nhl, chronic lymphocytic leukemia cll, multiple myeloma mm, hodgkin lymphoma hl, breast cancer, and smallcell lung cancer. Results of alliance north american intergroup study a041202 jennifer a. In this ongoing multicentre, openlabel, investigatorinitiated phase 2 trial, patients aged. Optimal use of bendamustine in chronic lymphocytic leukemia. Patients and methods seventyeight patients, including 22 patients with. Efficacy and safety of bendamustine and ibrutinib in. The expanding role of bendamustine in chronic lymphocytic leukemia kruti sheth nair, chaitra ujjani lombardi comprehensive cancer center, medstar georgetown university hospital, washington, dc, usa abstract. Cll and sll are essentially the same disease, with the only difference being the location where the cancer primarily oc curs. Chronic lymphocytic leukemia small lymphocytic lymphoma 2017.
Treatment of chronic lymphocytic leukemia cll has dramatically changed over the last. Acute lymphoblastic leukemia all diseases brand name. Free survival pfs compared with bendamustine plus rituximab in untreated older patients with chronic lymphocytic leukemia cll. We conducted this phase one study in relapsedrefractory nhl and cll patients. Bendamustine is now approved in the us for the treatment of chronic lymphocytic leukemia and low grade nonhodgkins lymphoma, and is currently being explored in the treatment of several solid tumor types. This study assesses its efficacy in patients with chronic lymphocytic leukemia pretreated with an alkylator, in comparison to fludarabine. Cll is considered a disease of adults, however it can occur in teenagers and.
A multicenter phase ii trial of the german chronic lymphocytic leukemia. Fit or unfit or relapsedrefractory chronic lymphocytic leukemia cll patients. Jul 28, 2009 bendamustine plus alemtuzumab for refractory chronic lymphocytic leukemia cll the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Bendamustine is one of the oldest approved drugs for cll treatment. Bendamustine and its role in the treatment of unfit. Pdf we conducted a phase ii, noncomparative, openlabel, multicenter. The expanding role of bendamustine in chronic lymphocytic leukemia. Bendamustine is a newly approved and bettertolerated alkylating agent. Bendamustine in combination with rituximab for previously. Chronic lymphocytic leukemia cll treanda is indicated for the treatment of patients with chronic lymphocytic leukemia.
Fludarabine followed by alemtuzumab consolidation for previously untreated chronic lymphocytic leukemia. Acalabrutinib for adult patients with chronic lymphocytic. There are scant reports on bendamustine induced immune. Combining duvelisib with either rituximab alone or rituximab and bendamustine may improve response rates and remission durability. The objective of this trial was to evaluate safety and ef. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Bendamustine combined with rituximab in patients with. In the german democratic republic, bendamustine was used in all kinds of nonhodgkins lymphomas, chronic lymphocytic leukemia cll, multiple myeloma,1, 2 hodgkins disease, and solid tumors. Indirect comparison iga andrasiak,1 justyna rybka,2 wanda knopinskaposluszny,3 tomasz wrobel2 abstract bendamustine and ibrutinib are commonly used in the treatment of patients suffering from chronic lymphocytic leukemia cll. Chronic lymphocytic leukemia small lymphocytic lymphoma.
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