Optimal use of bendamustine in chronic lymphocytic leukemia. November 29, 2012 please note that sections pertaining to the use of bendamustine. 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. Safety and efficacy of bendamustine and rituximab br regimen in indian chronic lymphocytic leukemia patients a gogia medical oncologu, b. Prognostic and predictive effect of ighv mutational status. 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. 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 safety of bendamustine in patients with chronic. The lifetime risk for developing cll is 1 in 216 men and women. 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. Lymphoma occurs when cells of the immune system called lymphocytes, a type of white blood cell, grow and multiply uncontrollably. 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. The expanding role of bendamustine in chronic lymphocytic.
In this ongoing multicentre, openlabel, investigatorinitiated phase 2 trial, patients aged. Hodgkin lymphoma nhl and chronic lymphocytic leukemia cll. Bendamustine and rituximab br is one of the most widely adopted cit. Efficacy of bendamustine and rituximab as first salvage treatment in.
Pdf we conducted a phase ii, noncomparative, openlabel, multicenter. Evaluation of bendamustine in combination with fludarabine. Efficacy and safety of bendamustine and ibrutinib in. Ruppert, nyla heerema, weiqiang zhao, allison m booth, wei ding, nancy l. 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. Cll is considered a disease of adults, however it can occur in teenagers and. Bendamustine therapy in chronic lymphocytic leukemia. Patients and methods seventyeight patients, including 22 patients with. Treatment of chronic lymphocytic leukemia cll has dramatically changed over the last. It was first synthesized in the former german democratic republic gdr by werner ozegowski and dietrich krebs in 1963 ozegowski, 1971.
Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia. Results of alliance north american intergroup study a041202 jennifer a. Despite its acceptable shortterm toxicity profile, longterm toxicities are less well established. Chronic lymphocytic leukemia small lymphocytic lymphoma 2017.
Chronic lymphocytic leukemia cll is the most common form of adult leukemia, estimated to comprise over one third of all new leukemia cases. Bendamustine for treatment of chronic lymphocytic leukemia. Bendamustine in chronic lymphocytic leukemia and nonhodgkin. Among patients with relapsed or refractory chronic lymphocytic leukemia, venetoclax plus rituximab resulted in significantly higher rates of progressionfree survival than bendamustine plus rituximab. Rituximab and bendamustine have demonstrated activity in non. Patients received rituximab plus bendamustine or rituximab plus chlorambucil every four weeks for six cycles. Although this is an effective treatment, it results in untoward toxicity. Chronic lymphocytic leukemia small lymphocytic lymphoma 2017 update john m pagel, md, phd swedish cancer institute seattle, washington. Extended followup of patients treated with bendamustine.
We evaluated the activities of ide in comparison to bendamusine ben, a commonly used alkylating agent, in primary cll cells ex vivo. The fludarabine and cyclophosphamide couplet has become the backbone of the chronic lymphocytic leukemia cll standard of care. 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. 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. The combination of bendamustine treanda and rituximab rituxan induced a 12month progressionfree survival pfs of 78. This study assesses its efficacy in patients with chronic lymphocytic leukemia pretreated with an alkylator, in comparison to fludarabine. Bendamustine and rituximab in combination with copanlisib. The two main forms of lymphoma are hodgkin lymphoma hl and nonhodgkin lymphoma nhl. Apr 27, 2018 green nct01905943 is a nonrandomized, openlabel phase iiib study investigating obinutuzumab alone or plus chemotherapy in chronic lymphocytic leukemia cll. Patients with chronic lymphocytic leukaemia cll have a median of 2 comorbidities thurmes et al, 2008, which compromise overall and.
Chronic lymphocytic leukemia cll and small lymphocytic lymphoma sll are forms of nhl that arise from b lymphocytes. Final results from the phase iiib green safety study with a focus on. The disease typically occurs in elderly patients and has a highly variable clinical course. Aug 25, 2011 bendamustine demonstrated clinical activity in pretreated hematological malignancies due to its unique mechanism of action distinct from standard alkylating agents. Bfr bendamustine, fludarabine, and rituximab allogeneic. The expanding role of bendamustine in chronic lymphocytic leukemia. Bendamustine followed by obinutuzumab and venetoclax in. Bendamustine for the firstline treatment of chronic. Pdf bendamustine in combination with ofatumumab in relapsed. Acute promyelocytic leukemia vyxeos daunorubicin cytarabine jazz pharmaceutical jump start program 18555899367. For treating some types of blood cancers such as nonhodgkins lymphoma nhl and chronic lymphocytic leukemia cll. This is the second article in a 4part series on bendamustine. 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.
Bendamustine versus fludarabine in chronic lymphocytic. As the most prevalent form of adult leukemia, chronic lymphocytic leukemia cll affects thousands of patients each year. Bendamustine in chronic lymphocytic leukemia and non. Chronic lymphocytic leukemia cll and small lymphocytic lymphoma sll.
Mable investigated the efficacy and safety of rituximab plus bendamustine or rituximab plus chlorambucil in fludarabineineligible patients with chronic lymphocytic leukemia. Bendamustine plus rituximab in chronic lymphocytic leukemia. 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. 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. Unfortunately, cll is considered incurable with the chemotherapeutic agents available today. Bendamustine for treatment of chronic lymphocytic leukemia ncbi. 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. 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. A multicenter phase ii trial of the german chronic lymphocytic leukemia. Bendamustine is one of the oldest approved drugs for cll treatment. Chronic lymphocytic leukemia small lymphocytic lymphoma overview lymphoma is the most common blood cancer. 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. Chronic lymphocytic leukemia cll and small lymphocytic lymphoma sll represent different clinical manifestations of a common lymphoproliferative disorder.
Chronic lymphocytic leukemia cll is the commonest leukemia in western countries. Positive efficacy achieved with bendamustine debulking. Phase iii randomized study of bendamustine compared with. 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. Bendamustine, followed by ofatumumab and ibrutinib in. Patients and methods in all, 117 patients, age 34 to 78 years, 46. Listing a study does not mean it has been evaluated by the u. Cll and sll are essentially the same disease, with the only difference being the location where the cancer primarily oc curs. Fludarabine followed by alemtuzumab consolidation for previously untreated chronic lymphocytic leukemia. We conducted this phase one study in relapsedrefractory nhl and cll patients. Guideline for the treatment of chronic lymphocytic leukaemia.
This multicenter, investigatorinitiated phaseii study evaluates a sequential treatment with two cycles of bendamustine. Efficacy relative to first line therapies other than chlorambucil has not been established. Knowing the subtype of your disease is important because your treatment approach may be based on your subtype. This is the third article in a 4part series on bendamustine. 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. Chronic lymphocytic leukemia cll treanda is indicated for the treatment of patients with chronic lymphocytic leukemia. 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. There are scant reports on bendamustine induced immune. Knauf, toshko lissichkov, ali aldaoud, anna liberati, javier loscertales, raoul herbrecht. 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. Phase iii randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia wolfgang u. The following information is not intended to endorse any particular medication. Standard treatments include alkylating agents chlorambucil, clb. 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.
Bendamustine in chronic lymphocytic leukemia and refractory. Food and drug administration fda oncology center of excellence. 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. When most of the cancer cells are located in the bloodstream and. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. Safety of bendamustine in chronic lymphocytic leukemia and. Chronic lymphocytic leukemia i 3 the four main types of leukemia are further classified into subtypes based on specific features of the leukemia cells. Fit or unfit or relapsedrefractory chronic lymphocytic leukemia cll patients. Bendamustinerituximab is an effective salvage therapy in cll. Preclinical studies indicate that bendamustine and rituximab. Pdf efficacy of bendamustine and rituximab as first salvage. Optimal use of bendamustine in chronic lymphocytic. Acalabrutinib for adult patients with chronic lymphocytic. Acute lymphoblastic leukemia all diseases brand name.
Bendamustine for patients with indolent b cell lymphoproliferative malignancies including chronic lymphocytic leukaemia an updated meta. In vitro studies have demonstrated synergistic proapoptotic effects of bendamustine and the cd20 antibody rituximab br in primary cll cells. Computerized and manual consistency checks were performed by the data. Appropriate use of bendamustine in firstline therapy of chronic. 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 was administered at a dose of 90 mgm2 on days 1 and 2 combined. Firstline chemoimmunotherapy with bendamustine and.
Bendamustine is an alkylating agent approved for the treatment of chronic lymphocytic leukemia cll and bcell nonhodgkin lymphoma. 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. Bendamustine treanda for chronic lymphocytic leukemia. Venetoclaxrituximab in relapsed or refractory chronic. In this phase 12 study, we tested the safety and efficacy of escalating doses of bendamustine. Bendamustine combined with rituximab in patients with. This study assesses its efficacy in patients with chronic lymphocytic leukemia pre. Copanlisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Leukemic transformation is initiated by specific genomic alterations that.
Efficacy of bendamustine in chronic lymphocytic leukemia. Jul 30, 2019 chronic lymphocytic leukemia is characterized by the clonal proliferation and accumulation of mature, typically cd5. Polatuzumab vedotin plus bendamustine with rituximab in relapsedrefractory diffuse large bcell lymphoma. Bendamustine is a newly approved and bettertolerated alkylating agent. Generally, a peripheral blood lymphocyte count 5000 x 10 9 lymphocytesliter is defined as the threshold to separate cll from sll. Bendamustine plus alemtuzumab for refractory chronic. Bendamustine in combination with rituximab for previously. 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. Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia cll and bcell nonhodgkin lymphoma. Chronic lymphocytic leukemia cll is the most common leukemia in the.
The ontario renal network advises the ontario government on chronic kidney disease and is a division of cco. Myelosuppression, graftversushost disease gvhd, and relapse remain major causes of morbidity after stem cell transplantation for relapsed lymphoma. 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. In this phase 12 study, we determined the tolerance and efficacy of an escalating dose of bendamustine 70, 90, 110, and mgm 2 per day for 3 days, coupled with historical fixed doses of fludarabine and rituximab, as an allosct conditioning regimen for patients with resistant or relapsed chronic lymphocytic leukemia cll and lymphoma. Cancers free fulltext transcriptional modulation by. Chronic lymphocytic leukemia small lymphocytic lymphoma.
Combining duvelisib with either rituximab alone or rituximab and bendamustine may improve response rates and remission durability. Given the indolent nature of the disease, symptomatic patients. 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, or bcell chronic lymphocytic leukemia, is the most common type of human leukemia. Bendamustine and its role in the treatment of unfit patients. Rituximab plus bendamustine vs standard therapy for cll. The objective of this trial was to evaluate safety and ef. Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia.
Bendamustine, an alkylating agent with additional properties of a purine analogue, has shown considerable activity in monotherapy for solid and lymphoid malignancies including chronic lymphocytic leukemia cll. Ambedkar institute rotary cancer hospital aims, new delhi, india. 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. Free survival pfs compared with bendamustine plus rituximab in untreated older patients with chronic lymphocytic leukemia cll. Efficacy of bendamustine and rituximab as first salvage treatment in chronic lymphocytic leukemia and indirect comparison with ibrutinib. Bendamustine demonstrated clinical activity in pretreated hematological malignancies due to its unique mechanism of action distinct from standard alkylating agents. Bendamustine for patients with indolent b cell lymphoproliferative. In the german chronic lymphocytic leukemia study group, it was demonstrated that 90. Chronic lymphocytic leukemia cll bendeka bendamustine hydrochloride injection is indicated for the treatment of patients with chronic lymphocytic leukemia. Chronic lymphocytic leukemia cll, the most common form of leukemia in europe and. Bendamustine and its role in the treatment of unfit. Rituximab plus bendamustine or chlorambucil for chronic.
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