scholarly journals Bendamustine in the treatment of B-cell non-Hodgkin lymphoma

2018 ◽  
Vol 20 (4) ◽  
pp. 41-46
Author(s):  
L G Babicheva ◽  
I V Poddubnaya
Keyword(s):  
Clinical Data ◽  
Therapeutic Index ◽  
Daily Practice ◽  
Phase Iii ◽  
Cross Resistance ◽  
Skin Reactions ◽  
Non Hodgkin Lymphoma ◽  
Antiemetic Prophylaxis ◽  
Mantle Cell ◽  
Phase Iii Trials

Bendamustine is a uniquely structuredalkylating agent that lacks cross-resistance with other alkylators. This agent has a high degreeof activity against a variety of tumor cell lines.Based on clinical data from randomized phase III trials, bendamustine, with or without rituximab, hasbeen shown to be an appropriate option for first-line treatment or treatment of relapsed/refractory patients with indolent non-Hodgkin’s lymphoma or elderly patients with mantle cell lymphoma. Bendamustine treatment is associated with abetter therapeutic index and offers an improved overall quality of life compared to R-CHOP or R-CVP. It is now often used as achemotherapy backbone for combination with novel drugs including ibrutinib or idelalisib. This article provides a comprehensivesummaryof the clinical data along with practical adviceonhowto optimallymanagepatients with bendamustine therapy, includingdose recommendations, antiemetic prophylaxis, prevention of infusion and skin reactions, as well as prophylaxis of opportunisticinfections. This information might be helpful for clinicians using bendamustine in their daily practice.

scholarly journals NOVEL DRUGS IN FOLLICULAR LYMPHOMA

2016 ◽  
Vol 8 ◽  
pp. 2016061 ◽  
Author(s):  
Giuseppe Rossi ◽  
Antonella Anastasia
Keyword(s):  
Follicular Lymphoma ◽  
Treatment Strategies ◽  
Cell Receptor ◽  
Phase Iii ◽  
Non Hodgkin Lymphoma ◽  
Free Treatment ◽  
Phase Iii Trials ◽  
New Treatment ◽  
Anti Cd20 ◽  
Key Steps

Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of a chieving a definite cure, have prompted investigations into the possible role of more effective and less toxic strategies with innovative therapeutic agents.  Recently Casulo et al demonstrated that approximately 20% of patients with FL actually relapse within 2 years after achieving remission with R-CHOP and have a poor prognosis. It is conceivable that this particularly chemoresistant population would benefit from specifically targeting the biologic and genetic factors that likely contribute to their poor prognosis.Evolving strategies for difficult to treat FL patients have recently considered  immunomodulatory agents, new monoclonal antibodies as well as drugs targeting selective intracellular pathways. The importance of targeting the microenvironment together with the malignant FL cell has been particularly underscored. We review the most promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs (Lenalidomide), with mAbs directed against other surface antigens such as CD22 and CD23 (epratuzumab, lumiliximab), with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling such as PI3K inibithors(idelalisib, duvelisib). Another highly attractive approach is the application of the bi-specific T-cell engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens. Moreover, we highlight the potential of these therapies,  taking into account their toxicity. Of course we must wait for Phase III trials results to confirm the benefit of these new treatment strategies toward a new era of chemotherapy-free treatment for follicular lymphoma.

Lenalidomide in Combination with Dexamethasone Was More Effective Than Dexamethasone in Patients Who Have Received Prior Thalidomide for Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3553-3553 ◽  
Author(s):  
Michael Wang ◽  
Robert Knight ◽  
Melitios Dimopoulos ◽  
David Siegel ◽  
S. Vincent Rajkumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Remission Rate ◽  
Phase Iii ◽  
Cross Resistance ◽  
Time To Progression ◽  
Double Blind ◽  
Refractory Multiple Myeloma ◽  
Hazards Model ◽  
Phase Iii Trials ◽  
Beta 2 Microglobulin

Abstract Lenalidomide (Len), an analog of thalidomide (thal) is a novel, oral, immunomodulatory agent that is effective against multiple myeloma (MM). In 2 prospective, randomized, double-blind, placebo-controlled Phase III trials. Len with dexamethasone (Dex) induced a significantly higher overall response rate (OR) and complete remission rate (CR), as well as longer time-to-progression (TTP) in comparison with Dex alone. This prospective analysis assessed whether prior thalidomide exposure might induce subsequent resistance to Len/Dex. We evaluated 704 patients (pts) from both trials (MM009, MM010) who had relapsed or refractory multiple myeloma, had not been resistant to Dex and were randomized to receive either oral Len (25 mg daily for 3 weeks every 4 weeks) plus Dex (40 mg on days 1–4, 9–12, 17–20 every 4 weeks for 4 cycles) or placebo plus Dex. Two hundred seventy four pts (39%) received prior thal, while 430 (61%) had not. The prior thal exposed pts and thal-naive pts were similar in regard to age, Beta-2-microglobulin, hemoglobin, serum M protein, albumin and history of previous transplantation. The frequency of deep venous thrombosis and pulmonary embolism (DVT/PE) with prior thal exposure was higher at 14% with Len/Dex than 4% with Dex alone (p < 0.01). However, the frequency of DVT/PE with no prior thal exposure was similar at 8% with Len/Dex to 6% with Dex alone (p = 0.49). In the prior thal pts, severe neuropathy occurred in 4% with Len/Dex, not significantly different from the 1% with Dex alone (p=0.2). The pooled data from all 704 pts showed that pts treated with Len/Dex, compared with those treated with Dex alone, had superior median Time-To-Progression (TTP) (48 vs 20 weeks) and OR (60% vs 22%, p <0.001). Similarly, among the subgroups exposed or not exposed to thal, Len/Dex was superior to Dex alone in OR and TTP. For the 126 patients who received prior thal, the OR with Len/Dex was significantly less (43%) among 54 Pts resistant to thal than that observed for 72 Pts who had been sensitive to thal (63%, p < 0.05). Multivariate analysis using Cox proportion hazards model indicated that after controlling for treatment (Len/Dex vs Dex) and baseline disease characteristics, independent and significant predictors of shorter TTP included prior thal exposure, duration of myeloma and number of prior therapies. Len in combination with Dex was more effective than Dex in patients with relapsed or refractory multiple myeloma despite prior thal exposure. Results with Len/Dex were superior for those not exposed to thal, suggesting some, but not complete, cross resistance between Len and thal. Len/Dex vs Dex with or without Prior Thal Thal (N=274) No Thal (N=430) LD D p LD D p Intent-to-Treat (n) 126 148 227 203 TTP (med. weeks) 36.9 19.9 <.001 61.3 20.4 <.001 OR (%) 54.0 14.9 <.001 63.4 27.6 <.001 PR (%) 42.1 12.8 <.001 32.2 23.2 <.05 NCR (%) 4.0 0.7 <.001 13.2 2.0 <.001 CR (%) 7.9 1.4 <.01 18.1 2.5 <.001

Tolerability and activity of combinations of the PI3Kδ inhibitor idelalisib (GS-1101) with rituximab and/or bendamustine in patients with previously treated, indolent non-Hodgkin lymphoma (iNHL): Updated results from a phase I study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8500-8500 ◽  
Author(s):  
John Leonard ◽  
Nina D. Wagner-Johnston ◽  
Steven E. Coutre ◽  
Ian Flinn ◽  
Marshall T. Schreeder ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Phase I ◽  
Phase I Study ◽  
Phase Iii ◽  
Duration Of Treatment ◽  
Non Hodgkin Lymphoma ◽  
Highly Active ◽  
Study Results ◽  
Asco 2012 ◽  
Phase Iii Trials

8500 Background: PI3K-delta signaling is critical for activation, proliferation and survival of B cells, and is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that has shown considerable monotherapy activity in recurrent iNHL (Kahl, ICML 2011), as well as combination therapy (Fowler, ASCO 2012). Methods: This phase I study evaluated the activity of continuous (48 weeks) idelalisib (Id), 100/150 mg BID, in combination with rituximab (R) (375 mg/m2 weekly x 8 doses) (Id+R), with bendamustine (B) (90 mg/m2 x 2, for 6 cycles) (Id+B), or in combination with R (375 mg/m2 monthly x 6) and B (90 mg/m2 x 2), for 6 cycles (Id+BR). Investigators assessed response according to standard criteria (Cheson 2007). Patients who continued to benefit were able to enroll on an extension study. Results: Study enrolled 78 pts with relapsed/refractory iNHL, with 34 (44%) pts continuing on treatment in the ongoing extension protocol. The 3 cohorts included Id+R (N=30), Id+B (N=34), and Id+BR (N=14). Pts were 67% male, median age [range] of 62 [37E84] years, 41% with refractory disease, 88% stage III/IV, and 36% of FL with high FLIPI scores. The median [range] number of prior therapies was 3 [1E10]. The median [range] duration of treatment was 10.6 [0.5-29.2] months. Overall response rate (ORR) was 63/78 (81%), with 22/78 (28%) CR. The ORR/CR for Id+R was 77%/20%, Id+B was 85%/29%, and Id+BR was 79%/43%. At 20 months, the PFS was 66%. For responders, 73% were progression-free at 20 months. Most common adverse events included (total%/≥G3%) pyrexia (56/4), fatigue (45/4), nausea (41/0), rash (40/8), cough (37/0), diarrhea (36/8), chills (18/0), URI (18/1), and pneumonia (17/15). Lab abnormalities included (total%/≥G3%) ALT/AST elevations (56/17). Conclusions: Idelalisib-based combination therapy is highly active and well tolerated in patients with relapsed/refractory iNHL. These data support further clinical development. Phase III trials evaluating the efficacy of idelalisib in combination with R, or BR in iNHL are ongoing (NCT01732913, NCT01732926). Clinical trial information: NCT01732913, NCT01732929.

Tolerability and efficacy of first-line bevacizumab (B) plus chemotherapy (CT) in elderly patients with advanced breast cancer (aBC): Subpopulation analysis of the MO19391 study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1032-1032
Author(s):  
L. Biganzoli ◽  
H. Cortes-Funes ◽  
C. Thomssen ◽  
K. I. Pritchard ◽  
J. Pierga ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Therapeutic Index ◽  
Phase Iii ◽  
Limited Data ◽  
Inclusion Criteria ◽  
Safety And Efficacy ◽  
Phase Iii Trials ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
The Impact

1032 Background: Limited data exist on the efficacy and safety of biological agents in elderly patients with aBC. This is essentially due to the lack of studies specifically targeting the older population and to strict inclusion criteria in clinical trials. B significantly improved the efficacy of 1st-line taxane therapy in two large, randomized phase III trials, E2100 and AVADO. Methods: In study MO19391, 1st-line B 10mg/kg q2w or 15mg/kg q3w + CT (primarily but not exclusively taxane monotherapy) was investigated in a broader, large aBC patient population, with the aim of understanding safety and efficacy in patients seen in routine clinical practice, including elderly patients. Results: A total of 2,027 patients were enrolled. Median age was 54 years (range 21–93); 359 patients (17.7%) were aged ≥65 years and 169 (8.3%) were ≥70 years. Baseline characteristics and safety and efficacy results according to age are shown below (Table). Conclusions: Treatment with B is feasible in elderly patients. Hypertension was the only grade 3 B-related side effect reported more frequently in the older than in the younger cohort. Efficacy was similar in the two subgroups. These results suggest that the combination of B with 1st-line CT shows a similar therapeutic index regardless of age. Data on compliance according to the different CT regimens, the impact of comorbidities on safety, and analyses in the subgroup of patients ≥70 years will be presented. [Table: see text] [Table: see text]

scholarly journals Anthracyclines Strike Back: Rediscovering Non-Pegylated Liposomal Doxorubicin in Current Therapeutic Scenarios of Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4421
Author(s):  
Francesco Schettini ◽  
Mario Giuliano ◽  
Matteo Lambertini ◽  
Rupert Bartsch ◽  
David James Pinato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Therapeutic Index ◽  
Phase Iii ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Therapeutic Algorithms ◽  
Phase Iii Trials ◽  
Standard Doxorubicin

Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non-pegylated liposomal doxorubicin (NPLD) has been developed to optimize the toxicity profile induced by anthracyclines, while maintaining its unquestionable therapeutic index, thanks to its delivering characteristics that increase its diffusion in tumor tissues and reduce it in normal tissues. This feature allows NPLD to be safely administered beyond the standard doxorubicin maximum cumulative dose of 450–480 mg/m2. Following three pivotal first-line phase III trials in HER2-negative metastatic BC (MBC), this drug was finally approved in combination with cyclophosphamide in this specific setting. Given the increasing complexity of the therapeutic scenario of HER2-negative MBC, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms.

Secondary efficacy subanalysis by histology from the phase III BRIGHT study: First-line bendamustine-rituximab (BR) compared with standard R-CHOP/R-CVP for patients with advanced indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8537-8537 ◽  
Author(s):  
Ian Flinn ◽  
Richard H. C. Van Der Jagt ◽  
Brad S. Kahl ◽  
Peter Wood ◽  
Tim E. Hawkins ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Complete Response ◽  
Phase Iii ◽  
Non Hodgkin Lymphoma ◽  
Small Subgroup ◽  
Mantle Cell ◽  
Efficacy Measure ◽  
Treatment Naïve ◽  
Independent Review ◽  
Efficacy Assessment

8537 Background: BR was previously reported to be statistically noninferior to R-CVP/R-CHOP for complete response rate in the treatment of patients with indolent NHL or MCL. Evaluation of time-to-event outcomes is immature. This subanalysis reports response by histology. Methods: Indolent NHL or MCL was histologically confirmed <6 months before study enrollment in patients who were therapy-naïve. Patients were stratified according to predetermined standard treatment (R-CHOP or RECVP) and lymphoma type, then assigned to receive BR (28-day cycles: bendamustine 90 mg/m2 on days 1 and 2, rituximab 375 mg/m2on day 1) or standard treatment (21-day cycles at standard doses) for 6-8 cycles. Responses were assessed by a blinded independent review committee. The primary efficacy measure was noninferiority of BR complete response (CR) rate for evaluable patients with ≥1 postbaseline efficacy assessment. If the noninferiority threshold was met, superiority was assessed. Secondary measures included tolerability. Results: Of 447 patients enrolled in the study, 213 receiving BR and 206 receiving R-CHOP/R-CVP were evaluable with postbaseline data (Table). BR achieved a statistically noninferior CR rate compared with R-CHOP/R-CVP in patients with indolent NHL and MCL. Conclusions: In patients with treatment-naïve indolent NHL and MCL, BR achieved the primary endpoint of noninferior CR rate. Most CR rates were numerically, but not significantly, higher with BR. Small subgroup results should be interpreted with caution. Support: Teva BPP R&D, Inc. Clinical trial information: NCT00877006. [Table: see text]

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