scholarly journals DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma

2019 ◽  
Vol 37 (11) ◽  
pp. 912-922 ◽  
Author(s):  
Ian W. Flinn ◽  
Carole B. Miller ◽  
Kirit M. Ardeshna ◽  
Scott Tetreault ◽  
Sarit E. Assouline ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Oral Treatment ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Open Label ◽  
Dual Inhibitor ◽  
Non Hodgkin Lymphoma ◽  
Phosphoinositide 3 Kinase

PURPOSE Indolent non-Hodgkin lymphoma (iNHL) remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies. Duvelisib was approved by the Food and Drug Administration for relapsed or refractory (RR) chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL) and RR follicular lymphoma (FL) after two or more prior systemic therapies. On the basis of the activity of duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, in RR iNHL in a phase I study, the safety and efficacy of duvelisib monotherapy was evaluated in iNHL refractory to rituximab and either chemotherapy or radioimmunotherapy. PATIENTS AND METHODS Eligible patients had measurable iNHL (FL, SLL, or marginal zone B-cell lymphoma) double refractory to rituximab (monotherapy or in combination) and to either chemotherapy or radioimmunotherapy. All were treated with duvelisib 25 mg orally twice daily in 28-day cycles until progression, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) using the revised International Working Group criteria for malignant lymphoma. RESULTS This open-label, global phase II trial enrolled 129 patients (median age, 65 years; median of three prior lines of therapy) with an ORR of 47.3% (SLL, 67.9%; FL, 42.2%; MZL, 38.9%). The estimated median duration of response was 10 months, and the estimated median progression-free survival was 9.5 months. The most frequent any-grade treatment-emergent adverse events (TEAEs) were diarrhea (48.8%), nausea (29.5%), neutropenia (28.7%), fatigue (27.9%), and cough (27.1%). Among the 88.4% of patients with at least one grade 3 or greater TEAE, the most common TEAEs were neutropenia (24.8%), diarrhea (14.7%), anemia (14.7%), and thrombocytopenia (11.6%). CONCLUSION In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory iNHL, consistent with previous observations. Duvelisib may provide a new oral treatment option for this patient population of which many are elderly and in need of additional therapies.

scholarly journals Integrated safety analysis of umbralisib, a dual PI3Kδ/CK1ε inhibitor, in relapsed/refractory lymphoid malignancies

2021 ◽  
Author(s):  
Matthew S. Davids ◽  
Owen A. O'Connor ◽  
Wojciech Jurczak ◽  
Felipe Samaniego ◽  
Timothy S. Fenske ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Phase 1 ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Tolerability Profile ◽  
Open Label ◽  
Dual Inhibitor ◽  
Lymphoid Malignancies ◽  
Non Hodgkin Lymphoma ◽  
Phosphoinositide 3 Kinase

Phosphoinositide 3-kinase-delta (PI3Kδ) inhibitors are active in lymphoid malignancies, though associated toxicities can limit their use. Umbralisib is a dual inhibitor of PI3Kδ and casein kinase-1ε (CK1ε). This study analyzed integrated comprehensive toxicity data from 4 open-label, phase 1 and 2 studies that included 371 adult patients (median age, 67 years) with relapsed/refractory non-Hodgkin lymphoma (follicular lymphoma [n = 147]; marginal zone lymphoma [n = 82]; diffuse large B-cell lymphoma/mantle cell lymphoma [n = 74]; chronic lymphocytic leukemia [n = 43]; and other [n = 25]) who were treated with recommended phase 2 dose of umbralisib 800 mg or higher once daily. At data cutoff, median duration of umbralisib treatment was 5.9 months (range, 0.1-75.1), and 107 patients (28.8%) received umbralisib for ≥12 months. Any-grade treatment-emergent adverse events (TEAEs) occurred in 366/371 patients (98.7%), with the most frequent being diarrhea (52.3%), nausea (41.5%), and fatigue (31.8%). Grade ≥3 TEAEs occurred in 189/371 of patients (50.9%), including neutropenia (11.3%), diarrhea (7.3%), and increased aminotransferases (5.7%). Treatment-emergent serious AEs occurred in 95/371 patients (25.6%). AEs of special interest were limited and included pneumonia (29/371 [7.8%]), noninfectious colitis (9/371 [2.4%]), and pneumonitis (4/371 [1.1%]). AEs led to discontinuation of umbralisib in 51 patients (13.7%). Four patients (1.1%) died due to AEs, none of which were deemed related to umbralisib. No cumulative toxicities were reported. The favorable long-term tolerability profile and low rates of immune-mediated toxicities support the potential use of umbralisib for the benefit of a broad population of patients with lymphoid malignancies.

scholarly journals Deep Learning for the Classification of Non-Hodgkin Lymphoma on Histopathological Images

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2419
Author(s):  
Georg Steinbuss ◽  
Mark Kriegsmann ◽  
Christiane Zgorzelski ◽  
Alexander Brobeil ◽  
Benjamin Goeppert ◽  
...  
Keyword(s):  
Deep Learning ◽  
Hodgkin Lymphoma ◽  
Expert Knowledge ◽  
B Cell Lymphoma ◽  
High Accuracy ◽  
Lymphocytic Leukemia ◽  
Non Hodgkin Lymphoma ◽  
Image Patches ◽  
Histopathological Images

The diagnosis and the subtyping of non-Hodgkin lymphoma (NHL) are challenging and require expert knowledge, great experience, thorough morphological analysis, and often additional expensive immunohistological and molecular methods. As these requirements are not always available, supplemental methods supporting morphological-based decision making and potentially entity subtyping are required. Deep learning methods have been shown to classify histopathological images with high accuracy, but data on NHL subtyping are limited. After annotation of histopathological whole-slide images and image patch extraction, we trained and optimized an EfficientNet convolutional neuronal network algorithm on 84,139 image patches from 629 patients and evaluated its potential to classify tumor-free reference lymph nodes, nodal small lymphocytic lymphoma/chronic lymphocytic leukemia, and nodal diffuse large B-cell lymphoma. The optimized algorithm achieved an accuracy of 95.56% on an independent test set including 16,960 image patches from 125 patients after the application of quality controls. Automatic classification of NHL is possible with high accuracy using deep learning on histopathological images and routine diagnostic applications should be pursued.

Obinutuzumab (GA101) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Results From the Phase II GAUGUIN Study

2013 ◽  
Vol 31 (23) ◽  
pp. 2920-2926 ◽  
Author(s):  
Gilles A. Salles ◽  
Franck Morschhauser ◽  
Philippe Solal-Céligny ◽  
Catherine Thieblemont ◽  
Thierry Lamy ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Group Versus ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Non Hodgkin Lymphoma ◽  
Flat Dose ◽  
End Of Treatment ◽  
Grade 3 ◽  
Anti Cd20

Purpose The phase II part of the phase I/II GAUGUIN study evaluated the efficacy and safety of two different doses of obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, in patients with relapsed/refractory indolent non-Hodgkin lymphoma. Patients and Methods Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) as a flat dose of 400 mg on days 1 and 8 of cycle 1 and also on day 1 of cycles 2 to 8 (400/400 mg) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8 (1,600/800 mg). Results Forty patients were enrolled, including 34 with follicular lymphoma; 38 of 40 patients had previously received rituximab and 22 of 40 were rituximab refractory. The overall response rate at the end of treatment was 55% (95% CI, 32% to 76%) in the 1,600/800-mg group (9% complete responders) and 17% (95% CI, 4% to 41%) in the 400/400-mg group (no complete responders). Five of 10 rituximab-refractory patients had an end-of-treatment response in the 1,600/800-mg group versus one of 12 in the 400/400-mg group. Median progression-free survival was 11.9 months in the 1,600/800-mg group (range, 1.8 to 33.9+ months) and 6.0 months in the 400/400-mg group (range, 1.0 to 33.9+ months). The most common adverse events were infusion-related reactions (IRRs) seen in 73% of patients, but only two patients had grade 3 to 4 IRRs (both in the 1,600/800-mg group). No IRRs were considered serious, and no patients withdrew for IRRs. Conclusion The 1,600/800-mg dose schedule of obinutuzumab (GA101) has encouraging activity with an acceptable safety profile in relapsed/refractory indolent non-Hodgkin lymphoma.

A Phase II Clinical Study of Rituximab and High-Dose Biweekly THP-COP (Pirarubicin, Cyclophosphamide, Vincristine and Predonisolone) with G-CSF for Non-Hodgkin Lymphoma: Results of a Multicentric Study of NMLSG (Niigata Malignant Lymphoma Study Group).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4734-4734
Author(s):  
Jun Takizawa ◽  
Sadao Aoki ◽  
Kazue Takai ◽  
Tohri Kurasaki ◽  
Keiichiro Honma ◽  
...  
Keyword(s):  
Clinical Study ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Histological Subtypes ◽  
Non Hodgkin Lymphoma

Abstract Introduction CHOP chemotherapy has been accepted as the standard treatment for patients with non-Hodgkin lymphoma (NHL), but in some histological or clinical subtypes the results are not satisfactory. We have shown the efficacy and safety of high-dose biweekly THP-COP with G-CSF support (HDBW-TCOP(G)) for NHL. In this regimen, we choose pirarubicin in stead of doxorubicin because it was proven high efficacy against NHL and the lower toxicity than doxorubicin. Recently, the combination of rituximab and standard CHOP has been shown to have a synergistic effect for NHL. We performed a phase II multicentric clinical study to assessed the feasibility and toxicity of the combination chemotherapy of rituximab and HDBW-TCOP(G) (HDBW-R-TCOP(G)) compared with those of HDBW-TCOP(G). Patients and methods Between August 1998 and December 2004, Forty-one Japanese patients with previously untreated NHL from whom informed consent was obtained were included in this study. Median age was 45 (range 19–63) years. There were 19 males and 22 females. According to WHO-classification diagnoses, histological subtypes included follicular lymphoma (FL) 15(37%); nodal marginal zone B-cell lymphoma (NMZBCL) 2(5%); mantle cell lymphoma (MCL) 3(7%); anaplastic large cell lymphoma (ALCL) 1(2%), diffuse large B-cell lymphoma (DLBCL) 18(44%); peripheral T-cell lymphoma (PTCL) 1(2%), angioimmunoblastic T-cell lymphoma (AILT) 1(2%). Of 41 patients, one patient was stage 1, stage 2, 11 stage 3 and 16 stage 4. International prognostic index (IPI) included L 6; LI 22; HI 7; H 6. HDBW-TCOP(G) consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 orally from day 1 to 5; lenograstim 2.0 μg/kg/day from day 3. Fifteen patients who enrolled after rituximab was approved in Japan received therapy combined HDBW-TCOP(G) with rituximab 375mg/ m2 on day -2 (HDBW-R-TCOP(G)). Six cycles were administered at intervals of two weeks. Results Of the 41 patients treated, 32 (78.0%) achieved a complete remission (CR) and nine (22.0%) achieved a partial remission (PR), for an overall response rate of 100%. After median follow-up of 36 months (range 2.9– 81.8), progression free survival (PFS) and overall survival (OS) were 68.2% and 97.5%, respectively. PFS was 90.9% for HDBW-R-TCOP(G), and 69.5% for HDBW-TCOP(G), but no significant differences was found among two regimen. There was no significant difference in the PFS and OS between aggressive and indolent histological subtypes. 76% of patients developed Grade4 leukopenia (according to NCI criteria) but no patients experienced febrile neutropenia. 15% of patients developed G4 anemia and 17% of patients G4 thrombocytopenia. Other adverse effects were minimal. Conclusion Both HDBW-TCOP(G) and HDBW-R-TCOP(G) are feasible for NHL with acceptable toxicity. The excellent result suggests they are effective for aggressive NHL patients with poor prognostic factors and advanced stage indolent NHL.

Results of a Phase II Study of Lenalidomide in Combination with Rituximab for the Treatment of Indolent Non Follicular Non Hodgkin Lymphoma (NHL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1645-1645
Author(s):  
Stefano Sacchi ◽  
Samantha Pozzi ◽  
Marina Cesaretti ◽  
Luigi Marcheselli ◽  
Eliana Valentina Liardo ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Conflicts Of Interest ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
Open Label ◽  
Free Survival ◽  
Small Series

Abstract Abstract 1645 Background: Indolent non follicular B-Cell Lymphomas (INFL) are an eterogenous group of lymphomas and include small lymphocityic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL). Relapsed INFLs in advanced stage have a relatively poor prognosis, with low complete response to conventional chemotherapy and short survival. Lenalidomide (R®) is an immunomodulatory drug with effects on the innate immune system that may enhance antibody-dependent cell mediated cytotoxicity as well as the development of specific anti-tumor immune responses. These immunologic effects may synergize with the action of rituximab (R). To test the efficacy of R® combined with R (R2), we have conducted a multi center, open label phase II clinical trial in patients (pts) with relapsed INFL. Methods: Eligible pts must have indolent non follicular B-cell lymphoma relapsed after at least 2 but less than 4 prior lines of R-containing immuno-chemotherapy with measurable disease. Patients received oral R® 20 mg once daily on days 1–21. R is administered at a dose of 375 mg/m2 at day 14 of every course. Treatment is repeated every 28 days for up to 6 courses. The primary objectives of the study were to evaluate the antitumor activity of oral R® when given in combination with R and to assess the safety of R2 evaluated by standard criteria (CTC-NCI 3.0). The secondary objectives were progression free survival (PFS), event free survival (EFS) and duration of remission (DR). Results: From July 2010 and June 2012, 39 patients were enrolled: 19 had SLL, 11 had LPL, 4 splenic MZL, 3 extranodal MZL and a 2 nodal MZL. Median age was 68 years (51–76) and 58% were male. LDH value was increased in 17% of pts and β-2-microglobulin in 87%; 41% of pts had Hb<12 g/dL and 62% were bone marrow positive. At time of current analysis treatment and response data were available in 27 pts. Overall treatment was completed in 18 pts (67%); in 9 cases treatment was interrupted prematurely primarily due to hematological toxicity (n=5) and due to disease progression (n=4). Of the 27 pts, 5 achieved a complete remission and 9 a partial remission with an ORR of 52%. In general, the regimen R2 was relatively well-tolerated. Grade 3–4 hematological events included neutropenia occurring in 50% of pts, infection in 7% and piastrinopenia in 3%. Growth factors were administered in 60% of pts. The median dose intensity was 0.94 for R and 0.92 for R®. With a median follow-up of 13 months (range 1–36), overall 9 pts had a lymphoma progression and 2 of them died. The 1-year overall survival and the 1-year PFS were 92% (IC95% 57–99%) and 78 months (IC95% 54–91%) respectively. Conclusions: In our trial follicular histology was an exclusion criteria and all pts were relapsed/refractory to immuno-chemotherapy rituximab-containing regimens. Thus the results observed with the chemo-free R2 scheme compare favorably with other previously reported results observed in relapsed indolent lymphoma treated with standard immuno-chenotherapy. Further the R2 combination was relatively well tolerated. In conclusion our results, although obtained in a small series of patient are encouraging and support further evaluation of R2 scheme in a larger cohort of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cytokine polymorphisms in Th1/Th2 pathway genes, body mass index, and risk of non-Hodgkin lymphoma

Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 585-590 ◽  
Author(s):  
Yingtai Chen ◽  
Tongzhang Zheng ◽  
Qing Lan ◽  
Francine Foss ◽  
Christopher Kim ◽  
...  
Keyword(s):  
Body Mass Index ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Body Mass ◽  
Significant Interaction ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Non Hodgkin Lymphoma ◽  
Increased Risk

Abstract We conducted a population-based, case-control study in Connecticut women to test the hypothesis that genetic variations in Th1 and Th2 cytokine genes modify the relationship between body mass index (BMI) and risk of non-Hodgkin lymphoma (NHL). Compared with those with BMI less than 25 kg/m2, women with BMI more than or equal to 25 kg/m2 had 50% to 90% increased risk of NHL among women who carried IFNGR2 (rs9808753) AA, IL5 (rs2069812) CT/TT, IL7R (rs1494555) AA, and TNF (rs1799724) CC genotypes, but no increased risk among women with IFNGR2 AG/GG, IL5 CC, IL7R AG/GG, and TNF CT/TT genotypes. A significant interaction with BMI was only observed for IFNGR2 (rs9808753 Pforinteraction = .034) and IL7R (rs1494555 Pforinteraction = .016) for NHL overall; IL7R (rs1494555 Pforinteraction = .016) and TNF (1799724 Pforinteraction = .031) for B-cell lymphoma; and IL5 (rs2069812 Pforinteraction = .034) for T-cell lymphoma. After stratification by common B-cell lymphoma subtypes, a significant interaction was observed for IFNGR2 (rs9808753 Pforinteraction = .006), IL13 (rs20541 Pforinteraction = .019), and IL7R (rs1494555 Pforinteraction = .012) for marginal zone B-cell lymphoma; IL7R (rs1494555 Pforinteraction = .017) for small lymphocytic lymphoma/chronic lymphocytic leukemia; and IL12A (rs568408 Pforinteraction = .013) and TNF (1799724 Pforinteraction = .04) for follicular lymphoma. The results suggest that common genetic variation in Th1/Th2 pathway genes may modify the association between BMI and NHL risk.

Serum nm23-H1 protein as a prognostic factor in aggressive non-Hodgkin lymphoma

Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1202-1210 ◽  
Author(s):  
Nozomi Niitsu ◽  
Junko Okabe-Kado ◽  
Masataka Okamoto ◽  
Toshiyuki Takagi ◽  
Takashi Yoshida ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Number Of Patients

Advances in chemotherapy have led to a favorable long-term prognosis in approximately 50% of patients with aggressive non-Hodgkin lymphoma (NHL). However, the remaining patients do not enjoy such prolonged survival after standard treatment. New prognostic factors are needed to define this poor-prognosis group and to plan an appropriate treatment strategy. It has been reported that serum nm23-H1 protein may be a new prognostic factor for aggressive NHL. In the present study involving multiple institutions and a large number of patients, the level of nm23-H1 protein was compared among different types of lymphoma; it was lowest for indolent lymphoma, followed by aggressive lymphoma and then highly aggressive lymphoma. In addition, patients with aggressive NHL and higher nm23-H1 levels had worse overall and progression-free survival rates than those with lower nm23-H1 levels. The nm23-H1 level was also compared between patients with diffuse large B-cell lymphoma and patients with peripheral T-cell lymphoma. The results suggest that the level of nm23-H1 could serve as a prognostic factor in both groups. Moreover, the prognosis of lymphoma patients could be ascertained even more precisely by combining soluble interleukin-2 receptor or soluble CD44 and nm23-H1 levels. A multivariate analysis confirmed that the nm23-H1 level is an independent and important prognostic factor in aggressive NHL. Therefore, it may provide useful information for clinicians to determine the appropriate therapy for each type of lymphoma.

scholarly journals Extended Use of Rituximab in Older Adults with Non-Hodgkin Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1279-1279
Author(s):  
Matthew J. Matasar ◽  
Coral L. Atoria ◽  
Elena B. Elkin ◽  
Chadi Nabhan
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Rural Areas ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
The United States ◽  
Non Hodgkin Lymphoma ◽  
To Receive

Abstract Background: The introduction of rituximab has improved outcomes in B-cell non-Hodgkin lymphoma (BCL) across all histologies. Extended use of rituximab, or maintenance rituximab, improves progression-free survival in follicular lymphoma (FL) patients who achieve a response to induction rituximab with or without chemotherapy, but there is no evidence of an overall survival benefit. There is currently little evidence to support extended use of rituximab in other histologic subgroups, and older patients in particular may be at risk of adverse events. Our objective was to characterize patterns and predictors of extended rituximab therapy in a population-based cohort of older BCL patients in the United States. Methods: In the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset,we identified patients 66 years and older diagnosed with BCL in 2000-2010. Histology was classified as diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), FL, mantle cell lymphoma (MCL), other indolent BCL, and BCL not otherwise specified (NOS). We identified Medicare claims for rituximab starting at any point following diagnosis. Extended rituximab therapy was defined as a duration of greater than 7 months with no gap in rituximab claims greater than 6 months. Demographic and clinical characteristics associated with extended rituximab were evaluated in multivariable logistic regression. Results: There were 24,232 BCL patients who received rituximab during the study period. The cohort was predominantly white (91%), half were men, 15% had a Charlson comorbidity score ≥2, and 12% were 85 years or older. DLBCL was the most common histology (44%), followed by FL (21%), other indolent BCL (17%), BCL-NOS (13%), MCL (6%), and BL (1%). Overall, most patients (85%) received rituximab for ≤7 months, but duration varied by histology (Table 1). More than a quarter of FL patients had extended therapy, including 7% who had rituximab for more than 24 months. Among patients with other histologies, receipt of extended therapy varied from 20% (other indolent BCL) to 8% (BL). Compared with FL patients and controlling for demographic and disease characteristics, patients with other histologies were less likely to receive extended rituximab therapy (p<0.0001). Adjusted odds ratios were 0.91 (95% CI 0.78-1.05) for MCL, 0.83 (0.75-0.91) for other indolent BCL, 0.67 (0.60-0.75) for BCL-NOS, 0.32 (0.29-0.36) for DLBCL, and 0.28 (0.15-0.53) for BL. However, 75% of patients who had extended rituximab, and 63% of those who had rituximab >24 months, were of non-FL histology. Controlling for histology and other characteristics, extended rituximab therapy was more likely among women (adjusted OR 1.09, 95% CI 1.01-1.18), and less likely among unmarried patients (0.92, 0.85-0.99) and those in rural areas (0.84, 0.75-0.94). There was significant regional variation (p<0.0001), with patients in the West (adjusted OR 0.86, 95% CI 0.79-0.95), and Midwest (0.75, 0.66-0.86) less likely to receive extended rituximab than those in the Northeast. There was no significant relationship between extended therapy and age, race, or comorbidity. Conclusions: While FL patients were more likely than others to receive extended rituximab, the majority of patients receiving extended rituximab had other diagnoses across the entire spectrum of B-cell lymphoma, for which extended rituximab is neither indicated nor supported by guidelines or prospective data. After controlling for histology, several demographic characteristics significantly influenced the duration of therapy. Extended use of rituximab – particularly in patients for whom it is not clearly indicated – may have important implications for clinical outcomes, toxicity, and costs. Table 1 Duration of rituximab use across B-cell lymphoma histologic subgroups Histology Duration of Rituximab N ≤7 mos >7-24 mos >24 mos DLBCL 10,567 91% 7% 2% FL 5,001 76% 17% 7% BL 127 92% 6% 2% MCL 1,339 79% 16% 5% Other indolent 4,095 80% 15% 5% BCL NOS 3,103 83% 13% 4% Total 24,232 80% 15% 5% Disclosures Matasar: Merck: Research Funding; GlaxoSmithKline: Research Funding; Genentech: Honoraria; Spectrum: Honoraria. Nabhan:Celgene: Honoraria, Research Funding.

scholarly journals An open-label expanded-access trial of bendamustine in patients with rituximab-refractory indolent non-Hodgkin lymphoma or previously untreated chronic lymphocytic leukemia: BEND-ACT

2015 ◽  
Vol 22 (4) ◽  
pp. 260 ◽  
Author(s):  
C.T. Kouroukis ◽  
M. Crump ◽  
D. MacDonald ◽  
J.F. Larouche ◽  
D.A. Stewart ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hodgkin Lymphoma ◽  
Treatment Cycle ◽  
Day Treatment ◽  
Intravenous Dose ◽  
Lymphocytic Leukemia ◽  
Open Label ◽  
Non Hodgkin Lymphoma ◽  
Post Marketing ◽  
Grade 3

BackgroundBendamustine is a bifunctional alkylating agent with unique properties that distinguish it from other agents in its class. Bendamustine is used as monotherapy or in combination with other agents to treat patients with non- hodgkin lymphoma (nhl) and chronic lymphocytic leukemia (cll). MethodsThe prospective interventional open-label bend-act trial evaluated bendamustine in patients with rituximab-refractory indolent nhl (inhl) and previously untreated cll. Study objectives were to assess the safety and tolerability of bendamustine monotherapy and to provide patients with access to bendamustine before Health Canada approval. The study aimed to enrol up to 100 patients. All patients with inhl received an intravenous dose of bendamustine 120 mg/m2 over 60 minutes on days 1 and 2 for up to eight 21- or 28-day treatment cycles. All patients with cll received an intravenous dose of bendamustine 100 mg/m2 over 30 minutes on days 1 and 2 for up to six 28-day treatment cycles.Results Of 90 patients treated on study (16 with cll and 74 with inhl), 35 completed the study (4 with cll and 31 with inhl). The most common treatment-emergent adverse events (teaes) were nausea (70%), fatigue (57%), vomiting (40%), and diarrhea (33%)—mostly grades 1 and 2. Ondansetron was the most common supportive medication used in the patients (63.5% of those with inhl and 68.8% of those with cll). Neutropenia (32%), anemia (23%), and thrombocytopenia (21%) were the most frequent hematologic teaes, with neutropenia being the most common grade 3 or 4 teae leading to dose modification. Dose delays occurred in 28 patients (31.3%) because of grade 3 or 4 teaes, with a higher incidence of dose delays being observed in inhl patients on the 21-day treatment cycle than in those on the 28-day treatment cycle (50.0% vs. 24.1%). During the study, 33 patients (36.7%) experienced at least 1 serious adverse event, and 4 deaths were reported (all in patients with inhl).ConclusionsThe type and frequency of the teaes reported accorded with observations in earlier clinical trials and post-marketing experiences, thus confirming the acceptable and manageable safety profile of bendamustine.

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