Therapeutic and palliative benefit from single-agent irinotecan in multiply treated and highly refractory cases of lymphoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19554-e19554
Author(s):  
D. D. Caces ◽  
J. Halaas ◽  
P. Hamlin ◽  
A. Noy ◽  
T. Kewalramani ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Adverse Reactions ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Bulky Disease ◽  
Non Hodgkin Lymphoma ◽  
Refractory Lymphoma

e19554 Background: Multiple reports corroborate a role for irinotecan in the treatment of lymphoma. This study describes the Memorial Sloan Kettering experience with single-agent irinotecan in the management of heavily pretreated and highly refractory cases of lymphoma. Methods: Adult patients with histologically diagnosed relapsed or refractory lymphoma treated with irinotecan between 1/2001 and 8/2008 were identified. Treatment responses were evaluated based on the Revised Response Criteria for Malignant Lymphoma. Adverse reactions were evaluated based on the NCI Common Terminology Criteria for Adverse Events. Results: 30 patients were identified, 27 (90%) of whom received irinotecan after 3 or more prior regimens. 4 patients had Hodgkin Lymphoma (HL) and 26 had Non-Hodgkin lymphoma (NHL): 17 DLBCL, 6 transformed follicular lymphoma, 1 mantle cell lymphoma, 1 T-cell lymphoma and 1 Burkitt's. 25 patients were evaluable for response. 5 achieved an objective response (overall response rate 20%); 2 achieved complete remission (CR) and 3 partial remissions (PR). 8 patients (32%) had stable disease and 12 (48%) progressed on treatment. The median duration of response was 2.8 months (2.6–3.2), the median progression-free survival was 1.3 months (0.36 to 7.67) and the median overall survival was 3.9 months (0.30–63.4). Of the total cohort, 11 (36.6%) attained a clinically demonstrable improvement in symptomatology; 3 had resolution of pain syndromes, 5 had a reduction in the size or quantity of palpable masses, 2 had diminished fluid retention and 1 had an overall improvement in functional status. Adverse events occurring in more than 20% of cases included diarrhea (80%), leukopenia (67%), fatigue (36.6%) and thrombocytopenia (26.7%). Less common reactions included fever, febrile neutropenia, neuropathy, nausea and vomiting. Conclusions: Irinotecan has utility even in multiply treated and highly refractory cases of lymphoma. It can mitigate symptoms resulting from bulky disease and shows potential as a palliative treatment option. Although ORR was only 20%, two CRs were achieved suggesting benefit in select patients. Strategies that limit adverse reactions may enhance the agent's effectiveness in refractory lymphoma. No significant financial relationships to disclose.

scholarly journals The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma

Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2807-2812 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Julie M. Vose ◽  
Jennifer L. Kelly ◽  
Faith Young ◽  
Steven H. Bernstein ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Objective Response ◽  
Synergistic Activity ◽  
Significant Activity ◽  
Serious Adverse Events ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell

AbstractGiven the significant activity and tolerability of bendamustine, rituximab, and bortezomib in patients with relapsed indolent and mantle cell non-Hodgkin lymphoma, and laboratory studies suggesting synergistic activity, we conducted a multicenter phase 2 study of the bendamustine/bortezomib/rituximab combination. Patients with relapsed or refractory indolent and mantle cell lymphoma with adequate organ function were treated with bendamustine 90 mg/m2 days 1 and 4; rituximab 375 mg/m2 day 1, and bortezomib 1.3 mg/m2 days 1, 4, 8, 11. Six 28-day cycles were planned. Thirty patients (7 with mantle cell lymphoma) were enrolled and treated. Eight patients experienced serious adverse events, including one event of grade 5 sepsis. Common nonhematologic adverse events were generally grade 1 or grade 2 and included nausea (50%), neuropathy (47%), fatigue (47%), constipation (40%), and fever (40%). Of 29 patients evaluable for efficacy, 24 (83%) achieved an objective response (including 15 with complete response). With median follow-up of 24 months, 2-year progression-free survival is 47% (95% confidence interval, 25%-69%). On the basis of these promising results, the US cooperative groups have initiated randomized trials to evaluate this regimen in follicular and mantle cell lymphoma. This trial was registered at www.clinicaltrials.gov as #NCT00547534.

Mediastinal Gray Zone Lymphoma with Features Intermediate between Classical Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma

2016 ◽  
Vol 136 (3) ◽  
pp. 186-190 ◽  
Author(s):  
Haa-Na Song ◽  
Seok Jin Kim ◽  
Young Hyeh Ko ◽  
Won Seog Kim
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Systemic Chemotherapy ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Gray Zone ◽  
Bulky Disease ◽  
Gray Zone Lymphoma ◽  
Frontline Therapy

Background: Mediastinal gray zone lymphoma (MGZL) shares clinical characteristics with primary mediastinal B-cell lymphoma (PMBCL) and nodular sclerosing Hodgkin lymphoma (NSHL). However, MGZL is extremely rare, and an appropriate treatment for it has not yet been established. Methods: We retrospectively analyzed 8 patients who were treated with systemic chemotherapy for MGZL between 2007 and 2014. Results: The patients with MGZL were predominantly young and male (median age 26 years), and 62.5% of patients had bulky disease. The overall response rate (ORR) and complete remission (CR) rate were both 75% (6/8) for all treated patients The median overall survival (OS) and progression-free survival (PFS) was 40.7 and 3.9 months, respectively. Most responders (4/6, 66.7%) were treated with R-CHOP (rituximab + cyclophosphamide, hydroxydaunorubicin, Oncovin and prednisolone) as the frontline therapy. The CR rate of patients who received R-CHOP and those who did not was 100% (4/4) and 50% (2/4), respectively. Particularly striking was the finding that the median PFS of patients who received R-CHOP frontline chemotherapy was 11.4 months, which was superior to the median PFS of patients who did not receive R-CHOP. Conclusions: Of the 8 patients with MGZL who were treated with systemic chemotherapy, superior treatment responses were observed in patients who received R-CHOP as the frontline therapy.

A phase II study of GW786034 (pazopanib) in patients with recurrent or metastatic invasive breast carcinoma: Results after completion of stage I: A trial of the Princess Margaret Hospital Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1133-1133 ◽  
Author(s):  
S. K. Taylor ◽  
S. Chia ◽  
S. Dent ◽  
M. Clemons ◽  
P. Grenci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Progressive Disease ◽  
Single Agent ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Grade 3

1133 Background: Pazopanib, an oral small molecule inhibitor of VEGFR, PDGFR, and KIT, has demonstrated activity in phase I, with a recommended phase II dose of 800 mg/d (Hurwitz H et al, J Clin Oncol. 2005;23[16 suppl]:3012.1). We evaluated the activity of single agent pazopanib in recurrent or metastatic breast cancer (MBC). Methods: In this 2-stage design, patients with recurrent or MBC received pazopanib 800 mg/d. The primary endpoint was objective response rate (ORR) of 20%. Response in 3 out of 18 patients was required to go to stage 2. Treatment was continued until progression. Results: 21 patients entered stage 1; 67% were ER positive and all were HER-2-negative. Prior lines of chemotherapy were 1 in 76% and 2 in 14%. Of the 19 evaluable patients, 2 patients remain on treatment. 14 (74%) stopped due to progressive disease, 2 (10%) due to adverse events, and 1 (5%) due to patient request. Best response was partial response (PR) in 1 (5%), stable disease (SD) in 11 (58%), and progressive disease in 7 (37%). Clinical benefit rate (CR, PR, or SD for ≥ 6 months) was 26%. Median time to progression (TTP) was 3.7 months (95% C.I. 1.7 months - not reached). 9 out of 18 patients (50%) with measurable target lesions had some decrease in target lesion size. Estimated progression-free survival at 3 months was 55%, and 28% at 6 months. Adverse events were grade 3/4 elevations in AST (14%) and ALT (10%), and grade 3 hypertension and neutropenia (14% each). Other common events were grade 1/2 lymphopenia, neutropenia, diarrhea, fatigue, skin hypopigmentation, hypertension, nausea, vomiting, anorexia, and headache. Conclusions: Pazopanib is well tolerated and demonstrates activity in pretreated breast cancer. While the target ORR of 20% has not been met, rates of SD and TTP are comparable to other active agents in this setting, and therefore pazopanib may be an interesting agent for future studies in breast cancer. [Table: see text]

Brentuximab vedotin for relapsed or refractory non-Hodgkin lymphoma: Preliminary results from a phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8070-8070
Author(s):  
Ranjana Advani ◽  
Yasuhiro Oki ◽  
Andrei R. Shustov ◽  
Laurie E. Grove ◽  
Nancy Bartlett
Keyword(s):  
Antitumor Activity ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Objective Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Brentuximab Vedotin ◽  
Non Hodgkin Lymphoma

8070 Background: Brentuximab vedotin is a CD30-directed antibody-drug conjugate approved for the treatment of Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL) after failure of other therapies. Based on the high objective response rate observed in patients with systemic ALCL, a type of non-Hodgkin lymphoma that is characterized by homogeneous CD30 expression, a study was initiated in other non-Hodgkin lymphomas that express the CD30 target. Methods: A phase 2 open-label single-arm study is underway in patients with relapsed or refractory CD30-positive non-Hodgkin lymphoma, excluding ALCL (NCT01421667). Brentuximab vedotin is administered IV at 1.8 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint is objective response rate assessed by the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Tumor specimens are assessed by central lab in order to characterize the relationship of CD30 expression with antitumor activity. Results: Ten patients (age range 28–83; 5 M, 5 F) have enrolled to date. Diagnoses include diffuse large B-cell lymphoma (DLBCL, n=2), EBV-positive DLBCL of the elderly (n=3), primary mediastinal B-cell lymphoma (n=2), peripheral T-cell lymphoma NOS (n=2), and angioimmunoblastic T-cell lymphoma (AITL). Patients had received 1–6 prior chemotherapy regimens; 3 patients had prior stem cell transplants. Of 6 patients who have completed the cycle 2 response assessment, 2 attained complete remission, 1 with DLBCL (90% CD30+) and 1 with AITL (8% CD30+), 1 had stable disease, and 3 had progressive disease. Treatment-related serious adverse events observed to date were rash, febrile neutropenia, and mastoiditis. Conclusions: Preliminary results suggest that brentuximab vedotin may have antitumor activity in patients with relapsed or refractory CD30-expressing non-Hodgkin lymphomas, in addition to the efficacy previously observed in systemic ALCL. Updated study results will be presented.

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.

Subcutaneous epcoritamab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma: Safety profile and antitumor activity.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7518-7518
Author(s):  
Michael Roost Clausen ◽  
Pieternella Lugtenburg ◽  
Martin Hutchings ◽  
Peter W. M. Johnson ◽  
Kim M. Linton ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Safety Profile ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Grade 3

7518 Background: Epcoritamab is a CD20xCD3 bispecific antibody that induces T-cell–mediated killing of CD20–positive malignant B-cells. We present updated data, including progression-free survival (PFS) from the dose escalation part of the first-in-human phase 1/2 study of epcoritamab in pts with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL; NCT03625037). Methods: Adults with R/R CD20+ B-NHL received flat-dose 1 mL SC epcoritamab (step-up dosing approach) in 28-day cycles (q1w: cycles 1–2; q2w: cycles 3–6; q4w thereafter) until disease progression or unacceptable toxicity. Step-up dosing and standard prophylaxis were used to mitigate severity of cytokine release syndrome (CRS). Results: At data cut off (1/31/2021), 68 pts with B-NHL were enrolled across histologies including diffuse large B-cell lymphoma (DLBCL; n = 46 [67.6%]; de novo and transformed), follicular lymphoma (FL; 12 [17.6%]), mantle cell lymphoma (MCL; 4 [5.9%]), and others (6 [8.8%]). Majority were heavily pretreated (median [range] prior lines: DLBCL, 3 [1–6]; FL, 4.5 [1–18]); including prior CAR-T (n = 6) and prior ASCT (n = 10). At median follow-up of 14.1 mo (DLBCL, 10.2 mo; FL, 15.2 mo), treatment was ongoing in 15 (22%) pts. Most common treatment-emergent adverse events (AEs) were pyrexia (69%), CRS (59%), and injection site reaction (47%). CRS events were all grade 1 or 2 and most occurred in cycle 1; neurotoxicity was limited (6%; grade 1: 3%; grade 3: 3%; all transient). One case of tumor lysis syndrome was observed (1.5%; grade 3); there were no cases of febrile neutropenia or treatment-related death. Overall response is shown for DLBCL ≥12 mg and ≥48 mg and FL ≥12 mg, corresponding to the minimal efficacy threshold (Table). Responses deepened over time (PR converted to CR: DLBCL, 6 pts; FL, 3 pts). Median time to response was 1.4 mo (DLBCL) and 1.9 mo (FL). Among DLBCL pts achieving CR with ≥6 mg (n = 11), none relapsed while on treatment. The median PFS for pts with DLBCL ≥12 mg (n = 22) was 9.1 mo (95% CI: 1.6, NE; median follow-up 9.3 mo) and for pts with DLBCL ≥48 mg (n = 11) median PFS was not reached (median follow-up 8.8 mo). Updated analyses will be presented. Conclusions: With longer follow-up, SC epcoritamab demonstrated substantial single-agent activity, inducing deep and durable clinically meaningful responses, with a consistent safety profile. Notably no severe (grade ≥3) CRS events, no febrile neutropenia, and limited neurotoxicity was observed. Clinical trial information: NCT03625037. [Table: see text]

Fludarabine, Aracytine and Rituximab Based Chemotherapy In Patients with Refractory and Relapsed Mantle Cell Non-Hodgkin Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4892-4892
Author(s):  
Tommasina Perrone ◽  
Francesco Gaudio ◽  
Annamaria Giordano ◽  
Paola Curci ◽  
Alessandro Spina ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Hodgkin Lymphoma ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Single Agent ◽  
High Dose ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell

Abstract Abstract 4892 Introduction Mantle cell lymphoma (MCL) is a distinct B cell non Hodgkin lymphoma characterized by CD 5 expression, t (11; 14)(q13; q32) translocation and over-expression of Cyclin D1, and frequently has an aggressive clinical course. There is no standard of care for the treatment of MCL. Current treatment approaches are non curative and pts median survival is 4–6 years. Various studies have reported promising results for a high dose Cytarabine-containing regimen in the treatment of MCL. Fludarabine has also been recognized as effective treatment in pts with MCL, either as a single agent or in combination with other drugs. The addition of Rituximab improves the response to the treatment. The aim of this study is to assess the efficacy and toxicity of a combination of Fludarabine, Aracytine and Rituximab treatment in refractory and relapsed MCL. Methods We retrospectively evaluated 20 pts with refractory or relapsed MCL treated in our institution between February 2007 and February 2010. Median age was 59 yrs (54-77 yrs), 14 pts (70%) were males, 18 pts (90 %) had stage IV, 16 pts (80%) had bone marrow involvement, 16 (80%) presented comorbidities. Eight pts (40%) were in first relapse, 12 (60%) in second relapse. Twelve pts (60%) had a “Mantle Cell Lymphoma International Prognostic Index” (MIPI) score ≥ 7. Therapy included: fludarabine 25 mg/m2/daily intravenously for 3 days, aracytine 500 mg/m2/daily for 3 days and Rituximab 375 mg/m2/daily for 1 day, Dexamethasone 8 mg daily for 3 days, every 28 days for 4 cycles. Results Eight pts (40%) achieved complete response (CR) and 4 pts (20%) a Partial Remission (PR) with an overall response rate (ORR) of 60%. Eight pts (40%) progressed and one of them died of active disease. After a median follow up of 17 months (range 8–36), OS is 70% and PFS is 55%. Toxicity was mainly hematological with grade >=3 neutropenia in 40 (50%) of the 80 cycles performed, grade >=2 anemia in 30 (37%) and grade 4 thrombocytopenia in 24 (30%). In 16 (20%) cycles pts required red blood cells transfusions, in 12 (15%) platelet transfusions. One episode of Herpes Zoster infection was observed. Conclusions This study suggests that the combination of Fludarabine, Aracytine and Rituximab appears to be an effective regimen with a promising response rate and manageable toxicity, for pretreated pts often affected by comorbidities and with poor prognosis. Further studies are needed to assess the efficacy of this combination therapy and to further test the role of this approach in MCL. Disclosures: No relevant conflicts of interest to declare.

Weekly Temsirolimus and Bortezomib For Relapsed Or Refractory B-Cell Non-Hodgkin Lymphoma: A Wisconsin Oncology Network Phase II Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3035-3035 ◽  
Author(s):  
Timothy S. Fenske ◽  
KyungMann Kim ◽  
Chong Zhang ◽  
John P. Farnen ◽  
Adedayo A. Onitilo ◽  
...  
Keyword(s):  
Partial Response ◽  
Adverse Events ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Mtor Inhibitors ◽  
Non Hodgkin Lymphoma ◽  
Grade 3

Abstract Background Proteosome inhibitors and mammalian target of rapamycin (mTOR) inhibitors are each known to have activity for various B-cell malignancies, and affect distinct cellular pathways. Preclinical data show synergy between bortezomib and various mTOR inhibitors, supporting this combination in non-Hodgkin lymphoma (NHL). We conducted a phase II trial of temsirolimus and bortezomib in relapsed and refractory B-cell NHL, using a weekly dosing scheme that was previously tested in multiple myeloma (Ghobrial et al, Lancet Oncology, 2011; 263-272). Methods Wisconsin Oncology Network study HO10407 is a single-arm phase II study of IV bortezomib and temsirolimus for patients with relapsed and refractory B-cell NHL. A 35 day cycle was employed with bortezomib given at 1.6 mg/m2 and temsirolimus given at 25 mg IV weekly on days 1, 8, 15, and 22. Initially temsirolimus was also given on day 29 but, due to a high rate of thrombocytopenia, after the first 14 patients were enrolled the protocol was amended and the day 29 temsirolimus dose was removed. Patients were enrolled from 10 sites within the Wisconsin Oncology Network. The primary endpoints were overall response rate (ORR) and progression-free survival (PFS). The secondary endpoints were to determine safety, tolerability, complete response (CR) rate, duration of response (DOR), and overall survival (OS). Results Forty patients were enrolled between February 2011 and May 2013; however one patient withdrew consent immediately after enrollment and was never treated. We are therefore reporting results for 39 patients. The median age was 68, with 72% male. NHL subtypes consisted of diffuse large B-cell lymphoma (DLBCL, n=17), follicular lymphoma (FL, n=10), mantle cell lymphoma (MCL, n=7), small lymphocytic lymphoma (SLL, n=3), and marginal zone lymphoma (MZL, n=2). Patients received a median of 4 prior therapies (range 1 to 11). Three patients were previously treated with bortezomib, one of whom was refractory to a prior bortezomib-containing regimen. As of July, 24, 2013, two patients remained on protocol therapy. The median number of cycles given was 3. Out of 39 patients, CR was achieved in 3 patients (7.7% (95% CI: 1.6% - 21%)), partial response (PR) in 9 patients (23% (95% CI: 11% - 39%)), and stable disease in 9 patients (23% (95% CI: 11% - 39%)). The ORR was therefore 12/39 (31% (95% CI: 17-48%)). Among responders, the DOR ranged from 1.7 to 13.8 months, with a median DOR of 8.5 months (95% CI: 2.9-11.5). The median PFS was 4.7 months (95% CI: 2.1-7.8). The ORR for DLBCL was 18% (3/17, with 2 CR), for FL was 50% (5/10, with no CR), and for MCL was 57% (4/7, with 1 CR). In one patient, protocol therapy led to a partial response which served as a bridge to allogeneic stem cell transplantation. Grade 3/4 adverse events were experienced by 69% of patients. The grade 3/4 adverse events that occurred in at least 10% of patients were anemia (13%), lymphopenia (15%), neutropenia (23%), thrombocytopenia (38%), and gastrointestinal toxicities (15%). Conclusions In this phase II study, the combination of temsirolimus and bortezomib demonstrated activity in a group of heavily pre-treated patients. In some patients dramatic responses were seen, including two DLBCL patients who achieved complete remission after having previously progressed following autologous hematopoietic cell transplantation. Toxicities were manageable and treatment was delivered on an outpatient basis. Further studies with this combination or other proteosome inhibitor + mTOR inhibitor combinations are warranted in specific subtypes of NHL. Disclosures: Fenske: Spectrum Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy. Off Label Use: Use of the combination of bortezomib and temsirolimus for relpased and refractory B-cell non-Hodgkin lymphoma. Ahuja:Bayer healthcare pharmaceuticals: Consultancy. Kahl:Millennium: Consultancy.

scholarly journals Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia

Blood ◽  
2010 ◽  
Vol 115 (13) ◽  
pp. 2578-2585 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Jeff Sharman ◽  
John Sweetenham ◽  
Patrick B. Johnston ◽  
Julie M. Vose ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Primary Tumors ◽  
Non Hodgkin Lymphoma

AbstractCertain malignant B cells rely on B-cell receptor (BCR)–mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095.

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