A Comparative Study of Early Response Rate between Patient Given Standard Chemotherapy with Patient Given Combination Targeted Therapy in Non-Hodgkin Lymphoma Patients

Abstract For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20–based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the “cold” anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

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Early Response Observed in Pediatric Patients with Refractory/Relapsed B-Cell Non-Hodgkin Lymphoma Treated with Sequential Chimeric Antigen Receptor T Cells

Blood ◽

10.1182/blood-2019-125753 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1945-1945 ◽

Cited By ~ 3

Author(s):

Wenqun Zhang ◽

Bo Hu ◽

Ling Jing ◽

Jing Yang ◽

Shan Wang ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

Pediatric Patients ◽

Response Rate ◽

Car T Cell ◽

Non Hodgkin Lymphoma ◽

Car T ◽

To Receive

Background:Outcomes for pediatric patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) are poor despite use of high-intensity chemotherapy. CAR-T has shown efficacy in treating refractory/relapsed leukemia in pediatric patients and non-Hodgkin lymphoma in adult patients. Objectives:To assess the safety and efficacy of sequential CAR-T in the treatment of refractory/ relapsed B-NHL in pediatric patients. Design/Methods:In our ongoing clinical trial (ChiCTR1800014457), we enrolled and treated 17 pediatric patients with refractory/relapsed B-NHL. Following leukapheresis, T cells were activated with CD3 and CD28 antibodies for 24h, then transduced with lentivirus encoding anti-CD19-CD3zeta-4-1BB CAR and cultured for 5-6 days in serum-free media containing IL2, IL7, IL15, IL21. Meanwhile, all patients briefly received lympho-depleting chemotherapies consisting of fludarabine (30 mg/m2/day) and cyclophosphamide (250 mg/m2/day) on days −5, −4 and −3 according to tumor burden and patient state. On day 0, all patients received a single-dose infusion of CAR-T cells. CAR-T cell dose ranged from 0.5 to 3 million/kg. CAR-T cell numbers and cytokines were measured weekly. Tumor responses were evaluated at day 30 and day 60 post infusion and every two months thereafter. Adverse events were graded according to CTCAEv4 except cytokine release syndrome (CRS) was graded according to Lee et al. Results:Treated patients had relapsed/refractory Burkitt lymphoma (BL) (13/17), diffuse large B cell lymphoma (DLBCL) (2/17), B-lymphoblastic lymphoma (B-LBL) (2/17), and ranged from 4.5-18.0 years old. By St Jude's staging, 9 cases (46.7%) were in stage III, 8 cases (53.3%) were in stage IV. There were 3 cases with CNS involvement (17.6%) and 7 cases with bone marrow involvement (41.2%). They all failed at prior treatment including an average of 8.9 (6-15) courses of chemotherapy. They were then treated with sequential CAR-T cell therapy. A total of 26 courses of CAR-T cell infusion were administered. The overall complete response rate (CRR) was 41.7% (7/17) when first course of CAR-T therapy was conducted, which were all CD19 targeted. Among the 10 patients who did not achieve CR, 2 patients achieved PR with ongoing response, 1 patient died of severe CRS and progression at day 6 and another patient refused to continue the following therapy when tumor progressed at day 99, and he died 1 week later, the other 6 continued to receive second course of CAR-T therapy targeting CD20 or CD22, and 3 of them achieved CR. Thus the overall CRR increased to 58.8% (10/17). The 3 patients, who still did not achieve CR, continued to receive third course of CAR-T therapy targeting CD20 or CD22. Two of them finally achieved CR and the other failed to get CR and is now retreated with chemotherapy and oral Olaparib and Venclexta. Thus, with a median follow-up of 6.2 months (1-18 months), the overall response rate of sequential CAR-T therapy was 94.1% (16/17) and the overall CRR was 70.6% (12/17). Toxicity information through day 30 revealed the occurrence of mild CRS in 8 subjects (47.1%, grade I n=8, grade II n=0), severe CRS in 9 subjects (52.9%, grade III n=8, grade IV n=1). Neurotoxicity was observed in 7 cases (41.2%, seizure in 3 cases, tremor in 4 cases, headache in 1 cases). One case who died rapidly at day 6 of therapy suffered severe CRS (high fever, Capillary leak syndrome, severe pleural effusion, respiratory failure, shock, cardiopulmonary arrest) and neurotoxicity besides disease progression. Other patients with severe CRS and neurotoxicity recovered fully after glucocorticoid use and symptomatic treatment including anti-epilepsy, fluid, dehydrating agent. No case used tocilizumab. Response assessments were performed at day 15, 30, 45, 60. Updated enrollment, toxicity and response assessments will be presented. Conclusion: CD19/CD20/CD22-CAR-T therapy showed promising efficacy for pediatric patients with r/r B-NHL and the toxicities are tolerable with proper symptomatic and supportive treatment. Sequential CAR-T therapy can improve the efficacy compared with a single course of CAR-T infusion. Disclosures No relevant conflicts of interest to declare.

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The Comparison of Efficacy Between MVEP Chemotherapy and R- MVEP Chemotherapy in Patients of Refractory and Relapsed Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood.v112.11.4963.4963 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4963-4963

Author(s):

Meihua Qian ◽

Wensong Wang

Keyword(s):

Complete Remission ◽

Lymph Nodes ◽

Hodgkin Lymphoma ◽

Overall Response Rate ◽

Response Rate ◽

Treatment Method ◽

Old Patients ◽

Overall Response ◽

Non Hodgkin Lymphoma ◽

Better Than

Abstract To observe the efficacy and toxicity of two groups of MVEP Chemotherapy and R-MVEP Chemotherapy in patients of Refractory and relapsed Non-Hodgkin Lymphoma. 19 cases patients of refractory and relapsed Non-Hodgkin Lymphoma, 9 females and 10 male, between 17–75 years of age (mean age 45.5 years), 2 cases IIa,, 11caseIII (9IIIa and 2IIIb), 6 cases IV(4 IVa and 2 IVb).Most of patients showed the enlargement of superficial and/or deep multiple lymph nodes, 4 cases had fever and the enlargement of spleen and/or liver, 2 cases with hydrothorax and ascites, 3 cases with bone marrow infiltration and 1 case with multiple lumps in liver, other 1 case with autoimmune hemolytic anemia (AIHA)and one with pericardial effusion. All patients were treated with chemotherapy included COP (or COPP), CHOP, BCAOP (or BECAOP), etc. and 2 patients of them Had been treated by radiotherapy before they were treated by MVEP Chemotherapy and R- MVEP Chemotherapy. In this experiment, A group of 13 patients were treated by MVEP Chemotherapy and G-CSF ( MVEP, Mitoxantrone 8mg/m2/d1, VP16 O.1/d1 ‘d5 (or,Wumon 0.1/d1 ‘d3),Vinorelbinum 20mg/m2/d1,Prednison 60mg/d1 ‘d7,or DXM 8mg/m2d1 ‘d7), other group of 6 patients were therapied by Rituximab plus MEVP Chemotherapy and G-CSF,( R-MVEP, Rituximab 375 mg/m2/d1,Mitoxantrone 8mg/m2/d3, Wumon 0.1/d3 ‘d5 (or VP16 O.1/d3 ‘d7),Vinorelbinum 20mg/m2/d3,Prednison 60mg/d3 ‘d9 (or DXM 8mg/m2d3 ‘d9 ), G-CSF 100 ‘300/d were injected when the number of WBC was <2.0×109/L after chemotherapy. Each cycle was 28–35 days and assessment was given after 2 cycles. The result is, The overall response rate and complete remission was 61.5 % and 38.4% respectively in treat group of MVEP, The overall response rate and complete remission was 83.3% and 50 % respectively in group of R- MVEP. One of patients of NHL with AIHA after a treating cycle achieved complete remission(all of enlarged lymph nodes disappeared and Hemoglobin return to normal).The main toxicity was mylosuppression, the minimum of WBC after chemotherapy reached 0.5 ‘1.4*109/L, few patients vomited during chemotherapy, All toxicity was no different in two groups of MVEP and R-MVEP BOur study result indicates: MEVP Chemotherapy and G-CSF is an Effective, safety and economy on patients of Refractory and relapsed Non-Hodgkin Lymphoma, but Rituximab in Combination with MEVP Chemotherapy and G-CSF is could improve the efficacy of MEVP Chemotherapy only in patients of Refractory and relapsed Non-Hodgkin Lymphoma. The efficacy of Rituximab in Combination with MEVP Chemotherapy is much better than that of MVEP Chemotherapy only on patients of Refractory and relapsed Non-Hodgkin Lymphoma, the treatment method of R-MVEP are suitable for old patients.

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Association of Hodgkin Lymphoma and Non-Hodgkin Lymphoma In the Same Patient. Clinicopathologic Characteristics and Outcome In a Series of 20 Cases

Blood ◽

10.1182/blood.v116.21.3886.3886 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3886-3886

Author(s):

Stefano Fogazzi ◽

Alessandra Tucci ◽

Chiara Bottelli ◽

Marco Ungari ◽

Fabio Facchetti ◽

...

Keyword(s):

T Cell ◽

Hodgkin Lymphoma ◽

Response Rate ◽

Conflicts Of Interest ◽

Stage Iii ◽

Classical Type ◽

Composite Lymphoma ◽

Histologic Subtype ◽

Non Hodgkin Lymphoma ◽

Systemic Symptoms

Abstract Abstract 3886 The possibility that a non-Hodgkin lymphoma (NHL) is diagnosed either simultaneously or at a different time in patients with Hodgkin lymphoma (HL) has been reported both as single case reports and in small series. However the significance of such an association is still unclear. We searched the database of HL consecutively diagnosed at our Institution in order to identify such cases and to detect any specific clinicopathological or prognostic characteristics. Twenty cases were retrieved representing to our knowledge the largest series reported so far. Fifteen of them were diagnosed over the last ten years and represented 4,6% of the 326 cases of HL diagnosed during the same time period. There were 12 males and 8 females. Median age was 58. It was lower in patients developing HL as the first lymphoma (35 vs 65). HL was diagnosed first in 7 cases and as the second lymphoma in 9 cases. The mean interval between the two diagnoses was longer when HL occurred first (112 vs 60 months). In four patients the two diagnoses were made simultaneously, on the same histologic specimen in two. Histologic diagnoses of NHL included diffuse large B cell in 6, T cell lymphoma in 4 (peripheral unspecified 2, cutaneous 2), follicular in 3, marginal in 3 and lymphocytic in 4 cases each. T cell, marginal and lymphocytic lymphoma were overrepresented in comparison with their general frequency among NHL. No differences emerged regarding the timing of NHL occurrence, except for lymphocytic lymphoma which never occurred after HL. Nodular sclerosis was the most frequent histologic subtype of HL, representing 58% of cases, whereas only two cases (10%) were nodular lymphocyte predominance HL (NLPHL). Immunohistochemistry on Reed Sternberg cells of HL classical type showed CD30+ in 16 (100%) and CD15+ in 10 (63%) of 16 evaluable cases. CD20+ was present in 3/14 classical HL (21%) and in the 2 cases of NLPHL. Clinical presentation of HL was more aggressive than expected with no patient in stage I, 60% of patients in advanced stage (stage II: 8, stage III: 6; stage IV: 6) and 50% with systemic symptoms. There were no differences between cases presenting as first or second lymphoma. Among NHL 15 cases presented in stage III/IV and 6 with systemic symptoms. In seven cases autoimmune abnormalities/disease coexisted, including Raynaud, thyroiditis, cutaneous lupus, and vasculitis. HL patients were treated with ABVD in 11 cases, or with other chemotherapy programs +/− radiotherapy. NHL received treatments according to histology. In composite lymphoma treatment was directed against the more aggressive lymphoma. In spite of the unfavourable presentation, the complete response rate (CRR) in HL was 74% and the overall response rate (ORR) 79%. It was worse (5/8: 63%) when HL presented after NHL. In NHL the CRR was 63% and the ORR 95%. Relapse occurred in 2 HL, in one composite lymphoma (HL+FL > DLBCL) and in 5 NHL. Seven patients died, with active disease in 6 (2 HL, 4 NHL). One patient died of lung cancer. With a median follow up of 6 years, the 5-year and 10-year survival are 83,5% +/−9% and 68%+/−12%, respectively. We conclude that the occurrence of HL and NHL in the same patient is not rare. T-cell, marginal and lymphocytic lymphoma seem to be more frequently associated with HL. Pathologic and immunohistochemical characteristics are otherwise not distinctive. Patients present with advanced disease and systemic symptoms but their response to treatment and overall prognosis seem not worse than that of patients affected by HL as single tumour. The selective association between some histologic types of NHL and HL as well as the possible association with autoimmunity warrants further investigation. Disclosures: No relevant conflicts of interest to declare.

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Response Assessment Using Early and End-of-Treatment 18F-FLT PET Can Predict Outcome in Patients with Non-Hodgkin Lymphoma,

Blood ◽

10.1182/blood.v118.21.3679.3679 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3679-3679

Author(s):

Hyewon Lee ◽

Seok-Ki Kim ◽

Tae Sung Kim ◽

Se Hun Kang ◽

Weon Seo Park ◽

...

Keyword(s):

Treatment Outcome ◽

Hodgkin Lymphoma ◽

Predictive Factor ◽

Response Assessment ◽

Early Response ◽

Independent Predictive Factor ◽

Predictive Values ◽

Non Hodgkin Lymphoma ◽

Flt Pet ◽

End Of Treatment

Abstract Abstract 3679 Background Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan has been known as a useful modality for response assessment in malignant lymphoma. However, FDG is not tumor-specific and can be false positive in inflammatory lesions. To overcome these limitations, a new PET tracer, thymidine analog 3'-deoxy-3'-18F-fluorothymidine (FLT), was introduced recently. Preliminary data showed close correlation between FLT uptake and tumor cell proliferation in lymphoma, suggesting the possibility of noninvasive tumor grading and early response assessment. Therefore, we performed a prospective trial to evaluate the feasibility of FLT-PET in risk stratification and prediction for treatment outcome, especially in early interim analysis, in patients with non-Hodgkin lymphoma (NHL). Methods Seventy-five patients newly diagnosed with NHL were prospectively enrolled at National Cancer Center, Korea, from Oct 2005 to Oct 2008. All received standard chemotherapy for their pathologic classifications. Patients were evaluated with FLT-PET at baseline (FLT0), after 1 cycle of chemotherapy (FLT1, early), and after completion of the 1st line chemotherapy (FLTE, end-of-treatment). FLT-PET results were assessed according to the International Workshop Criteria (IWC). Maximum standardized uptake values (SUVmax) of each FLT-PET were calculated to evaluate its correlation with the clinical characteristics and treatment outcome. Treatment outcome was estimated using 3-year progression-free survival (3yr-PFS) and overall survival (3yr-OS). Results Of the 75 enrolled patients, 63 (84%) had diffuse large B-cell lymphoma. Median age at diagnosis was 57 years (range, 29–87). Twenty-eight (37.3%) presented with stage III or IV diseases and 20 (26.7%) showed more than 3 IPI scores. Median follow up duration was 4.5 years (range, 3.5–5.8). Five (6.7%) patients underwent hematopoietic stem cell transplantation at last. Three-year PFS and OS rates for all enrolled patients were 68% and 78.7%. Seventy-three (97.3%) had their FLT-PET at baseline, 69 (92%) after 1 cycle of chemotherapy, and 66 (88%) at the end of the 1st line treatment. By IWC, 50 (66.7%) patients achieved complete remission (CR) on FLT1 and 56 (74.7%) had CR on FLTE. Positive predictive values (PPV) of residual uptake on FLT1 and FLTE for relapse or disease progression were 83.3% (95%CI 57.7–95.6) and 80% (95%CI 44.2–96.5), respectively. Negative predictive values (NPV) of them were 88% (95%CI 75.0–95.0) and 82.1% (95%CI 69.2–90.7). Sensitivity and specificity were 71.4% (47.7–87.8) and 93.6% (81.4–98.3) for FLT1 and 44.4% (22.4–67.8) and 95.8% (84.6–99.3) for FLTE, respectively. Complete disappearance of uptake on FLT1 was significantly associated with better PFS compared to residual uptake on FLT1 (3yr-PFS rates, 87.5% and 12.2%, p<0.001). Three-year OS rates according to CR achievement on FLT1 were 96.0% and 27.8%, significantly lower in patients with residual disease after 1 cycle of chemotherapy (p<0.001). SUVmax of FLT0 correlated with LDH level significantly (p=0.044), but not with age (p=0.214), Ki-67 index (p=0.073), IPI score (p=0.270), and Ann Arbor stage (p=0.089). SUVmax of FLT0 were not associated with survival outcomes, however, residual SUVmax of FLT1 reflecting early response to treatment was significantly associated with poor survival outcome (PFS, HR 1.29, 95%CI 1.14–1.47; OS, HR 1.27, 95%CI 1.08–1.49). In multivariate analysis, SUVmax of FLT1 remained as an independent predictive factor for PFS (HR 1.63, 95%CI 1.25–2.13) and for OS (HR 1.89, 95%CI 1.38–2.58). Residual SUVmax of FLTE also revealed to be significantly associated with PFS (HR 1.43, 95%CI 1.05–1.94) and OS (HR 1.59, 95%CI 1.12–2.26) in the same multivariate model. Conclusion Response assessment in cooperation with FLT-PET provided accurate prediction for clinical outcome including PFS and OS in patients with NHL. Especially, early FLT-PET result after 1 cycle of chemotherapy was an independent predictive factor for survival as well as relapse or disease progression, with comparable performance with end-of-treatment FLT-PET. Disclosures: No relevant conflicts of interest to declare.

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RIT with 90Y Ibritumomab Tiuxetan in Patients with Non-Hodgkin Lymphoma Over 65 Years.

Blood ◽

10.1182/blood.v120.21.2742.2742 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2742-2742

Author(s):

Marcio M Andrade ◽

Anel Montes ◽

Ilda Murillo ◽

Jose M Grasa ◽

Teresa Baringo ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Median Time ◽

Response Rate ◽

Haematological Toxicity ◽

Red Blood Cell Transfusion ◽

First Line ◽

Ibritumomab Tiuxetan ◽

Non Hodgkin Lymphoma ◽

First Line Therapy ◽

Line Therapy

Abstract Abstract 2742 Introduction: 90Y Ibritumomab tiuxetan (90Y-IT) has become an efficient alternative to therapy in non-Hodgkin Lymphoma, mainly in elderly patients. The aim of this study is to analyse our updated information of patients treated with 90YIbritumomab/tiuxetan in a prospective study according clinical practice setting and to analyse treatment outcome. Subjects and Methods: 39 non Hodgkin lymphoma patients were included in a clinical protocol conducted by a multidisciplinary team and treated in the same centre. According the inclusion criteria: patients over 65 years old diagnosed as CD20+ NHL with neutrophils ≥ 1,5 × 109/L, platelets ≥ 100 × 109/L, bone marrow lymphocytes CD20+ ≤ 25%. All patients received 0,3 or 0,4 mCi /kg IV (88%) of 90YIbritumomab/tiuxetan and response evaluation was performed 12 weeks after. Period of study: September 2005/July 2012. The 90Y-IT was administered as consolidation of first line therapy (Rituximab alone, R-COP, R-CHOP21) or in relapsed/refractory status. Endpoints: Objective response rate (ORR), time to relapse (PFS) overall survival (OS) and safety. Other clinical prognostic factors were observed to assess their possible influence upon treatment value. Results: Until May 2012, 39 patients had received treatment with 90YIbritumomab/tiuxetan and completed the evaluation protocol and were considered to analysis; M/F 18/21 mean age 72.8 years (65–87); ECOG 0–1 92.3%. According OMS classification: NHL-follicular 27 (69.2%), mantle cell Lymphoma 7 (17.9%), DLBCL 4 (10.3%) and 1MALT (2.6%). Score distribution: low risk 19 (48.7%), intermediate 12 (30.8.2%) and advanced 8 (20.5%). Previous therapy schedules ≤2 (66.7%), >2 (33.3%). The median follow-up time: 42.0 months (95% CI: 4.0; 62.0), mean PFS: 38.1 months (95% CI: 30.8; 45.4) median NR. 13 patients received 90Y-IT as consolidation of first line therapy (33.3%) and 26 relapsed/refractory (66.6%). ORR was 84.6 % CR: 29 (74.3%); PR 4 (10.2%) and 6 failures (15.4%) in relapsed/refractory disease. Mean estimated OS since 90Y-IT: 54.4 months (95% CI: 49.4; 59.3) and mean estimated OS since diagnosis 159 months. Median PFS was NR. The mean PFS for patients in consolidation therapy was 54.2 months (95% CI: 47.4; 61.1). Safety: thrombocytopenia being the most frequent, G3–4 (35.9%), median time to developed haematological toxicity: fourth week, and neutropenia G3–4 (41.0%), the median time to recover normal values was 4.2 and 2.6 weeks respectively. In 5 (12.9%) of patients red blood cell transfusion was required, and 10 platelet transfusions (25.6%). The most frequent non haematological toxicity was asthenia. One patient developed a severe mucositis. Four patients have concomitant associated tumours (colon, breast, lung and prostate) and two patients over 77 years developed a rectum carcinoma after 18 months of 90Y-IT and another prostate and renal tumour after 8 years. Comments: In our experience 90Y Ibritumomab tiuxetan is a safety and effective therapy in patients with NHL over 65 years. According to obtained PFS results, it seems like the use of this kind of therapy as used in early part of therapy offers good and maintained response rate with lower toxicity in this fragile population. The OS in this population was not inferior to observed in younger NHL patients. Disclosures: No relevant conflicts of interest to declare.

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Phase I/II Trial of Ofatumumab/Lenalidamide for Patients with Relasped/Refractory B-Cell Non-Hodgkin Lymphoma: High Response Rate in Indolent Lymphoma

Blood ◽

10.1182/blood.v120.21.3692.3692 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3692-3692

Author(s):

Julie M Vose ◽

Fausto R. Loberiza ◽

R. Gregory Bociek ◽

Philip Bierman ◽

James O. Armitage

Keyword(s):

Phase I ◽

B Cell ◽

Hodgkin Lymphoma ◽

Research Funding ◽

Response Rate ◽

Cell Lymphoma ◽

High Response Rate ◽

Indolent Lymphoma ◽

Non Hodgkin Lymphoma

Abstract Abstract 3692 Introduction: Lenalidomide and ofatumumab have demonstrated clinical activity as single agents in a variety of types of non-Hodgkin lymphoma (NHL). This trial is a phase I/II trial combining these two agents for treatment of patients with relapsed and refractory B-cell NHL. Methods: Patients with relapsed and refractory B-cell NHL of any histology were enrolled on a phase I/II trial combining lenalidomide and ofatumumab. Nine patients were on the phase I part of the trial and received a fixed dose of ofatumumab 1000 mg weekly × 8 doses along with lenalidomide 15 mg (N=3), or10 mg (N=6) for 21/28 days until the time of progression. The phase II portion of the study has 28 patients on the study with adequate follow-up at the time of analysis. The phase II doses were ofatumumab 1000 mg weekly × 8 along with lenalidomide 10 mg on 21/28 days. The lenalidomide was dose adjusted according to standard dose reduction criteria. All patients were on either a daily aspirin or other anticoagulation for thrombosis (DVT) prophylaxis. Results: Thirty seven evaluable patients had adequate follow-up at the time of the analysis. The patients had a median age of 65 years (range 36–81), 76% were male, and 89% have an ECOG performance status of 0–1. The majority of patients had a relapsed indolent lymphoma with 12/37 (32%) follicular lymphoma (FL), 6/37 (16%) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), 7/37 (19%) mantle cell lymphoma (MCL), one unclassifiable indolent lymphoma (3%), and 11/37 (30%) diffuse large B-cell lymphoma (DLBLC). The median duration of follow-up of surviving patients was 13 months (range 4–24). The complete response (CR) rate was 2/37 (5%) (one each FL and DLBCL) and the partial response (PR) rate was 13/37 (35%) for an overall response rate (ORR) of 15/37 (40%). The 1 year progression-free survival (PFS) was 41% (95% CI; 23–58) and the 1-year overall survival (OS) was 68% (95% CI; 49–82). In an analysis of response by patient variables, those significant included the patients with an FL histology (ORR 83%) vs. DLBCL (ORR 18%) or other(SLL, MCL, unclassifiable) (ORR 21%) (p= 0.001) and lactic dehydrogenase (LDH) normal (ORR 56%) vs. elevated (ORR 14%) (p= 0.01). In an analysis of variables for PFS, the variables with significance include diagnosis of FL (1-year PFS 67%) vs. DLBCL (9%) and SLL, MCL, unclassifiable (45%) (p=0.002), LDH normal (1-year PFS 55%) vs. elevated LDH (1-year PFS 19%), and number of prior chemotherapies 1–2 (1-year PFS 58%) vs. > 3 (1-year PFS 19%). Higher grade toxicities included grade 4 neutropenia in 9/37 (24%), one each of grade 4 bacteremia, one grade 4 DVT, stroke, and acute renal failure. Conclusions: The combination of lenalidomide and ofatumumab was well tolerated by most patients. The patients with indolent NHL had a high response rate of 83% and a 1-year PFS of 67%. Disclosures: Vose: Glaxo Smith Kline: Research Funding; Celgene: Research Funding. Off Label Use: Lenalidamide and Ofatumumab will be discussed for use in indolent and aggressive non-Hodgkin lymphoma.

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8070 ◽

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.

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PS1079 CLINICAL OUTCOME OF INTENSIFIED CHEMO-TARGETED THERAPY IN ACTIVATED B CELL NON HODGKIN LYMPHOMA

HemaSphere ◽

10.1097/01.hs9.0000562608.78733.02 ◽

2019 ◽

Vol 3 (S1) ◽

pp. 489

Author(s):

A. Sohaib ◽

T. Hashim ◽

M. Abouelfetouh ◽

E. Elkhouly ◽

A. Alhanafy ◽

...

Keyword(s):

Targeted Therapy ◽

Clinical Outcome ◽

B Cell ◽

Hodgkin Lymphoma ◽

Non Hodgkin Lymphoma

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Fludarabine, Mitoxantrone and Dexamethasone for the First Line Treatment of Patients with Indolent Non-Hodgkin Lymphoma (NHL): GATLA First Interim Report (Grupo Argentino de Tratamiento de la Leucemia Aguda).

Blood ◽

10.1182/blood.v108.11.4680.4680 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4680-4680

Author(s):

Gustavo Milone ◽

A. Rodriguez ◽

Jorge Milone ◽

R.F. Bezares ◽

S. Rudoy ◽

...

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Response Rate ◽

Response Rates ◽

Low Grade ◽

Line Treatment ◽

First Line ◽

Free Survival ◽

Non Hodgkin Lymphoma ◽

First Line Treatment

Abstract Background: fludarabine (F) is licensed for the management of indolent non-Hodgkin lymphoma in countries such as Canada and Switzerland. Clinical evidence suggests that fludarabine monotherapy is as least as effective, than conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first and second line treatment of B-cell low grade NHL achieving objective response rates. Better response rates can be achieved combining F with Mitoxantrone (N) and Dexamethasone (D) in indolent NHL patients (pts). The GATLA (Grupo Argentino de Tratamiento de la Leucemia Aguda) started a prospective multicenter national study to evaluate the use FND as a first line treatment for low grade NHL. Aims: to assess the response rate, safety, disease free survival (DFS) and overall survival (OS) of FND as first line treatment for indolent NHL during (2002–2006). Methods: Ninety-six patients in the period of January 2002 to April 2006 were recruited. Sixty-nine patients were valuable at the time of analysis. Median age 54 years old (range: 21–79). Gender: male 51% and female 49%. Inclusion criteria for low grade NHL-LG was: non-previous, age > 18 years old with symptomatic disease, ECOG performance status 0–2 and written informed consent. Ann Arbor staging: 5,8%, 14,5%, 24,6% and 55%. FND treatment consisted of F 25 mg/m2 i.v. (days 1–3), N 10 mg/m m2 i.v. (day 1) and D 20 mg (days 1–5) each 28 days for 6 cycles. All patients received oral antibiotics for intestinal decontamination, antifungal prophylaxis and Trimethoprim-Sulfamethoxazole as P. carinii prophylaxis for one year. Results: on this low grade NHL cohort the overall response rate (ORR) was 93% (ORR) with 70% (48 pts) with complete response (CR) and 23% (16 pts) with partial response; progressive disease and non-response 7% (5 pts). The probability of event free survival (EFS) and overall survival (OS) at 24 months was 60% and 90% respectively. Two patients developed secondary malignancies after treatment and one died. Only one patient died in CR. Conclusions: in this population FND treatment demonstrate a high CR rate with low toxicity and high probability of EFS and OS as previous experience published in the literature.

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