Efficacy and Safety of Yttrium-90 Ibritumomab Tiuxetan in Older Patients with Indolent Non-Hodgkin Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4795-4795
Author(s):  
Silvana Capalbo ◽  
Gaetano Palumbo ◽  
Matteo Dell'Olio ◽  
Maria Grazia Franzese ◽  
Attilio Guarini ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Older Patients ◽  
Response Rate ◽  
Significant Activity ◽  
Severe Toxicity ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin Lymphoma ◽  
Grade 3 ◽  
Yttrium 90

Abstract Abstract 4795 Introduction Radioimmunotherapy (RIT) has emerged as an important treatment options for patients with non-Hodgkin lymphoma (NHL). Yttrium-90 ibritumomab tiuxetan (Zevalin®) consist of ibritumomab, a murine monoclonal antibody to CD20, conjugated to the metal chelator tiuxetan for retention of the beta emitter Yttrium-90. Clinical trials with this agent have demonstrated significant activity in indolent NHL with mild toxicity. The median age of NHL patients included in these trials is mainly < 65 years. Our aim was to evaluate the effectiveness of Zevalin as treatment option for patient > 65 years old with indolent NHL. Patients and Methods Between November 2005 to June 2009 fifteen patients, five males and ten females, median age 76 years (range 67-82), with indolent NHL (13 follicular and 2 small lymphocytic) were treated with Zevalin. Six patients had stage IV disease, five stage III and four stage II. All patients received an initial infusion of rituximab at a dose of 250 mg/m(e)2 on day 1 and a second infusion at same dose on day 8 followed by a weight-based dose of Zevalin (median dose 1006 MBq; range 668-1260). Eight patients perfomed Zevalin as consolidation after first line therapy with Rituximab plus chemotherapy (6 R-CHOP, 1 R-FN, 1 R-COMP): of these three were in complete remission (CR) and five in partial remission (PR). Seven patients perfomed Zevalin in relapse (four in first and three in second relapse). Results After RIT 13 of 15 patients were evaluable. Overall response rate was 92% (10 CR, 2 PR); in particular all patients in first line of treatment achieved CR. One patient had stable disease. At a median follow-up of 15 months (range 2-34), all patients are alive in persistent CR or PR. One of two patients in PR achieved CR after successive therapy. Treatment was well tolerated; transient thrombocytopenia (grade 3-4) was seen in 9 patients and transient neutropenia (grade 3-4 ) in 6 patients. Only one patient developed herpex-zoster virus infection. Conclusion In our experience, Zevalin produces high response rate (up to 90%) and durable remission without severe toxicity in older patients with indolent NHL. Notably, in first-line treatment, RIT resulted in PR-to-CR conversion in all five patients in PR after the R-chemotherapy. The favourable safety profile of this regimen makes it an effective consolidation treatment for older patients who, because of age and comorbidity, are not eligible for intensive treatment as high-dose therapy and stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
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.

Yttrium-90-Ibritumomab Tiuxetan and BuCyE High-Dose Chemotherapy Compared with BuCyE Alone As Conditioning Regimen in Patients with B-Cell Non-Hodgkin Lymphoma: IPI Matched Case Control Study At a Single Center,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3703-3703
Author(s):  
Jae-Cheol Jo ◽  
Dok Hyun Yoon ◽  
Shin Kim ◽  
Seongsoo Jang ◽  
Chan-Jeoung Park ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Efficacy And Safety ◽  
Event Free Survival ◽  
Ibritumomab Tiuxetan ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Yttrium 90

Abstract Abstract 3703 Background: Currently, there are accumulating data on the role of radioimmunotherapy in autologous stem cell transplantation (ASCT) with promising results. We compared the efficacy and safety of yttrium-90-ibritumomab tiuxetan (90Y-ibritumomab) combined with intravenous busulfan, cyclophosphamide, and etoposide (BuCyE) with those of BuCyE alone followed by ASCT in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Patients and Methods: From October 2005 to May 2011, 71 NHL patients underwent high-dose chemotherapy with BuCyE (n=52) or 90Y-ibritumomab plus BuCyE (n=19) followed by ASCT at the Asan Medical Center. Of 52 patients receiving BuCyE, we found 19 patients who had B-cell NHL and they comprised control group of BuCyE alone (n=19). Retrospective comparison matched by the same IPI was performed for the efficacy and safety between two groups. Results: The patient cohort consisted of 38 individuals (19 males), of median age 52 years (range, 27–65 years). The baseline characteristics were well balanced between the two groups. The median time to platelet engraftment (>20,000/mm3) and the median time to neutrophil engraftment (>500/mm3) did not differ between 90Y-ibritumomab plus BuCyE (12 days [range, 3–103 days] and 10 days [range, 8–12 days], respectively) and BuCyE alone (12 days [range, 8–35 days] and 10 days [range, 9–12 days], respectively). The objective overall response rate was 89.5% (17/19): continued CR, 42.1% (8/19); induced CR, 36.8% (7/19); PR, 10.5% (2/19) in 90Y-ibritumomab plus BuCyE group, and 78.9% (15/19): continued CR, 26.3% (5/19); induced CR, 47.4% (9/19); PR, 5.3% (1/19) in BuCyE group, respectively (p =0.649). Median follow-up duration for survivors was 30 months. Event-free survival tended to be better in 90Y-ibritumomab plus BuCyE group with a median event-free survival duration of 12.5 months in 90Y-ibritumomab plus BuCyE group and 6.2 months in BuCyE group (p =0.236) (figure 1-a).There seemed to be no significant difference in overall survival between the two groups (p =0.767, figure 1-b). The toxicities including the incidence of grade 3 or higher stomatitis, nausea, vomiting, diarrhea, hyperbilirubinemia were similar in the two groups. Conclusion: Addition of 90Y-ibritumomab to BuCyE high-dose chemotherapy may potentially benefit patients with relapsed or refractory B-cell NHL at no cost of additional toxicity, which warrants further investigation. Disclosures: No relevant conflicts of interest to declare.

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 ◽  
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 &gt; 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.

Bortezomib May Be Safely Combined with Y-90 Ibritumomab Tiuxetan In Patients with Relapsed/Refractory Follicular or Transformed Non-Hodgkin Lymphoma: A Phase I Trial of Combined Induction Therapy and Bortezomib Consolidation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1749-1749
Author(s):  
Rupali Roy ◽  
Andrew M Evens ◽  
David P. Patton ◽  
Annette Larsen ◽  
Alfred Rademaker ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Induction Therapy ◽  
Research Funding ◽  
Phase I Trial ◽  
Ibritumomab Tiuxetan ◽  
Advisory Committees ◽  
Non Hodgkin Lymphoma ◽  
Previously Treated ◽  
Grade 3

Abstract Abstract 1749 Background: Preclinical studies suggest that bortezomib, through inhibition of NF-kB activation, may act as a radiosensitizer and enhance the effects of radioimmunotherapy. Methods: This phase I trial was designed to determine the maximum tolerated dose (MTD) of weekly bortezomib induction combined with Y-90-ibritumomab tiuxetan in patients 18 years or older with relapsed/refractory follicular or transformed non-Hodgkin lymphoma. In addition, we assessed the tolerability of weekly bortezomib consolidation following induction therapy. Cohorts consisting of three patients each were treated with bortezomib induction at doses of 1.0, 1.3, or 1.6 mg/m2 on days 1, 8, 15, and 22, rituximab 250 mg/m2 on days 8 and 15, and Y-90 ibritumomab tiuxetan 0.4 mCi/kg on day 15. Consolidation, consisting of bortezomib 1.6 mg/m2 weekly on days 1, 8, and 15 of three 28 day cycles, was initiated on day 71 after recovery of the platelet count to 100,000/uL and ANC> 1,000/uL. At least three patients per cohort were followed for 7 weeks or had recovery of blood counts without dose-limiting toxicities (DLTs) before dose escalation was allowed. MTD was defined as the dose previous to that in which two patients had DLTs. To be evaluable, patients were required to have received at least two doses of bortezomib and the Y-90-ibritumomab tiuxetan therapeutic dose. Response was assessed by CT scanning following induction therapy and PET/CT and diagnostic CT scans after completion of consolidation. Results: Nine patients with a median age of 55 (range: 29–71) were treated with bortezomib combined with Y-90-ibritumomab tiuxetan. Eight patients had FL and one had evidence of a transformation to diffuse, large B-cell lymphoma. All had a performance status of 0 or 1, and all had been previously treated with rituximab either as a single agent or in combination with chemotherapy. All but one had received prior chemotherapy [R-CHOP (n=7), chlorambucil (n=1), or R-CVP (n=2)], and three had received radiotherapy. Only one had bone marrow involvement. The median number of prior therapies was one (range: 1–3). Grade 3 or 4 toxicities were observed in all but one of the patients and as expected, all but one of these toxicities were hematologic (leukopenia, lymphopenia, neutropenia, and/or thrombocytopenia). One patient had grade 3 cardiotoxicity characterized by palpitations and shortness of breath on day 15 of her first consolidation, with PVC's noted on subsequent EKG. Though uncommon, cardiotoxicity has been reported in association with bortezomib in the form of systolic heart failure, arrhythmias, and angina. It should be noted that this patient was previously treated with an anthracycline as have the majority of patients reported to have experienced cardiotoxicity in association with bortezomib. A DLT of grade 4 thrombocytopenia lasting more than ten days was observed in two of three patients treated with bortezomib at 1.6 mg/m2. One of these two patients was the only one to receive .3 mCi/kg rather than .4 mCi/kg of the radioisotope because of thrombocytopenia on the day of treatment. Thus, the MTD of bortezomib was 1.3 mg/m2. All patients are alive, and the median followup for those patients who have not progressed is 6.5 months (range: 3 – 15 mo.). All but one patient responded to therapy (4 CR/CRu, 4PR, 1 SD). The four complete responders remain in remission at 3.0, 5.0, 5.0 and 15.0 months. All of the partial responders have progressed (3.5, 3.5, 11.5, and 17.5 months), as has the patient with stable disease (5.0 months). Conclusions: The MTD for weekly bortezomib combined with Y-90 ibritumomab tiuxetan induction therapy is 1.3 mg/m2. Consolidation with bortezomib at 1.6 mg/m2 was well tolerated in this group of relapsed/refractory follicular and transformed non-Hodgkin lymphoma patients. Nearly all patients responded. A phase II trial at the MTD is underway to better define the toxicity and effectiveness of this regimen in patients with relapsed/refractory FL. Disclosures: Evens: Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrm: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Ziopharm: Membership on an entity's Board of Directors or advisory committees; Lilly: Research Funding; Ortho- Biotec: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Gordon:Cure Tech, Ltd: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics, Inc: Research Funding; Genentech: Speakers Bureau; Millenium: Research Funding; Spectrum: Membership on an entity's Board of Directors or advisory committees. Winter:Millenium: Consultancy, Research Funding; Pfizer/Wyeth: Research Funding; Novartis: Consultancy, Research Funding; Genentech: Research Funding; Seattle Genetics: Research Funding; Spectrum: Honoraria.

Safety of Subcutaneous Administration of Rituximab during the First-Line Treatment of Patients with Non-Hodgkin Lymphoma: The MabRella Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2971-2971 ◽  
Author(s):  
Carlos Panizo ◽  
Mohamed Amine Bekadja ◽  
Balkis Meddeb ◽  
Maria Rigoroso Mendoza ◽  
Matt Truman ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
North Africa ◽  
Safety Profile ◽  
B Cell Lymphoma ◽  
First Line ◽  
Advisory Committees ◽  
Non Hodgkin Lymphoma ◽  
Grade 3

Abstract Background: Rituximab, administered intravenously (IV), is the mainstay of treatment for CD20+ B-cell non-Hodgkin lymphoma (NHL). A subcutaneous (SC) formulation has been approved in Europe and other countries based on the SABRINA study, which showed non-inferior pharmacokinetics and comparable safety and efficacy for rituximab SC compared with IV in treatment-naïve patients with follicular lymphoma (FL) (Davies A, et al. Lancet Oncol 2014;15:343-52). Furthermore, rituximab SC reduces healthcare resource burden (De Cock et al. PLoS One 2016;11:eD157957) and improves patient satisfaction and convenience compared with IV (Rummel et al. Blood 2015;18:A469). MabRella is a global umbrella study comprising three local open-label, single-arm, Phase 3b studies evaluating the safety of first-line (1L) rituximab SC treatment in patients with FL or diffuse large B-cell lymphoma (DLBCL) with a focus on administration-related reactions (ARRs). The studies share a core protocol, study endpoints, and timepoints, but have flexibility for modifications at local level. Data from participating countries is pooled for pre-defined global analyses. Methods: Patients were aged 18-80 years with grade 1-3a FL or DLBCL, and ECOG PS of ≤3. All patients had received ≥1 full dose of rituximab IV as 1L induction or maintenance prior to study entry, and were eligible to receive at least 4 additional cycles of induction or 6 additional cycles of maintenance. Patients with FL or DLBCL receiving induction therapy were treated with rituximab SC 1400mg every cycle (14, 21, or 28 days) for 4-7 cycles, in combination with standard chemotherapy. FL patients undergoing maintenance treatment received single-agent rituximab SC 1400mg every 2 months for 6-12 cycles. The primary endpoint was incidence of ARRs following multiple doses of rituximab SC; ARRs were defined as all adverse events (AEs) occurring within 24 hours of rituximab administration and considered related to the study drug by the investigator. Secondary safety endpoints included grade ≥3 AEs and serious AEs (SAEs). The safety analysis included all patients who received ≥1 dose of study treatment. Safety data were not collected for rituximab IV, as patients entered the trial after they had switched to SC. Data are presented from a planned interim analysis of safety (cut-off March 31, 2016). Results: At the data cut-off, the safety population comprised 336 patients: 157 from Italy; 139 from Spain; and 40 from North Africa (Tunisia and Algeria). The median (range) age was 59 (19-80) years and 50% patients were male; 205 patients had FL and 131 had DLBCL. With respect to patients with FL, 84 completed ≥1 cycle of rituximab SC induction (37 completed all 7 cycles) and 190 completed ≥1 cycle of maintenance (169 completed 6 cycles and 26 completed all 12 cycles). Among DLBCL patients, 37 completed all 7 cycles of induction. Overall, 282 patients (84%) experienced an AE during treatment (Table 1). ARRs were observed in 75 patients (22%), the most common of which (≥2% incidence) were erythema (12%) and injection-site erythema (4%). Other AEs reported in ≥10% of patients were neutropenia, asthenia, erythema, pyrexia, and diarrhea (Table 1). Grade ≥3 AEs occurring in ≥5% of patients were neutropenia (24%) and febrile neutropenia (6%). Grade ≥3 ARRs were observed in 4 patients (1%). SAEs were reported in 29% of patients (8% drug-related). Of 11 deaths attributed to AEs, 2 were considered to be related to treatment (Klebsiella infection and sepsis). The safety profile of rituximab SC was generally comparable between FL and DLBCL patients, although neutropenia (any grade and grade ≥3) was more prevalent in DLBCL patients, while erythema (any grade) was more common in FL patients (Table 1). The profile of AEs was similar during induction and maintenance, but the intensity and seriousness of events was lower during maintenance (Table 2). Geographic location (Spain, Italy, North Africa) of study sites did not appear to impact on the safety profile of rituximab SC. Conclusions: In line with previous reports (Davies et al. 2014), rituximab SC is well tolerated during the 1L treatment of patients with NHL. The safety profile of 1L rituximab SC is similar to reports for IV administration, with the exception of an expected increase in ARRs, the majority of which are mild or moderate in intensity, and resolve spontaneously. Disclosures Panizo: Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche Pharmaceuticals: Speakers Bureau. Rigoroso Mendoza:F Hoffmann La Roche Ltd: Employment. Truman:Aurinia Pharmaceuticals: Consultancy; F Hoffmann La Roche Ltd: Consultancy, Equity Ownership. Smith:F. Hoffmann La Roche Ltd.: Employment.

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