Fractionated 90y Ibritumomab Tiuxetan (Zevalin™) Radioimmunotherapy As An Initial Therapy of Follicular Lymphoma – First Results From a Phase II Study in Patients Requiring Treatment According to GELF/BNLI Criteria

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 102-102 ◽  
Author(s):  
Timothy M Illidge ◽  
Ruth Pettengell ◽  
Michael Bayne ◽  
Steven Le Gouill ◽  
Andrew Bates ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Median Duration ◽  
Bone Marrow Involvement ◽  
Response Rates ◽  
Initial Therapy ◽  
Tumor Burden ◽  
Hematologic Toxicity ◽  
Treatment Schedule ◽  
Ibritumomab Tiuxetan

Abstract Abstract 102 Background: Radioimmunotherapy (RIT) has proven to be highly active in relapsed follicular lymphoma (FL) and the best single agent efficacy results in frontline therapy of FL were obtained with Iodine-131 Tositumomab (Bexxar™) (Kaminski et al NEJM 2005); albeit half of the patients had low tumor burden. In patients with higher tumor burden, using more than one fraction of RIT increases the overall radiation dose over that of a single fraction of treatment, thereby potentially improving both the response rates and survival (Illidge et al, Blood 2009). Methods: We conducted an international, multicenter phase 2 trial to evaluate the efficacy and toxicity of Fractionated 90Y Ibritumomab tiuxetan (Zevalin™) RIT as an initial therapy of Follicular Lymphoma. Eligible patients had untreated follicular lymphoma (grade 1, 2, or 3a) and at least one criterion of high tumour burden - one lymphoma lesion greater than 7 cm or three separate nodes of 3 cm or more; symptomatic splenic enlargement; raised serum concentrations of either lactate dehydrogenase or β2-microglobulin; compressive syndrome; or the presence of B symptoms. Treatment consisted of two doses of 90Y-ibritumomab tiuxetan (11.1 MBq/kg) given 8–12 weeks apart. Patients with greater than 20% bone marrow involvement (BM) with lymphoma received 4 weekly infusions Rituximab (375 mg/m2) and proceeded to fractionated RIT only if a repeat BM biopsy demonstrated clearing of lymphoma with less than or equal to 20% involvement. The primary endpoint was end of treatment response (EOR) of the intent-to-treat (ITT) population according to IWC 1999, assessed 12 weeks after last 90Y Ibritumomab tiuxetan infusion (21 weeks after treatment start). Secondary objectives were safety and progression free survival (PFS). Results: 74 patients with a median age of 61 years (28−80), including 58 (78%) with stage III–IV stage, 23 (31%) intermediate risk FLIPI 2 and 34 (46%) with high risk FLIPI 3–5; were included between June 2007 and June 2010 in 7 centres. Thirteen (18%) patients with >20% BM involvement required rituximab pre-treatment, 2/74 did not qualify for RIT, meaning 72 received the first 90Y Ibritumomab tiuxetan infusion and 55 (76%) completed the full treatment schedule. The 2nd infusion of RIT was withheld secondary to hematologic toxicity with 1st infusion (n=12, 17%) or human anti murine antibodies positive testing (n = 4; 5.6%) or other (n = 1, 1.4%). Two out of 72 patients did not have recorded response data and the EOR was 95.7% (67/70) with CR/CRu of 57.1% (40/71). Six patients subsequently improved response making an ORR of 97.1% (68/70) (95% CI 90.0% – 99.7%), and CR/CRu of 64.3%% (45/70) (95% CI 51.9% – 75.4%). For the subset of 17 patients who only received a single 90Y Ibritumomab tiuxetan infusion, ORR (CR/CRu) was 100% (76,5%). At a median follow-up of 1.52 years (range 0.13 – 3.69 years) the PFS is 67 %, 20 patients have progressed and 12 of these have required further treatment (8 chemotherapy, 2 radiotherapy, 2 other). Updated data with median follow-up of more than 2 years will be presented. Ten patients experienced at least one SAE during the treatment period, with 3 related to study treatment (one case of rigors associated with the first infusion of rituximab and 2 cases of neutropenic sepsis both associated with the second RIT dose. The most common toxicity was hematologic: after the first 90Y Ibritumomab tiuxetan dose, related G3-4 hematological AEs were transient neutropenia (20.8%, 18 days median duration) and thrombocytopenia (20.8%; 20 days median duration). After the second 90Y Ibritumomab tiuxetan dose, related G3-4 hematological AEs increased to 36.4% for neutropenia (31days median duration), 14% for anemia (8/55 required transfusion) and 56.4% for thrombocytopenia (40 days median duration). There has been one case of MDS diagnosed 26 months after treatment and one death due to metastatic breast cancer diagnosed 9 months post last dose of 90Y Ibritumomab tiuxetan Conclusion: Fractionated RIT using 90Y-ibritumomab tiuxetan is an effective frontline treatment of advanced-stage follicular lymphoma in patients with high tumor burden requiring treatment and delivers high response rates. The treatment was well tolerated by patients with few infectious episodes and AE's and manageable hematologic toxicity. Disclosures: Illidge: Bayer Schering Pharma: Honoraria, Research Funding, Speakers Bureau. Morschhauser:Roche: Consultancy, Honoraria.

Tositumomab and Iodine I-131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma: Median 10 Year Follow-up Results.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3759-3759 ◽  
Author(s):  
Mark S. Kaminski ◽  
Melissa Tuck ◽  
Judith Estes ◽  
Arne Kolstad ◽  
Charles Warren Ross ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Hormone Replacement ◽  
Bone Marrow Involvement ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Therapeutic Regimen ◽  
Risk Scores ◽  
Hematologic Toxicity ◽  
Label Use

Abstract Abstract 3759 Poster Board III-695 Purpose Tositumomab and iodine I 131 tositumomab (Bexxar® Therapeutic Regimen) has been found effective in relapsed/refractory follicular lymphoma. We now report updated results of a single center, single-arm, Phase II trial of a single one-week course of this treatment for 76 previously untreated, stage III and IV, follicular lymphoma patients (reporting period June 1996 to May 2009). Patients and Methods Patients had a median age of 49 years (range 23 to 69) and received a dosimetric dose followed by a single total body dose of 75 cGy iodine I-131 tositumomab one week later. Seventy percent had stage IV disease and 70% of patients had histological grade 1 follicular lymphoma, 29% had grade 2, and 1 patient had mantle-cell lymphoma. Bone marrow involvement was present in 64% of patients; 43% of patients had at least one tumor 3 5 cm in diameter; LDH was elevated in 30%. Overall, 35% of patients had high risk Follicular Lymphoma International Prognostic Index (FLIPI) scores and 50% had intermediate risk scores. Patients entered long-term follow-up after disease progression or after 2 years on study. Response, second malignancy occurrence and thyroid medication use were assessed every 6 months for 5 years and yearly thereafter up to 12 years post treatment. Results As previously reported (NEJM 352:441, 2005), the overall response rate was 97% with 57 patients (75%) achieving a complete remission. Hematologic toxicity, although common, was modest to moderate (grade 4 neutropenia in 5% of patients and no grade 4 thrombocytopenia). After a median of 10 years follow-up (range 0.7 to 12.3 years), the median duration of response was 6 years (95% CI: 2.5, 10.8), with approximately 40% remaining progression-free at 10 years. For the 57 complete responders, median progression-free survival was 10.9 years (95% CI: 8.3, NR). Ten-year overall survival was approximately 82%. Five cases (7%) of hypothyroidism occurred 0.5 to 2.9 years after treatment and were managed with thyroid hormone replacement. Eleven patients (14%) were diagnosed with second malignancies including 4 skin neoplasms (2 basal cell and 2 squamous cell) and 7 visceral neoplasms (3 breast, 2 prostate, 1 endometrial cancer, 1 glioblastoma). One case of myelodsyplastic syndrome was diagnosed about 8 years after treatment. Conclusion A single course of treatment with Bexxar therapeutic regimen can commonly produce durable responses, especially durable complete responses lasting over a decade in patients with untreated follicular lymphoma. Further studies comparing this monotherapy to other regimens, including combination therapies, are warranted. Disclosures: Kaminski: GlaxoSmithKline: Honoraria, Patents & Royalties, Research Funding, Speakers Bureau. Off Label Use: Radioimmunotherapeutic for treatment of frontline treatment of follicular lymphoma. On-label use is for relapsed/refractory patients. Horner:GlaxoSmithKline: Employment. Williams:GlaxoSmithKline: Employment. Vleisides:GlaxoSmithKline: Employment. Wahl:Nordion: Honoraria; GlaxoSmithKline: Patents & Royalties.

90Y Ibritumomab Tiuxetan and Rituximab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Non-Hodgkin’s Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2752-2752
Author(s):  
Michael S. Buff ◽  
Anna Royer ◽  
Pamela Ely ◽  
Barbara Grant ◽  
J. Anthony Parker ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Bone Marrow Involvement ◽  
Response Rates ◽  
Ibritumomab Tiuxetan ◽  
Baseline Platelet Count ◽  
Grade 3 ◽  
Experienced Grade ◽  
Large B Cell

Abstract Approximately 60% of adult patients (pts) with diffuse large B cell lymphoma (DLBCL) will relapse after first line therapy. Second line chemotherapy has response rates of 45–66% with median response duration of 3 to 5 months.90Y ibritumomab tiuxetan (90Y-IT) is a murine IgG1 kappa antibody against CD20 linked with a beta-emitting isotope approved for use in relapsed indolent lymphoma. Maintenance rituximab (R) has been reported to increase response rates and prolong remission duration in some lymphomas. We performed a phase II multicenter clinical trial to examine the efficacy of 90Y-IT induction followed by maintenance R in pts with DLBCL. Eligible pts had histologically confirmed CD20+ DLBCL according to WHO criteria. Pts had disease that was either relapsed or refractory to anthracycline-based chemotherapy or pts were intolerant of anthracycline-based chemotherapy. Adequate baseline hematologic and organ function was required. Pts were required to have <25% bone marrow involvement based on bilateral bone marrow aspirate and biopsy. Pts were required to have bidimensionally measurable disease by CT with at least one lesion measuring over 2.0 cm. Pts received R 250 mg/m2 immediately followed by 111In-ibritumomab tiuxetan. Scans were then performed at 24 and 48 hours to insure there was no altered biodistribution. On week 2 pts received a second infusion of R 250 mg/m2 followed by 0.4 mCi/kg 90Y-IT if baseline platelet count >150,000/mm3 or 0.3 mCi/kg 90Y-IT if baseline platelet count 100,000 to 149,000/mm3, total dose not to exceed 32 mCi. Pts received R 375 mg/m2 on weeks 3–6. Pts with multiple extranodal sites or prior bone marrow involvement received CNS prophylaxis with intrathecal methotrexate or cytarabine. Non-progressing pts received maintenance R 375 mg/m2 weekly x 4 every 6 months x 4 or until progression. Toxicity analysis was planned after 15 pts were enrolled. Stopping rules were not met. As of 7/12/2006, 16 pts have been treated of a planned 40. Pts ranged in age from 45 to 95 with a median age of 77. Forty-four percent of patients had a secondary IPI score ≥ 3. The median number of prior regimens is 2 ranging from 1–5. The 90Y–IT treatment regimen produced an overall response rate of 37.5% with 25% CR at 12 weeks. All pts with a CR had a secondary IPI of 1. All pts with PD had a secondary IPI ≥ 2. To date, the median EFS is 2.5 months with a median follow-up of 6.3 months. Among responding patients, the median EFS is not reached with a median follow-up of over 11 [5.7- 22.2] months. Five patients (31%) continue to be in remission greater than 6 months, and three patients (19%) remain in remission for 1 year. The most frequently observed grade 3 or 4 toxicity was hematologic. 55.5% of pts experienced grade 3 or 4 neutropenia. 66.7% of pts experienced grade 3 or 4 thrombocytopenia. The most frequent non-hematologic adverse event was hypotension experienced during the R infusion. The 90Y-IT treatment regimen has an acceptable toxicity profile in pts with relapsed/refractory DLBCL. The two week outpatient 90Y-IT infusion produces response rates and durations similar to that of more prolonged cytotoxic chemotherapy regimens.

Fractionated 90Y-Ibritumomab Tiuxetan Radioimmunotherapy As an Initial Therapy of Follicular Lymphoma: An International Phase II Study in Patients Requiring Treatment According to GELF/BNLI Criteria

2014 ◽  
Vol 32 (3) ◽  
pp. 212-218 ◽  
Author(s):  
Tim M. Illidge ◽  
Sam Mayes ◽  
Ruth Pettengell ◽  
Andrew T. Bates ◽  
Mike Bayne ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Complete Response ◽  
Initial Therapy ◽  
Hematologic Toxicity ◽  
Ibritumomab Tiuxetan ◽  
Free Survival

Purpose We report an international, multicenter phase II trial to evaluate the efficacy and toxicity of fractionated 90Y-ibritumomab tiuxetan (90Y-IT) as initial therapy of follicular lymphoma (FL). Patients and Methods A total of 74 patients, with a median age of 61 years (range, 28 to 80 years), were recruited requiring initial therapy by Groupe d'Etude des Lymphomes Folliculaires (GELF)/British National Lymphoma Investigation (BNLI) criteria. Among them, 78% had stage III-IV disease, 32% intermediate, and 44% high-risk (according to FL International Prognostic Index). Treatment consisted of two doses of 90Y-IT (11.1 MBq/kg) administered 8 to 12 weeks apart. Patients with more than 20% lymphoma infiltration of bone marrow (BM) received one infusion per week for 4 consecutive weeks of rituximab (375 mg/m2) and proceeded to fractionated radioimmunotherapy (RIT) only if a repeat BM biopsy demonstrated clearing of lymphoma to less than 20% involvement. The primary end point was end of treatment response of the intention-to-treat population. Secondary objectives were safety and progression-free survival (PFS). Results Initial overall response rate (ORR) was 94.4% (68 of 72 patients) with combined complete response (CR/CRu) of 58.3% (42 of 72 patients). Nine patients subsequently improved response making an ORR of 95.8% (69 of 72 patients) and CR/CRu of 69.4% (50 of 72 patients). At a median follow-up of 3.1 years (range, 0.2 to 5.2 years) estimated 3-year PFS is 58%, treatment-free survival 66%, and overall survival 95%. Median PFS is 40.2 months. Thirty patients have experienced disease progression and 24 have required further treatment. The treatment was well tolerated with few (2.8%) grade 3 or 4 infectious episodes or adverse events and manageable hematologic toxicity. Conclusion Fractionated RIT using 90Y-IT is an effective initial treatment for advanced-stage FL in patients with higher tumor burden requiring treatment.

Y90 ibritumomab tiuxetan with maintenance rituximab as initial therapy for high tumor burden follicular lymphoma: A Wisconsin Oncology Network study.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e18503-e18503
Author(s):  
K. Thorhildur ◽  
J. E. Chang ◽  
J. C. Eickhoff ◽  
J. E. Werndli ◽  
R. A. Kirby ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Initial Therapy ◽  
Tumor Burden ◽  
Ibritumomab Tiuxetan ◽  
High Tumor Burden

scholarly journals Early Stage Follicular Lymphoma. Predictive Role of Minimal Residual Disease (MRD) and Impact of MRD-Driven Treatment with Radiotherapy and Rituximab on Clinical Outcome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2959-2959 ◽  
Author(s):  
Alessandro Pulsoni ◽  
Irene Della Starza ◽  
Maria Elena Tosti ◽  
Luca Vincenzo Cappelli ◽  
Giorgia Annechini ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Molecular Marker ◽  
Follicular Lymphoma ◽  
Early Stage ◽  
Tumor Burden ◽  
Stage I ◽  
Predictive Role ◽  
Qualitative Pcr

Abstract Background. In localized follicular lymphoma (FL, stage I-II), BCL2/IGH+ cells can be detected in the peripheral blood (PB) and/or bone marrow (BM) in 66.7% of cases (Pulsoni et al, BJH 2007). We hereby analyzed the prognostic impact of MRD in localized FL and explored the possibility of a MRD-guided therapeutic approach on a series of patients with a long follow-up. Methods. Between April 2000 and February 2015, 67 consecutive patients with a confirmed histologic diagnosis of stage I/II FL followed at our Center were enrolled in the study. PB and BM samples were collected at enrollment in all patients and investigated by qualitative PCR to identify the presence of a BCL2/IGH rearrangement. Paraffin-embedded lymph nodes (LN) were studied when available. Patients who proved positive at baseline were studied for MRD every 6 months. Real-Time Quantitative PCR (RQ-PCR) was retrospectively performed according to material availability. All patients were treated with involved field radiotherapy (RT) (24-30 Gy); from 2005, patients who were MRD+ after RT received rituximab (R) (375 mg/m2, 4 weekly administration). The median follow-up is 67 months (17-183); 21 patients (31%) have relapsed after a median of 37 months (17-165) from diagnosis. Results. At baseline, a clonal marker was found by qualitative PCR in 48/67 cases (72%): 36 were MBR+ (54%), 6 mcr+ (9%), 6 showed a minor BCL2 rearrangement (9%), while 19 (28%) were negative. Fifteen of the latter 19 were analyzed by RQ-PCR and 4 proved MBR+. Of the 13 available LNs, 11 showed the same molecular marker identified in the PB/BM; 2 cases, negative in the PB/BM, showed a rearrangement in the LN only. After RT, 40/42 MBR+/mcr+ patients were analyzed: 20 resulted MRD-, while 20 persisted MRD+. Regardless of the post-RT MRD status, an equal number of relapses was recorded in both groups (7 each). R treatment was administered to the 20 MRD+ patients after RT. Sixteen (80%) achieved a MRD- status after R: over time, 7/16 patients converted to MRD+ and 4 relapsed, whilst 9/16 patients (56.2%) remain persistently MRD- and none has relapsed so far. To evaluate the impact of R, we considered a series of 27 patients MRD+ after RT or who were MRD- and became MRD+ during the follow-up. Of the 19 patients who received R (1 could not be studied), 15 (79%) did not relapse, while of the 8 untreated patients (pre-2005), 6 (75%) relapsed (p=0.025). Progression-free survival (PFS) was significantly longer for R-treated patients (p=0.0412) (Fig. 1). To define the predictive role of MRD in the entire cohort regardless of post-RT treatment, we considered the 39 patients with molecular follow-up. Thirteen have relapsed: 10/13 (77%) were MRD+ in the follow-up, including the pre-relapse time point, while 3 resulted persistently MRD-. Contrariwise, of the 26/39 patients in continuous remission, 18 (69%) were persistently MRD- while 8 were MRD+ (p=0.015). PFS was significantly better for MRD- patients (p=0.0163) (Fig. 2). RQ-PCR was performed in 30 MBR+ patients: 17 (57%) showed a tumor burden ≥10-5 and 13 <10-5. Tumor burden at diagnosis predicted the MRD clearance following RT: 9/13 (69%) cases with low tumor burden resulted MRD- after RT compared to 2/17 (12%) cases with high tumor burden (p=0.0027). Contrariwise, tumor burden did not predict the occurrence of relapse. Conclusions. Early stage FL at diagnosis can have a heterogenous disease extension: 2 of our cases were truly localized, showing a molecular marker only in the LN. However, in most cases the use of combined qualitative approaches, including canonical MBR/mcr and minor rearrangements, together with RQ-PCR has allowed to identify circulating BCL2/IGH+ cells (52/67 cases: 77.6%), despite a negative BM biopsy. RT induced a MRD negativity in 50% of BCL2/IGH+ patients, but this did not impact on clinical outcome. The administration of R in MRD+ patients decreased significantly the risk of a subsequent relapse and improved PFS. Regardless of treatment, MRD positivity during the follow-up is a predictor of relapse and PFS. Tumor burden at diagnosis is associated with MRD clearance after RT. We support the use of a MRD-driven treatment with anti-CD20 monoclonal antibodies in patients with localized FL after RT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Stage I and II Follicular Lymphoma With Gastrointestinal Involvement: Long-Term Follow-up of No Initial Therapy

2011 ◽  
Vol 140 (5) ◽  
pp. S-874
Author(s):  
Hiroyuki Okada ◽  
Katsuyoshi Takata ◽  
Yoshiro Kawahara ◽  
Masahumi Inoue ◽  
Seiji Kawano ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Initial Therapy ◽  
Stage I ◽  
Gastrointestinal Involvement ◽  
Long Term Follow Up

90Yttrium-Ibritumomab-Tiuxetan as First-Line Treatment for Follicular Lymphoma: 30 Months of Follow-Up Data From an International Multicenter Phase II Clinical Trial

2013 ◽  
Vol 31 (3) ◽  
pp. 308-313 ◽  
Author(s):  
Christian W. Scholz ◽  
Antonello Pinto ◽  
Werner Linkesch ◽  
Ola Lindén ◽  
Andreas Viardot ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Residual Disease ◽  
Standard Procedure ◽  
Complete Response ◽  
Molecular Response ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Multicenter Phase

Purpose We report on a multicenter phase II trial of 90yttrium-ibritumomab-tiuxetan (90YIT) as first-line stand-alone therapy for patients with follicular lymphoma (FL). Patients and Methods Fifty-nine patients with CD20+ FL grade 1 to 3a in stages II, III, or IV, age 50 years old or older requiring therapy were enrolled. They received 90YIT according to standard procedure. If complete response (CR) or unconfirmed complete response (CRu) without evidence for minimal residual disease (MRD) 6 months after application of 90YIT was achieved, patients were observed without further intervention. The same applied to patients with partial response (PR) or with stable disease (SD). Patients with CR but with persisting MRD were to receive a consolidation treatment with rituximab. Primary end point was the clinical and molecular response rate. Secondary end points were time to progression, safety, and tolerability. Results Six months after treatment with 90YIT, 56% of the patients showed a CR or CRu and 31% achieved a PR. After a median follow-up of 30.6 months, the progression-free survival (PFS) was 26 months. There was a trend for shorter PFS in patients with increased lactate dehydrogenase (LDH). Of the 26 patients who had CR 12 months after 90YIT, only three had relapsed. Median time to next treatment has not been reached. The most common toxicities were transient thrombocytopenia and leukocytopenia. Nonhematologic toxicities never exceeded grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE v2.0). Conclusion 90YIT is well tolerated and achieves high response rates. Patients with increased LDH tend to relapse earlier, and individuals in remission 1 year after 90YIT appear to have long- lasting responses.

Tositumomab and Iodine I 131 Tositumomab (the BEXXAR® Therapeutic Regimen) Shows Efficacy in Elderly Patients (pts) with Relapsed/Refractory Low-Grade (LG), Follicular, and Transformed Non-Hodgkin’s Lymphoma (NHL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2630-2630
Author(s):  
Stephanie A. Gregory ◽  
Andrew Zelenetz ◽  
Susan J. Knox ◽  
Julie Vose ◽  
John P. Leonard ◽  
...  
Keyword(s):  
Bone Marrow Involvement ◽  
Response Rates ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Age Group ◽  
Prognostic Features ◽  
Prior Therapy ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Objective: Pts are first diagnosed with NHL at a median age of 60 yrs. There is increasing support for the idea that physicians should evaluate older pts for cancer treatment on the basis of their health status and cognitive function rather than on chronologic age. Five core clinical trials and an expanded-access program included 995 pts with relapsed/refractory LG follicular or transformed NHL treated with BEXXAR. Data were analyzed to establish the efficacy and safety of BEXXAR as a function of age. Safety data have been presented previously (Gregory et al. Blood. 2003;102. Abstract 1485). Overall toxicity and acute hematologic toxicity associated with BEXXAR in older pts is similar to that observed in pts ≤60 yrs. Methods: BEXXAR efficacy was analyzed by age: group 1 pts, ≤60 yrs (n=586); group 2 pts, >60–≤70 yrs (n=250); group 3 pts, >70 yrs (n=159). Median age at time of BEXXAR was 58 yrs (range, 21–88 yrs). Inclusion criteria included KPS ≥60, platelet count ≥100,000/mm3, ANC ≥1,500 cells/mm3, bone marrow involvement ≤25%, and no impaired renal, hepatic, or cardiac function. Results: All 3 pt groups had received multiple therapies for NHL before receiving BEXXAR (1–3 prior treatments, 63%–65%; ≥4 prior treatments, 34%–37%). In addition to the known poorer prognosis with older age, pts in groups 2 and 3 more frequently had other poor prognostic features, ie, transformed histology and prior radiotherapy (P <.001). Complete response rates (CR+CCR) to the most recent pre-BEXXAR therapy decreased with increasing age (group 1, 21%; group 2, 12%; group 3, 7%), and progressive disease as the initial “response” to prior therapy increased with age (group 1, 20%; group 2, 29%; group 3, 33%). Table 1 shows response rates and CR post- BEXXAR for the 3 groups. Post-BEXXAR CR+CCR rates were higher for pts in every age group compared with CR rates to prior therapy. These rates were nearly doubled for pts >60–≤70 yrs (23% vs 12%) and tripled for pts >70 yrs (23% vs 7%). Conclusions: Of all previously treated pts >60 yrs, ≥50% achieved a response post-BEXXAR. Nearly 25% of pts >60 yrs achieved a CR, with a median duration of CR of 32.3 mos. Response rates and durations of response are somewhat better in younger pts than in pts >60 yrs, but pts >60 yrs presented with poorer prognostic features (as above). Overall toxicity and acute hematologic toxicity associated with BEXXAR in older pts is similar to that observed in pts ≤60 yrs (Gregory et al. Blood. 2003;102. Abstract 1485). BEXXAR can be administered safely and effectively to older pts with low-grade follicular or transformed NHL. Table 1 Response results to BEXXAR by age, N = 995 Age groups Overall response, % CR, % Median CR duration, mos ≤ 60 66 37 59.1 (n=586) 95% CI = 45.8, NR) 60 to ≤70 N = 250 50 23 21.8 (n=250) (95% CI = 15.7, 69.1) >70 54 23 36.4 (n=159) (95% CI = 22.6, NR)

R-FND Followed by Radioimmunotherapy for High-Risk Follicular Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3056-3056 ◽  
Author(s):  
Peter McLaughlin ◽  
Sattva Neelapu ◽  
Michelle Fanale ◽  
Maria Rodriguez ◽  
Ana Ayala ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Ibritumomab Tiuxetan ◽  
Free Survival ◽  
Grade 3 ◽  
Anti Cd20 ◽  
Better Than

Abstract Follicular lymphoma (FL) patients, (pts) with high-risk features using the FL International Prognostic Index (FLIPI) have an expected 5-year survival of only about 50% with conventional therapy. With the incorporation of anti-CD20 monoclonal antibody (mAb) therapy, results are improving (e.g., Buske, Blood2006; 108: 1504). Starting in 2003, we have treated high-risk (FLIPI ≥3) FL pts with R-FND (rituximab, fludarabine, mitoxantrone, dexamethasone) for 4 cycles, followed by radioimmunotherapy (RIT) with ibritumomab tiuxetan, and subsequent rituximab maintenance. Results for the first 35 pts are: complete (CR) and partial (PR) remission 83% and 14%; 3-year overall (OS) and failure-free survival (FFS) 89% and 74% (median follow-up 24 mo.). RIT converted 5 PR pts to CR. Toxicity was mainly hematologic. Five pts did not receive RIT, one because of neutropenia after R-FND. Following RIT, platelet and neutrophil nadirs were 28 and 0.3, occurring at 4–7 weeks. 16 pts required transfusions, and 27 received growth factors. 13 pts had infections, only 2 of which were grade 3. Recovery occurred by 3 weeks in most, with prolonged cytopenias in 6. There has been 1 case of myelodysplasia. In conclusion, the additional complexity of this RIT intensification strategy is warranted in this high-risk FL population, resulting in OS and FFS outcomes that are better than non-mAb therapies, and at least as good as published chemotherapy-rituximab combination therapy.

Dasatinib Is Well-Tolerated and Efficacious in Imatinib-Intolerant Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1128-1128 ◽  
Author(s):  
Hanna Jean Khoury ◽  
Michael J. Mauro ◽  
Yousif Matloub ◽  
Tai-Tsang Chen ◽  
Erkut Bahceci ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Median Duration ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Molecular Response

Abstract Abstract 1128 Poster Board I-150 Imatinib (IM), a tyrosine kinase inhibitor (TKI), has been the mainstay of treatment for chronic phase chronic myeloid leukemia (CP-CML). However, IM resistance and intolerance are of considerable clinical relevance. Dasatinib (DAS), a second-line TKI, is effective in the IM-intolerant patient population. The purpose of this study was to determine baseline factors that can affect DAS response and evaluate long term efficacy in this population. Intolerance to IM was defined as ≥ Grade 3 non-hematologic toxicity and/or Grade 4 hematologic toxicity lasting > 7 days. A total of 271 Ph+ CP-CML IM-intolerant patients who received DAS were pooled from two randomized trials (Phase II-trial, CA 180013 and Phase III trial, CA 180034). DAS doses were 50 mg BID (n=43), 70 mg BID (n=141), 100 mg QD (n=43) or 140 mg QD (n=44). At baseline, the median duration of disease for the IM-intolerant patients was 24 months (range: 0.9-182.5) and the median duration of IM therapy was 9 months (range: 0.03-69.06). Of these patients, 46 (17%) had hematologic toxicity and 228 (84.1%) had non-hematologic toxicity to IM. Seventy-nine (29%) patients had prior complete cytogenetic response (CCyR) on IM and 171 (63%) patients did not. The data for prior CyR to IM was not reported for 21 (7.7%) patients. Of the 79 patients who had achieved CCyR on IM, 30 patients had maintained CCyR and 49 patients had lost this response prior to start of DAS. Of the 171 patients who did not achieve CCyR on IM, 62 (36.3%) had been on IM for 3 12 months and 109 (63.7%) for < 12 months. At 2-year follow up of the 271 patients treated with DAS, 121 (44.6%) discontinued DAS (7.4% due to hematologic toxicity and 14% due to non-hematologic toxicity). Of the patients who were intolerant of IM due to hematologic toxicity (n=46), 10 (21.7%) discontinued DAS due to hematologic toxicity, and 3 (6.5%) due to other toxicities. Of the patients with non-hematologic IM-intolerance (n=228), 10 (4.4%) discontinued DAS due to hematologic toxicity, and 35 (15.4%) due to other toxicities. The median average daily dose of DAS was 99 mg/day in the population who achieved CCyR on DAS and 71.5 mg/day in the population who did not achieve CCyR on DAS. The probability of achieving CCyR on DAS was 43.5% in patients with hematologic IM-intolerance versus 78.9% with non-hematologic IM-intolerance. The CCyR, major molecular response (MMR), progression-free survival (PFS) and overall survival (OS) at 2-year follow up for the groups classified by their CCyR status at start of DAS or IM-intolerance status are summarized in Table 1. Conclusions DAS was well-tolerated and associated with high rates of CyR in IM-intolerant patients. Patients with a prior CCyR to IM and those who switched due to non-hematologic imatinib-intolerance had the highest rates of CCyR and MMR on DAS, while patients without CCyR after more than 12 months of IM therapy or IM-intolerance due to hematologic toxicity had the lowest rates of CCyR and MMR. Disclosures Khoury: BMS: Honoraria; Wyeth: Honoraria; Novartis Pharmaceuticals: Honoraria; Chemgenex: Honoraria; Genzyme: Honoraria. Mauro:Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding. Matloub:Bristol-Myers Squibb: Employment. Chen:Bristol-Myers Squibb: Employment. Bahceci:Bristol-Myers Squibb: Employment. Deininger:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Calistoga: Research Funding; Genzyme: Research Funding.

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