Role of Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) in Inducing and Maintaining Complete Molecular Response in B Non Hodgkin’s Lymphoma Patients in Clinical Complete Remission after Chemotherapy Regimen.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4498-4498 ◽  
Author(s):  
Enrico Orciuolo ◽  
Gabriele Buda ◽  
Sara Galimberti ◽  
Giuseppe Boni ◽  
Nadia Cecconi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
B Cell ◽  
Hodgkin's Lymphoma ◽  
Molecular Response ◽  
Consolidation Therapy ◽  
Ibritumomab Tiuxetan ◽  
Complete Molecular Response

Abstract Introduction: Radioimmunotherapy (RIT) is a new treatment for B non Hodgkin’s lymphoma (NHL) patients. 90Y ibritumomab tiuxetan (Zevalin®) consists of a murine monoclonal antibody to CD20, conjugated to a metal chelator tiuxetan for retention of the beta emitter 90Y. Thus Zevalin® delivers radiation to B-NHL, combining the tumor targeting attributes of a monoclonal antibody and the beta radiation of 90Y. Zevalin® is approved for the treatment of follicular lymphoma (FL) refractory to or relapsed after rituximab, on the bases of clinical trials where it achieved a response rate as high as 83%. Several ongoing registrational trials are evaluating the efficacy of Zevalin® in other NHL, as diffuse large B cell (DLCL) and mantle cell lymphoma (MCL). We are here evaluating the effect of Zevalin® as consolidation therapy in NHL patients that achieved a complete clinical response (CCR) with chemotherapy. Methods: In B cell NHL patients that achieved a CCR after 1st or multiple lines anthracyclines based chemotherapy +/− Rituximab, minimal residual disease was evaluated by PCR on bone marrow samples, for the following rearrangements: JH, Bcl-1, Bcl-2. Patients received Zevalin® 6-9 weeks post chemotherapy. Evaluation of molecular response was assessed after a follow up period at 12 weeks. The aim of the study was the role of Zevalin® in inducing a complete molecular response (CMR). Results: 23 B-NHL patients (13 FL, 6 MCL, 4 DLCL; male:female 13:10, median age 63, range 42–73. See table) in a CCR after chemotherapy (documented by TC scan and/or PET-scan negative for abnormal lesions or glucose captation) have been enrolled. 10 patients had a pathological rearrangement before RIT, while 13 were already in a CMR condition. Zevalin® was completed in all 23 patients and the post infusion evaluation was performed after 12 weeks. In the follow-up period thrombocitopenia was commonly documented, but it was not associated to bleeding or need of platelet transfusion, but in one singular case. After 12 weeks from RIT a new molecular evaluation was performed on bone marrow samples. All the 23 patients have completed the 12 weeks follow-up: 8 of 10 (80%) patients positive before RIT achieved a CMR with Zevalin® administration. The 13 PCR negative patients maintained the CMR. The 21 PCR negative patients are now under follow-up to evaluate the molecular disease free survival after Zevalin® RIT. Conclusion: Zevalin® is an efficient consolidation therapy in B cell NHL patients after chemotherapy. In this series of patients Zevalin® administration allowed to convert 8 of 10 CCR to CMR. In the remaining 13 patients Zevalin® maintained the CMR. Zevalin® addition to medication treatment is feasible and associated with manageable hematological toxicity. Pts disease sex age previous chemotherapy lines molecular response before RIT molecular response after RIT 1 FL M 68 1 POS NEG 2 FL F 53 1 NEG NEG 3 FL M 54 1 NEG NEG 4 FL M 51 4 NEG NEG 5 DLCL F 66 2 POS NEG 6 DLCL F 67 1 NEG NEG 7 FL F 42 1 POS POS 8 FL M 52 1 POS NEG 9 FL F 54 3 NEG NEG 10 FL M 57 2 POS NEG 11 FL F 62 2 POS NEG 12 FL M 58 2 POS NEG 13 FL F 69 2 NEG NEG 14 MCL M 62 1 POS NEG 15 MCL M 66 1 POS POS 16 MCL M 66 2 NEG NEG 17 MCL M 67 1 POS NEG 18 FL F 67 2 NEG NEG 19 DLCL F 67 3 NEG NEG 20 MCL M 70 2 NEG NEG 21 FL M 61 4 NEG NEG 22 DLCL M 43 2 NEG NEG 23 MCL F 73 2 NEG NEG

90Y-Ibritumomab Tiuxetan Followed by Rituximab Is a Safe Treatment Option for Relapsed or Refractory Diffuse Large B-Cell Non-Hodgkin s Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2866-2866
Author(s):  
Katarina Luptakova ◽  
Michelle Kim ◽  
Pamela Ely ◽  
Barbara Grant ◽  
John Anthony Parker ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Research Funding ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Baseline Platelet Count ◽  
Large B Cell

Abstract Abstract 2866 Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy and is generally responsive to anthracycline-containing chemotherapy. However, 60% of patients (pts) will relapse after their first line treatment. At the time of relapse the only curative approach includes the use of a stem cell transplant (SCT). The incidence of DLBCL increases with age which creates a subset of pts who are not candidates for first line anthracycline-based chemotherapy, and a large subset of pts who are not candidates for SCT due to advanced age and/or co-morbidities. Thus, there is a significant unmet need for therapies with a low toxicity profile in elderly or medically unfit pts with DLBCL. 90Y-ibritumomab tiuxetan (90Y-IT) is an anti-CD20 murine antibody linked with a beta-emitting isotope approved for use in 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. Patients and Methods: Eligible pts were either intolerant of anthracycline-based chemotherapy or had relapsed or refractory CD20+ DLBCL with measurable disease. Pts had to be ineligible for SCT for reasons other than failure to harvest stem cells. Bone marrow involvement by lymphoma of less than 25% based on bilateral bone marrow aspirate and biopsy was required. R 250 mg/m2 was administered IV immediately followed by 111In-ibritumomab tiuxetan. Nuclear scans were performed at 24 and 48 hours to insure there was no altered biodistribution. On day 8 a second infusion of R 250 mg/m2 followed by 0.4 mCi/kg (for pts with a baseline platelet count >150,000/mm3) or 0.3 mCi/kg 90Y-IT (for pts with a baseline platelet count 100,000-149,000/mm3) was given. Pts with multiple extranodal sites or prior bone marrow involvement received CNS prophylaxis with intrathecal methotrexate or cytarabine. Maintenance R 375 mg/m2 was given on weeks 3–6, then weekly × 4 every 6 months × 4 cycles or until progression. Results: Between 10/2003 and 9/2009, 25 pts have been treated. During the course of the study, the ownership of the therapeutic agent changed three times and therefore enrollment was interrupted on two occasions. The median age of pts was 79 (range 45–91), 36% pts had a sIPI score 3 or more. The median number of prior regimens is 2 [0-5]. The 90Y-IT treatment regimen produced an overall response rate of 36% [9 pts] with 28% CR [7 pts]. To date, the mean OS is 18 months (median 8.1 months) with a median follow-up of 11.2 months. Among responding pts, the median OS has not been reached with a median follow-up of over 26.2 [0.1-71.4] months. Thirteen pts died within the first year, 6 patients (24%) continue to be in remission greater than 18 months, and 4 patients (16%) remain in long-term remission [39.9-71.4 months]. The most frequently observed toxicity was hematologic. Eleven percent of pts had grade 4 neutropenia with only one patient experiencing febrile neutropenia, and 16% of pts experienced grade 4 thrombocytopenia. There were no unexpected non-hematologic toxicities except for 1 patient that experienced extravasation. One late-occurring case of MDS/AML was reported that is possibly related to the study regimen, and one case of adenocarcinoma of the GI tract that is likely unrelated. Of note, none of the pts that progressed on the chemotherapy preceding this study achieved a response to the study regimen. Conclusions: The 90Y-IT treatment regimen has an acceptable toxicity profile in elderly or heavily pretreated pts with DLBCL. The two week outpatient 90Y-IT infusion produces response rates and durations similar to that of more prolonged cytotoxic chemotherapy regimens. Progression on previous chemotherapy predicts for poor response to 90Y-IT. Treatment with 90Y-IT can provide durable remission to a select subset of pts who are not candidates for SCT, or intensive anthracycline based chemotherapy. Disclosures: Off Label Use: We are describing a phase II study of the use of 90Y-Ibritumomab Tiuxetan for treatment of diffuse large B-cell lymphoma. Current FDA approved use of 90Y-Ibritumomab Tiuxetan includes relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL) or previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy. Joyce:Spectrum Pharmaceuticals, Inc.: Research Funding; Cell Therapeutics Inc: Research Funding; Biogen Idec: Research Funding.

Phase I Trial of Combination Therapy with 90Y Ibritumomab Tiuxetan and Gemcitabine in Patients with Non-Hodgkin’s Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4710-4710
Author(s):  
Hossein Borghaei ◽  
Mitchell Smith ◽  
Michael Millenson ◽  
Danielle Shafer ◽  
Linda Thibodeau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Phase I Trial ◽  
Hodgkin's Lymphoma ◽  
Hematologic Toxicity ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin's Lymphoma ◽  
Grade 3

Abstract Y90-ibritumomab tiuxetan, or Zevalin (Z), is an effective therapy against CD20+ lymphomas and is approved for use in patients with relapsed or refractory low grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL). Gemcitabine also is active against NHL and is a potent radiation sensitizer. We are conducting a phase I trial to assess the safety of concomitant administration of Z and gemcitabine in patients with NHL. Nine patients in three cohorts will be treated with 250 mg/m2 of gemcitabine IV on days 1 and 8 of the Z treatment program of rituximab + In 111-ibritumomab on day 1 and rituximab + Y90 ibritumomab on day 8, with Z at 0.2, 0.3 or 0.4 mCi/kg respectively. The next cohort can only accrue after all patients in the prior cohort have hematologic toxicity that has recovered to grade 0–2 or after 60 days from the date of the last treated patient in the previous cohort. Once it is confirmed that a Z dose of 0.4 mg/kg can be safely administered with gemcitabine 250 mg/m2, Z will remain constant at 0.4 mCi/kg while gemcitabine will be escalated according to a Bayesian based system. Response evaluation is by standard criteria. Eligibility criteria include: any histology of recurrent NHL (not candidates for high dose therapy), platelets ≥ 150,000/ul; < 25% bone marrow involvement by lymphoma; prior radiation to <25% radiation of bone marrow and no prior bone marrow or stem cell transplant. Seven patients have been treated thus far, four with follicular NHL (FL) and three with diffuse large B cell (DLBCL). Median age is 74 (range 55–82). The median number of prior treatments is 3 (range 1–6). The first three patients received Z at 0.2 mCi/kg, next three patients 0.3 mCi/kg and the seventh patient has received standard 0.4 mCi/kg of Z, all with 250 mg/m2 of gemcitabine on days 1 and 8. Toxicity has consisted of: one grade 3 and two grade 2 neutropenia in the first three weeks, three grade 3 leukopenia and one grade 2 in the first 4 weeks of the trial, three grade 2 anemia (one patient has remained with grade 2 anemia for 14 weeks), four grade 2 thrombocytopenia in weeks 6 through 12, and one grade 3 thrombocytopenia in weeks 8&9 resolving to grade 2 (this patient received standard dose of Z). One grade 3 infection occurred, unrelated to the protocol or the study drugs. No grade 3 or 4 non-hematologic toxicity has been seen. In follow up, two patients with FL and one with DLBCL achieved CRu. Two patients with DLBCL and one with FL have progressed. One patient with FL is not yet evaluable. Conclusion: Our preliminary findings suggest that Zevalin can be safely combined with gemcitabine 250 mg/m2 in the treatment of patients with NHL. Accrual to the cohort with full dose Zevalin and gemcitabine is continuing.

Phase I Trial of Combination Therapy with 90y Ibritumomab Tiuxetan and Gemcitabine in Patients with Non-Hodgkin's Lymphoma, Final Report.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2753-2753
Author(s):  
Hossein Borghaei ◽  
Russell J. Schilder ◽  
Samuel Litwin ◽  
Michael Millenson ◽  
Adam D Cohen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
B Cell ◽  
Research Funding ◽  
Phase I Trial ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin's Lymphoma ◽  
Grade 3

Abstract Abstract 2753 Y90-ibritumomab tiuxetan radioimmuotherapy (Y90-RIT) is an effective therapy against CD20+ lymphomas approved for use in patients (pts) with relapsed/refractory low grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), as well as consolidation of first remission low grade NHL. Gemcitabine (Gem) also is active against NHL and is a potent radiation sensitizer. We conducted a phase I trial to assess the safety of concomitant administration of Y90-RIT and G in patients with NHL. Eligible pts had any histologic subtype of recurrent CD20+ NHL (not candidates for potentially curative options) and met standard Y90-RIT criteria: platelets 150,000/ul; < 25% bone marrow involvement by lymphoma; prior radiation to <25% of bone marrow and no prior bone marrow or stem cell transplant. Initially, nine pts in three cohorts were treated with 250 mg/m2 of Gem IV on days 1 and 8 of the Y90-RIT treatment program (rituximab + 111In-ibritumomab day 1 and rituximab + Y90 ibritumomab day 8), with Y90-RIT at 0.2, 0.3 or 0.4 mCi/kg respectively. We confirmed that a standard Y90-RIT dose of 0.4 mg/kg can be safely administered with Gem at 250 mg/m2. In subsequent cohorts, escalating doses of Gem were used according to a Bayesian based system. Response evaluation was by CT scan criteria (IWG JCO 1999). Between 2004–2012, twenty pts were treated (10 follicular (FL), 3 marginal zone (MZL), 7 diffuse large B-cell (DLBCL) lymphomas). Median age is 71.5 (range 55–82). The median number of prior treatments is 3 (range 1–6). Gem doses ranged from 250 mg/m2 to the maximum planned dose of 800 mg/m2 on days 1 and 8. One DLT occurred (thrombocytopenia) and MTD was not reached. Treatment-related toxicities consisted of grades 3 (N=11) and 4 (N = 2) neutropenia, grade 3 (N=11) leukopenia, grades 3 (N=14) and 4 (N=8) thrombocytopenia. One grade 3 infection occurred, unrelated to study drugs. All pts recovered counts to ≤ grade 1 by week 12. The only grade 3 non-hematologic toxicity was elevated bilirubin in 1 and increased GGT in 2 pts. Best responses seen include: 3 CR/CRu, 7 PR, 4 SD, 4 PD and 2 patients still in follow up. Median PFS for all patients is 192 days. Median PFS for all non-DLBCL histologies (10 FL and 3 MALT) is 202 days and for DLBCL is 77 days. Conclusion: Standard dose Y90-RIT combined with gemcitabine days 1 and 8 is safe and well-tolerated at doses up to 800 mg/m2 in pts with relapsed/refractory NHL. Further investigation with the established doses in non-DLBCL histologies is warranted. Disclosures: Borghaei: Biogen-IDEC: Research Funding. Off Label Use: 90Y Ibritumomab Tiuxetan in relapsed DLBCL. Schilder:Biogen-IDEC: Research Funding. Smith:Biogen-IDEC: Research Funding.

CAMPATH-1H monoclonal antibody in therapy for previously treated low-grade non-Hodgkin's lymphomas: a phase II multicenter study. European Study Group of CAMPATH-1H Treatment in Low-Grade Non-Hodgkin's Lymphoma.

1998 ◽  
Vol 16 (10) ◽  
pp. 3257-3263 ◽  
Author(s):  
J Lundin ◽  
A Osterborg ◽  
G Brittinger ◽  
D Crowther ◽  
H Dombret ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
B Cell ◽  
Mycosis Fungoides ◽  
Phase Ii ◽  
Infectious Complications ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Non Hodgkin's Lymphoma ◽  
Previously Treated

PURPOSE CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B-cell and T-cell lymphomas. We report here the results of a multicenter phase II trial of CAMPATH-1H in patients with advanced, low-grade non-Hodgkin's lymphoma (NHL) who were previously treated with chemotherapy. PATIENTS AND METHODS Fifty patients who had relapsed (n=25) after or were resistant (n = 25) to chemotherapy were treated with CAMPATH-1H 30 mg administered as a 2-hour intravenous (i.v.) infusion three times weekly for a maximum period of 12 weeks. RESULTS Six patients (14%) with B-cell lymphomas achieved a partial remission (PR). Patients with mycosis fungoides appeared to respond more frequently (50%; four of eight patients, which included two complete remissions [CRs]). Lymphoma cells were rapidly eliminated from blood in 16 of 17 patients (94%). CR in the bone marrow was obtained in 32% of the patients. Lymphoma skin lesions disappeared completely in four of 10 patients and partial regression was obtained in three patients. Lymphadenopathy and splenomegaly were normalized in only 5% and 15% of patients, respectively. Lymphopenia (< 0.5 x 10(9)/L) occurred in all patients. World Health Organization (WHO) grade IV neutropenia occurred in 14 patients (28%). Opportunistic infections were diagnosed in seven patients and nine patients had bacterial septicemia. Death related to infectious complications occurred in three patients. CONCLUSION CAMPATH-1H had a significant but limited activity in patients with advanced, heavily pretreated NHL. The most pronounced effects were noted in the blood and bone marrow and in patients with mycosis fungoides. The risk for serious infectious complications needs to be considered for severely ill patients who are evaluated for CAMPATH-1H treatment.

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