Spectrum announces various clinical studies on ZEVALIN at ICML 2011

Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in oncology, today announced that various studies on ZEVALIN^® (ibritumomab tiuxetan) for Injection were presented at the 11^th International Conference on Malignant Lymphoma (ICML), held June 15-18, 2011, in Lugano, Switzerland. The ICML is a major international scientific conference held every two years and is focused specifically on lymphomas.

"We are pleased that ZEVALIN continues to be a significant focus of research in the treatment of lymphoma, both indolent and aggressive subtypes, and in the autologous transplant setting," said Rajesh C. Shrotriya, MD, Chairman, Chief Executive Officer, and President of Spectrum Pharmaceuticals. "All of the studies presented conclude that ZEVALIN is a safe and effective treatment option for the treatment of lymphoma."

Oral Session - Controversies in Follicular Lymphomas

ZEVALIN Consolidation vs. Rituximab-Maintenance in First Remission Follicular Non-Hodgkin's Lymphoma - The Case for RIT

In an oral discussion on the topic of "Controversies in Follicular Lymphomas," Anton Hagenbeek, MD, from the Academic Medical Center in Amsterdam, Netherlands, and one of the principal investigators of the FIT Study, which served as the basis for ZEVALIN's 2009 approval in the first-line consolidation setting, gave an oral presentation entitled Radio-Immunotherapy Consolidation vs. Rituximab-Maintenance in First Remission Follicular Non-Hodgkin's Lymphoma - The Case for RIT. During his oral presentation, Dr. Hagenbeek provided a comparative evaluation of the ECOG 1496 Study, in which newly diagnosed patients with indolent lymphoma were induced with CVP and responders were subsequently randomized between rituximab maintenance, once per week for 4 weeks every 6 months x4; and the FIT trial, where various chemo-induction regimens were allowed after which partial responders (PR) or complete responders (CR) were randomized between one infusion of ZEVALIN versus no further treatment. CR rates after induction chemotherapy were 16% (ECOG) versus 52% (FIT), increasing to 37% (ECOG) and 87% (FIT), due to 22% and 78%, respectively, of patients in PR converting to CR. With more than 4 years (ECOG) and 6-½ years (FIT) median follow-up, the median PFS was prolonged with ZEVALIN by 3 years in both studies, as compared to controls. In patients achieving a CR after ZEVALIN, the PFS increased more than 5 years as compared to controls (median PFS >92 months after 1 infusion of ZEVALIN).

"A single infusion of ZEVALIN matched roughly 16 infusions of rituximab in terms of achieving the same increase in PFS," said Dr. Hagenbeek. "I leave it up to the audience to draw conclusions about cost effectiveness. Thus, in conclusion, RIT represents the most effective single drug in the treatment of follicular NHL."

Poster Session - Mantle Cell Lymphoma

Abstract #017 - Phase 2 Study of R-CHOP followed by ⁹⁰Y-Ibritumomab Tiuxetan (ZEVALIN) in Untreated Mantle Cell Lymphoma (MCL): 5-Year Follow-Up of Eastern Cooperative Oncology Group E1499

M.R. Smith, MD, from the Medical Oncology division of the Fox Chase Cancer Center in Philadelphia, PA, reported on a study to determine safety and efficacy of the anti-CD20 radioimmunoconjugate ⁹⁰Y-ibritumomab tiuxetan following 4 cycles of R-CHOP induction.

Dr. Smith, et al., concluded that ⁹⁰Y radioimmunotherapy (RIT) after R-CHOP x4 in untreated MCL is safe and improves percent of response and the quality of response. ⁹⁰Y-RIT consolidation is applicable to most patients with MCL and met the primary endpoint of 50% prolongation of time to treatment failure (TTF) over that expected for R-CHOP x6 alone. While there is no apparent plateau in TTF, median overall survival is not yet reached at 5 years. Overall survival at 3 and 5 year compares favorably with reports using more intensive therapy, calling into question the need for intensive initial therapy.

Poster Session - Autologous Transplant

Poster #256 - Upfront Consolidation with Targeted Intensification Utilizing Yttrium-90 Ibritumomab Tiuxetan (ZEVALIN) and High Dose Therapy in Poor Prognosis Patients with Diffuse Large B-Cell Lymphoma - Z-BEAM 2 Study

In a poster session on transplantation, Christophe Fruchart, MD, from the Centre Francois Baclesse, in Caen, France, described a Phase 2 trial that evaluated the safety and efficacy of standard-dose 90Y ibritumomab tiuxetan (ZEVALIN) combined with high-dose BEAM (Z-BEAM) after first line treatment in patients under 65 years of age with poor prognosis DLBCL.

The role of high dose therapy (HDT) and autologous stem cell transplantation (ASCT) as a first line therapy in poor risk patients with DLBCL is still discussed. The addition of ZEVALIN to HDT regimen has been preliminarily tested in refractory or relapsed B-cell lymphomas. Overall studies have shown that this approach offered minimal additional toxicity compared with chemotherapy alone and had also yielded good efficacy.

Dr. Fruchart, et al., concluded that in selected patients with poor prognosis factors, adding ZEVALIN to high-dose BEAM is safe without an increase in transplant-related toxicity or delayed engraftment. Rate of progression free survival is encouraging and warrants a randomized study.

Poster Session - Autologous Transplant

Abstract #254 - Minimum Tolerable Interval of ⁹⁰Yttrium Ibritumomab-Tiuxetan (ZEVALIN) to Autologous Stem Cell Transplantation After High-Dose Chemotherapy with Carmustin, Etoposide, Cytarabine, Melphalan is 10 days. First Results From DSHNHL Esc Z-BEAM Trial for Relapsed or Refractory Aggressive B-NHL

J. Hasenkamp, MD, from the Hematology and Oncology Division of the University Medicine Goettingen, in Goettingen, Germany, presented a poster reporting on the interval for ZEVALIN administration when combined with autologous transplantation. Previously it was reported that high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) is significantly less effective in patients with aggressive B-cell lymphoma if first-line therapy included rituximab (Gisselbrecht et al. JCO 2010). Combining BEAM with radioimmunotherapy (ZEVALIN) is a promising option to enhance the efficacy of the high-dose regimen.

ZEVALIN (0.4 mCi/kg body weight) at day -10 before ASCT was determined as minimum tolerated interval of radioimmunotherapy to ASCT after BEAM. Median follow-up is 18 months. Three-year PFS and OS is 59% and 73%, respectively. Z-BEAM followed by ASCT was safe and feasible and results in a high response rate in rituximab pretreated patients with aggressive B-cell lymphoma. Extended studies at the maximum tolerated dose are warranted.

Abstract #257 - Significant Improvement in Overall Survival in High-Risk Aggressive B Cell Non-Hodgkin's Lymphoma After ⁹⁰Yttrium Ibritumomab Tiuxetan-Beam Followed by Autologous Stem Cell Transplantation

M. Wondergerm, MD, from the Hematology division of the VU University Medical Center in Amsterdam, Netherlands, presented a poster stating high dose chemotherapy followed by autologous stem cell transplantation (AuSCT) induces long term disease free survival in 50-60% of patients with diffuse large B cell lymphoma (DLBCL) after rituximab containing (re-) induction therapy. Adding ⁹⁰Yttrium ibritumomab tiuxetan prior to the BEAM conditioning regimen has proven to be feasible and shows promising results with respect to disease free and overall survival in high risk DLBCL patients. At the VU University Medical center, rituximab was added to (re-) induction therapy starting July 2001. From 2006 they started to add ⁹⁰Yttrium ibritumomab tiuxetan (ZEVALIN) to BEAM (Z-BEAM) in DLBCL patients. In this retrospective analysis they compare outcome after Z-BEAM with outcome after BEAM, both followed by AuSCT.

Dr. Wondergerm, et al., concluded that adding ⁹⁰Yttrium ibritumomab tiuxetan to the BEAM conditioning regimen preceding AuSCT leads to a significant improvement in overall survival in relapsed, refractory or transformed NHL patients. Addition of ⁹⁰Yttrium ibritumomab tiuxetan did not result in decreased bone marrow reserve or non haematological long term sequelae enabling treatment of relapse including allogeneic SCT.

Poster Session - Positron Emission Tomography

Abstract #216 - Discriminatory Power of the ¹¹¹Indium Scan (¹¹¹In) in the Prediction of Altered Biodistribution of Radio-Immunoconjugate in the ⁹⁰-Yttrium Ibritumomab Tiuxetan (ZEVALIN) Therapeutic Regimen: Meta-Analysis of Five Clinical Trials and 9 Years of Clinical Experience in 45 Countries

Jelle Kylstra, MD, Clinical Development, Spectrum Pharmaceuticals, discussed in a poster data supporting the removal of the bioscan requirement.

At the time of regulatory approval of Y-90 ibritumomab tiuxetan (ZEVALIN^®), 3 countries (USA, Switzerland, Japan) required labeling specifying that an Indium-111 (¹¹¹In) scan be performed 7-9 days before the therapeutic dose, to guard against the hypothetical risk that altered bio-distribution (AB) of the immunoconjugate could cause unintended end-organ damage; 42 other countries (incl. EU, Canada) approved ZEVALIN without requiring the ¹¹¹In scan.

Methods:

In 5 clinical trials, 11 of 253 scans (4.3%) showed AB based on local review. In only 3 of these patients, the local finding of AB was confirmed in central review. Of patients with 111-In scans reviewed by a trained reader in central review, 3/233 (1.3%) were found to have true AB and 7/233 (3%) were found to have had a false positive local judgment of AB. Three patients with true AB on central review who had proceeded with 90-Y Z treatment based on a scan result locally judged normal, showed safety and efficacy outcomes within the range of those shown by other patients on study. Comparison of post-marketing safety databases between countries with (USA, CH, JP) and without (Rest of World) 111-In requirement showed no differences in the general pattern of safety signals reported, with respectively 3% and 4% of patients reporting grade III/IV bone marrow suppressive states, and anaphylactoid responses reported at 0.3% in both geographic clusters.

Dr. Kylstra, et al., concluded that the 111-In scan shows poor discriminatory power in identifying cases of AB. Analysis of safety results of patients treated with 90-Y Z despite true AB does not indicate that removal of the 111-In requirement from the ZEVALIN labeling in countries currently requiring it would constitute a safety risk.

Poster Session - New Drug Combinations

Abstract #113 - Short Course Fludarabine, Mitoxantrone, Rituximab Followed by ⁹⁰Y-Ibritumomab Tiuxetan in Untreated Intermediate/High-Risk Follicular Lymphoma: A Phase II Trial

P.L. Zinzani, MD, from the Institute of Haematology and Medical Oncology from the University of Bologna, Italy, presented a poster describing the use of ZEVALIN in combination with fludarabine, mitoxantrone and rituximab (FMR) for the treatment of untreated intermediate/high-risk follicular lymphoma in a Phase 2 clinical trial.

An innovative approach combining induction chemotherapy and subsequent consolidation with ⁹⁰Yttrium-ibritumomab-tiuxetan (⁹⁰Y-IT) has been upgraded by shortening the chemotherapy duration and by insertion of rituximab, in untreated follicular non-Hodgkin's lymphoma (NHL).

Dr. Zinzani, et al., concluded that this study has established the feasibility, tolerability, and efficacy of a regimen composed by a short FMR induction with a ⁹⁰Y-IT consolidation in untreated intermediate/high-risk follicular NHL patients.

Source: Spectrum Pharmaceuticals, Inc.