Zevalin clinical data presented at 2009 ASH meeting

Spectrum PharmaceuticalsDec 11 2009

Spectrum Pharmaceuticals, Inc. (NasdaqGM:SPPI), a commercial stage biotechnology company with a primary focus in oncology, today announced that clinical data on ZEVALIN (ibritumomab tiuxetan) was presented at the 51st Annual Meeting of the American Society of Hematology (ASH), which was held December 5-8, 2009 at the Ernest N. Morial Convention Center in New Orleans, Louisiana.

The following are three key ZEVALIN-related abstracts of the 14 that were presented at the conference.

Shown below are the summary descriptions of study Patients and Methods, Results, and Conclusions, as shown on the ASH website.

Abstract #2720 – A Phase II Trial of Rituximab-CHOP Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (90Y-IT) for Previously Untreated Elderly Diffuse Large B-Cell Lymphoma (DLBCL) Patients

Introduction: In 2008 we published a phase II trial about the combination of 6 cycles of CHOP plus 90Y-IT for previously untreated elderly patients with DLBCL. The CCR was 95% with OS at 2 years of 95% and PFS at 2 years of 75%. The results of this study support a further evaluation of 90Y-IT in combination of chemotherapy. We conducted a prospective, single-arm, non-randomized, phase II trial with CHOP plus Rituximab followed by 90Y-IT reducing the number of CHOP cycles from 6 to 4 but introducing Rituximab. The rationale is to utilize all the therapeutic approaches (chemotherapy, immunotherapy and radioimmunotherapy) reducing conventional chemotherapy and probably related toxicity.

Patients and Methods: Patient eligibility was represented by: patients older than 60 years with biopsy proven, untreated, bidimensionally measurable stage II, III or IV DLBCL. Expression the CD-20 antigen; WHO performance status of 0 to 2. Patients were treated with standard CHOP chemotherapy plus Rituximab every 21 days for 4 cycles. Patients were restaged 4 to 6 weeks after completion of 4 cycles of R-CHOP chemotherapy. Patients achieving CR, PR or SD after chemotherapy were eligible for consolidation with 90Y-IT provided the granulocyte count was greater than 1500/microl, the platelet count exceeded 100.000/microl and the bone marrow examination at the completion of chemotherapy demonstrated no more than 25% involvement with lymphoma. All patients were to receive a single dose of 90Y-IT 14.8 MBq/kg (0.4 mCi/kg). Fifty-five patients have been enrolled: 26 were male and 29 female; the median age was 70 years (range 60-83); 17 were stage II, 38 were stage III-IV.

Results: Fifty-one patients had completed the R-CHOP treatment and the overall response rate was 94.1% including 30 (58.8%) of patients in CR and 17 (35.3%) in PR. Treatment was well tolerated; grade 3-4 AEs are comparable with previous experience and the most common grade 3-4 AEs was neutropenia. At this time 47 patients had just received 90Y-IT and 45 are evaluable. In particular, 9/17 (52.9%) patients converted from PR to CR after treatment with 90Y-IT.

Conclusions: These preliminary data indicate that radioimmunotherapy appears highly effective and feasible as “consolidation” after 4 cycles of immunochemotherapy in elderly DLBCL patients, improving quality of response without any cumulative toxicity.

Disclosures: Off Label Use: The drug Yttrium 90 (90Y) Ibritumomab Tiuxetan (90Y-IT) (Zevalin) is off-label for Diffuse Large B-Cell Lymphoma (DLBCL).

ZEVALIN is not approved for the use described in the above abstract.

Abstract #3743 – A Phase II Trial of R-FM (Rituximab, Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (90Y-IT) for Untreated Follicular Lymphoma (FL) Patients

Introduction: In 2008 we published a multicenter non-randomized phase II trial of fludarabine and mitoxantrone plus 90Y-IT in untreated patients with FL. By the end of the entire treatment regimen 95% of the patients achieved complete remission (CR). With a median follow-up of 30 months, 3-year PFS was estimated to be 76% and 3-year OS 100%. On the basis of these results we are currently conducting a prospective, multicenter, non-randomized, phase II study of R-FM followed by 90Y-IT in untreated patients with FL in which the number of fludarabine and mitoxantrone cycles has been decreased to four and in which rituximab is administered before each cycle. The rationale of the trial is to use different forms of treatment and to reduce the use of conventional chemotherapy and its related toxic effects.

Patients and Methods: Patients eligibility is represented by: age more than 18, stage II-IV, FL grade I-II, WHO performance status 0-2. Patients are treated with standard FM chemotherapy plus rituximab every 28 days for 4 cycles. Patients are restaged 4 to 8 weeks after completion of immunochemotherapy and those achieving at least a partial response are eligible for 90Y-IT. All patients receive a single dose of 90Y-IT 14.8 MBq/kg. At the time of the analysis we enrolled 55 patients. 25 patients were male and 30 female; the median age was 56 years (range 26-84); 12 patients were stage II, 13 stage III and 30 stage IV; 11 patients had a bulky disease. 52 patients completed the induction chemotherapy, all except 5 were eligible for the consolidation treatment with 90Y-IT and 44 patients were restaged after the entire treatment regimen.

Results: After the R-FM chemotherapy, the overall response rate was 92.3% (48/52) including 39 (75%) CR and 9 (17.3%) partial remissions (PR). Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated grade 3-4 haematologic AEs (mostly neutropenia) were seen in 50% of the patients. Among the 44 patients (9 PR and 35 CR) subsequently treated with 90Y-IT and reassessed for the response, 8/9 (88.9%) PR patients improved their remission status from PR to CR. 90Y-IT toxicity included mostly grade 3-4 neutropenia and thrombocytopenia and was comparable to the literature data.

Conclusions: These preliminary data indicate that radioimmunotherapy appears highly effective and feasible as “consolidation” after short (4 cycles) immunochemotherapy in FL patients, improving quality of response without any cumulative toxicity.

Abstract 868 – Stem Cell Transplantation with 90yttrium Ibritumomab Tiuxetan (90YIT) in Non-Hodgkin’s Lymphoma (NHL): Observations from PET Pre-Treatment Imaging and Responses in Allografted Refractory Follicular Histologies

Background: Relapse continues to be the primary cause of treatment failure in patients (pts) with NHL undergoing transplantation. We have previously reported the adverse prognostic value of PET+ in autologous transplants (AUTO) and disease refractoriness in pts undertaking a non-myeloablative allogeneic transplantation (NST). In order to improve outcome, we and others have previously established the feasibility of addition of 90YIT to the transplant conditioning. Herein, we report the long-term efficacy of this strategy in 74 pts.

Methods: Each pt received a single dose of 90YIT (0.4 mCi/kg on day -14) with BEAM as a conditioning regimen in AUTO candidates [relapsed chemosensitive diffuse large cell b-cell (DLBCL); relapsed chemosensitive follicular (FL) if no matched sibling donor was available; mantle cell (MCL) in first remission; age ≤ 65], or with fludarabine, cyclophosphamide and rituximab (Blood 2008:111:5530) in candidates for NST (relapsed chemosensitive or refractory FL and MCL, transformed NHL if not candidates for AUTO, CLL, up to 50% marrow involvement with disease, age ≤ 70).

Results: This cohort included 40 pts>

Conclusions: These data provide evidence that combining 90YIT at 0.4mCI/kg with the conditioning improves outcomes in NHL pts undergoing AUTO or NST, but not in CLL. Our results also represent the first report showing that the combination may overcome the negative prognostic value of PET+ in NHL, and that the addition of 90YIT to NST conditioning can induce long-term remission in relapsed refractory FL without added toxicity. Verification of our results in a larger cohort of pts is highly warranted.

ZEVALIN is not approved for the use described in the above abstract.

For more information about the ASH annual meeting and for a complete list of abstracts, including additional abstracts presented about ZEVALIN, please refer to the conference Web site at www.hematology.org.