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.