Millennium presents three studies in relapsed multiple myeloma at IMW meeting

May 6 2011

Millennium: The Takeda Oncology Company today reported results from three studies in relapsed multiple myeloma (MM). Two of the studies examined the use of VELCADE® (bortezomib) for Injection; the third study presents clinical data on MLN9708, the first investigational oral proteasome inhibitor.

"In these studies, VELCADE based therapy provided median overall survival results ranging from 20 to 29 months, underscoring the importance of VELCADE in treating patients with relapsed multiple myeloma, including those who had previously been treated with it," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "Further, the presentation of clinical data from MLN9708 represents an important milestone in Millennium's continued leadership as pioneers in the field of protein homeostasis."

Bortezomib Retreatment in Patients With Relapsed Multiple Myeloma (MM) In Switzerland

This retrospective analysis examined 42 patients who had previously responded to VELCADE therapy and were retreated with Velcade either as monotherapy or in combination. The results, which were presented by Christian Taverna, M.D., Medizinische Klinik, Munsterlingen, Switzerland, showed:

• After initial VELCADE therapy, ORR was 100 percent and the CR/nCR rate was 33 percent
• After retreatment with VELCADE, ORR was 64 percent and the CR/nCR rate was 29 percent
• Of the patients who achieved an initial CR/nCR, 86 percent achieved a CR/nCR with retreatment
• Median duration of response with VELCADE retreatment was 12.6 months
• Median overall survival since initial VELCADE treatment was 3.5 years
• Median overall survival after VELCADE retreatment was 20 months
• The most common adverse events were nervous system (12 percent), heme-lymphatic (7 percent) and general disorders (7 percent)

The study was retrospective and conducted at 26 Swiss centers. Adults with relapsed MM who had responded to prior VELCADE treatment (partial response or better) were eligible to receive VELCADE retreatment, either as monotherapy or in combination. From 2005-2009, data from patient forms and clinical records were collected to evaluate the efficacy and safety of VELCADE retreatment in patients with MM. Patients were heavily pretreated and received a mean of three prior therapies (range 1-11) before initial VELCADE treatment.

Efficacy of Bortezomib plus Dexamethasone versus Bortezomib Monotherapy in Patients with Relapsed/Refractory Multiple Myeloma (MM): Interim Results from an International Electronic Observational Study
This prospective observational study evaluated 432 relapsed/refractory multiple myeloma patients. The results, presented by Meletios-Athanassios Dimopoulos, M.D., University of Athens School of Medicine, Athens, Greece, showed:

• ORR was 72.7 percent in the VELCADE-dexamethasone arm, compared to 68.4 percent in the VELCADE arm (p>0.05)
• CR rate was 24.1 percent in the VELCADE-dexamethasone arm, compared to 8.2 percent in the VELCADE arm
• Median overall survival was 29 months in the VELCADE-dexamethasone arm, compared to 26 months in the VELCADE arm (p>0.05)
• Forty-seven percent of patients in the VELCADE arm had received at least two prior therapies; 39 percent of patients in the VELCADE-dexamethasone arm had received at least two prior therapies
• Safety data were not reported

This international, non-interventional electronic VELCADE^® observational study (eVOBS) is ongoing to prospectively assess clinical and health economic outcomes of VELCADE based therapies for relapsed/refractory MM in a clinical practice setting. Only patients who received VELCADE monotherapy or VELCADE + dexamethasone during the three-year study period were included in this analysis. All administered VELCADE doses and concomitant treatments (except investigational therapies) were permitted. Investigator-defined responses were based on EBMT, SWOG, or M-protein criteria, and outcomes were analyzed using Kaplan-Meier methodology.

Phase 1 Dose-Escalation Study of Investigational Agent MLN9708, An Oral Proteasome Inhibitor, in Patients with Relapsed or Refractory Multiple Myeloma
The interim data from this ongoing study were collected from 35 relapsed/refractory multiple myeloma patients, all of whom had received at least two prior therapies, which must have included VELCADE, lenalidomide or thalidomide, and corticosteroids.

Of the 26 patients in the dose-escalation cohorts, 15 were refractory to VELCADE; of the 15 patients in the expansion cohorts, seven were refractory to VELCADE. The results, presented by Paul Richardson, M.D., Dana Farber Cancer Institute, Boston, Mass., showed:

• Maximum tolerated dose was established as 2.0 mg/m²
• Dose-limiting toxicities (DLT) of grade 3 rash and grade 4 thrombocytopenia were seen at 2.23 mg/m²
• The preliminary tumor response data showed two partial responses, one at 1.2 mg/m² and the second at 2.23 mg/m^2.
• The patient at 1.2 mg/m² remains on treatment at cycle 12; the patient 2.23 mg/m² has received 10 cycles and remains on-study
• 17 patients had stable disease
• Response evaluation is ongoing
• The most common adverse events of any grade reported in more than 20 percent of patients were fatigue, diarrhea, upper respiratory infection, nausea, thrombocytopenia, cough, dyspnea, pyrexia and vomiting
• The most common grade 3/4 adverse events were thrombocytopenia (23 percent), neutropenia (8 percent) and non-cardiac chest pain (8 percent)
  • No drug-related grade 2 or higher peripheral neuropathy was reported

Adults with relapsed/refractory MM after at least two prior therapies, which must have included bortezomib, thalidomide/lenalidomide, and corticosteroids, received oral MLN9708 on Days 1, 4, 8 and 11 every 21 days. Starting dose was 0.24 mg/m², escalated using a 3+3 scheme based on dose-limiting toxicities in cycle 1. Toxicity was graded by NCI-CTCAE v3. Response was assessed by modified EBMT criteria.