December 12, 2011

MMRF Newsflash from ASH


Monday was a big day for MM research at ASH 2011, with numerous preclinical and clinical oral presentation sessions. We couldn’t cover them all, but we did cover 4 excellent clinical sessions describing advances in current treatments and the development of novel agents.

Highlights include data from pivotal front-line trials:

  • Final, 5-year follow-up data from the VISTA study of Velcade (bortezomib), melphalan, prednisone (VMP) versus melphalan and prednisone (MP) in patients with previously untreated MM, confirming the OS benefit seen originally at 3 years of follow-up (published by Dr. María-Victoria Mateos and colleagues in 2010 in the Journal of Clinical Oncology). Unlike the original follow-up report, a survival benefit was not seen for patients with high-risk cytogenetics. The report also confirmed the preferential benefit of receiving Velcade during induction rather than after progression. Additionally, no safety signal for second primary malignancies was observed.
  • Updated data on maintenance therapy following 3 years of follow-up for the GEM2005MAS65 Spanish study of VMP vs VTP induction followed by maintenance with VP or VT, and confirmed the benefit or both maintenance regimens for all patients except those with high-risk cytogenetics.
  • An update from the MM-015 study of melphlan-prednisone (MP) versus MP plus Revlimid (lenalidomide) followed by Revlimid maintenance (MPR-R) in newly diagnosed, transplant ineligible MM patients, which demonstrated statistically and clinically significant improvements in progression free survival (PFS) for the MPR-R arm. Including Revlimid in induction also appeared to significantly benefit this patient population, in contrast to older patients (>75 years), where MPR and MP showed similar response rates and PFS.
  • Final results of the community-based, phase 3b UPFRONT study of VD, VTD, or VMP in newly diagnosed patients ineligible for transplant were presented by Dr. Ruben Niesvizky, demonstrating similar response and survival for all patient groups. Triplet therapies tended to result in greater dose reduction and discontinuation; Dr. Niesvizky noted that relatively high comorbidities were seen in this community study, which highlights that the more intensive triplet therapy may not add benefit for these patients.

Additional data were presented on novel agents in clinical trials, all of which have been studied through our affiliate organization, the MMRC:

  • Final data from the global phase 3 study of the histone deactylase (HDAC) inhibitor Zolinza (vorinostat), which is FDA-approved for a type of lymphoma, in combination with Velcade for patients with relapsed/refractory MM, presented by Dr. Meletios Dimopoulos, demonstrated a statistically significant though clinical modest improvement in PFS for the combination. High-grade fatigue was more common in the Zolinza arm. An additional phase 2b study of Zolinza with Velcadeas salvage therapy for patients who were resistant to Velcade was presented by Dr. David Siegel. The MMRC had partnered with Merck to contribute patients to this large, multi-national trial which showed that a significant number of Velcade-refractory patients had relatively high response rates, indicating that retreatment is possible.
  • Three presentations described phase 2 data for carfilzomib as single agent or in combination with Revlimid/low-dose dexamethasone or Thalomid (thalidomide)/dexamethasone. The combination with Revlimid in particular showed rapid and almost universal responses which deepened over time. Each study demonstrated impressive responses in patients with high-risk cytogenetics.
  • Four presentations described new phase 1/2 data for pomalidomide alone or in combination with dexamethasone, cyclophosphamide-prednisone, or clarithromycin-dexamethasone, showing good response especially in combination, and efficacy in subsets of patients refractory to Revlimid or with high-risk cytogenetics.
  • Dr. Sagar Lonial provided updated data for a phase 2 study of the monoclonal antibody elotuzumab with lenalidomide and low-dose dexamethasone, which resulted in excellent responses (>80%) in relapsed/refractory patients. The possibility of an effective monoclonal antibody for MM is quite exciting!

Equally exciting is the rich pipeline of drugs in development for MM. Oral sessions today described promising phase 1 and phase 2 data for a dizzying variety of agents: the HDAC inhibitor panobinostat; the bifunctional alkylator bendamustine; novel proteasome inhibitors MLN9708 and marizomib (NPI-0052) – both of which are currently being studied in the MMRC; BT062, an anti-CD38 monoclonal antibody conjugated to the maytansinoid cytotoxin; the MEK 1/2 inhibitor AZD6244; the dendritic cell vaccine APC8020; and the AKT inhibitor perifosine. The large number of drugs in the pipeline bodes well for the future of MM treatment.

Stay tuned tomorrow for our final blog from ASH 2011!