December 11, 2011

MMRF Newsflash from ASH


The MMRF team is on site at the American Society of Hematology (ASH) Annual Meeting in San Diego and is pleased to share with you highlights from key sessions over the next 3 days.

MMRF Symposium
On Friday, the MMRF kicked off the meeting with a standing-room-only CME symposium, which more than 560 healthcare professionals attended. Dr. Paul Richardson chaired the novel format which included presentations from leading specialists Drs. Herve Avet-L’oiseau, Andrzej Jakubowiak, Maria-Victoria Mateos, and Philip McCarthy. Live cases from community physicians were presented for audience response and faculty discussion.

MM Education Session
On Saturday, the multiple myeloma scientific sessions began with a scintillating educational session chaired by Dr. Ken Anderson with Drs. Sergio Giralt and Donna Reece as additional speakers.

  • Dr. Reece covered the latest data related to first-line treatment as well as post-transplant maintenance. Overall, she concluded that with incorporation of novel agents Revlimid and Velcade, as induction, as well as consolidation and maintenance, with high-dose chemotherapy and stem cell transplant, we are seeing unprecedented response rates, with complete responses in the 65% range. There are proven benefits in terms of progression-free survival (PFS – the amount of time a patient remains disease free) and strong hints of a survival benefit particularly with the incorporation of Revlimid maintenance post-transplant. With regard to maintenance, we still need to understand who is most likely to benefit and who may be at risk for second primary malignancies (SPMs). We are also continuing to see that these agents, particularly Velcade, can overcome some of the adverse features of MM, such as translocation of chromosomes 4 and 14 (t(4;14)).
  • Dr. Giralt looked at the role of high-dose chemotherapy in the age of novel agents. To date, there are no data showing the superiority of one or the other, but, in truth, trials asking those types of questions are still underway. He introduced several thought-provoking questions that have yet to be answered such as:
    • Does everyone need triple therapy upfront or are there patients with lower risk disease that would benefit from a doublet?
    • What is the optimal duration of induction therapy?
    • Is there an optimal timing for high-dose chemotherapy and stem cell transplant?
    Ongoing clinical trials are critical to answer these questions. As for the future, it will be important to start to stratify patients by risk and determine treatments regimens most appropriate for each risk level. Once we know this, we can work toward maximizing response rates, minimizing side effects and reducing overall symptom burden of disease.
  • Dr. Anderson focused on the future – though much of the future is now! – for myeloma therapy. Right now, there is an unprecedented number of treatments in clinical trials – some second-generation treatment like carfilzomib and pomalidomide, as well as agents with totally new mechanisms of action such as HDAC inhibitors (eg, Zolinza and panobinostat), Akt inhibitors (such as perifosine), antibodies (such as elotuzumab and siltuximab), and MEK inhibitors among many others. He concluded by discussing the future of personalized therapy whereby a patient’s treatment regimen is determined by his/her molecular profile – exactly what the MMRF is seeking to do with our CoMMpass StudySM.

Oral and Poster Sessions
Poster sessions on Saturday and Sunday covered risk stratification, risk of optimizing current frontline treatments, SPMs, and the development of novel therapies, including several for which the MMRC has played a significant role.

Both oral abstracts and posters presented by researchers at several institutions including the Mayo Clinic-Scottsdale and the University of Arkansas for Medical Sciences looked at genetic markers to predict response and side effects to various therapies and to optimize risk stratification. Risk stratification remains a goal in MM, and research to develop risk-based tools for improving prognosis and therapy continues. Dr. Leif Bergsagel credited the MMRF’s Genomics Initiative with uncovering potentially important new targets for drug development.

SPMs have become an important topic for patients receiving Revlimid in combination with akylating agents such as melphalan, as several recent studies reported higher incidences of SPMs following Revlimid treatment. Dr. Jesus San Miguel analyzed the risk of SPMs following Velcade treatment using data from 4 large phase 3 trials, and demonstrated rates of SPMs similar to that expected for the general US population. Several papers on SPMs following Revlimid treatment will also be presented at ASH this year, providing further evidence that recurrence of myeloma is much more of an issue than is the development of SPMs following Revlimid; however, the topic is important and continues to be investigated.

Several posters addressed optimizing the use of current treatments in the upfront setting:

  • Most notably, Dr. Antonio Palumbo presented final data from a phase 3 study of melphalan, prednisone, and Revlimid (MPR) versus high-dose melphalan (MEL200) and autologous stem cell transplant in newly diagnosed MM patients younger than 65 years. As described previously at ASCO this year, responses were similar but significant PFS improvement was seen in the transplant arm. MEL200 was associated with greater side effects, although few patients in either arm discontinued as a result.
  • Dr. Ajai Chari presented data from a small study of treatment of newly diagnosed MM with Revlimid, Velcade, and dexamethasone (RVD) therapy on a 28-day cycle with Velcade 1.3 mg/m2 given on days 1, 4, 11, and 18, in contrast to the typical 21-days; peripheral neuropathy appeared to be reduced without loss of efficacy in the 38 patients analyzed.

Finally, there were many posters Sunday describing novel treatments for MM. Two of the most anticipated new drugs continue to be carfilzomib, the novel proteasome inhibitor that has been developed with the facilitation of the MMRC, and pomalidomide, the novel immunomodulatory agent that has been tested in multiple MMRC trials. Data for both agents continue to be impressive; both drugs are now in phase 3 development. At Saturday’s poster session, data were presented indicating that even patients with higher risk features such as deletion of chromosome 13 or t(4;14) responded as favorably as patients with lower risk disease.

Additional agents are showing exciting early results in the relapsed/refractory setting. Several posters demonstrate that Treanda (bendamustine), which is approved for CLL and NHL also studied in an MMRC trial, continues to show promise in relapsed/refractory MM patients with Velcade- and Revlimid-based regimens. Posters demonstrated impressive early efficacy data for novel kinesin spindle protein (KSP) inhibitor ARRY-520 (also being studied in an MMRC trial) in phase 1 and phase 2 studies, as single agent and in combination with standard therapies. Additional posters described early but intriguing data for PD 0332991, a novel cyclin-dependent kinase (CDK) 4/6 inhibitor; GSK2110183, a novel Akt inhibitor which just entered an MMRC-facilitated trial; daratumumab, an antiCD38 antibody; and BLP25 liposome vaccine.

Stay tuned for continued updates over the next couple of days as more data are presented!