POWERFUL NEWS:

January 26, 2010

Perspectives on Recent Clinical Trials Development, Susan Kelley, MD

Recently, two new drugs have entered into phase III clinical trials, representing the final stages of clinical development intended to create a data dossier for submission to health regulators, such as the US FDA as part of the approval process for new drugs. These new trials will include patients with relapsed (recurrent) MM from the US and around the world. One trial, sponsored by Keryx and AEterna Zentaris, evaluates the combination of Velcade (bortezomib) and KRX-0401 (perifosine), a novel inhibitor of key signaling pathways involved in tumor cell growth. The second new phase III trial evaluates the combination of Velcade with panobinostat, an inhibitor of histone deacetylase, which is thought to influence gene messaging in tumor growth processes (Novartis). Myeloma patients should be encouraged by the increasing numbers of myeloma clinical studies and the transition of new agents into late stage drug trials. The challenge now is to ensure that the clinical trials that are being conducted can be enrolled rapidly. MMRF and MMRC will continue to work closely with the sponsors and clinical investigators on these trials to improve patient enrollment to these and other ongoing trials.

There have also been several announcements of new study results confirming the importance of “maintenance” therapy administered after initial chemotherapy and stem cell transplant. This maintenance therapy frequently consists of 1-2 drugs, including an IMID, such as Revlimid (lenalidomide), administered for up to 2-3 years after initial response is documented. Preliminary data were presented by Professor Palumbo from the Celgene MM 015 trial at ASH. Then, during later December and early January, press releases were issued by Celgene with the IFM (France) and by the US NCI (cooperative group CALGB) about two additional studies (one in Europe and one in US), where patients receiving maintenance with Revlimid had a longer time until myeloma recurrence than patients who were not receiving long-term maintenance treatment.

Furthermore, several new clinical trials are evaluating the possible role of treatment with new or existing drugs for patients with Smoldering (Stage I) MM, and preliminary positive data were presented at ASH in December, from a trial evaluating Revlimid and dexamethasone, with very positive outcome, but it was an analysis on only 40 patients so it is premature to conclude that smoldering patients should receive treatment.

Finally, data from phase I-II (early clinical development) trials facilitated by the MMRC were also presented at ASH. The new drugs/studies presented included updates on the ongoing trials with carfilzomib, elotuzumab, Torisel, NPI-0052, pomalidomide and combined treatment using Revlimid, Velcade, Doxil and dexamethasone. There was an important session on advances in genomics studies and preliminary findings from the ongoing MMRF Genomics Initiative were presented.

So, what should patients take away from these recent data? The data from several of these important “maintenance” protocols will be released for greater scrutiny by the medical community during 2010. It is important that all patients currently receiving treatment for newly diagnosed MM speak with their hematologists/oncologists about the role of maintenance therapy and whether they should be considered for maintenance treatment starting some time after completion of stem cell transplant (if transplanted) or after attaining the maximal benefit from induction chemotherapy. As always, please ask your physicians about clinical trials which might suit your stage of disease, whether you are a newly diagnosed patient or a patient whose MM has recurred after initial therapy. There are important new drugs emerging and increased trial participation rates will mean that the important results from these trials can become available sooner.

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December 7, 2009

Homing in on answers related to optimal combinations for induction therapy and the role of maintenance, Anne Quinn Young, MPH

Yesterday, more than 6,000 attendees packed into a hall the size of a small airport to hear Dr. Maria-Victoria Mateos from Dr. Jesus San Miguel’s group in Salamanca, Spain, deliver her plenary presentation at the ASH meeting. Just six abstracts out of thousands submitted for consideration are selected for plenary presentations at the meeting, so the myeloma community was thrilled that one of the six this year focused on our disease. The trial she presented built on the knowledge from the VISTA trial, which showed the overwhelming superiority of Velcade plus melphalan-prednisone versus melphalan-prednisone. The objective was to determine whether the best partner for Velcade was an IMiD (in this case, Thalomid – the only IMiD available in Spain when the study began) or an alkylator (in this case, melphalan) and whether there was a benefit to maintenance therapy. The results indicated that both combinations (VMP and VTP) had high response rates, include a high complete response (CR) rate, but VMP had fewer side effects. Furthermore, maintenance therapy – further bolstered the already high CR and near CR rates. Mateos also looked at using weekly Velcade which yielded high response rates while cutting the rate of peripheral neuropathy in half.

Following Mateos’s presentation were a series of abstracts looking at different induction regimens prior to high dose chemotherapy and stem cell transplant. For the most part, the results were preliminary as the trials were either phase I/II trials or had not reached endpoints like median time to progression or overall survival. Though the data are preliminary, several themes emerged though in all of these cases, more data are needed:

1. Maintenance therapy appears to enhance the depth of response
2. Weekly Velcade may provide similar benefit but with a lower rate of neuropathy
3. It is not yet clear whether 3 or 4 drugs need to be combined upfront to maximize outcomes – data are not yet mature enough to show the benefits outweigh the added toxicities
4. Data continue to indicate that Velcade overcomes adverse outcomes previously associated with certain genetic abnormalities such as the translocation of chromosomes 4 and 14

Finally, it is critical to note that none of the larger European trials included Revlimid as it was not available when these trials began several years ago so the regimens tested are not indicative of current standards of care in the US. We are fortunate that treatment options continue to evolve but this means that at times, when large phase III trials are finally completed, one or more of the treatment regimens tested may no longer represent a reasonable standard of care.

The take home message is that while we don’t yet know the “best” regimen for untreated myeloma patients – whether they are transplant candidates or not – there are a number of important ongoing trials that will help us to answer this question. In the meantime, if you’re eligible, consider enrolling in a clinical trial to speed the pace of these trials for the benefit of the entire community.

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December 3, 2009

FasterCures - Partnering for Cures, Susan Kelley, MD

Nearly 600 medical research executives, scientists, policy makers, and funders today convened in NY to explore novel development approaches and innovative funding strategies at the inaugural Partnering for Cures meeting. The MMRF and MMRC were well –represented at the meeting.

FasterCures, part of the Milken Institute, convened Partnering for Cures to facilitate multi-sector collaborations needed to turn a scientific discovery into an accessible therapy. The meeting was intended to highlight best practices in the conduct and management of medical research and approaches that could streamline the process. The leadership of the MMRF and MMRC was invited to make several presentations about the innovative collaborative research and development model that is the hallmark of the MMRF. Kathy Giusti, MMRF Founder and CEO, presented her perspectives as the leader of the MMRF during the opening plenary session on Wednesday morning. On that same panel was Bob Beall, CFF President and CEO and MMRF Board member. Bob's leadership in the area of venture philanthropy is unparalleled and we are incredibly lucky to have him as a member of our Board. Leading the panel was Margaret Anderson, Executive Director of FasterCures. Kudos to Margaret for her work on this amazing meeting and Mike Milken, head of Fastercures, for his insights into improving medical research.

Susan Kelley, MD, CMO of the MMRC, participated in a panel discussion to allow the audience to learn first-hand from “cure entrepreneurs”, nonprofit leaders who are implementing unique business models to produce dramatic results for patients. Louise Perkins, PhD, CSO of the MMRF, presented further details of the MMRF and MMRC collaborative model for myeloma drug research and development at a session which included many interested philanthropists, executives and scientists from various organizations. One-on-one connections between the meeting participants were facilitated through a number of partnering sessions.

Overall, it is invigorating to see a groundswell of interest to build bridges among the key stakeholders (patients, researchers and industry) to advance medical science in an approach we have pursued for many years.

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