Powerful News:

MMRF Blog


July 26, 2010

MMRC Plays Critical Role in Advancing Development of Carfilzomib, Kathy Giusti, CEO

Despite incredible odds of bringing a new treatment to market — just 11 new cancer drugs have been approved by the FDA in the last three years – multiple myeloma patients may have another treatment option available by the end of next year, thanks in part to the efforts of the Multiple Myeloma Research Consortium (MMRC) and its Member Institutions.

Earlier today, Onyx Pharmaceuticals announced promising top-line results from the Phase II trial of carfilzomib, a next-generation proteasome inhibitor in the same class as Velcade®, in patients with relapsed and refractory multiple myeloma. We could not be more proud that the MMRC played such a critical role in advancing this potential new treatment, particularly because carfilzomib shows promise in treating even the most heavily pre-treated patients, including those whose disease no longer responds to neither Velcade® nor Revlimid®.

Over the last four years, the MMRC has worked tirelessly to fast-track the development of carfilzomib:

  • We first introduced Proteolix in 2006 to our experts from the MMRC, and then streamlined the start of the trial by providing the company with access to centralized contracts and guidance on site selection and protocol design — saving the company critical time and resources.
  • When Onyx acquired Proteolix late last year, our strong leadership ensured that the trial's momentum continued and that research efforts were not delayed.
  • MMRC Member Institutions enrolled a majority — 60 percent — of patients into the trial while representing just over one-third of the sites. This was essential in completing the trial's enrollment, often the most time-consuming part of the drug development process.

In the results announced today, an incredible 36 percent of patients demonstrated at least a minor response to carfilzomib. These same patients had previously relapsed following a median of five types of multiple myeloma treatments — representing 13 different agents — and did not respond to their last treatment. Based on these impressive results in a population that has so few treatment options available outside of clinical trials, Onyx is in continuing discussions with the FDA, and anticipates submitting for potential accelerated approval by the end of the year. This means that patients would have access to carfilzomib before the Phase III clinical trial is complete.

As a patient, I am grateful to Onyx for demonstrating such remarkable commitment to the myeloma community and to all of our MMRC Members and the patients who participated in this trial. Final results from the trial are expected by year-end — stay tuned!


June 7, 2010

New data from ASCO provide much hope for myeloma patients

On Saturday (6/5) afternoon and on Sunday (6/6) morning, 13 oral abstracts based on data from clinical trials in multiple myeloma were presented at the ASCO meeting. Selection as an oral abstract signifies that the ASCO scientific committee had deemed these presentations to be the strongest scientifically and potentially most important in terms of their impact on clinical practice and patient care. Saturday’s session featured early-stage (Phase I and II) data on four exciting new compounds – carfilzomib, pomalidomide, panobinostat, and elotuzumab. What was most encouraging – in addition to three of the trials having been partially or fully facilitated by the MMRC – is that every one of these new treatments showed efficacy in patients whose disease had progressed following treatment with Velcade (bortezomib) and/or Revlimid (lenalidomide). Undoubtedly all patients will need (and the vast majority will benefit from) Velcade and Revlimid, but unfortunately, many will relapse, and it will be important to have treatments in our armamentarium that may re-sensitize patients to these treatments (eg, panobinostat) or work in the face of patients who are refractory to both (eg, pomalidomide). The toxicity profiles of these agents were also encouraging, as neither carfilzomib nor pomalidomide appears to be associated with an increased risk of peripheral neuropathy unlike other proteasome inhibitors (eg, Velcade) and ImiDs (eg, Thalomid).

On Sunday, there were three hours of data from trials involving all patient populations. The data that will likely have the most immediate impact on patient care were from two trials that examined the role of single agent Revlimid (typically 10-15 mg) as maintenance therapy following high-dose chemotherapy and stem cell transplant. These two trials, both involving hundreds of patients, were conducted relatively concurrently by the cooperative groups in the US and by the IFM in France. In both trials, patients were randomized to either Revlimid or placebo, and both trials were stopped early following review by an independent data monitoring board, allowing patients in the placebo arm to cross over and receive Revlimid. This is because those on the Revlimid arm enjoyed a sustained remission (both studies found similar reduction in risk of disease progression – 58% and 54%). Both trials found that, regardless of their induction therapy or risk, patients on the Revlimid arm clearly enjoyed a lower risk of progression. While it is too early to assess whether there is a survival benefit, many felt that this benefit would reveal itself over time.

In transplant ineligible patients, updated data from an Italian trial of VMPT (Velcade-melphalan-prednisone-Thalomid) followed by VT maintenance showed higher response rates, in particular complete response rate (38% vs. 24%), and longer progression free survival than VMP. These data suggest that the four drug combination, which featured lower doses of Velcade and Thalomid than are typically prescribed, may become a standard for this population, and that maintenance therapy may also be important to preventing disease progression in this population.

Also included in this session was the much anticipated final data from Dana-Farber’s Phase I/II single arm trial evaluating RVd in newly diagnosed patients. In this final analysis, all patients (66 in the Phase I trial and 35 in the Phase II trial) enjoyed a partial response or better with manageable toxicity. The French group also presented some interesting data suggesting benefit to a reduced dose of Velcade in combination with reduced doses of Thalomid and dex compared to Velcade-dex for four cycles prior to high-dose chemo and stem cell transplant. Patients on the vTD arm had less toxicity – not a single patient discontinued therapy – as opposed to those on the VD arm while enjoying similar, if not better, efficacy. Also interesting, though early, were data presented by the Italian group suggesting that some patients may derive equal benefit in terms of time to disease progression by foregoing high-dose chemo and stem cell transplant – and considerable toxicity – and instead opting for standard therapies (in this case, Rd followed by MPR). It is too early to tell whether there would a difference in progression free survival and/or overall survival but the data will be important to follow.

The session also featured data from another study facilitated by the MMRC – elotuzumab in combination with Rev-dex – presented by Dr. Sagar Lonial of Emory. This trial showed very high (80+%) response rates in a pretty heavily pre-treated population. Moreover, the combination showed the ability to re-sensitize some patients to Revlimid. A Phase II study is now underway and expected to complete accrual in the next couple of months.

The final abstract compares Zometa (zoledronic acid) to clondronate, an oral bisphophonate, in a large UK study of nearly 2,000 patients. The trial not only found that those randomized to Zometa had fewer skeletal related events (fractures, etc) but also enjoyed a survival advantage (even those who did not have bone disease!), suggesting an antimyeloma effect with Zometa. Also encouraging was the fact that the incidence of osteonecrosis of the jaw was low (about 3%) in the group treated with Zometa and the condition was reversible in most of the cases.

In summary, there really is such hope emerging from this meeting. These data indicate that most patients will benefit from extended therapy, provided the benefits outweighs the toxicities – this assessment needs to be made on an individual basis in conjunction with one’s doctor – and that when today’s standard therapies fail, there will be effective options. For more detailed information and expert perspective on these abstracts, be sure to listen to the MMRF webcast which will be posted on the MMRF’s website later this week and features a discussion with Drs. Paul Richardson and Todd Zimmerman.


June 6, 2010

Partnering for the Patient, Louise Perkins, PhD

Greetings from Chicago. On Saturday at the American Society of Clinical Oncology (ASCO) meeting here, MMRF and MMRC representatives met with 10 pharmaceutical companies throughout the day on the subject of new drugs for myeloma patients. This is such an important activity for us to undertake on behalf of patients, because it is through these kinds of discussions that the MMRF and MMRC identifies partnerships that will catalyze the advancement of new drugs. Also, we work diligently to advocate for myeloma therapeutics development since companies don't routinely prioritize myeloma: unfortunately the market incentives are not perceived as being as great as in some other cancer fields like breast cancer or colon cancer.

What was gratifying in our meetings with companies and is encouraging for patients is that companies recognize the achievements of the MMRF and MMRC and are willing to try to work with us in a number of different ways to move new agents forward. One way to work together is towards prioritization of which drugs should be accelerated into trials using pre-clinical myeloma-specific models - and that is where the MMRC Validation Team plays a key role. Yesterday's meeting confirmed the interest in this valuable activity of the MMRC Validation Team.

Related to this and very importantly, companies are continuing to generate new and different drugs that will complement the currently used treatments and, in the future, help those patients who have run out of options. The MMRF and MMRC are working with companies and with the support of patients to push and advance those new treatments as quickly and efficiently as possible. Some of our discussions are sure to lead to new trials and new drugs that may benefit patients is years to come.


June 5, 2010

MMRC Reporting from American Society of Oncology Meeting (ASCO), Chicago, IL, Susan Kelley, MD

Friday, June 4 marked the opening day of the Amercian Society of Clinical Oncology (ASCO) meeting in Chicago, IL. The meeting is the largest gathering of oncology clinicians and researchers in the world and convenes in June each year. Approximately 33,000 attendees are expected. MMRF and MMRC staff are present at these meetings to attend scientific presentations on clinical studies conducted in myeloma and to interact with our academic, clinical research and pharmaceutical industry colleagues about ongoing or planned collaborations to advance the field of myeloma treatment. During the course of the congress, from Friday through Tuesday, there will be presentations of recent clinical trial results in myeloma studies, with updates on the development progress of several new drugs that hold promise for myeloma.

On Friday, the MMRC gathered together myeloma physicians from 11 of our 13 member institutions for a full day of intense and energized discussions about the MMRC activities, ongoing MMRC clinical trials, new trends in myeloma research and how MMRF and MMRC can continue to lead the way in advancing myeloma research progress. The key activities of the MMRC, including our clinical trials portfolio, our tissue banking and genomics initiative and our future plans were discussed in detail with our clinical research collaborators from our Consortium member institutions. Clinical studies ongoing within the Consortium were reviewed, and plans for additional clinical studies to be started with pharmaceutical collaborators in 2010 were finalized. We worked closely with our member institution partners to strategize about MMRC activites and further plans for investment of MMRF and MMRC resources to bring personalized medicine treatment approaches to the clinic for patients with myeloma.

At the ASCO congress on Friday, there were presentations of data documenting progress and encouraging results in early phase I-II clinical trials with several new drugs in myeloma, including combinations of new, emerging drug candidates with existing cornerstone drugs like Velcade® (bortezomib) and Revlimid® (lenalidomide). Presentations of research on the role of particular gene abnormalities in predicting outcome for patients treated with particular drugs lets us know that, similar to the overall theme of the ASCO congress, we in the myeloma research community are more intensely focused than ever on the effots to personalize or tailor therapy to optimize patient outcome.

Finally, capping a busy but exciting day, on Friday evening the MMRF sponsored a successful and interactive Continuing Medical Education symposium for physicians, entitled ‘Current Controversies in Myeloma Management: A Case- Based Management Assessment”. Attendees heard presentations on the expanding treatment options for patients with myeloma and how experts in the field recommend that current knowledge be applied to optimize results of treatment at all stages of the disease. The audience included hematologist- oncologists, and other health care professionals involved in the care of patients with MM. The faculty consisted of leading experts in MM treatment from around the world, including several of our MMRC member physicians. The discussions were moderated by Ken Anderson, MD of Dana-Farber Cancer Institute, Jean-Luc Harousseau, MD of French National Cancer Institute, Sagar Lonial, MD of Emory University, Paul Richardson of Dana-Farber Cancer Institute, and Jesus San Miguel, MD, PhD of University of Salamanca.

We look forward to exciting presentations of data and discussions with our collaborators over the next several busy days here in Chicago and we will post updates about highlights of the meetings. Stay tuned….


April 26, 2010

Exciting results from the MMRF-funded Genomics Initiative at AACR, Louise Perkins, PhD

Some of you may know that the MMRF-funded, MMRC Multiple Myeloma Genomics Initiative (MMGI) was designed to deeply explore the multiple myeloma tumor genome in more than 250 patient samples. What does that mean for folks who don't think about genomes every day? Briefly, the study was to understand the unique genetic alterations in patient tumor cells compared to their normal cells; those genetic changes are 'smoking guns' as to what has gone wrong and therefore what could be fixed to either destroy those myeloma cells or restore a more normal state to them. That's relatively easy to say (okay, for me, it is relatively easy to say) but this is difficult, time-consuming work requiring incredible technical expertise as well as patient tissue. We were blessed to be able to bring together the world-class researchers from the TGen and Broad Institutes together in a collaboration with tissue from our MMRC centers processed under standardized conditions at the MMRC Tissue Bank to undertake this 4-year, $10M project.

In terms of the time it takes to begin to see results, consider this analogy. If you have ever planted a garden, you know that careful planning and patience is needed. Many seeds are sewn and not all sprout. But when you see the first green sprouts and then the first blooms, you know that more is yet to come. The results presented at this year's American Association of Cancer Research (AACR) annual meeting are like some of those first flowers. The findings are extremely encouraging and more will come leading to new drugs and new treatments in the future. The AACR meeting, for those of you who may not know it, is one of the two largest cancer research meetings in the world bringing together scientists studying all types of cancers with attendance of 17,000 researchers.

The presentations fell into two main areas: Dr. Todd Golub of the Broad Institute disclosed results of our genome sequencing study on 38 patients’ tumor and matched normal samples and the second study was presented by Dr. Angela Baker of the TGen Institute who described genomics findings from 16 African American (AA) patient samples compared to patient samples from those of European descent.

Why are the results so exciting? First of all, the data revealed several new targets for which drugs are already at various stages of discovery and development including one target (BRAF) not previously known to be associated with MM. BRAF drugs have been created for a number of other cancers where its role in disease is clear. As compared to our sequencing study, nothing else at the AACR meeting described results on tumor genome sequences in as high a level of detail or on as many samples. In a complementary way, the findings from the AA patient study hint that other drugs in development might be particularly beneficial in AA patients. Those of us from the MMRF and MMRC are actively engaged with companies working on relevant drugs already in company pipelines and also ensuring that all of the findings are followed to lead to the next generation of drugs.

There really is a bright future here and with continued generous support we will be able to build on this momentum to benefit all patients with multiple myeloma!


Items 41 - 45 of 68  Previous12345678910Next