May 5, 2011
Day 2 kicked off a full day of sessions beginning with a discussion around the treatment of newly diagnosed patients who are not eligible for high-dose chemotherapy and stem cell transplant (SCT) with leading clinicians from around the world – US, France, Germany, Italy, Netherland, Spain and the UK sharing their individual perspectives. While treatment patterns differ by country, particularly because some treatments like Revlimid are not widely available outside the US for first-line treatment, encouragingly, when treatments like Revlimid and Velcade are used – regardless of the combination, we are virtually seeing everyone achieve a response though the depth and duration of response does vary between individuals.
So, the ongoing question remains whether, now that we have such highly effective combinations that include proteasome inhibitors and immunomodulatory agents (IMiDs) as backbone therapies, the high dose chemotherapy and SCT should remain as a standard treatment for younger patients (see tomorrow’s highlights for more discussion on this topic). And, as recently as the ASH meeting in December 2010, the impressive results in terms of delayed disease progression from the use of prolonged maintenance therapy post-SCT has given rise to more questions about whether we need to consider incorporating this into standard of care for patients. Possible answers may come out of a newly opened trial being led in the United States by one of MMRC’s member institutions – Dana-Farber Cancer Institute and in France, by the IFM. The IFM/DFCI randomized trial will enroll 1,000 patients in the US and France and will examine the role of high dose chemotherapy followed by SCT in the era of novel agents (is high dose chemo + transplant + novel agents needed, or not, to achieve a good level of response when compared to using novel agents alone?) and is maintenance therapy something we must seriously consider for use in future (is it effective or not at prolonging a patient’s initial response, regardless of the initial treatment and, for how long should it be administered?).
High risk myeloma was also covered in depth at this meeting with the MMRF’s Nature paper with sequencing results from the MMRF-funded Genomics Initiative once again garnering recognition for its contribution to our increased understanding of myeloma tumor cell biology. High risk presentations highlighted how complicated the MM biology really is – and not just at time of diagnosis as there can be multiple myeloma “clones” within one individual, and, as an individual’s disease progresses, new clones can emerge. New genomic discoveries have provided early direction in terms of druggable targets not previously explored in MM. Briefly, we can focus on drugs to address abnormalities of the BRAF cellular pathway and over-expression of a protein called MMSET which is clearly present in patients that have t(4;14) multiple myeloma. Although the myeloma tumor cell by nature is a ‘survivalist’, the only real way we can keep it at bay is by deepening our understanding of how it operates and have ready at hand all of the tools needed to overcome its peculiarities every step of the way.
May 4, 2011
Greetings from the XIIIth International Myeloma Workshop in Paris! The meeting kicked off on Tuesday with presentations on the biology and genetics of myeloma as well as bone diease, followed by the opening ceremony and presentation of the prestigious Waldenstrom’s Award. Overall, there continue to be advancements with regards to the understanding of cell biology in multiple myeloma; however, understanding classifications of various subtypes is still evolving. In the end, each one of us is unique and therefore will require tailored therapies. In this regard, the importance of focusing on mechanisms of various cytokines and mTOR pathways were highlighted. The MMRC is currently examining a novel mTOR (TORC-1 and TORC-2 inhibitor) with the INK 128 trial currently in Phase 1 and enrolling.
There was some interesting news for patients in the evolving field of bone disease. There were detailed presentations on the synergies between HDAC, HDACi and Velcade/Revlimid combination therapy (Zolinza (vorinostat)/Velcade in particular). We’re learning that there are synergistic effects on the ability to ‘turn on’ the osteoblasts (bone building cell mechanism) which in turn has negative effect on the myeloma tumor cells. In normal biology, we’re constantly building and deconstructing bone. Like the skin, the old is sloughed off to make way for the new. In multiple myeloma, the osteoclasts go into overdrive and break down more bone than normal. In myeloma, it’s thought that by healing the bones, the environment in which tumor cells thrive becomes less hospitable and this may have the additive effect of “flushing the fox out of the hole”. Clearly this frontier, although not entirely new with the introduction of biphosphonates back in the 90s, warrants more advanced research.
The MMRF was acknowledged by several speakers for the funding we’ve provided to support their work. Walter Capone, our COO, gave a comprehensive overview of the MMRF and MMRC highlighting all of our funding to date and clear stewardship of the funds we raise. Michael Kuehl, PhD, an old friend of the MMRF and myeloma community, deservedly received the Waldenstrom’s award and specifically highlighted Kathy Giusti, citing her for the enormous contribution she’s made to MM genomics and in particular, the recent Nature paper that detailed the genome sequencing of samples from the MMRC tissue bank as part of the MMRF’s Genomics Initiative. Stay tuned – busy day ahead and I look forward to sharing the updates with you.
February 21, 2011
Today, a patient diagnosed with breast cancer is most likely to be treated in one of three ways, as determined by a molecular analysis of her tumor. For a patient with lung cancer, treatment decisions are often informed by the existence of a specific genetic mutation known to make certain treatments more successful. In these and other cancers, multiple clinical trials are currently underway testing new medicines among genetically defined subgroups of patients.
In multiple myeloma, this kind of “personalized” clinical decision-making is not so advanced. We have made enormous strides in bringing new therapies to patients in the past decade – and in improving patients’ prognosis as a result – but there is still much to be done to advance our basic biological understanding of the disease and to tailor an individualized course of treatment.
In the near-term, we need answers to why some patients respond better than others to today’s medicines, and how we should respond when they develop resistance. Longer-term, we need a greater understanding of the biological changes that occur throughout the course of a person’s disease, in order to steer our clinical development efforts toward known mechanisms in multiple myeloma.
At MMRF and MMRC we are laying important groundwork toward these goals across the entire drug development continuum: supporting basic research to identify important molecular pathways that may be targets for drug development; advancing clinical development strategies that exploit this understanding; and organizing a community response that unites as many patients and physicians as possible to improve treatment for all.
Last week we previewed our long-term vision for personalized medicine in a half-day meeting with 40 of the leading minds in the field. We heard about the state of the art in cancer care from several perspectives – academic research institutions, community cancer centers, drug developers, diagnostics companies, IT companies, and others. We gained enormously helpful feedback that will be critically important to all of us as we move ahead.
As a group we also found many points of intersection that underscore the value in looking across the many forms of cancer, rather than segmenting our efforts. We talked about common pathways through which multiple cancers develop, where finding a way to intervene may have huge implications for several disease types.
I left the Roundtable more energized than ever about the progress we have already made against personalized medicine and the bold vision we will advance in the months to come. To do so we need patients’ support of this effort – specifically donating their tissue to our Tissue Bank – like never before. As a patient myself, I am truly excited at the prospect of helping to bring patients better, more personalized treatments, and I ask all those who can to join me by banking their tissue at their next bone marrow biopsy.
January 26, 2011
You never forget the moment you hear, “You have cancer.” Even after 15 years, the heartbreak of that day doesn’t seem to fade. Each January, as the anniversary of my diagnosis draws near, I brace myself for what has always been a bittersweet day—one laced with feelings of devastation and fear that never quite go away, yet mixed with immense gratitude for the beginning of another year I never imagined I’d live to see.
This January also marked another anniversary in my life with multiple myeloma—five years since my stem cell transplant with my twin sister, Karen, as my donor. I will always remember that day as a re-birth—a new chance for me to fight the disease and the belief that I just might make it through. I am thankful for each and every moment the transplant bought me, but it has gone by so unbelievably fast that I didn’t see the anniversary coming. And I certainly did not think it was on anyone else’s radar.
So imagine my shock when, at the end of Michael Reinert’s incredible show about his journey with multiple myeloma, “So Tell Me, What Can I Do?” there was a surprise party in honor of my fifth “re-birthday.” I felt so blessed that everyone was able to come together to celebrate the incredible gift of time my sister gave me and reminded me to never take for granted the hope that my transplant brought. It is moments like these, surrounded by the people who mean the most, that patients live and breathe for. Thank you, thank you, thank you to family and my dear friends, who have never left my side, my doctors at Dana-Farber, Ken Anderson and Paul Richardson, and the talented Michael Reinert, who together made my re-birthday one that I will never forget.
Me, Michael Reinert, and my twin sister Karen Andrews
Michael and I cutting into my beautiful 're-birthday' cake!
December 8, 2010
The Multiple Myeloma Research Foundation (MMRF) team continues to report from the American Society of Hematology (ASH) Annual Meeting in Orlando. The Annual ASH Meeting featured several dozen abstracts on next-generation treatments for the treatment of multiple myeloma. Below are a few highlights of the data presented over the past few days:
- Encouraging results of a Phase II study of carfilzomib, a next-generation proteasome inhibitor that was facilitated by the MMRC, were presented by Dr. David Siegel. Of 257 patients evaluated in the study, patients had an overall response rate of 24% to carfilzomib and a median duration of response of more than 7 months. Notably, no patients discontinued treatment due to either new or worsening peripheral neuropathy. A separate analysis of patient responses revealed that patients who had high-risk features such as chromosome 13 deletions, deletion of chromosome 17p and/or translocations of chromosomes 4 and 14 or chromosomes 14 and 16 had similar response rates. Based on these positive results, Onyx, the manufacturer, expects to file for FDA approval sometime in 2011. Meanwhile, a Phase III trial comparing carfilzomib-Rev-dex to Rev-dex is open and accruing patients.
- New data from several trials involving the exciting new IMiD pomalidomide were also presented. The trials, conducted in the US (one of which was conducted through the MMRC) and in France, included patients who were refractory to both Velcade and Revlimid - patients who are in urgent need of new treatment options. Regardless of the dose schedule under study, at least 30% of patients receiving 4 mg in each trial responded to therapy. There was no evidence of the incidence or worsening of peripheral neuropathy. A Phase III trial is expected to open in early 2011.
- The novel therapy Zolinza (vorinostat), a histone deacetylase inhibitor, continues to appear to be a promising new option for myeloma patients in combination with standard therapies like Velcade (bortezomib) and Revlimid (lenalidomide). Poster presentations revealed compelling, but early, data on Zolinza in combination with Velcade and/or Revlimid, both for newly diagnosed and for relapsed/refractory patients. Excitingly, one trial, conducted in part through the MMRC, found it could re-sensitize Velcade-resistant patients to the combination of Velcade and Zolinza. This combination drug is being studied in a Phase III trial and, if the results are promising, it could be FDA-approved for myeloma as early as 2012.
- The results of a Phase II study of elotuzumab in combination with Revlimid and dexamethasone, a trial that advanced from an earlier MMRC study, were presented. Although treated patients had not previously received Revlimid, the ORR was 28 percent, and 23 percent in patients receiving 10 or 20 mg/m2, respectively. This is a very early study, but the results are encouraging. Additional data on early studies of elotuzumab plus Rev-dex, as well as elotuzumab plus Velcade-dex, both of which were advanced through the MMRC, show similarly encouraging data. A Phase III clinical trial comparing elotuzumab-Rev-dex to Rev-dex is expected to open early next year.
By the end of the week audiocast highlights from the meeting will be available, featuring the expert commentary of Dr. Sagar Lonial of Emory University and of Dr. David Siegel of the University of Hackensack Medical Center. This will be followed by a live teleconference in mid-January (stay tuned for details!) and a detailed report of findings from the meeting in the February 2011 issue of FOCUS, the MMRF's bi-annual newsletter.