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June 14, 2014

European Hematology Association – 19th Annual Congress

The MMRF has been on-site at the European Hematology Association (EHA) Annual Meeting for the past few days. Much of the data presented were previously presented at the 2014 ASCO Meeting including results from trials involving exciting new treatments like daratumumab, SAR650984 and panobinostat, but several insights were notable.

Minimal Residual Disease
Dr. Joaquin Martinez-Lopez, University of Salamanca, presented data comparing next-generation sequencing (NGS) with flow cytometry and polymerase chain reaction (PCR) to measure minimal residual disease (MRD). Sequencing is like “fingerprinting” cells; there is high sensitivity and specificity, and millions of cells can be counted and analyzed. NGS will also not only identify all of the different myeloma clones within a patient but also will be able to determine the frequency of each clone. Dr. Martinez-Lopez concluded that the data underscored the promise of using NGS based MRD assessment, which is a useful method for patient risk stratification and can be used to determine molecular complete remission (CR) in myeloma. As part of the MMRF CoMMpassSM Study, the MMRF is working with Dr. Antonio Palumbo, University of Torino, and his team on a trial to definitively identify the best way to measure MRD.

Revised International Staging System
Dr. Stephania Oliva, University of Torino, presented proposed updates to the International Staging System (R-ISS). The revised criteria combine and sequence three prognostic factors (ISS status, cytogenetic status by Fluorescence in situ hybridization (FISH), and serum LDH levels), ie:

  • R-ISS Stage I (n=636, 27%): ISS stage I, no abnormal FISH result and low serum LDH
  • R-ISS Stage III (n=246, 11%): ISS stage III and HR Cytogenetics, or/and serum LDH high
  • R-ISS Stage II (n=1477, 62%): the rest

Correlation of R-ISS with survival:

Survival Endpoint R-ISS Stage I R-ISS Stage II R-ISS Stage III
5yr OS % 81 62 39
5yr PFS % 56 37 20
mPFS % 65 41 25

OS: Overall Survival
PFS: Progression Free Survival
mPFS: Median Progression Free Survival

June 3, 2014

MMRF Newsflash from ASCO 2014 - Volume 3

Welcome to our third and final report on the 2014 American Society of Clinical Oncology Annual meeting featuring the Multiple Myeloma poster session.

Posters featured ongoing trials in newly diagnosed and relapsed/refractory patients, updates and potential new ways to use Pomalyst and Kyprolis, as well as early studies of new drugs.

Ongoing trials in newly diagnosed high risk patients

  • A Phase II study is ongoing in newly diagnosed patients with high risk (aggressive) myeloma. This study will evaluate whether adding elotuzumab, a new monoclonal antibody in late-stage clinical development, to Revlimid-Velcade-dex is beneficial.
  • An ongoing Phase III trial is evaluating this combination.

Updated data and ongoing trials in relapsed/refractory patients

Several posters focused on the use of Pomalyst-low-dose dexamethasone and one study highlighted a new combination treatment with this drug.

  • Previously, a large Phase III study showed that Pomalyst plus low-dose-dex extended survival and time to disease progression in relapsed/refractory patients vs dexamethasone alone. An updated analysis indicated that the advantage of Pomalyst plus low-dose dex as compared to high-dose dex may be even greater than previously reported.
  • Additional studies are underway to learn more about the use of Pomalyst.
    • A large study is underway to look at the role of Pomalyst based on the genetics of patients’ myeloma. Data presented at last year’s American Society of Hematology (ASH) meeting indicated that Pomalyst may be effective in patients with genetic mutations like del17(p), whose disease is typically harder to control.
    • Two Phase II trials are underway to learn more about the use of Pomalyst-low-dose dex in different patient types including patients who have recently progressed on Revlimid-based therapy and those with moderate or severe kidney problems. Early results look promising, confirming that Pomalyst works effectively in many patients with difficult to treat myeloma.
  • The combination of Pomalyst and Velcade-dex was evaluated in an early study. Preliminary data showed that this combination was highly effective in patients who were both refractory to Revlimid and had previously received Velcade. 70% of patients responded and on average the responses lasted for 7.4 months. A Phase III trial evaluating this combination is underway.

In addition, one small study is looking at the combination of Kyprolis and dexamethasone. Preliminary data showed that 63% of patients responded and the combination was well tolerated.

Early studies with novel agents in relapsed/refractory patients

  • Among the new drugs being studied in early trials in combination with Revlimid are MK-3475 and romidepsin. MK-3475 is monoclonal antibody (part of a class called checkpoint inhibitors that are showing tremendous promise in some solid tumors like melanoma and lung cancer) that works to utilize the immune system to kill cancer cells. Romidepsin is a HDAC inhibitor (like panobinostat) but is already FDA approved for a type of lymphoma.
  • A laboratory study demonstrated that marizomib, an oral proteasome inhibitor in development, may work well in combination with Pomalyst. This combination is currently being studied in a trial sponsored by the Multiple Myeloma Research Consortium (MMRC), an affiliate organization of the MMRF.

Other Studies

  • One study looked at ways to identify which patients with smoldering myeloma are at higher risk of progression to symptomatic myeloma. In this study, patients with higher levels of free light chains (a portion of an antibody) and certain types of DNA abnormalities were more likely to progress to symptomatic myeloma.
  • Another study evaluated the different tests used to assess bone in patients with MGUS, smoldering and active myeloma. Like other studies, this one confirms that newer imaging techniques such as MRI and CT-Scan can be more effective in detecting disease progression than whole body scans (standard x-rays).

June 2, 2014

MMRF Newsflash from ASCO 2014 - Volume 2


Welcome to our second day of on-site coverage of the 2014 American Society of Clinical Oncology (ASCO) Annual meeting featuring the oral sessions presented this morning.

Exciting results for three new, novel drugs studied in patients with relapsed/refractory myeloma were presented.

  • Results of a large Phase III trial of panobinostat, a new type of myeloma drug called a HDAC inhibitor, were reported. Panobinostat is likely to be the next new agent to be approved by the FDA for relapsed/refractory multiple myeloma. This study evaluated panobinostat in combination with Velcade-dex and showed significantly improved outcomes as compared to Velcade-dex alone. The Multiple Myeloma Research Consortium (MMRC), an affiliation organization of the MMRF, participated in the early Phase I study of this combination. See the press release describing today’s results and the FDA review status.
    • In the Phase III study, time without progression of myeloma was prolonged –an average of 12 months with the panobinostat-Velcade-dex versus 8.1 months with Velcade-dex alone. While there was no difference in overall response rates, complete/near complete responses were much higher with panobinostat (28% versus 15% with Velcade-dex) and patients with high-risk myeloma appeared to benefit.
    • However, there were severe side effects including low platelet counts (which led to hemorrhage in a few patients), diarrhea and fatigue.
    • One of the experts commented on the data, stating that panobinostat offered an advance and was worthy of FDA approval. Of note, there are other HDAC inhibitors in development that may potentially have the potential to offer benefits with possibly of fewer side effects.

  • Impressive data from small early studies was presented for two new monoclonal antibodies, SAR650984 and daratumumab.
    • Dr. Thomas Martin reported the results of the study evaluating the combination of SAR650984 and Revlimid-dex in highly refractory patients who had previously received six prior myeloma treatments. 58% of patients responded to this combination and side effects tended to be mild. This study was conducted by the MMRC and the MMRC is closely collaborating with Dr. Martin and Sanofi, the manufacturer of SAR650984, on the development of this drug.
    • 67% of patients who had previously received an average of 4-5 prior therapies responded to daratumumab. This is the first trial in which anti-myeloma activity was seen with a monoclonal antibody used as a single agent. Daratumumab was also well tolerated. Phase III trials evaluating daratumumab in combination with Revlimid-dex are ongoing.

The question of how long newly diagnosed patients should be treated has been the subject of debate. One large study with Revlimid-dex previously reported that better outcomes were achieved when patients were treated continuously as opposed to a fixed duration of therapy. Today, an analysis of three large studies, including approximately 1200 newly diagnosed patients, confirmed these findings. Myeloma treatments included both Revlimid and Velcade-based therapies.

  • Patients receiving continuous treatment lived longer: 4 year survival was 69% versus 60%
  • Time without progression of myeloma was doubled in patients receiving continuous therapy: 32 months versus 16 months

One of the experts discussing this presentation, noted that questions still remain about which patients will derive the greatest benefit from continuous therapy based on the specific characteristics of their disease. The answer to this question is a potential outcome of the MMRF CoMMpass Study in which 1,000 newly diagnosed patients will be followed for at least 5 years.

MMRF ASCO Coverage

To see the full MMRF coverage from ASCO with ongoing updates, please visit: www.themmrf.org/asco.

May 31, 2014

MMRF Newsflash from ASCO 2014 - Volume 1


Welcome to our first day of on-site coverage of the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.

Yesterday, there were several poster presentations featuring novel therapies in early stage development which showed promising activity in patients with relapsed/refractory multiple myeloma, many of whom had failed not only Velcade and Revlimid but also Kyprolis and Pomalyst. New drugs included two monoclonal antibodies, SAR650984 (which has been in studied in the MMRC, our clinical network) and daratumumab as well as a new formulation of chemotherapy, TH-302.

  • 24% of patients who had been previously treated with an average of six prior therapies responded to SAR650984. Further, myeloma was controlled in another 41% of patients. Data from an MMRC trial which studied SAR650984 in combination with Rev-dex will be presented on Monday.

  • 75% of patients responded to the combination of daratumumab and Revlimid-dex. Two Phase III studies evaluating this drug are expected to begin soon.

Further, a response rate of 53% was seen using a four drug regimen including Revlimid-dex, Kyprolis and Zolinza. However, there were significant reductions in blood counts in some of these patients. Zolinza is FDA approved for a type of lymphoma, so it could be used on an “off-label” basis for some myeloma patients. Data on a related compound in the same class, panobinostat, will be presented during an oral presentation session on Monday.

Stay tuned for further updates on Monday where there is an oral and another poster session!

MMRF ASCO Coverage

To see the full MMRF coverage from ASCO with ongoing updates, please visit: www.themmrf.org/asco.

February 10, 2014

MMRF Scientific Steering Committee Roundtable

Aiming even higher, with a little help from our friends…

Despite heavy snow and freezing rain, some of the most esteemed scientists and researchers in academic institutions and the pharma/biotech industry in North America convened this week in Boston for the MMRF Scientific Steering Committee roundtable to help identify and prioritize the most promising science and new therapy areas as part of the Research Agenda for our next three-year Strategic Plan.

It was a rare opportunity to exchange ideas and learn from an impressive array of preeminent experts, many specialists outside the myeloma field (from CML to melanoma to lung cancer), who dedicated their time to enthusiastically address our most critical challenges:

  • How can we enable all myeloma patients to understand and obtain the most effective treatments for their specific subtype or version of multiple myeloma?
  • How can we harness the power of the immune system to rapidly advance immunotherapy in myeloma, particularly for patients at greatest risk of disease progression?

Participants outside of the myeloma field also took note of lessons learned by the MMRF. Like other cancers such as leukemias or melanoma, a proportion of myeloma patients who may respond well to initial therapies are confronted with more aggressive forms of disease later on. Even worse is the case where patients have little to no response from the outset. It was clearly recognized that many of the techniques and initiatives the MMRF developed over the past five years are the benchmarks that other types of cancers are working to achieve as well.

In many respects we’re ahead of the curve in helping to inform scientists and research partners on how to proceed; the disadvantage is that there does not appear to be a ‘smoking gun’ that we can target in myeloma to help a large proportion of patients. With at least four and up to 10 different subtypes or versions of myeloma in patients – even when they are newly diagnosed, a truly comprehensive approach is needed to reach a cure.

The main takeaways, in this regard, fall into three main categories as we map our MMRF research plan over the next three years:

  1. Pursue a ‘three-pillar’ approach to get new treatments to patients: immunotherapies, targeted/precision therapies, and therapies from new classes/novel mechanisms
  2. Standardize access to and the tools used in identifying subtypes or versions of myeloma in patients during the course of their disease to provide the best treatments and speed new approaches, even in those with smoldering or the earliest forms of myeloma
  3. Develop and standardize the tools used to reveal how immune and targeted therapies work in myeloma, and in understanding how patients respond to therapy

A great deal of progress has been made in our understanding of myeloma and new ways to overcome this disease. With two new drugs approved in the last year, and the potential for double that number over the next three years, the horizon for patients is improving. However, the new research programs outlined above and the support to put them into action offer the most promise for long-term remission – and possibly a cure – over the next five years.

For all of the support that has led to our results thus far, and that which will enable the next breakthroughs, we are eternally grateful to our donors, patients, patients' families and all of our partners who make what we do possible.

Walter M. Capone
Multiple Myeloma Research Foundation

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