December 11, 2012
MMRF Newsflash from ASH 2012 - Volume 4
Welcome to our fourth and final day of coverage of the 2012 American Society of Hematology (ASH) Annual meeting. Today during the oral session, treatment for patients with relapsed/refractory disease and papers on infection and kidney impairment, common in multiple myeloma, were presented.
Pomalidomide Extends Overall Survival
The phase 3 trial of pomalidomide plus dexamethasone vs dexamethasone that was predominantly conducted in Europe was accepted by ASH as a late-breaking abstract. This means that data were not available when original abstracts were due but the data were so compelling that the abstract was accepted after the deadline. Dr. Meletios Dimopoulos from the University of Athens, Greece presented data from this study that showed pomalidomide plus low-dose dexamethasone significantly increased progression-free survival (PFS) and overall survival (OS) compared with high-dose dexamethasone in patients who were refractory to Revlimid and Velcade! Median PFS was nearly four months for the pomalidomide arm versus about two months for the dex arm. Median overall survival for the pomalidomide arm had not yet been reached. We hope to hear positive news from the FDA on the potential accelerated approval of this promising new treatment in the coming weeks.
Treanda (bendamustine) is a chemotherapy treatment that is widely used outside the US to treat multiple myeloma. In the US, Treanda is FDA approved to treat a type of lymphoma. Several studies were presented at this meeting, including an MMRC trial of Treanda plus Revlimid and dexamethasone, showing promising activity when combined with Velcade and/or Revlimid. In an oral presentation today, Dr. Heinz Ludwig of the University of Vienna, Austria presented results from a trial of Treanda combined with Velcade and dexamethasone in patients with relapsed/refractory multiple myeloma. There were 66 evaluable patients, most of who had received 1 or 2 prior therapies; 43 of these patients had responses (response rate of 65.2%) including 14 patients with a complete response; all patients had a clinical benefit to this treatment. Median progression-free survival was 9.7 months when all patients were considered, but was 12.9 months in patients with 1-2 prior treatments. Median overall survival in the entire cohort was 21 months. Prior treatment with Revlimid had a negative effect on response rate to this treatment. Toxicities to this regimen included a low incidence of infections and gastrointestinal events, with a few cases of peripheral neuropathy.
Dr. Dimopoulos also provided an update on second line treatment of patients who relapsed in the phase III trial, MM-015 that compared melphalan plus prednisone and Revlimid followed by Revlimid maintenance (arm 1) with melphalan and prednisone (arm 2), or with melphalan, prednisone, and Revlimid (arm 3). After frontline treatment, fewer patients from arm 1 (54%) progressed compared with patients in arms 2 (77%) and 3 (83%), confirming the benefit of maintenance therapy. After progression, patients could opt to receive open-label Revlimid plus dexamethasone or another treatment. Revlimid-based second-line treatments were active in these patients, regardless of which treatment they received as the first-line therapy. Importantly, this study showed that maintenance treatment with Revlimid does not appear to result in disease that is resistant to this agent at relapse.
About half of myeloma patients have some impairment of the kidneys, and an estimated 20% have “myeloma kidney” or severe renal failure at diagnosis. This condition can cause patients to have more toxicity from treatment. However, several novel agents have been incorporated into new treatments for myeloma and have improved the survival of this disease.
Dr. Meletios Dimopoulos presented a study of impact of these novel therapies like Velcade and Revlimid on the survival of myeloma patients with impaired kidneys. In total, 1773 patients with symptomatic myeloma who were treated in the Greek Myeloma Study Group were included. Patients were divided into 5-year groups between 1990 and 2004 according to the date of their initial treatment, then from 2005 onward. The response and median survival to frontline therapy for all myeloma patients improved in the years after 2000 compared with the prior years as a result of the availability of these newer treatments. When looking only at patients with impaired kidney function, the study showed that survival of these patients also improved after the introduction of novel therapies, especially for patients with severe kidney impairment.
Myeloma Preclinical Studies
Several studies presented today, too numerous to detail here, covered potential risk assessment strategies and tumor biology studies, which will help us identify better drugs in the future, and also help us to achieve our aim of personalized medicine! This is certainly an exciting time in myeloma research.
For additional information on what was covered at this year's ASH meeting, please view our interview with Gareth Morgan, MD, PhD, and Antonio Palumbo, MD.
It is also not too late to sign up for our patient telephone/web education program Highlights From the 2012 American Society of Hematology (ASH) Annual Meeting for Patients and Caregivers on Tuesday, December 18, 2012 at 1:00-2:00 PM ET/10:00-11:00 AM PT by visiting www.cancereducation.com/cancersyspagesnb/a/mmrf/mm1209/Register.html