Study shows three-drug combination delays recurrence and lengthens life for myeloma patients

In continuation of my update on lenalidomide, bortezomib and dexamethasone

The International Myeloma Foundation (IMF) today announced the publication in The Lancet of the results of a randomized, phase III trial, conducted by SWOG, a publicly funded international cancer clinical trials network, and led by IMF chairman of the board Brian G.M. Durie, MD. This important trial compared the effectiveness of two drug regimens in patients undergoing their first round of treatment for multiple myeloma. The trial shows that a three-drug combination - known as VRd - delays recurrence and lengthens life for myeloma patients, indicating a possible new standard of care.

One regimen used in the study was lenalidomide with dexamethasone, a standard first-line treatment for myeloma patients. The other drug regimen also included bortezomib, a second-line drug typically given to myeloma patients whose cancer progresses after initial therapy. SWOG researchers found that the addition of bortezomib earlier made a difference for myeloma patients, giving them about another year of remission and another year of life compared to the standard two-drug regimen.

"Our results are clear. Using bortezomib in combination with lenalidomide and dexamethasone in front-line treatment - hitting the disease early and hard - makes a meaningful difference for myeloma patients," said study principal investigator Dr. Durie, a physician at Cedars-Sinai Outpatient Cancer Center in Los Angeles. "Our results represent a potential new standard of care."

"This is a landmark study that lends clarity to frontline therapy of myeloma," said Dr. S. Vincent Rajkumar of Mayo Clinic and a co-author of the study. "Newer alternatives to VRd may be more expensive, cumbersome, or toxic. These regimens will therefore need to show superiority over VRd in randomized trials."

Also worth noting, Dr. Rajkumar said, is that the VRd regimen will become even more cost effective as the drugs in this combination become generic over time.

 bortezomib     lenalidomide

  dexamethasone

Patients in the trial receiving bortezomib, along with lenalidomide and dexamethasone, in their first six months of treatment had a median remission time of 43 months compared to a median remission of 30 months for patients who received lenalidomide and dexamethasone alone. Researchers also found that patients who received bortezomib lived a median of 75 months, or about six years, after their initial treatment. Patients who received the standard two-drug treatment lived a median of 64 months, or about five years, after initial treatment.

Celebrating its 60th year, SWOG has conducted more than 1,300 cancer trials that have led to FDA approval of 14 new drugs and led to more than 100 changes to cancer standards of care. SWOG is part of the NCI's National Clinical Trials Network (NCTN), the nation's largest and oldest publicly funded cancer research network. SWOG members and other members in the NCTN enrolled 471 eligible and consented adult patients in the study, known as S0777, between February 2008 and February 2012, at 139 institutions across the US.

Patients ranged in age from 28 to 87, had active myeloma, and had not had a stem-cell transplant or any prior treatment for their disease. Patients were randomized into two groups. One group received the standard two-drug treatment for six cycles over six months. That includes lenalidomide, an immunomodulating therapy marketed as Revlimid by Celegene Corporation. The other group received a three-drug combination that included bortezomib, a proteasome inhibitor marketed as Velcade by Millennium Pharmaceuticals. These patients received the triple combination therapy for eight cycles over six months.

Maintenance lenalidomide treatment improves overall survival in multiple myeloma patients

In continuation of my update on lenalidomide 

 lenalidomide 

While several clinical trials have demonstrated that maintenance therapy with lenalidomide reduces the risk of disease progression in patients with multiple myeloma, there have been no definitive results regarding overall survival. While some previous studies found that maintenance lenalidomide after autologous hematopoietic stem cell transplant improved overall survival for newly diagnosed multiple myeloma patients, others showed no benefit to this approach. Philip McCarthy, MD, Director of Blood & Marrow Transplant at Roswell Park Cancer Institute (RPCI), will present the findings of an international team of researchers at the American Society of Clinical Oncology (ASCO) 52nd Annual Meeting in Chicago.

The new study is a meta-analysis of three randomized controlled trials conducted by the Alliance for Clinical Trials in Oncology (formerly Cancer and Leukemia Group B) (CALGB) with support from the NCI, Intergroupe Francophone du Myélome (IFM), and the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA). It involved more than 1,200 participants. For this analysis, 605 patients with newly diagnosed multiple myeloma and treated with continuous lenalidomide (brand name Revlimid) following autologous stem cell transplant were compared to 604 patients who were treated with placebo or no maintenance. At seven years, 62% of those treated with maintenance lenalidomide had survived, compared to 50% of those in the control group. The benefit in overall survival was consistent across subgroups.

"Lenalidomide maintenance following autologous stem cell transplant can now be considered a standard of care for people with multiple myeloma," says Dr. McCarthy, senior author on the meta-analysis and Principal Investigator of the U.S. study, CALGB (Alliance) 100104. "The improvements over the last decade in terms of both survival and quality of life for patients with this disease are striking, and very encouraging."

Phase III study: REVLIMID meets primary endpoint in patients newly diagnosed with multiple myeloma

In continuation of my update on lenalidomide

Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ: CELG), recently announced that its phase III study (MM-020/IFM 07-01) of REVLIMID®(lenalidomide) in combination with dexamethasone in patients newly diagnosed withmultiple myeloma met its primary endpoint of progression-free survival (PFS). In the study, a doublet regimen of continuous oral lenalidomide in combination with low-dose dexamethasone (Rd) demonstrated a statistically significant improvement in PFS compared to patients receiving a comparator arm with a triplet regimen consisting of melphalan, prednisone and thalidomide (MPT).

Phase III study: REVLIMID meets primary endpoint in patients newly diagnosed with multiple myeloma

Lenalidomide offers an effective alternative treatment for cutaneus lupus erythematosus, study suggests

In continuation of my update on lenalidomide

A new study into the thalidomide derivative lenalidomide,  shows that treatment with lenalidomide is safe, with patients seeing an improvement in as little as two weeks. 

There have been several small scale clinical studies into the use of thalidomide for cutaneus lupus erythematosus,  CLE for the third of patients which do not respond to the standard therapy including steroids, antimalarials and immunosuppressive agents. Although thalidomide has a bad press because of its effects on embryonic development, properly administered it is an effective alternative treatment for several types of cancer and inflammatory conditions, albeit with severe side effects which can limit continuous use.

Lenalidomide has been suggested as a more potent, but less toxic, alternative, and previous studies on a small number of patients have had encouraging results. In order to examine the efficacy of lenalidomide more thoroughly researchers from Vall d´Hebron University Hospital Research Institute, Spain, initiated a phase II clinical study, following 15 people with CLE, for between 7 and 30 months, all of which had previously not responded to traditional therapy.

All but one of the people involved in the trial saw clinical improvement and most of these (86%) had complete response, reaching a CLASI score of 0. Three quarters of people who improved with lenalidomide relapsed within 2-8 weeks of the medication being stopped or reduced.

In this study side effects were minor. Only two people reported side effects  although for one person their gastrointestinal symptoms meant that they stopped taking lenalidomide after one week. For both people the side effects disappeared once they stopped taking the drug.

Ref : http://arthritis-research.com/content/14/6/R265/abstract

Lenalidomide offers an effective alternative treatment for cutaneus lupus erythematosus, study suggests

Three-drug regimen provides rapid, durable responses for multiple myeloma

In continuation of my update on three drug combination

A three-drug treatment for the blood cancer multiple myeloma provided rapid, deep and potentially durable responses, researchers report today online in Blood, the Journal of the American Society of Hematology, and yesterday, Sunday, June 3, 2012, at the American Society of Clinical Oncology's Annual Meeting in Chicago, IL, USA.

The researchers, led by Andrzej J. Jakubowiak, MD, PhD, professor of medicine and director of the multiple myeloma program at the University of Chicago Medical Center, found that combining carfilzomib, a next generation proteasome inhibitor, with two standard drugs -- lenalidomide and low-dose dexamethasone compared favorably to other frontline regimens.
The longer patients stayed on the therapy, the better their response. After at least eight 28-day cycles of treatment, 61 percent of the 36 patients who remained on the therapy had a stringent complete response, defined as no detectable tumor cells or myeloma protein in the blood or bone marrow; 78 percent had at least a near complete response. More than 90 percent of patients had no progression of their disease at two years.

"These rapid and durable response rates are higher than those achieved by the best established regimens for newly diagnosed multiple myeloma," said Jakubowiak. "We have observed excellent efficacy, the best reported to date, and very good tolerability, including limited peripheral neuropathy that has been problematic with other drug combinations."

 Ref : http://www.uchospitals.edu/news/2012/20120604-myeloma.html

 Three-drug regimen provides rapid, durable responses for multiple myeloma

Lenalidomide Shows Significant Benefit for Myeloma Patients, Phase III Study Suggests

In continuation of my update on lenalidomide...

Data from the first large U.S. study assessing the effectiveness of long-term "maintenance" therapy with lenalidomide for patients with multiple myeloma show that the drug significantly improves the time to progression and overall survival for patients with this often-deadly hematologic cancer. 

Among 460 patients aged 18 to 70 (median age 59), 321 were randomly assigned to the lenalidomide arm, and 229 to the placebo group. All participants had received prior autologous hematopoietic stem-cell transplantation and had stable (non-progressing) disease. The participants' assignments and responses to date were unblinded in December 2009 when the primary endpoint of the study (time to disease progression) showed a statistically significant difference between the two study groups. After January 2010, 86 of 128 eligible patients crossed over from the placebo arm to the active arm.

The researchers found that the therapy extended the time to disease progression by 19 months overall, even with the majority of placebo patients without progression crossing over to lenalidomide. The treatment was fairly well-tolerated particularly as compared to other treatments for multiple myeloma, such as thalidomide. There was more hematologic toxicity, particularly neutropenia, in the lenalidomide group. When the study data was analyzed again in October 2011, at a median follow-up of 34 months, 37% of participants receiving lenalidomide had disease progression or had died, compared to 58% of those in the placebo group.

"These findings fill a gap that existed previously in terms of data on whether maintenance therapy with lenalidomide prolongs the time to disease progression after initial therapy. We now have evidence that it does, in this and the two other lenalidomide studies that are presented in this issue of the Journal," said Dr. McCarthy. "This shows that patients with multiple myeloma now have options for prolonging the response to initial therapy. The next steps will be trying to improve on these responses by adding new agents that may prove even more effective in combination with lenalidomide following transplant."

Drug combination highly effective for newly diagnosed myeloma patients......

A three-drug combination treatment for the blood cancer multiple myeloma compares favorably to the best established therapy for newly diagnosed patients, according to a multi-center study led by Andrzej Jakubowiak, MD, PhD, professor of medicine and director of the multiple myeloma program at the University of Chicago Medical Center.

( Carfilzomib)

 (Lenalidomide)

( Thalidomide)

The combination includes an investigational medicine called carfilzomib combined with two standard medications: lenalidomide, an analogue of thalidomide, and low-dose dexamethasone, an anti-inflammatory with anti-cancer properties.

"This combination appears to deliver everything we expected and more," said Jakubowiak, who came to the University of Chicago this fall from the University of Michigan. "We have seen excellent efficacy — the best reported to date — without the neurotoxicity that has been problematic with other drug combinations."

Ref : http://www.uchospitals.edu/news/2011/20111206-myeloma.html

Promising treatment for aggressive lymphoma identified in new study

In continuation of my update on Lenalidomide... I found this info interesting to share with...

Promising treatment for aggressive lymphoma identified in new study

New three-drug combination for multiple myeloma ! ...

The regimen, known as RVD, combined the drugs Revlimid - (lenalidomide), Velcade - (bortezomib) and dexamethasone, which previously were found to be highly effective in multiple myeloma patients who had relapsed or no longer responded to first-line therapies.

Fifteen of the 35 newly diagnosed patients in the open-label phase 2 portion of the study subsequently underwent autologous (using their own blood-forming stem cells) transplants, a standard treatment for multiple myeloma and did very well.

For the entire group, after a median 19.3 months of follow up, the median time-to-progression (TTP) of the disease, progression-free survival (PFS), and overall survival (OS) had not yet been reached, according to the presentation. The estimated TTP and PFS at one year are 76 percent, and the estimated one-year overall survival is 100 percent, the results showed.

The more interesting part of the study is that the high response rate was not affected by the specific genetic characteristics of the patients' disease. Patients with so-called "adverse cytogenetics" are at higher risk for treatment failure and death, but in the current study the drug combination worked as well for them as it did in patients with more favorable cytogenetic features.

Except for the main adverse effect, peripheral neuropathy (numbness or pain in the extremities), which typically cleared up after dosages were lowered and the treatment was completed.

The combination has now gone into large phase 3 clinical trials, and the researchers think that this regimen has the potential to be a new standard of treatment in multiple myeloma....

http://www.dana-farber.org/abo/news/press/2009/multiple-myeloma-patients-experience-high-response-rate-with-new-three-drug-combination.html