Phase I study of triple drug combination shows promise in multiple myeloma patients

In continuation of my updates on Dexamethasone,  Plitidepsin and  Bortezomib 

Dexamethasone    Plitidepsin

 Bortezomib 

PharmaMar (MSE:PHM) announces the positive results from a Phase I study of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Dr María Victoria Mateos, MD of the Hematological Department of the University Hospital of Salamanca, Spain, the principal investigator of the study, will present the results in an oral session on June 3rd, 2016 during the 52nd Congress of the American Society of the Clinical Oncology (ASCO), taking place in Chicago (USA), June 3 - 7.

The primary objective of this 20-patient study was to identify the recommended dose for the triple combination (dexamethasone / bortezomib / plitidepsin) administered every four weeks. Efficacy and the safety profile were also evaluated. The overall response rate (ORR) was 56%, including very good partial responses (VGPR) in 33% of the patients and a remarkable partial remission in one triple refractory patient. The median progression free survival (PFS) was 8.3 months. Additionally, 90% of the patients showed a DOR of 6 months or more and clinical benefit was observed in 72% of the patients.

Dose limiting toxicities were not seen in any of the evaluated patients; therefore, the full dose of plitidepsin and bortezomib when used alone were established as the recommended dose for the triple combination. The treatment was well tolerated. The hematological toxicity was manageable and the non-hematological toxicity was in general mild, with the exception of one case of creatinine increase.

Out of the 20 patients that participated in the study, 10 are still under the treatment. The median age was 65. All patients had relapsed after previously receiving, on average, 3.5 therapeutic regimens (range 1-10). Forty-five percent of these patients had been subject to a hematopoietic stem cell transplant (8 autologous, 1 allogeneic). Of the 18 patients evaluable for efficacy, 83% (15 patients) had previously received bortezomib and lenalidomide. One was refractory to bortezomib and seven to lenalidomide.

In abstract #8006, Dr María Victoria Mateos and her team explain that despite the recent progress in the treatment of multiple myeloma due to the introduction of proteasome inhibitors (PIs), the new immunomodulatory drugs (IMIDs), and monoclonal antibodies, the illness is still incurable. Therefore, active compounds with novel mechanisms of action and adequate safety profile are needed. Plitidepsin targets the eukaryotic Elongation Factor eEF1A2, an overexpressed protein in multiple myeloma that contributes to its pathogenesis. The positive results from this study will be added to the already extensive data package from Phase II and Phase III trials, where plitidepsin has shown activity and a favorable safety profile in combination with dexamethasone.

One-dose of dexamethasone can improve outcomes of asthmatic patients in ER

In continuation of my update on dexamethasone

Adults with asthma who were treated with one-dose dexamethasone in the emergency department had only slightly higher relapse than patients who were treated with a 5-day course of prednisone. "Enhanced compliance and convenience may support the use of dexamethasone" is the conclusion of a study that was published online Friday inAnnals of Emergency Medicine ("A Randomized Controlled Noninferiority Trial of Single Dose vs. Five Days of Oral Dexamethasone in Acute Adult Asthma").

"Any time we can reduce the role of patient compliance with asthma, we have a chance of improving outcomes," said lead study author Matthew W. Rehrer, MD, of the Department of Emergency Medicine with Kaiser Permanente in Oakland, Calif. "Dexamethasone allows the emergency physician to administer treatment in one dose and doesn't rely on the patient to remember to take her pills for four more days after leaving the ER. A single dose of medication eliminates prescription adherence barriers such as forgetfulness, cost and dose omission."

Japanese P2 study shows potential of combined vaccine and steroid drug in castration resistant PCa

 In continuation of my update on dexamethasone

Multi-peptide vaccination therapy combined with the low-dose steroid drug dexamethasone shows promise in treating chemotherapy-naive castration resistant prostate cancer (CRPC) patients.

Japanese P2 study shows potential of combined vaccine and steroid drug in castration resistant PCa

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

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

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