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Phase 1 Trial Of All-Oral Ricolinostat-Revlimid-Dexamethasone Combo Begins – Acetylon Pharmaceuticals announced last week the initiation of a Phase 1b clinical trial of ricolinostat (ACY-1215) in combination with Revlimid (lenalidomide) and dexamethasone (Decadron) for the treatment of patients with relapsed or refractory multiple myeloma. Ricolinostat is an oral treatment that belongs to a family of anti-cancer drugs called HDAC inhibitors. Other HDAC inhibitors under investigation for multiple myeloma include Zolinza (vorinostat) and panobinostat. Acetylon believes that ricolinostat could produce fewer side effects than other non-specific HDAC inhibitors, as it selectively inhibits the enzyme HDAC6. The primary aim of the trial is to establish an optimal dose of ricolinostat over a 28-day treatment cycle and to assess the potential anti-myeloma activity of the three-drug combination. In addition, Acetylon is enrolling patients for a Phase 1/2 trial of ricolinostat in combination with Velcade (bortezomib) and dexamethasone in patients with relapsed or refractory myeloma. For more information on both trials, please see the Acetylon press release and the U.S. clinical trial registry.

Lucatumumab Shows Modest Activity As Single Agent In Relapsed/Refractory Myeloma – Results from a recent Phase 1 study indicate that lucatumumab, an antibody developed by Novartis, is well tolerated in relapsed or refractory myeloma patients; however, the compound only showed modest activity in the study participants. Specifically, 4 percent of patients maintained a partial response for a period of eight months or longer, and 43 percent maintained stable disease. The most common severe side effects included anemia (7 percent), chills (7 percent), and fever (7 percent). Side effects severe enough to limit drug dosage were seen in about 10 percent of patients. Based on these results, the researchers recommend that lucatumumab be tested in combination with other anti-myeloma drugs. For more information, please see the study in the British Journal of Hematology (abstract).

Viracept-Velcade Combo Kills Myeloma Cells Better Than Either Drug Alone – Researchers at the National Cancer Institute have found that a combination of the anti-HIV drug Viracept (nelfinavir) and Velcade kills myeloma cells better than either drug alone in a preclinical study. Viracept belongs to a class of drugs called protease inhibitors and was approved by the FDA to treat HIV in 1997. Both Viracept and Velcade limit a cell’s ability to chop up and discard unwanted proteins. Simultaneous treatment with both drugs resulted in an accumulation of such unwanted proteins in the cell, eventually resulting in cell death. For more information, please refer to the study in Cell Death and Disease.

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The results of a recent Greek study indicate that kidney impairment is highly reversible in newly diagnosed multiple myeloma patients treated with regimens containing Velcade, thalidomide, and Revlimid.

Additionally, the Greek researchers found that Velcade (bortezomib)-based treatments were associated with a shorter time to response  and higher rates of restoration of kidney function than thalidomide (Thalomid)- and Revlimid (lenalidomide)-based regimens.

Based on their findings, the researchers recommend that Velcade be used as initial therapy for myeloma patients with kidney impairment.

Dr. Baldeep Wirk of the University of Florida, who …

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Kyprolis Is Now Available In The United States – The newly approved myeloma treat­ment Kyprolis (car­filz­o­mib) is available on the U.S. market starting today. The U.S. Food and Drug Administration (FDA) approved Kyprolis on July 20 for the treat­ment of multiple myeloma patients who have received at least two prior ther­a­pies (see related Beacon news). Physicians can now prescribe Kyprolis to myeloma patients throughout the U.S. To learn more about the recent FDA approval of Kyprolis and the drug's launch, please see The Beacon’s detailed questions and answers article published last week.

Exelixis Starts Clinical Trial Of Cabozantinib In Patients With Relapsed Or Refractory Myeloma – Exelixis, a bio­pharma­ceu­tical com­pany based in South San Francisco, announced last week the start of a Phase 1 trial of cabozantinib (XL184) in multiple myeloma. Cabozantinib is a com­­pound that inhibits the activity of two key enzymes, at least one of which is known to promote the growth of myeloma cells. The study will in­ves­ti­gate the safety, tolerability, and preliminary activity of cabozantinib in patients with re­lapsed or refractory multiple myeloma with bone disease. Cabozantinib is also being in­ves­ti­gated as treat­ment for several other types of cancers, including non-small cell lung cancer, prostate cancer, and thyroid cancer. For more in­­for­ma­tion, please see the Exelixis press release and the clinical trial description.

KW-2478 Plus Velcade Shows Potent Anti-Myeloma Activity In Preclinical Study - Results from a recent preclinical study indicate that a com­bi­na­tion of the investigational drug KW-2478 with Velcade (bor­tez­o­mib) has potent anti-myeloma activity. KW-2478 belongs to a class of anti-myeloma drugs called Hsp90 inhibitors and is being developed by Japanese drug manu­­fac­­turer Kyowa Hakko Kirin. Other Hsp90 inhibitors which have been in­ves­ti­gated as potential myeloma treat­ments include ganetespib and tanespimycin.  In the recent study involving KW-2478, researchers found that the drug increased the ability of Velcade to kill myeloma cells. In mice, the com­bi­na­tion also reduced bone lesions and mono­clonal protein levels (M-spike) more effectively than either drug alone. According to the study investigators, these results strongly suggest that the com­bi­na­tion could be an effective treat­ment for multiple myeloma patients. For more in­­for­ma­tion, please refer to the study in the Blood Cancer Journal (abstract).

Purifying Plasma Cells From Bone Marrow Samples May Facilitate Detection of Chromosomal Abnormalities – Findings from a recent Dutch study suggest that chromosomal ab­nor­mal­i­ties in cancerous plasma cells may be easier to detect in purified plasma cell samples from bone marrow samples, as compared to unpurified (whole) marrow samples from myeloma patients. Previous studies have shown that certain chromosomal ab­nor­mal­i­ties in cancerous plasma cells can predict poorer myeloma prognosis. In this study, researchers could identify plasma cell chromosomal ab­nor­mal­i­ties in 96 per­cent of purified samples from bone marrow samples, as compared to 61 per­cent in unpurified samples. They argued that the low frequency of plasma cells in unpurified bone marrow samples hindered the detection of ab­nor­mal­i­ties. The researchers found that genetic material isolated from purified plasma cells could also be analyzed by molecular techniques to yield addi­tional in­­for­ma­tion about each patient's myeloma. For more in­­for­ma­tion, please see the study in Genes, Chromosomes and Cancer (abstract).

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Dr. Michel Attal from the Purpan Hospital in Toulouse, France, presented a review of current maintenance therapies for multiple myeloma during the American Society of Clinical Oncology (ASCO) annual meeting last month.

The focus of Dr. Attal’s presentation was on whether there is evidence to support the use of the novel anti-myeloma agents thalidomide (Thalo­mid), Revlimid (lenalidomide), and Velcade (bortezomib) as mainte­nance therapy after initial therapy and stem cell transplantation.

Maintenance therapy refers to a prolonged, and often low-dose, form of treatment given to myeloma patients after their initial …

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The results of a recent Phase 3 study conducted throughout Europe show that treatment with a combination of Velcade, thalidomide, and dexamethasone leads to superior clinical benefits compared to treatment with thalidomide and dexamethasone alone in multiple myeloma patients who have relapsed or progressed after a stem cell transplant.

Specifically, more patients responded to the three-drug regimen.  In addition, the group of patients treated with the three-drug combination responded longer and did not progress as quickly as those treated with the two-drug combination. However, the three-drug combination led to a higher rate …

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Phase 3 Trial To Compare Carfilzomib and Velcade For Relapsed Multiple Myeloma – On Monday, Onyx Pharmaceuticals announced the start of a Phase 3 trial comparing the safety and efficacy of its investigational drug carfilzomib (Kyprolis) to that of Velcade (bor­tez­o­mib). In particular, the trial will in­ves­ti­gate the efficacy and safety of car­filz­o­mib in com­bi­na­tion with dexamethasone (Decadron) versus Velcade plus dexa­meth­a­sone in patients who have received one to three prior lines of ther­apy. Carfilzomib is in the same class of drugs as Velcade, known as proteasome inhibitors. It is cur­rently under review by the U.S. Food and Drug Administration for potential approval as a new treat­ment for myeloma (see related Beacon news). For more in­­for­ma­tion, please see the Onyx Pharmaceuticals press release and the clinical trial description.

Phase 3 Trial Of MLN9708 Begins In Patients With Relapsed Or Refractory Myeloma – Millennium Pharmaceuticals, the com­pany that developed Velcade and markets the drug in the United States, announced last week the initiation of an inter­na­tional Phase 3 clinical trial of its investigational com­­pound MLN9708 (ixazomib) in patients with re­lapsed or refractory multiple myeloma. The study will in­ves­ti­gate the efficacy and safety of MLN9708 in com­bi­na­tion with Revlimid (lena­lido­mide) and dexa­meth­a­sone. Like car­filz­o­mib and Velcade, MLN9708 is a proteasome inhibitor; however, it is admin­istered orally. In recent Phase 1/2 clinical trials, MLN9708 showed promising results as a single agent as well as in com­bi­na­tion with Revlimid and dexa­meth­a­sone in both newly diagnosed and re­lapsed/refractory myeloma patients (see related Beacon news). For more in­­for­ma­tion, please see the Millennium press release and the clinical trial description.

Researchers Identify Potential Reason For Drug Resistance In Some High-Risk Multiple Myeloma Patients – Researchers from the United States and Singapore have found that a small molecule of RNA called ACA11 may be the reason for drug resistance in multiple myeloma patients with the chromosomal ab­nor­mal­ity t(4;14). Specifically, the researchers found that ACA11 was present in all the cancer cells of patients with t(4;14). As the amount of ACA11 increased, levels of oxidative stress that damage cells went down, protecting cancer cells from damage. As a result, the cancer cells were more resistant to chemotherapy. Patients with t(4;14), which is a translocation of a region of chromosome 4 to chromosome 14, are considered high-risk patients (see related Beacon news). For more in­­for­ma­tion, please see the study in The Journal of Clinical Investigation and the Washington University in St. Louis press release.

Japanese Phase 1 Trial To Study Perifosine For Refractory Myeloma – The Canadian bio­tech com­pany Aeterna Zentaris announced last week that its partner in Japan, Yakult Honsha, has begun a Phase 1 clinical trial of perifosine (KRX-0401) in multiple myeloma patients who are resistant to Velcade treat­ment. The study will evaluate the safety of  perifosine in com­bi­na­tion with Velcade and dexa­meth­a­sone in 18 patients. Perifosine is an orally admin­istered drug that belongs to a new class of anti-cancer drugs called “Akt inhibitors.” In the United States, perifosine in com­bi­na­tion with Velcade and dexa­meth­a­sone is in Phase 3 trials for multiple myeloma (see related Beacon news). For more in­­for­ma­tion, please see the Aeterna Zentaris press release.

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Upfront therapy for newly diagnosed multiple myeloma patients should be risk-adapted and individualized, according to Dr. Vincent Rajkumar from the Mayo Clinic.

Dr. Rajkumar presented his opinions about upfront therapy for myeloma during an education session at the recent annual meeting of the American Society of Clinical Oncology (ASCO). During his presentation, he reviewed the induction treatment options for newly diagnosed multiple myeloma patients and dis­cussed his opinions of the various options.

Induction therapy refers to the initial treatment given to newly diagnosed multiple myeloma patients to combat their cancer.

According to …