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Antidepressant Demonstrates Anti-Myeloma Activity - Results of a preclinical study conducted in China indicate that the antidepressant amitriptyline (Elavil) may have anti-myeloma activity.  Amitriptyline is an older drug, first approved for use in the United States in the early 1960s.  It belongs to a class of drugs known as tricyclic antidepressants.  Myeloma patients may be aware of the drug be­cause it sometimes is prescribed as a treat­ment for periph­eral neu­rop­athy (pain, tingling, and loss of sensation in the extremities due to nerve damage).  In the recent Chinese study, researchers found that orally admin­istered ami­trip­tyline significantly reduced the growth of myeloma cells in mice implanted with either mouse or human myeloma cells.  As a result, the drug substantially ex­tended the survival of the mice with the myeloma cells.  The researchers also found that combining ami­trip­ty­line with Velcade (bor­tez­o­mib) had a greater anti-myeloma effect than would have been expected given the anti-myeloma effect of each individual drug on its own.  For more in­­for­ma­tion, please see the study in the journal Anti-Cancer Drugs (abstract).

Phase 3 Clinical Trial To Study Ixazomib Combination In Newly Diagnosed Multiple Myeloma Patients – The pharma­ceu­tical com­pany Millennium has launched a Phase 3 trial of its investigational drug ixazomib (MLN9708) in newly diagnosed multiple myeloma patients who are not can­di­dates for stem cell trans­plan­ta­tion. The study, which will be carried out in North America and Europe, will in­ves­ti­gate the efficacy and safety of ixazomib in com­bi­na­tion with Revlimid (lena­lido­mide) and dexamethasone (Decadron). Ixazomib is an oral drug that belongs to the same class of drugs as Velcade and Kyprolis (car­filz­o­mib), called proteasome inhibitors. In recent Phase 1/2 clinical trials, ixazomib showed promise 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.

Human Cytomegalovirus Virus Reactivation After Donor Transplant Does Not Impact Survival In Myeloma Patients – The human cytomegalovirus virus (HCMV) is a type of herpes virus which infects over half the U.S. population.  The virus is usually dormant, but if it is reactivated, it can result in eye or lung in­fec­tions which, if they occur in patients who have received a donor stem cell trans­plant, can have serious consequences, including death.  The results of a recent French study show that myeloma patients who carry HCMV are at high risk of virus reactivation after reduced-intensity donor stem cell trans­plan­ta­tion, irrespective of whether the donor also carried the virus. Patients’ whose donors carried HCMV were also at risk of virus reac­ti­va­tion after trans­plan­ta­tion. Another factor that contributed to virus reactivation was if the patient, within 100 days of their trans­plant, developed graft-versus-host disease (a potentially serious side effect of donor stem cell trans­plan­ta­tion in which donor immune system cells attack the patient's cells).  The French researchers also found, however, that virus reactivation did not negatively impact post-transplant out­comes, such as pro­gres­sion-free and over­all survival.  In fact, there was a trend toward better out­comes for patients who were at higher risk of virus reactivation.  For more in­­for­ma­tion, please see the study in the Mediterranean Journal of Hema­tology and Infectious Diseases (full text).

LLS Teleconference On Myeloma Treatment And Side Effect Management – On June 3, the Leukemia & Lymphoma Society (LLS) will sponsor a free teleconference call about the treat­ment of multiple myeloma and man­agement of side effects.  Dr. Vincent Rajkumar from the Mayo Clinic will lead the pro­gram, which runs from noon to 1:30 p.m. Eastern Time.  Dr. Rajkumar will speak about current and emerging myeloma treat­ments, the role of clinical trials in the devel­op­ment of myeloma treat­ments, and the importance of com­munication between patient and provider about treat­ment-related side effects and man­agement of them. For more in­­for­ma­tion or to register, please see the LLS website.

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GDC-0941 May Be Active In Multiple Myeloma – Results of a recent pre­clinical study suggest that the investigational drug GDC-0941, which is being developed by the biotech company Genentech, may have anti-myeloma activity and may increase the activity of Revlimid (lenalidomide) and dexa­methasone (Decadron). Like perifosine, another investigational myeloma treatment, GDC-0941 inhibits an enzyme in cancer cells known as phos­pho­inositide 3-kinase (PI3K). By in­hibit­ing PI3K, GDC-0941 disrupts the cell division cycle and causes cancer cell death. It is being investigated as a treatment for a variety of different cancers, including breast cancer and lung cancer. Based on their findings, the re­searchers recommend that GDC-0941 be further developed as a potential treatment for myeloma. For more information, please see the study in the journal Oncogene (abstract).

Phase 1 Clinical Trial To Study CUDC-907 In Multiple Myeloma And Lymphoma Patients – The pharma­ceutical company Curis (NASDAQ:CRIS) has launched a Phase 1 trial of CUDC-907 in patients with relapsed and refractory multiple myeloma or lymphoma. Patients must have received at least two prior thera­pies to be eligible for the study. CUDC-907 is a multi-targeted agent that inhibits both PI3K and histone deacetylase (HDAC) in cancer cells. Other HDAC inhibitors that are being investigated as potential treat­ments for multiple myeloma include Zolinza (vorinostat), panobinostat, and ricolinostat (ACY-1215). For more information, including trial locations, please see the clinical trial description.

LLS Teleconference About Latest Myeloma Research From ASH – On January 29, the Leukemia & Lym­phoma Society (LLS) will sponsor a free teleconference call about the latest myeloma research from the American Society of Hematology (ASH) annual meeting.  Dr. Kenneth Anderson, director of the Jerome Lipper Myeloma Center at the Dana-Farber Cancer Institute in Boston, will lead the program, which will run from noon till 1:30 p.m. Eastern Time.  Dr. Anderson will speak about current and emerging myeloma treatments, the role of clinical trials in the development of myeloma treatment, and advances in the management of treatment side effects. For more information or to register, please see the LLS website.

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Heart Medication Propranolol May Be Effective For Multiple Myeloma – Results from a recent preclinical study show that the betablocker propranolol (Inderal) may be an effective treatment for multiple myeloma. Propranolol is approved as a treatment for various heart conditions, including high blood pressure, chest pain, and heart attacks.  In the current study, Turkish researchers showed that propranolol triggers cancer cell death in human myeloma cell lines. They suggest that the drug be investigated further for the treatment of multiple myeloma. For more information, please refer to the study in the Journal of Cancer Research and Clinical Oncology (abstract).

First Results Of Delanzomib In Cancer Patients Published – European researchers recently published the first results from a Phase 1 study investigating the safety of delanzomib (CEP-18770) in patients with multiple myeloma and solid tumors. Delanzomib, which is being developed by the pharmaceutical company Teva (NASDAQ: TEVA), belongs to the same class of drugs as Velcade (bortezomib) and Kyprolis (carfilzomib) called proteasome inhibitors. Proteasome inhibitors prevent the breakdown of proteins in cancer cells, triggering their death. The study investigators conclude delanzomib has a favorable safety profile.  The most common side effects included skin rash (53 percent of patients), weakness (29 percent), mouth ulcers (21 percent), and fever (16 percent). The researchers did not observe any significant rates of peripheral neuropathy (pain, tingling, or loss of sensation in the extremities), a common side effect of Velcade. Since skin rash was dose-limiting, the researchers are working to determine the optimal dosing schedule for delanzomib. For more information, please see the study in the European Journal of Cancer (abstract).

IMF Myeloma Workshop For Patients And Families – The International Myeloma Foundation (IMF) will be hosting a workshop for multiple myeloma patients and their families on November 3 in Sacramento, CA. Dr. Robert Kyle from the Mayo Clinic and nurse Page Bertolotti from the Samuel Oschin Comprehensive Cancer Institute in Los Angeles will speak about topics including treatment options, managing side effects, and local clinical trials. For more information or to register, please visit the IMF website.

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J&J Restores Full Access To Doxil – Johnson & Johnson announced last week that the company has restored full access to a reliable supply of Doxil (doxorubicin liposomal), which is approved in combination with Velcade (bortezomib) for previously treated multiple myeloma patients. Doxil has been in short supply since August 2011 after the company had announced delays in manufacturing a month earlier. Johnson & Johnson also announced last week that it will be suspending its Doxil CARES Physician Access Program, which it had created in response to the temporary Doxil shortage. For more information, please see the Doxil Supply website.

Study Shows No Link Between Tobacco Smoking And Multiple Myeloma – Results of a recent Greek analysis indicate that tobacco smoking does not increase the risk of developing multiple myeloma. The Greek researchers point out that their findings apply to both current and former smokers. The analysis was based on 40 studies, which included a total of approximately two million people. For more information, please see the study in The International Journal of Cancer (abstract).

Physical Activity Declines After Myeloma Diagnosis – Results of an Australian study show that levels of physical activity decline after people are diagnosed with multiple myeloma. The researchers identified fatigue, injuries, and pain as the strongest perceived barriers to participation in physical activity. However, they also found that 41 percent of patients were willing to participate in an exercise program if one was offered to them. Based on their findings, the researchers recommended that measures to increase physical activity should aim to decrease the perceived barriers. For more information, please see the study in Supportive Care in Cancer (pdf).

LLS Teleconference On Myeloma Diagnosis And Treatment – On October 30, the Leukemia & Lymphoma Society (LLS) will sponsor a free teleconference call entitled “Myeloma Diagnosis and Treatment Update.”  The call will begin at 12:30 p.m. Eastern Time and will be led by Dr. Ruben Niesvizky from the Weill Medical College of Cornell University in New York City.  Dr. Niesvizky will speak about the goals of myeloma treatment, current treatments and emerging therapies, management of side effects, and the importance of patient and health care team communications.  After the talk, Dr. Niesvizky will answer questions from participants.  For more information or to register, please see the LLS website.

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Multiple Myeloma Patients Have Low Risk Of Heart Problems Following Stem Cell Transplantation –  Results of a recent retrospective analysis show that 1.6 percent of patients with multiple myeloma develop heart problems following treatment with high-dose melphalan (Alkeran) and autologous stem cell transplantation; however, 5.6 percent of amyloidosis patients develop heart problems after the same procedure. Amyloidosis is a blood disorder that results in the abnormal accumulation of proteins in tissues and organs throughout the body.  An estimated 10 percent to 15 percent of myeloma patients also develop symptoms associated with amyloidosis (see related Beacon news). For amyloidosis patients, a melphalan dose of less than 200 mg/m², pre-existing heart problems, and abnormal protein accumulation in more than three organs were associated with an increased risk of heart problems following treatment. For more information, please see the study in the European Journal of Haematology (abstract).

AZD7762 May Increase The Efficacy Of Certain Chemotherapy Agents Against Myeloma – Results of a preclinical study indicate that the protein AZD7762 may increase the efficacy of alkylating chemotherapy agents, such as Treanda (bendamustine), melphalan (Alkeran), or doxorubicin (Adriamycin). Specifically AZD7762 increased the agents’ ability to kill multiple myeloma cells. However, AZD7762 did not enhance the efficacy of Velcade (bortezomib), which is not an alkylating agent. AZD7762 is a protein that decreases the ability of cells to repair damaged DNA. Based on their findings, the researchers recommended that AZD7762 be further investigated in combination with alkylating agents. For more information, please see the study in Molecular Cancer Therapeutics (abstract).

Anti-CD47 Antibodies May Inhibit The Growth Of Multiple Myeloma Cells – Results of another preclinical study suggest that treatment with an anti-CD47 antibody may slow the growth of myeloma cells. CD47, a protein frequently found on the surface of myeloma cells, prevents immune cells from engulfing and killing myeloma cells. The anti-CD47 antibody, which belongs to a class of drugs called monoclonal antibodies, blocks CD47 and allows immune cells to function properly and to kill myeloma cells. Other monoclonal antibodies that are already in clinical testing for multiple myeloma include elotuzumab, siltuximab, and daratumumab. For more information, please see the study in Leukemia (abstract).

MMRF Teleconference On Highlights From The ASCO Meeting For Patients And Caregivers – On June 14, the Multiple Myeloma Research Foundation (MMRF) will sponsor a teleconference call entitled “Highlights From the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting for Patients and Caregivers.” The call will begin at 1 p.m. Eastern Time and will be led by myeloma experts Dr. Ravi Vij from the Washington University School of Medicine in St. Louis and by Dr. Todd M. Zimmerman from the University of Chicago Medical Center. They will talk about the latest advances in myeloma treatment from the 2012 ASCO Annual Meeting in Chicago. After the talk, they will answer questions from participants. For more information or to register, please see the MMRF website.

For a more detailed listing of myeloma-related events, please check the Myeloma Beacon Events Calendar.

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INNO-206 Shows Activity Against Myeloma - Results of a preclinical study show that the investigational drug INNO-206 inhibits blood vessel formation and reduces cell growth in myeloma cell lines.  The drug showed these effects when tested alone; additionally it enhanced the efficacy of Velcade (bortezomib) when tested in combination.  INNO-206 is a derivative of the chemotherapy agent doxorubicin (Adriamycin).  This study also showed that INNO-206 was safer in mice than doxorubicin and therefore could be administered at higher doses. For information, please see the study in Clinical Cancer Research (abstract).

TRAIL-Doxorubicin Combination May Eradicate Myeloma Cells – Results of a preclinical study show that a combination of doxorubicin and TRAIL, a protein that induces cell death, was able to eradicate myeloma cell lines. In particular, the TRAIL-doxorubicin combination successfully eliminated cells that are implicated in tumor initiation as well as tumor growth. According to the study investigators, these findings offer a promising new approach to finding a cure for multiple myeloma. For more information, please see the study in PloS One.

Relatives Of Multiple Myeloma Patients Have Increased Risk Of MGUS – Results of a study conducted at the Mayo Clinic indicate that first-degree relatives of multiple myeloma patients are 3.4 times as likely to develop light-chain monoclonal gammopathy of undetermined significance (MGUS) compared to the general population.  A previous study also showed that these relatives are at an increased risk of developing heavy-chain MGUS. For more information, please see the study in the British Journal of Hematology (abstract).

IMF Myeloma Workshop For Patients And Families – The International Myeloma Foundation (IMF) will be hosting a workshop for multiple myeloma patients and their families on June 23 in Milwaukee, WI. Dr. Ayman Saad from the Medical College of Wisconsin, Dr. Natalie Callander from the University of Wisconsin School of Medicine, and nurse Tiffany Richards from the MD Anderson Cancer Center in Houston will speak about topics including treatment options, managing side effects, and local clinical trials. For more information or to register, please visit the IMF website.

For a more detailed listing of myeloma-related events, please check the Myeloma Beacon Events Calendar.

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Study Reveals Genetic Differences Between MGUS And Multiple Myeloma – In a recent study, Spanish researchers identified chromosomal abnormalities that were more frequent in patients with active mutiple myeloma than in patients with smoldering myeloma and monoclonal gammopathy of undetermined significance (MGUS), a condition that may later progress to smoldering or active myeloma. The researchers also found that chromosomal abnormalities tend to be more frequent in active myeloma patients than in smoldering myeloma patients, and also more frequent in smoldering myeloma patients than in MGUS patients.  For more information, please see the study in Leukemia (abstract).

sCD105 Protein May Be An Indicator For Myeloma Severity – Results of a recent study show that levels of the protein sCD105 circulating in the blood are higher in multiple myeloma patients than in healthy individuals. Higher levels of sCD105 also were associated with more advanced stages of disease. sCD105 is known to play a role in the growth of new blood vessels and may thus contribute to tumor progression in myeloma. Researchers believe these findings warrant further study of sCD105 levels as an indicator for disease activity. For more information, please see the study in the European Journal of Internal Medicine (abstract).

Whole Body MRI Adds Limited Value To Routine Myeloma Remission Testing After Transplantation – A recent study found that the use of whole body magnetic resonance imaging (MRI) to detect persisting or relapsing multiple myeloma post transplant offers little added value compared to current routine laboratory tests. The results of the whole body MRI and routine laboratory tests were in agreement in 79 percent of the patients assessed. For more information, please see the study in European Radiology (abstract).

IMF Myeloma Workshop For Patients And Families – The International Myeloma Foundation (IMF) will be hosting a workshop for multiple myeloma patients and their families on May 19 in Indianapolis, IN. Dr. Rafat Abonour from the Indiana University Bone Marrow and Stem Cell Transplantation Program and nurse Kena Miller from the Roswell Park Cancer Institute in Buffalo, NY, will speak about topics including treatment options, managing side effects, and local clinical trials. For more information or to register, please visit the IMF website.

For a more detailed listing of myeloma-related events, please check the Myeloma Beacon Events Calendar.