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    WNMyeloma posted an update

    Pereira Offers View on Maintenance Therapy for Patients with Multiple Myeloma

    Denise. L. Pereira, MD, recently shared the treatment considerations and decisions she makes when treating patients with multiple myeloma. Pereira, assistant professor of clinical medicine, University of Miami, Sylvester Comprehensive Cancer Center, Miami, Florida, explained her treatment decisions based on 2 case scenarios during a Targeted Oncology live case-based peer perspectives presentation.

    Case 1

    July 2011
    A 61-year-old Caucasian female was diagnosed with stage II multiple myeloma
    Genetic testing showed t(4:16)
    At the time, she was treated with lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVD) induction therapy, followed by autologous stem cell transplantation
    She achieved a complete remission with RVD and transplant
    The patient was placed on lenalidomide maintenance therapy
    TARGETED ONCOLOGY: Discuss the rationale for the choice of upfront therapy in this patient. What do you think of using lenalidomide, carfilzomib, and dexamethasone (KRd) instead?

    Pereira: We know that triplets are better than doublets. The combination of a proteasome inhibitor and an immunomodulatory drug (IMiD) is linked to very good response rates with an acceptable toxicity profile. So, in general, within the United States, we are more likely to use RVD outside a clinical trial. This patient has no impaired kidney function or anything else that would make me lean toward using bortezomib, cyclophosphamide, and dexamethasone (CyBorD) instead.

    I would use RVD, as was done in this case, to establish a very high response rate. There are other people who would suggest KRd as an even better option, and there is an ongoing ECOG trial to test this hypothesis with KRd as the experimental arm. I don’t think that it is close to the first-line yet because RVD is more established; however, KRd is far from a bad regimen.

    TARGETED ONCOLOGY: What is the role of transplant as part of frontline therapy for myeloma?

    Pereira: As a transplant physician, I must be a believer. I would transplant any patient who I think can safely go through the procedure. I don’t really have an age limit. I offer potential transplant-eligible candidates this option because I believe it has the potential to further deepen the response to therapy, and better responses are associated with better outcomes.

    TARGETED ONCOLOGY: Which patients are typically candidates for maintenance therapy?

    Pereira: I think all patients are candidates for maintenance therapy because maintenance therapy has been associated with an improvement in survival. There are multiple randomized trials that show progression-free survival (PFS) definitely improves with the use of maintenance therapy. Regarding overall survival (OS), there are some trials that are positive as well as a meta-analyses (when you collect all the trials together to pull the data and results into 1 study). In this case, PFS was better and OS was also better.

    It is standard to use lenalidomide at a dose of 10 mg daily, with the option to switch to 21 out of 28 days. I use bortezomib in very specific circumstances. High-risk patients are the patient population in which I consider bortezomib and I use it every 2 weeks. Maintenance therapy should be given until progression or intolerable adverse effects.

    TARGETED ONCOLOGY: What is the typical follow-up for this type of patient? Does minimal residual disease (MRD) testing play a role in this follow-up?

    Pereira: This patient must be seen every 3 months and should have their blood checked every month.

    I am not using MRD testing today, but I think more than anything else, MRD testing is a signal of improvement that can effectively gauge the effectiveness of a regimen. MRD is very important in research and clinical trials, but in the clinical setting I don’t believe that we are ready yet to move toward its use. I have not yet established it in my patients’ day-to-day care.

    TARGETED ONCOLOGY: What is the potential impact of these data?

    Pereira: The issue more than anything else with this trial is that bortezomib, melphalan, and prednisone (VMP) is not considered standard in the United States. The trial is important for proof of concept, but I don’t think that it will immediately change whether or not physicians will prescribe it in the United States. The proof of concept is that the addition of daratumumab would improve the results of the triplet.

    TARGETED ONCOLOGY: Are these results strong enough to potentially replace transplant-eligible patients?

    Pereira: No, the regimen has melphalan. Nobody will use melphalan on a transplant-eligible patient that early. Melphalan is toxic to the stem cells and is associated with increased risk of myelodysplasia. It is a drug that, aside from conditioning regimens for transplant on transplant-eligible patients, should not be used for transplant-eligible patients.

    I would also add that being transplant-eligible is a moving target here in the United States. This means that what was not considered transplant-eligible 5 years ago is transplant-eligible nowadays. The melphalan makes it very hard to collect the stem cells for patients who could potentially be transplant-eligible at some point in their illness.

    TARGETED ONCOLOGY: If daratumumab becomes available, how would you select a patient for this therapy versus other available frontline options?

    Pereira: In the United States, I think you will be seeing people use this option in transplant-eligible and transplant-ineligible patients. However, the lack of familiarity with VMP is a significant barrier to the adoption of this regimen.

    August 2016
    On routine follow-up, the patient reported having mild fatigue, but continued to work full-time; she had grade 1 neuropathy
    M-protein, 1.4 g/dL
    Light chain levels continued to rise
    Hemoglobin (Hb), 10.3 g/dL
    Creatinine, 1.3 mg/dL
    TARGETED ONCOLOGY: How do you define progression in myeloma?

    I think there are 2 definitions. One is biochemical relapse, when you have some changes in the bloodwork when you can see that the protein studies are getting worse and the patient remains symptomatic. The other is clinical relapse, where the patient has anemia, new lesions, change in calcium levels, or a rise or fall of creatinine. That to me would be a clinical relapse.

    TARGETED ONCOLOGY: When do you start therapy for relapsed disease?

    Pereira: I start therapy when they have clinical relapse, and only in some cases when they have biochemical relapse.

    TARGETED ONCOLOGY: What are the options for treatment of a patient who is largely asymptomatic with good performance status but who is developing biochemical relapse on lenalidomide?

    Pereira: I would tend to make minor changes. If they were on a low dose of lenalidomide, I would add steroids to the regimen. The other option is to add elotuzumab to a patient who is on low-dose lenalidomide and is starting to have biochemical relapse. There are data with the combination and it is a well-tolerated regimen with lenalidomide and dexamethasone.

    This case, however, is not a case of a biochemical relapse. This patient has a drop of hemoglobin levels and a worsening of her creatinine, which does not qualify as biochemical relapse. It would be a biochemical relapse only if there were changes in the protein studies, without any organ damage. [Therefore, this would be considered a clinical relapse.]

    TARGETED ONCOLOGY: How does tolerance to previous therapy affect your choice?

    Pereira: If I have a patient who is older and has poor tolerance to adverse effects, I tend to keep a lower profile. I tend not to give a very aggressive regimen. But with a younger and fit patient, I tend to treat with a triplet again.

    Case 2

    December 2010
    A 54-year-old Caucasian male presented with anemia
    Bone marrow biopsy showed 40% plasma cells
    Florescence in situ hybridization t(14:20), del 13, del 17p (80% of the myeloma cells had a 17p deletion)
    TARGETED ONCOLOGY: What is the prognosis of this patient?

    Pereira: This patient has a worse prognosis than the majority of patients with myeloma because he has a combination of high-risk cytogenetics. Specifically, the deletion of 17p is associated with mostly poor prognoses.

    TARGETED ONCOLOGY: What are the treatment choices for this patient?

    Pereira: I would usually use [as induction therapy] something that has, in the backbone, a proteasome inhibitor. Most of us would agree that you should also use an IMiD. I would say that most of us at this point will be using RVD.

    I would consolidate this patient with an autologous stem cell transplant. I don’t tend to use consolidation post transplant because the most recent trial—the [Blood and Marrow Transplant Clinical Trials Network’s] StaMINA trial, which has not yet been published but has been presented—shows that patients in general, not specifically high-risk patients, seem to have no benefit with consolidation. I would have to wait for the subset analysis to come back to see if there are any specific benefits in the high-risk patient population. So far, I have not seen very convincing data on whether or not they should get chemotherapy consolidation after transplant, and I would not give it.

    As for maintenance therapy, everyone should get it. This patient specifically should be treated with a proteasome inhibitor regimen, reusing bortezomib every 2 weeks plus or minus lenalidomide. The proteasome inhibitor seems to be a better class of drugs when treating high-risk patients. Lenalidomide is the 1 drug that has the majority of data in the maintenance therapy setting.

    TARGETED ONCOLOGY: What factors do you consider when deciding on treatment?

    Pereira: Age, performance status, and the ability to comply with such a demanding maintenance schedule. Even though it is every 2 weeks, it still requires the patient to come to the medical center. They have to have a willingness to do this kind of thing for a long period of time.
    The patient was treated with KRd for 6 cycles, followed by autologous stem cell transplant (MEL 200), then 6 cycles of consolidation with KRd, and then transitioned to maintenance with KRd for another 6 months. This was followed by lenalidomide maintenance

    TARGETED ONCOLOGY: Do you think daratumumab could be added to this regimen in the frontline setting?

    Pereira: Absolutely; it is a very appealing concept. Although the data are not fully there yet with KRd, it is very appealing. I have seen some of the data of the small study that was done in the first line, which was not isolated for high-risk patients, but I think the results are very interesting.

    TARGETED ONCOLOGY: What would you give the patient if he again develops symptomatic relapse?

    Pereira: In this case, I would say for sure a regimen that would have daratumumab, assuming that the patient did not get it in the first line. I would certainly give the patient a daratumumab-containing regimen, probably daratumumab, carfilzomib (Kyprolis), and pomalidomide (Pomalyst), plus dexamethasone.

    Posted on Targeted Oncology http://www.targetedonc.com/news/pereira-offers-view-on-maintenance-therapy-for-patients-with-multiple-myeloma

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    WNMyeloma posted an update

    Phase 1/2 Trial of Medigene’s MDG1011 Immunotherapy in Blood Cancer Patients Set to Begin

    A Phase 1/2 clinical trial testing an experimental T-cell therapy for the first time in human patients will begin in the coming weeks after receiving approval from the German regulatory authority, Medigene recently announced.

    The treatment, called MDG1011, will be tested in 92 patients with blood cancer, including acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma.

    MDG1011 is Medigene’s first immunotherapy to reach clinical stage. It is made of a patient’s own T-cells, armed with T-cell receptors (TCR) that target the tumor-associated protein PRAME. Called TCR-modified T-cell therapy, it is designed to overcome patients’ tolerance toward cancer cells.

    The multicenter, open-label trial, which will be conducted in Germany, will address the safety, feasibility, and preliminary effectiveness of MDG1011.

    It will be carried out in two parts. In Phase 1, researchers will enroll approximately 12 patients with PRAME-positive advanced disease to test different doses of MDG1011. Patients will receive initial treatment with chemotherapy medications cyclophosphamide and fludarabine, followed by MDG1011 transfusion. After completing the treatment, participants will be followed for four weeks.

    Each dose will be tested in all three blood cancers. The effects of MG1011 will be analyzed at three months of treatment with a total follow-up period of up to 12 months.

    After the treatment has been determined safe by independent evaluation, Phase 2 will be conducted in two of the three cancer indications. A total of 40 PRAME- and HLA-A*02:01-positive patients will be treated with MDG1011. HLA-A*02:01 is a specific type of human leukocyte antigen that is critical for effective T-cell binding to cancer cells.

    Forty more patients, who exhibit PRAME but not HLA-A*02:01 will make up the control groups.

    Scientists will primarily address safety and tumor reduction with MSG1011 at three months of treatment. Other assessments will include duration of response, time to disease progression, quality of life, correlation of PRAME levels with anti-cancer response, and overall survival, which is the length of time patients live after starting treatment. Patients will be followed for an additional 12 months after treatment.

    “Attaining these approvals for MDG1011 is an important step towards the start of our clinical trial, and a further validation of our research and product development work,” Kai Pinkernell, MD, senior vice president of clinical affairs and chief medical officer at Medigene, said in a press release.

    “With our specific study design, we are able to evaluate our T-cell therapy simultaneously in various diseases and to generate data in three hematological indications in parallel,” he said.

    From Myeloma Research News

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    WNMyeloma posted an update

    Now being a firefighter is a cancer risk

    A new danger: Firefighters take on cancer threat

    A 2010 study conducted by the Centers for Disease Control and National Institute for Occupational Safety and Health of 30,000 firefighters across the country found higher rates of cancer than the general population.

    “What has become almost an epidemic in the fire service is the increase in the number of cancer-related illnesses across the world in the fire service,” said Brian Jones, president of the Professional Firefighters of West Virginia.

    A firefighter in Morgantown, Jones is one of the estimated 800 firefighters from around the country who attended the annual Alfred K. Whitehead Legislative Conference in Washington, D.C. March 5-7.

    Firefighters roughly 30 years ago were most often diagnosed with asbestos-related cancers, Jones said. Today, the cancers are more often leukemia, lymphoma or myeloma.

    “The studies really didn’t start to the early 2000s; we’re kind of late to the ball,” Jones said.

    Firefighters are backing legislation introduced in Congress to establish a national firefighter cancer registry to get a firm handle on the number of deaths, Jones said. Firefighters hope such a cancer database will get them a better handle on the problem.

    “Any firefighter — no matter what the cause — if they’ve contracted any type of cancer, the information would be put into a database,” Jones said. “It would give us a picture of who is getting cancer, what type they’re getting and what might be leading to that.”

    Up until the early1970s, building materials were, for the most part, natural products, Jones said. Subsequently, petro products started to be used in household plumbing and furniture products.

    “The building material and such that have been used for the past 30 to 40 years are a lot more carcinogenic than previous materials,” Jones said. “With the carcinogens in all the plastics and such, when they burn they give off a lot of different things that are directly related to certain types of cancer.

    “When they burn, there is nastier, thicker black smoke in the fire than years ago–a lot of that stuff is carcinogenic,” Jones said. “They’ve identified hundreds of carcinogens that are bi-products of some the fires that we see in all types of incidents.”

    Jones said a better understanding of the demographic getting these cancers is needed.

    “When we’ve done these studies, you are at the mercy of a small size,” he said. “We need a better sample size, so that we can see men vs. women, some types of minorities, whether it’s a West Coast problem or an East Coast problem.”

    The West Virginia House of Delegates is considering a bill that would presume certain kinds of cancers and specific respiratory ailments suffered by firefighters are work-related. The Senate passed the measure with a 33-0 vote Feb. 27.

    Introduced by Sen. Ryan Ferns, R-Ohio, SB 82 amends the state’s workers compensation laws to include rebuttable presumptions for certain injuries and diseases for professional firefighters. Injuries covered would include leukemia, lymphoma, or multiple myeloma arising out of and in the course of employment as a firefighter on July1, 2023.

    Jones said firefighters are also looking to extend federal funding for “Staffing for Adequate Fire and Emergency Response,” or SAFER program, and the federal fire grant program.

    A SAFER grant enabled the Morgantown Fire Company to hire 12 new firefighters in November.

    “It’s been our first real increase in manpower, probably since the late 1960s,” Jones said.

    Staff writer Jim McConville can be reached at 304-*263*-8931, ext. 215, or [email redacted].

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    WNMyeloma posted an update

    Distress Score Could Shape Myeloma Treatment Interventions

    While recent breakthroughs have led to more treatment options for multiple myeloma, patients are also experiencing new side effects, stressful financial issues and psychological burdens. In turn, recent research found that this increased distress may actually have negative implications for patient outcomes.

    While recent breakthroughs have led to more treatment options for multiple myeloma, patients are also experiencing new side effects, stressful financial issues and psychological burdens. In turn, recent research found that this increased distress may actually have negative implications for patient outcomes.

    “This is a critical time to evaluate things on a global standpoint. We need to be concerned about the system as a whole, but we also need to get more granular and focus on what the deleterious effects seen on a patient-by-patient level are, in terms of financial burden,” Joshua R. Richter, M.D., a myeloma specialist at the John Theurer Cancer Center said in an interview with OncLive, a sister publication of CURE.

    Richter and his team examined 239 patients with multiple myeloma who completed the Living With Cancer patient-reported outcomes tool – designed for patients to report on aspects such as distress, depression and financial burden.

    Nearly half of the patients (48 percent) reported that they were concerned that could no longer do the activities that they wanted to do, while one-third (33 percent) reported a decrease in performance status. When asked about money, 44 percent of patients reported having financial toxicity.

    Only 76 percent of patients who reported having higher distress scores experienced 12-month survival compared with 87 percent in those with low distress scores.

    One finding that Richter found particularly surprising was regarding depression and anhedonia, or the inability to feel pleasure. While only 15 percent of patients reported depression, 41 percent reported anhedonia – a symptom that is highly connected with depression.

    “It was interesting how patients report their symptoms,” he added. “Ultimately, we gained patient insight in terms of when they are ready to transition towards palliative care or cessation of chemotherapy.”

    These findings could help physicians better understand issues their patients may be facing, and can open the door to patient-provider conversations about certain interventions, such as palliative care, hospice care or ending chemotherapy treatment.

    “One of the things that this tool allows is a shift in paternalism, where the physician sits down and gives the power back to the patient,” Richter said. “That tool gives us an idea that they are ready for a transition. It puts the power in the hands of the patient to help guide their plan of care.”

    Moving forward, Richter hopes to standardize the approach, as well as make it more universal. And while participants only completed the study once, Richter also mentioned that it would be valuable to track the patients’ responses over time, and to use the results to craft a model of the best times to implement interventions.

    “It is important to explore the possibilities of establishing a standard,” Richter said. “Right now, especially in hematologic malignancies, it is difficult to know where the patient is in terms of the disease.”

    From www.curetoday.com

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    WNMyeloma asked a questionMultiple Myeloma

    How were you diagnosed with Multiple Myeloma? What were your symptoms?

    • annetteOR's Avatar

      I had extreme pain back pain that worsened over two months, despite trying heat, ice, chiropractic, stretching, resting, and massage. I was also fatigued, but assumed that was because I wasn't sleeping well because of the pain. After a few visits the chiropractor suggested blood tests; she felt something wasn't adding up right. I'd made a recent move and was on a wait list for a primary care physician, so I went to the walk-in clinic associated with our local hospital. I was blessed to see a semi-retired doctor who sent me for blood tests at 9a.m., and called me at 6pm saying, "I don't know how medically savvy you are, but have you ever heard of Multiple Myeloma?" I said yes, my mother died of it in 1972, and what I'm going through matches my memories of her experience, so let's move on whatever tests we need to do, because this is really resonating with me. He got me in to a primary care physician, who in turn got me in to the oncologist, and within two weeks I was receiving my first chemo. I've since learned that it's often difficult to diagnose, so I count my blessings!

      5 days ago
    • Conor@Casey's Avatar

      I had recently left my company after 27 years in sales, “downsizing” I had played HS,College,Professional ( just enough time to have a cup of coffee) I had a decent severance package, and with that I had a much needed knee replacement, after 2 months rehab I started to feel better , within a few weeks I started to feel tired and had terrible pain in my back and rib cage, when after 3 weeks of feeling like this I went to my primary and he took blood tastes and found that my were out whack, he suggested I go to Dana Farber in Boston,I live only 40 miles away and when I got there I spoke to a very good oncologist, after tests all day , he told me I had multible Myeloma and we were going to you and get well again,I was in the hospital for 5 days

      1 day ago
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