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Risk Of Infection Among Multiple Myeloma Patients Is High And Rising (ASH 2012)

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Published: Jan 11, 2013 1:31 pm

Results from a recent retrospective study demonstrate that the risk of infection is significantly higher in multiple myeloma patients compared to the general population.

Furthermore, the study investigators found that the rate of infection in myeloma patients has increased in recent years.

“Our study raises the question whether modern myeloma therapy increases the risk of infections,” said Dr. Cecilie Blimark from the Sahlgrenska University Hospital in Gothenburg, Sweden, who presented the study findings at the American Society of Hematology (ASH) annual meeting last month.

“The increasing risk [of developing an infection] in later years [of the study period] calls for more studies concerning new strategies regarding infectious complications and its prevention,” she concluded.

Dr. Blimark pointed out that myeloma patients are particularly prone to developing infections due to their weakened immune system. “The unique immune deficiency of myeloma patients is caused not only by treatment but by the disease itself,” she said.

According to Dr. Blimark, the risk of infection in multiple myeloma patients has not previously been directly compared to that of the general population.

Dr. Blimark and her colleagues therefore compared the risk of infections in myeloma patients and the general population in Sweden.

The study was based on data from 9,253 multiple myeloma patients diagnosed between 1988 and 2004 and 34,931 matched individuals from the general Swedish population. The median age was 72 years in both groups.

For each myeloma patient in the study, approximately four comparable individuals from the general population were chosen based on age, gender, and geographic location (county).

Overall, the study found that myeloma patients were found to be 7.1 times more likely to develop a bacterial or viral infection than the general population.  The risk was especially high during the first year after diagnosis: myeloma patients were 11.6 times more likely to develop an infection during this time compared to the general population.

More specifically, the risk of developing a bacterial infection was 7.1 times higher in myeloma patients than in the general population. Myeloma patients were especially susceptible to septicemia (blood poisoning), meningitis, and pneumonia.

This risk of developing a viral infection – such as viral flu or shingles – was 10 times higher for myeloma patients compared to the general population.

About 10 percent of the myeloma patients in the study died within two months of their diagnosis, and about 20 percent of those who died in that period died as a result of an infection.

Infection also accounted for about 20 percent of the deaths among myeloma patients who died within a year of diagnosis.  About one quarter of the myeloma patients in the study died within that time period after diagnosis.

Another key finding by Dr. Blimark and her colleagues was that the risk of infection among multiple myeloma patients increased over time.

Between 1988 and 1993, myeloma patients were 5.7 times more likely to develop an infection than the general population. This risk increased to 7.0 between 1994 and 1999, and 8.9 between 2000 and 2004.

The Swedish study was not designed to determine what may have caused the increase over time in the risk of infection.  However, the study results raise the possibility that changes over the past 25 years in the way myeloma is treated may be responsible for the increased risk of infection experienced by myeloma patients.

For more information, please see abstract 945 at the ASH meeting website.

Photo by Raeky on Wikipedia – some rights reserved.
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19 Comments »

  • a.franklin MD said:

    Should MM pts receive H.Zoster vaccine?

  • terryl1 said:

    Sobering data….just got my flu shot. Whether it works or not is another story.

  • Myeloma Beacon Staff said:

    Hello A.Franklin,

    The herpes zoster (shingles) vaccine is a so-called “live” vaccine, so it’s not one that myeloma patients typically should be given. Some patients are given it if their myeloma has responded well to treatment, but this only should occur if it’s been carefully discussed with your physician.

    Here are some links you may find useful that have further discussions of vaccines for myeloma patients.

    First, a summary of some recommendations from a panel of myeloma experts:

    http://www.myelomabeacon.com/news/2011/06/24/experts-provide-guidelines-to-help-multiple-myeloma-patients-prevent-infections-imw-2011/

    Second, the experience of one of our columnists, Nancy Shamanna:

    http://www.myelomabeacon.com/headline/2012/08/09/northern-lights-getting-my-cv-in-order/

    Third, several discussions in the Myeloma Beacon’s forum:

    http://www.myelomabeacon.com/forum/vaccination-childhood-vaccine-t1343.html

    http://www.myelomabeacon.com/forum/post-transplant-vaccines-t1219.html

    http://www.myelomabeacon.com/forum/clinical-trial-for-shingles-vaccine-t1116.html

    Best of luck!

  • Joey S said:

    Must be all those debilitating upfront, fooolish transplants, forever compromising immunity in most patients except for a select few….IMHO

  • Myeloma Beacon Staff said:

    Hi Joey,

    What you’ve suggested could be a potential explanation. There are data for the U.S., for example, showing that the share of myeloma patients receiving a transplant within a year of diagnosis has gone up over the time covered by Dr. Blimark’s study. This probably happened in Sweden as well.

    However, the period covered by Dr. Blimark’s study is also one that saw the introduction of the first novel therapy for myeloma (thalidomide).

    So was it transplantation that caused the increase in infections? Or thalidomide? Or something else?

    Of course, it’s also worth pointing out that this was a period that saw an increase in overall life expectancy for myeloma patients.

  • Lys2012 said:

    I’m a few years out from treatment, no maintenence treatment, all my blood tests have been in the “normal” range (including M-spike / lites)since my transplant, but I’m dealing with frequent infections!

    perhaps it was just a bad year for me, but I’ve had 5 colds, one ear infection, one bronchitis, one sinus infection, a bad bout of the stomach flu. (since October). I’ve been on antibiotics a few times for these secondary infections. I did get the pneumovaccine and flu shot in October.

  • Ron Harvot said:

    I have been on novel agents for almost 4 years. Although I am in a remissive state I have always has low immunoglobulins and slightly low overall white counts. I have a history of sinus infections and contracted C Diff and Viral Meningitis this past summer. My oncologist responded by putting my on monthly infusions of IVIG. (4 bottles).

    I wonder if IVIG infustions may be a response that other ongologists recommend to combat the increase in infections?

    Ron

  • nancy shamanna said:

    Thanks for summarizing the interesting Swedish study on infections in MM patients. What is so sad is how many patients died of infections. Hopefully the overall mortality is decreased from 2004, since there are better treatments available now than there were even 8 years ago.

    When I had all possible childhood vaccines given back, the ‘non live’ vaccines were given one year post transplant, and the ‘live’ vaccines 2 years post transplant. I was not given the shingles vaccine, but did have the one for chickenpox, which is thought to provide the same immunity against shingles. Had been taking an anti-viral drug, for two years post transplant until i could get the chickenpox vaccine. This was all monitored and approved through the cancer centre’s transplant unit as well as our public health dep’t. I couldn’t just ring up the vaccination clinic and book my own vaccines!

    Right now, there are two epidemics raging here…influenza and noro-virus (a gastrointestinal infection). So the public health dep’t is urging everyone to take precautions against catching or spreading those infections. Winter!! Will be glad when the flu season is over for this year (of course I took the flu shot, since I have no allergies or anything else to contra-indicate that).

  • Mark said:

    Hi Ron,

    IVIG has been looked at for this purpose. It is questionable how effective it is. I looked at my insurance policy after I took it (for 4 months) after my allo. My insurance company only approves it for use after allo. For many patients this would likely be a cost/insurance issue as well. My Doctor only thinks it is mildly effective. It took 6 hours for my infusions, so it is a QOL issue as well. Who wants to spend 6 hours getting treatment every month? Fortunately all my blood/immune counts have been in the normal range for some time, so I no longer need any help in this area.

    “Haematologists have traditionally used IVIG to prevent cytomegalovirus (CMV) infection following bone marrow transplantation (BMT). Mühleisen and colleagues SHOWED THAT INFECTION RATES AND SURVIVAL ARE SIMILAR, WHETHER OR NOT IVIG IS GIVEN [41]. IVIG should probably be reserved only for patients who are hypogammaglobulinaemic (IgG < 4 g/l) after BMT. Paediatricians have used IVIG at 0·5 g/kg in a single dose on the first day of life in children with haemolytic disease of the newborn [43]. This is effective at reducing haemolysis and hence reduces the need for exchange transfusions. Adults with secondary antibody deficiency (SAD) associated with chronic lymphocytic leukaemia and myeloma have both been shown to benefit from IVIG replacement therapy, if incapable of mounting an adequate response to diagnostic immunization with polysaccharide antigens (Pneumovax II) [44,45]. Although the clinical efficacy of IVIG replacement in SAD is accepted, its cost-effectiveness has been questioned [46]. Continuous antibiotic prophylaxis with cotrimoxazole alone has been shown to be effective in early myeloma, albeit with a significant incidence of adverse effects [47], thus prompting calls for randomised trials comparing antibiotic prophylaxis alone with IVIG in these disease groups."
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809480/

    Mark

  • Terry L said:

    Hi Mark, after reading this article, it was surprising to me how vulnerable patients are left after SCT’s in the immunological sense. With your allo, did you develop the immune system of your donor wholly to the point where there is no immune paresis? I chose a different path from you initially (CRD w/o SCT) but much of what you write makes sense about allos and it is strange that they are still considered experimental. As such, most insurance companies won’t pay for them upfront.

  • Myeloma Beacon Staff said:

    Just so that everyone is clear, the Swedish study included myeloma patients regardless of the therapy they pursued. It did *not* just include patients who have had stem cell transplants.

    Patients who did not receive a stem cell transplant were included as well as those who did.

  • nancy shamanna said:

    I maybe should have added that in addition to taking anti-vial meds for two years, I also took antibiotics for one year after SCT, so as to avoid getting infections. Obviously my immune system was at a low ebb at that time, but thankfully my blood tests are normal again now and I do feel that getting all of the vaccinations, including Pneumococcal and Hepatitis, gives me some protection agains infections.

  • Jade said:

    Hi,
    I’m wondering if the dex myeloma patients stay contributes to the increased risk of infection. My husband had an auto transplant about 2 years ago and was given all his shots after that. His MD also has him on an anti viral, an anti fungal, and bactrum (antibiotic) 3x week, just to prevent infection. He is on 10mg revlamid daily, and dex 20mg once a week. Is this usual practice for myeloma patients on dex ? and do these meds cut down the rate of infections?

  • Ron Harvot said:

    Jade,

    Maintenance using Revlimid and Dex following as Auto transplant is becoming standard proceedure. I did not get an AST. Instead I went down the route that used a combination of RVD that has been backed off once I was in a stable remission. My protocal is a velcade shot once every two weeks and 20 mg of dex at the same time. I was on Revlimid unti I devleloped the meningits then my oncologist took me off of that. I have seen an minor increase in my red and white counts since I was taken off of Revlimid but nothing dramatic. Dex is given since it has been shown to increase the effectiveness of both Revlimid and Velcade. Perhaps you and your husband can discuss moving the dex dosage to once every two weeks instead of once a week. The suppression of white cells is more likely the result of the Revlimid and not the Dex. But if you go to once every two weeks you can see if that helps in your blood work.

  • Mark said:

    Hi Terry L.

    I turned over fairly quickly to 100% donor cells. Having a mix of cells is usually associated with “mini” or reduced instensity conditioning. In addition to high dose melphalan I used a high dose of fludarabine. FLU kills both active and resting B cells. It is nicknamed “AIDS in a bottle” because it is so immunosuppressive. I think it is safe to say my old immune system only exists in a bag of frozen stem cells at this point! Yes, we are very prone to infections immediately after the transplant. I look at it like patients are just switching times for better or worse QOL. Mine was obviously worse during and in the months after transplant, but it is very good now. Just note some of the comments here and in Pats recent column about problems patients on continuos therapy have with their immune systems.

    The insurance companies will never be big fans of allo transplant. The total cost of donor search, medical tests for my donor, and transplant were in the area of $650K. After care is expensive as well. IVIG is around $5K per month and my other meds were about $6K. Allos are definitely not an insurance friendly therapy.

    Mark

  • nancy shamanna said:

    Mark, after the ‘allo’ transplant, did you get your childhood vaccinations and other vaccinations? What would be the recommendations on that issue? How would you know what protective immunities were in the donor cells?

  • Mark said:

    Hi Nancy,

    I am going to get the “live” vaccines in a few months. I recieved all of the others 1 year after transplant. I am truly starting over with my donors immune system. Her immune system seems great – I have not even had a cold for over 8 months. It will be getting put to the test this flu season!

    Mark

  • Multibilly said:

    It’s really a shame that the study doesn’t differentiate between transplant and non-transplant patients. My first question when reading this article (before reading any of the comments)was whether they they did break the study into these two groups and only the combined data was shown here. I find it hard to believe that this question wasn’t asked when the researchers gathered the raw data and I wonder if the data could still be surfaced?

  • Multibilly said:

    It’s interesting to look at this abstract on the risk of infection for those with MGUS (2X more likely to have infections than the general population…so much for my naive impression that MGUS is a benign stage of myeloma). http://www.ncbi.nlm.nih.gov/pubmed/22180421

    If MM patients are 7X more likely to have an infection and MGUS patients are 2X more likely, I wonder what the infection risk is for smoldering myeloma patients? One does wonder just how much of the increase in infection risk is just due to the disease itself (and its stage) versus the effects of just chemo versus the chemo/transplant process?