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Researchers Identify Risk Factors For Infectious Complications In Myeloma Patients Treated With Thalidomide-Based Combination Therapies

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Published: Apr 6, 2011 12:46 pm

A group of Italian researchers found that elevated monoclonal protein levels and decreased platelet counts are associated with an increased risk of severe infection in multiple myeloma patients treated with thalidomide-based combination therapies.

The researchers also showed that patients who were at a low or intermediate risk for severe infections did not benefit from preventative treatment with antibiotics.

“I think it is reasonable to stop taking prophylaxis in low-intermediate risk patients,” said Dr. Massimo Offidani, lead author of the study. “If a patient is at a high risk of infection, thalidomide and high-dose dexamethasone should be used with caution. Velcade combinations would be preferable,” he explained.

Dr. Offidani added that additional studies are needed to confirm their findings.

Patients with multiple myeloma are more susceptible to infections due to their compromised immune systems. The cancerous myeloma cells accumulate in the bone marrow, where they crowd out healthy red and white blood cells and prevent them from functioning effectively. Since white blood cells are responsible for the production of antibodies, the body’s ability to fight off foreign pathogens is limited.

There are several known factors that increase a patient’s susceptibility to infection, including treatment with novel agents, such as thalidomide (Thalomid). In a recent study, 22 percent of patients treated with thalidomide developed a severe infection, which, according to the Italian researchers, is far higher than reported with conventional chemotherapy combinations.

Dr. Offidani and his colleagues investigated infectious complications that occurred in myeloma patients during treatment with thalidomide-based combination therapies in order to identify patients who should receive prophylaxis (preventative treatment) for infections.

The researchers retrospectively analysed data from 202 myeloma patients treated with thalidomide-based combination therapies between 2003 and 2009.

Of the 202 patients included in the analysis, 160 received thalidomide in combination with Doxil (pegylated liposomal doxorubicin) and dexamethasone (Decadron), and the remaining 42 patients received the same combination therapy at slightly different doses plus Velcade (bortezomib). In addition, the majority of patients (73 percent) received antibiotics for the prevention of infections.

The researchers found that 42 percent of patients developed infections. Nineteen percent of patients developed severe infections, with 80 percent of these cases occurring during the first course of therapy.

The most common severe infection was pneumonia, which occurred in 55 percent of patients.

The majority of patients with infections were successfully treated with a broad-spectrum antibiotic. One patient died from septic shock, a serious complication associated with low blood pressure and poor organ function.

The researchers found that elevated monoclonal protein levels (greater than 3 g/dL) and low platelet counts (less than 130,000/mL) were associated with an increased risk of severe infections.

Using these two variables, the researchers created a scoring system that categorized patients based on the risk of developing a severe infection at six months. Patients with both elevated monoclonal protein levels and low platelet counts were considered high-risk, patients with one variable were considered intermediate risk, and patients with none were considered low-risk.

They found that patients in the high-risk group had a risk of severe infection twice that of patients in the low-intermediate risk group (32 percent versus 16 percent).

The researchers also found that treatment with antibiotic prophylaxis was much more effective in reducing the risk of severe infection in patients in the high-risk group. Of the patients who had received antibiotic prophylaxis, 23 percent developed severe infections at six months, compared to 75 percent of patients who had not received antibiotic prophylaxis.

In the low-intermediate risk group, 18 percent of patients who had received antibiotic prophylaxis developed severe infections at six months, compared to 16 percent of patients who had not received antibiotic prophylaxis.

Although the occurrence of severe infections did delay treatment, it did not have a significant impact on response and survival rates in these patients. The overall response for patients with severe infections was 80 percent, compared to 87 percent for patients without severe infections. The median overall survival was 36 months for patients with severe infections, compared to 42 months for patients without severe infections.

The researchers also found that patients with a severe infection had an increased rate of deep vein thrombosis (DVT), which is a blood clotting complication that primarily occurs in the deep veins of legs or the lower thigh. Approximately 22 percent of patients with a severe infection developed DVT, compared to 10 percent of patients without a severe infection. All cases of DVT except one occurred after the patients had developed infections.

For more information about the study, please see the journal Leukemia and Lymphoma (abstract).

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  • Anne said:

    I can confirm that this was the case for my husband who was diagnosed with MM in August 2009. He began treatment with Thalidomide and had only had 1 course of treatment when he contracted meningitis in October. Luckily we caught it early enough and he responded well to treatment. He made a full recovery and was then switched to Velcade and had only had one dose when he contracted pneumonia and RSV in time for the New Year. Once again he recovered well and went on to respond reasonbly well to the Velcade treatment and had his stem cell transplant last April. I can't remember what his levels were but I remember the doctors saying that his form of MM was quite aggressive which showed in the results of tests which they had carried out.

    It's interesting to note that he had a DVT at 34 on his right leg, followed by another in the same place some 18 months later, and then had one in 2009 in his arm where the canula had been during a stay in hospital. He is now on warfarin for life. He's a fighter and we continue to battle this together.