2 Minute Medicine Rewind October 10, 2016

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma

Daratumumab is a human monoclonal antibody that has shown efficacy and safety in phase 1 and 2 trials for patients with refractory or relapsed multiple myeloma. This phase 3 randomized trial investigated daratumumab as an adjunct to lenalidomide and dexamethasone in 569 patients with multiple myeloma that had failed at least one previous treatment.  Patients were randomized to receive just lenalidomide and dexamethasone or lenalidomide and dexamethasone with daratumumab and were observed for a primary end-point of progression-free survival. Results yielded a rate of progression-free survival of 83.2% (95% CI: 78.3 to 87.2%) for the group that received lenalidomide, dexamethasone, and daratumumab, relative to 60.1% (95% CI: 54.0 to 65.7%) in the control group. In addition, as compared to the control group, there was a hazard ratio of 0.37 for disease progression or death (95% CI: 0.27 to 0.52, P<0.001), as well as a significantly higher rate of overall response and a higher rate of complete responses or better. However, daratumumab was associated with infusion-related reactions, as well as a higher rate of neutropenia. The investigators were able to conclude that daratumumab’s addition to lenalidomide and dexamethasone significantly increased the progression-free survival time in refractory or relapsed multiple myeloma.

OnabotulinumtoxinA vs. Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women

Urgency urinary incontinence has a high prevalence that increases as women age, affecting 17% of women older than 45 and 27% of women older than 75. This study aimed to investigate whether onabotulinumtoxinA is a superior treatment option for women with refractory urgency urinary incontinence, as compared to sacral neuromodulation. This randomized trial was conducted at 9 medical centers across the United States from 2012 to 2015 and enrolled 381 women who have a refractory urgency urinary incontinence. 192 women were randomized to receive 200 U of onabotulinumtoxinA while 189 received sacral neuromodulation, as the investigators looked for a primary outcome of mean number of daily urgency urinary incontinence episodes over six months. This resulted in a mean difference of 0.63 less episodes for those treated with onabotulinumtoxinA (95% CI: 0.13 to 1.14, P=0.01). Patients treated with onabotulinumtoxinA also had higher treatment satisfaction, were more likely to endorse the treatment, and less symptom bother, as measured by a questionnaire. However, there were no significant differences between the treatment groups in terms of convenience or adverse effects and, urinary tract infections (UTIs) were significantly higher in the onabotulinumtoxinA treatment group, in addition to an increased risk of self-catheterization. Though the superiority of onabotulinumtoxinA was shown in terms of the primary outcome, the investigators are unsure that this is clinically significant due to the increased risk for UTIs and catheterization.

Symptoms and Patient Factors Associated with Diagnostic Intervals for Pancreatic Cancer

Pancreatic cancer has less than a 5% survival rate at 1 year after diagnosis. In part, that may be due to late presentation and a long interval between presentation and diagnosis (diagnostic interval). This study aimed to identify symptoms of pancreatic cancer and their association with diagnosis and the diagnostic interval. A prospective cohort study was conducted in England between 2011 and 2014, enrolling 391 patients aged 40 or older who were referred for suspicion of pancreatic cancer.  Of these patients, 30% were diagnosed with pancreatic cancer while 58% had no cancer. It was found that no presenting symptoms were reported more frequently in the group that had a confirmed diagnosis of pancreatic cancer.  However, several symptoms present before diagnosis but after initial presentation were significantly higher in the pancreatic cancer group relative to the group with no cancer, including jaundice (P<0.0001), decreased appetite (P<0.0001), weight loss (P<0.0001), and bowel habit changes (P<0.0001). Additionally, the diagnostic interval was longer for presentation with back pain, indigestion, weight loss, and diabetes, but shorter for patients presenting with jaundice and decreased appetite. The investigators concluded that, though no initial presenting symptom was effective in discerning pancreatic cancer, being vigilant about the symptoms that follow will aid in diagnosis.

Association Between Therapeutic Hypothermia and Survival After In-Hospital Cardiac Arrest

Therapeutic hypothermia is currently recommended as a treatment for comatose patients after in-hospital or out-of-hospital cardiac arrest. This study aims to further investigate the use of therapeutic hypothermia in patients with in-hospital cardiac arrest and its effects on survival to hospital discharge. This cohort study looked at a registry of 26,183 patients who were successfully resuscitated from in-hospital cardiac arrest between 2002 and 2014. 1,524 of the patients that received therapeutic hypothermia were enrolled and matched by a propensity score to 3,714 patients who did not receive therapeutic hypothermia. Treatment that included therapeutic hypothermia was associated with a relative risk of 0.88 for survival to discharge (95% CI: 0.80 to 0.97) and a risk difference of -3.6% for that same endpoint (95% CI: -6.3 to -0.9, P=0.01). The use of hypothermia was also associated with lower favorable neurological survival.  The investigators conclude that, based on this observational study, a randomized clinical trial is warranted to study the efficacy of the currently recommended practice of therapeutic hypothermia in patients with in-hospital cardiac arrest, as it appears to be associated with lower survival to hospital discharge.

Guillain-Barre Syndrome Associated with Zika Virus Infection in Colombia

Zika virus is a mosquito-borne illness that has broken out in North and South America since 2014 and has been associated with Guillain-Barre syndrome. This study aimed to further elucidate the relationship between Zika virus and Guillain-Barre. 68 patients with Guillain-Barre syndrome were observed in Colombian hospitals and it was found that, before the onset of the syndrome, 97% of them had symptoms matching the Zika virus, with a median period of 7 days between Zika virus symptom onset and Guillain-Barre symptom onset. Guillain-Barre symptoms included limb weakness (97%), ascending paralysis (62%), and cranial neuropathies (63%). 40% of patients tested positive for the Zika virus when tested by RT-PCR and 78% of patients had nerve-conduction and electromyography results consistent with acute inflammatory demyelinating polyneuropathy, a sub-type of Guillain-Barre. Finally, 43% of patients with Guillain-Barre that underwent laboratory testing had both clinical and immunological findings consistent with Zika virus. It was concluded that Zika virus infection does play a role in the development of Guillain-Barre syndrome.

Image: PD

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