Results of a recent study conducted by the Mayo Clinic in Rochester, Minnesota, indicate that pomalidomide (Pomalyst) may be effective in patients who develop extramedullary disease during treatment with thalidomide, Revlimid, or Velcade.

However, the results also showed these patients had shorter overall survival times than patients who did not develop extramedullary disease during treatment.

The study authors indicated that further studies are required to determine whether novel drugs directly increase the likelihood of developing extramedullary disease.

“We don't know if we are seeing [the development of extramedullary disease] because (1) with so many effective therapies, patients are living long enough to get extramedullary disease, (2) better imaging picks up more [cases of] extramedullary disease, or (3) the new therapies somehow drive the development of extramedullary disease,” explained Dr. Martha Lacy, one of the study investigators.

Extramedullary disease, or non-marrow tumors, occurs when malignant plasma cells develop in organs or soft tissues outside the bone marrow. It is commonly associated with relapsed/refractory myeloma.

Dr. William Matsui of Johns Hopkins Medical Institute, who was not involved in the study, explained that treatment for myeloma patients with extramedullary disease is similar to that for patients without the non-marrow tumors. “Typically, the approaches are similar to non-extramedullary disease progression, perhaps with the exception of the use of radiation for local treatment,” he said.

According to the study authors, there is growing concern that treatment with novel agents such as thalidomide (Thalomid), Revlimid (lenalidomide), or Velcade (bortezomib) may have increased the occurrence of extramedullary disease among myeloma patients in recent years.

To shed some light on this issue and to evaluate the activity of pomalidomide in patients with extramedullary disease, Dr. Lacy and her colleagues from Mayo Clinic analyzed data from 174 relapsed/refractory myeloma patients who had been enrolled in a Phase 2 clinical trial of pomalidomide with low-dose dexamethasone (Decadron) between November 2007 and May 2010.

During this period, the patients received 2 mg to 4 mg pomalidomide once daily and 40 mg low-dose dexamethasone once weekly.

All patients had previously received treatment with novel agents. The median number of previous therapies was six, ranging from one to twelve.

Of the 174 patients, 16 patients (9.2 percent) had extramedullary disease. Three patients (1.7 percent) had the disease at the time of diagnosis, and 13 patients (7.5 percent) developed the disease during treatment with novel agents (treatment-emergent extramedullary disease). The median length of time from the start of therapy to the onset of extramedullary disease was 24 months, ranging from 18 months to 180 months.

All patients who experienced treatment-emergent extramedullary disease had previously received thalidomide or Revlimid, and 78 percent had previously received Velcade.

The most common sites affected by the disease included the brain, muscle, chest wall, abdomen, kidney, and scrotum. Most patients had extramedullary disease at one site, although one patient had 11 affected sites and another patient had 20 affected sites.

The researchers found that four of the 13 patients with treatment-emergent extramedullary disease (31 percent) responded to treatment with pomalidomide and low-dose dexamethasone. Two patients achieved a complete response with a complete disappearance of extramedullary disease, and two patients achieved a partial response with as a greater than 50 percent reduction in extramedullary disease.

The researchers also found that patients with extramedullary disease had a shorter overall survival than patients without extramedullary disease. Patients with the disease had a median survival of 16 months, while the median survival of patients without the disease was not yet reached.

“Since the emergence of extramedullary disease is likely associated with disease progression, it may portend a relatively worse prognosis,” said Dr. Matsui.

“There should be a better awareness to look for extramedullary disease when patients have been treated with novel agents, since it’s possible that many of the response indicators used clinically may miss the emergence of extramedullary disease,” he added.

For more information, please see the article in Leukemia (abstract).