Results of a recent study show that multiple myeloma patients who relapse after pomalidomide therapy may benefit from certain salvage therapies, including Velcade, Revlimid, and stem cell transplantation.

Furthermore, patients who received a stem cell transplant after relapse achieved the highest response rate among all patients who received salvage therapy. The results also suggest that Revlimid retains its activity in patients who relapse after pomalidomide therapy.

“[The study] gives a sense of what therapies still continue to have activity [after patients relapse on pomalidomide],” said Dr. Shaji Kumar of the Mayo Clinic in Rochester, Minnesota, and one of the study authors.

“The treatment selection should be based on the therapies the patients had prior to pomalidomide,” he added.

Dr. Xavier Leleu of the Chru Lille University Hospital in France, who was not involved in the study, agreed that salvage therapies for patients who relapse on pomalidomide depend on their response to previous therapies.

“I am not surprised to read that patients who have received pomalidomide might benefit from [salvage therapies], including stem cell transplantation and Velcade (bortezomib). This, however, is probably true solely for patients who were not previously resistant to stem cell transplantation and Velcade,” Dr. Leleu told The Myeloma Beacon.

Pomalidomide (Pomalyst), which belongs to the same class of drugs as thalidomide (Thalomid) and Revlimid (lenalidomide), is currently being investigated as a potential treatment for multiple myeloma. Results of two Phase 2 trials indicate that pomalidomide is effective in myeloma patients who are resistant to Velcade and Revlimid (see related Beacon news).

Dr. Leleu explained that myeloma patients who relapse after Velcade therapy are more likely to respond to pomalidomide than patients who relapse after Revlimid therapy.

“Pomalidomide is an immunomodulatory agent, and its mechanisms of action are [similar to those of] Revlimid. Therefore, only 30 percent to 40 percent of patients previously treated with Revlimid respond to pomalidomide. The situation is different for Velcade, as there is no reason for patients who are resistant to Velcade not to respond to pomalidomide,” said Dr. Leleu.

According to the recent study's authors, it has been unclear until now how patients respond to existing therapies once they have become resistant to pomalidomide. Therapies given to patients after they have relapsed or become resistant to previous treatment are known as salvage therapies.

The researchers therefore retrospectively analyzed the medical records of 74 myeloma patients who relapsed after pomalidomide therapy to determine the efficacy of various salvage therapies in these patients.

The median patient age at the time of progression on pomalidomide was 63 years. Forty-two percent of patients had high-risk disease based on presence of the chromosomal abnormalities del13, del17p, t(4;14),  t(14;16), or extra chromosomes.

Patients received pomalidomide for a median of 4.3 months before relapse. The median time from diagnosis to progression on pomalidomide was 5.0 years.

The researchers found that 70 percent of patients received at least one salvage therapy following relapse on pomalidomide.  The most common initial salvage therapies, given to patients immediately following relapse, were Velcade-based combinations (46 percent) and Revlimid-based combinations (13 percent). Eight percent of patients received a stem cell transplant as the first salvage therapy following relapse.

Thirty-one percent of patients achieved at least a partial response to the first salvage therapy following relapse. Specifically, 75 percent of patients who received a stem cell transplant, 29 percent of patients who received Revlimid-based therapies, and 25 percent of patients who received Velcade-based therapies achieved at least a partial response to the first salvage therapy.

According to the study authors, these response rates are similar to those observed in patients who have become resistant to Velcade and either thalidomide or Revlimid treatment.

Overall, patients included in this retrospective analysis received a median of one salvage therapy after relapse.

Across all salvage therapies -- not just first therapies after relapse -- the salvage regimens included Velcade-based combinations (36 percent); stem cell transplantation (13 percent); thalidomide plus cisplatin, doxorubicin (Adriamycin), cyclophosphamide (Cytoxan), and etoposide (VDT-PACE) (12 percent); steroid combinations (15 percent); and Revlimid-based combinations (11 percent).

Overall across all instances of salvage therapy, whether first or later, a partial response or better was achieved in 80 percent of patients who received a stem cell transplant, 28 percent of patients who received Velcade-based therapies, and 13 percent of patients who received Revlimid-based combinations.

For the majority of patients (73 percent) in the study who received a salvage stem cell transplant, it was their second transplant.

The median overall survival time after progression on pomalidomide was 13.2 months. The researchers found that the overall survival was similar between patients who responded to pomalidomide and those who did not.

However, overall survival was shorter for patients who were resistant to Revlimid and Velcade at study entry (3.3 months) than for patients who were not resistant to these drugs (overall survival not yet reached). Overall survival was also shorter for high-risk patients (9.5 months) than for standard-risk patients (14.7 months).

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