A recent Greek study looks at the efficacy and safety of Revlimid plus dexa­metha­sone for re­lapsed and refractory multiple myeloma patients in ‘the real world’ -- that is, in patients being treated in standard clin­i­cal practice rather than clin­i­cal trials.

The study's findings con­firm that Revlimid ^[1] (lena­lido­mide) plus dexa­metha­sone ^[2] (Decadron) is effective and safe in day-to-day use among re­lapsed myeloma patients.

The majority of the patients in the study (77 per­cent) responded to treat­ment with Revlimid and dexa­metha­sone, with 20 per­cent achieving a com­plete response. According to the investigators, these results are com­par­able to those reported from clin­i­cal trials.

Importantly, the Greek researchers found that the number of prior lines of ther­apy and prior treat­ment with other novel agents, such as Velcade ^[3] (bor­tez­o­mib) or thalidomide ^[4] (Thalomid), did not sig­nif­i­cantly affect response to the Revlimid-dexa­metha­sone com­bi­na­tion.

In addi­tion, the Revlimid-dexa­metha­sone com­bi­na­tion appeared to be at least as safe and well-tolerated when used in standard clin­i­cal practice as in clin­i­cal studies.

Although nearly half of the patients in the current study (46 per­cent) developed low blood cell counts, the most common side effect of the treat­ment com­bi­na­tion, it was less common in this study than in pre­vi­ously reported clin­i­cal trials (69 per­cent).

Likewise, Revlimid-dexa­metha­sone was less often dis­con­tinued in standard clin­i­cal practice (39 per­cent of patients) than in clin­i­cal trials (58 per­cent).

Background

The introduction of novel agents such as thalido­mide, Velcade, and Revlimid has sig­nif­i­cantly im­proved the survival of myeloma patients (see related Beacon ^[5] news).

Two pre­vi­ous Phase 3 clin­i­cal trials, by French and American researchers, showed that Revlimid plus dexa­metha­sone is more effective as a treat­ment for re­lapsed myeloma than dexa­metha­sone alone, and numer­ous clin­i­cal studies have further studied the efficacy and safety of the com­bi­na­tion.

Based on these findings from clin­i­cal trials, Revlimid in com­bi­na­tion with dexa­metha­sone has become a common treat­ment for patients with re­lapsed or refractory myeloma.

In the United States, the com­bi­na­tion of Revlimid and dexa­metha­sone is also one of the most common treat­ments for newly diag­nosed multiple myeloma.  This is not the case in most other countries, how­ever, because the com­bi­na­tion is not yet officially approved for use in newly diag­nosed myeloma, and "off-label" pre­scrib­ing is less common outside the U.S.

In the current study, Greek researchers sought to better understand the efficacy and safety of the Revlimid-dexa­metha­sone regi­men among re­lapsed and refractory myeloma patients treated during standard clin­i­cal practice in Greece.

Study Design

The researchers retrospectively analyzed data from 211 patients who had received Revlimid-dexa­metha­sone treat­ment for re­lapsed or refractory myeloma at various treat­ment centers across Greece between June 2010 and December 2011.

All patients who were in­cluded in the analysis were at least 18 years of age and had not received prior treat­ment with Revlimid.

About 35 per­cent of patients received Revlimid-dexa­metha­sone as second-line ther­apy, 30 per­cent as third-line ther­apy, and the rest as fourth-line to seventh-line ther­apy.

Among those who received Revlimid-dexa­metha­sone as second-line ther­apy, 34 per­cent had pre­vi­ously received Velcade-based ther­apy, 15 per­cent thalido­mide-based ther­apy (15 per­cent), and 8 per­cent a regi­men con­taining both.  The other 42 per­cent had received treat­ment with conventional chemotherapeutic regi­mens that did not in­clude these novel agents.

Among those who received Revlimid-dexa­metha­sone beyond second-line ther­apy, 77 per­cent had been treated pre­vi­ously with novel agent com­bi­na­tions and 23 per­cent with conventional chemotherapy.

About 26 per­cent of all patients had received high-dose mel­phalan (Alkeran) plus au­tol­o­gous stem cell trans­plan­ta­tion before Revlimid-dexa­metha­sone treat­ment.

Overall, 22 per­cent of study participants received Revlimid-dexa­metha­sone within a year of diag­nosis. Another 18 per­cent received the com­bi­na­tion between one year and two years after diag­nosis, while 60 per­cent were treated with it more than two years after diag­nosis.

Nearly 78 per­cent of participants received Revlimid-dexa­metha­sone until disease pro­gres­sion. The others received the com­bi­na­tion for a fixed number of cycles. The median number of cycles was 12.

The majority of patients (72 per­cent) received an initial dose of 25 mg of Revlimid per day for 21 days in a 28-day treat­ment cycle. The share of patients who initially received 25 mg of Revlimid was higher among patients younger than 65 years (85 per­cent) than in older patients (65 per­cent).

The researchers point out that older patients frequently received a lower starting dose and started Revlimid-dexa­metha­sone earlier in the course of the disease, probably because the com­bi­na­tion is con­sidered less toxic than other treat­ment options.

The median follow-up period was 13 months.

Results

More than three-quarters (77 per­cent) of the patients in­cluded in the study achieved a partial response or better on the Revlimid-dexa­metha­sone regi­men, with 20 per­cent reaching a com­plete response.

Median time to best response was five months.

Patients who received Revlimid-dexa­metha­sone as second-line ther­apy achieved a com­plete response in a median of four months, while those receiving the com­bi­na­tion beyond second-line ther­apy achieved the same in a median of 11 months.

However, further analysis showed that the number of pre­vi­ous ther­a­pies and pre­vi­ous treat­ment with novel agents (Velcade or thalido­mide) did not affect the response rate or quality of response, which according to the investigators con­firms the high efficacy of the Revlimid-dexa­metha­sone com­bi­na­tion in all lines of ther­apy.

The median duration of response was about 35 months.

There was a sig­nif­i­cant difference in duration of response, however, between patients who con­tinued treat­ment until disease pro­gres­sion, and those who did not.

Patients who were treated with the Revlimid-dexamethasone com­bi­na­tion until disease pro­gres­sion had a median duration of response which has not yet been reached, but which will be at least 50 months based on the latest avail­able data.

In contrast, patients who dis­con­tinued ther­apy prior to pro­gres­sion had a median duration of response of 19 months.

According to investigators, these findings show that treat­ment dis­con­tinu­a­tion has a sizable negative effect on duration of response. They therefore recommend that treat­ment be con­tinued until disease pro­gres­sion.

The initial dose of Revlimid was also found to predict duration of response, with higher initial dose being asso­ci­ated with a longer duration of response.

Side effects were observed in 69 per­cent of patients, and 13 per­cent of patients required hospi­tal­iza­tion.

The most common side effect was low blood cell counts (46 per­cent of patients), which was sig­nif­i­cantly lower than the rate reported in pre­vi­ous ran­dom­ized clin­i­cal trials of the Revlimid-dexa­metha­sone com­bi­na­tion (69 per­cent).

About 11 per­cent of patients suffered from various in­fec­tions, 6 per­cent developed blood clots in the deep veins, and 3 per­cent suffered from periph­eral neu­rop­athy (pain, tingling, and loss of sensation in the extremities). The rate of neu­rop­athy was similar to the rates reported in pre­vi­ous ran­dom­ized clin­i­cal trials.

The rate of blood clots was much lower than in pre­vi­ous ran­dom­ized clin­i­cal trials, which the investigators explain by the fact that the vast majority of patients in their study (93 per­cent) received medication for the prevention of blood clots.

About 39 per­cent of patients had to dis­con­tinue treat­ment because of side effects or disease pro­gres­sion. The researchers point out that the dis­con­tinu­a­tion rate was lower than that reported in clin­i­cal trials (58 per­cent), which they attribute to dis­con­tinu­a­tion criteria being stricter in clin­i­cal trials.

For further in­­for­ma­tion, please see the study in Annals of Hematology ^[6] (abstract).