Lenalidomide, thalidomide similar when combined with melphalan and prednisone for multiple myeloma

Combination treatment with melphalan, prednisone and either thalidomide or lenalidomide had comparable efficacy in elderly patients who were newly diagnosed with multiple myeloma. Lenalidomide was associated with less toxicity, however, and higher quality of life, according to results from a phase III trial.

The Eastern Cooperative Oncology Group (ECOG) E1a06 trial showed similar progression-free survival (PFS), overall survival (OS), and response rates for thalidomide and lenalidomide groups. PFS was 21 and 19 months, respectively (hazard ratio [HR], 0.84; 95% CI, 0.64-1.09; P = .186); OS was 53 and 48 months (HR, 0.88; 0.63-1.24; P = .476); partial response rates were 75% and 70%; and very good partial response rates were 25% and 32%.

Patients in the thalidomide group reported significantly more overall toxicity of grade 3 or greater, compared with the lenalidomide group, 73% vs. 58% (P = .007) (Blood 2015 Sep 17. doi:10.1182/blood-2014-12-613927).

The E1a06 trial included 306 patients, median age 76 years, with newly diagnosed multiple myeloma. The median follow up was 41 months, and 139 patients received maintenance therapy, with similar proportions from each arm.

The researchers compared melphalan, prednisone and thalidomide (MPT) with melphalan, prednisone, and lenalidomide (MPR), but administered lower doses of melphalan, with the hope that it would be better tolerated with less myelosuppression. Emerging data suggest benefit in using thalidomide or lenalidomide continuously, and the drugs were incorporated as ongoing maintenance therapy in both arms, MPT-T and MPR-R.

The data are similar to the recent Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) trial, which had median participant age of 73 years. Although response rates were higher in the HOVON study, possibly due to higher doses of melphalan and lenalidomide, PFS was essentially identical.

For reasons unclear but possibly due in part to higher median age, outcomes in this trial were inferior to the MM-015 trial, which examined continuous lenalidomide therapy and included patients of median age 71 years. In the MM-015 trial MPR-R arm, median PFS and OS were much higher at 31 and 56 months, respectively.

The difference was most obvious in younger patients, who are able to tolerate higher melphalan doses and myelosuppression, according to Dr. Keith Stewart of the division of hematology, Mayo Clinic Arizona, Scottsdale, and colleagues.

“We assume this explains the wide difference in the MM-015 and E1a06 and suggests that a dose-intense approach in younger patients receiving MPR-R is advisable,” they wrote.

In the this study’s MPR-R arm, patients older than 75 years had shorter PFS by 5 months than did younger patients, but toxicity reports were similar across ages.

The majority of patients experienced at least grade 3 toxicity: 58% of MPR-R and 73% of MPT-T patients. Only hematologic toxicities of grade 4 or higher were recorded, so estimates of overall hematologic toxicity are incomplete. Patients in the MPR-R group reported better quality of life, mostly attributable to lower neuropathy rates.

Dr. Stewart disclosed ties with Celgene, maker of lenalidomide (Revlimid); Novartis, Bristol Meyers Squib, Sanofi Aventis, and Janssen.

Combination treatment with melphalan, prednisone and either thalidomide or lenalidomide had comparable efficacy in elderly patients who were newly diagnosed with multiple myeloma. Lenalidomide was associated with less toxicity, however, and higher quality of life, according to results from a phase III trial.

The Eastern Cooperative Oncology Group (ECOG) E1a06 trial showed similar progression-free survival (PFS), overall survival (OS), and response rates for thalidomide and lenalidomide groups. PFS was 21 and 19 months, respectively (hazard ratio [HR], 0.84; 95% CI, 0.64-1.09; P = .186); OS was 53 and 48 months (HR, 0.88; 0.63-1.24; P = .476); partial response rates were 75% and 70%; and very good partial response rates were 25% and 32%.

Patients in the thalidomide group reported significantly more overall toxicity of grade 3 or greater, compared with the lenalidomide group, 73% vs. 58% (P = .007) (Blood 2015 Sep 17. doi:10.1182/blood-2014-12-613927).

The E1a06 trial included 306 patients, median age 76 years, with newly diagnosed multiple myeloma. The median follow up was 41 months, and 139 patients received maintenance therapy, with similar proportions from each arm.

The researchers compared melphalan, prednisone and thalidomide (MPT) with melphalan, prednisone, and lenalidomide (MPR), but administered lower doses of melphalan, with the hope that it would be better tolerated with less myelosuppression. Emerging data suggest benefit in using thalidomide or lenalidomide continuously, and the drugs were incorporated as ongoing maintenance therapy in both arms, MPT-T and MPR-R.

The data are similar to the recent Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) trial, which had median participant age of 73 years. Although response rates were higher in the HOVON study, possibly due to higher doses of melphalan and lenalidomide, PFS was essentially identical.

For reasons unclear but possibly due in part to higher median age, outcomes in this trial were inferior to the MM-015 trial, which examined continuous lenalidomide therapy and included patients of median age 71 years. In the MM-015 trial MPR-R arm, median PFS and OS were much higher at 31 and 56 months, respectively.

The difference was most obvious in younger patients, who are able to tolerate higher melphalan doses and myelosuppression, according to Dr. Keith Stewart of the division of hematology, Mayo Clinic Arizona, Scottsdale, and colleagues.

“We assume this explains the wide difference in the MM-015 and E1a06 and suggests that a dose-intense approach in younger patients receiving MPR-R is advisable,” they wrote.

In the this study’s MPR-R arm, patients older than 75 years had shorter PFS by 5 months than did younger patients, but toxicity reports were similar across ages.

The majority of patients experienced at least grade 3 toxicity: 58% of MPR-R and 73% of MPT-T patients. Only hematologic toxicities of grade 4 or higher were recorded, so estimates of overall hematologic toxicity are incomplete. Patients in the MPR-R group reported better quality of life, mostly attributable to lower neuropathy rates.

Dr. Stewart disclosed ties with Celgene, maker of lenalidomide (Revlimid); Novartis, Bristol Meyers Squib, Sanofi Aventis, and Janssen.

Combination treatment with melphalan, prednisone and either thalidomide or lenalidomide had comparable efficacy in elderly patients who were newly diagnosed with multiple myeloma. Lenalidomide was associated with less toxicity, however, and higher quality of life, according to results from a phase III trial.

The Eastern Cooperative Oncology Group (ECOG) E1a06 trial showed similar progression-free survival (PFS), overall survival (OS), and response rates for thalidomide and lenalidomide groups. PFS was 21 and 19 months, respectively (hazard ratio [HR], 0.84; 95% CI, 0.64-1.09; P = .186); OS was 53 and 48 months (HR, 0.88; 0.63-1.24; P = .476); partial response rates were 75% and 70%; and very good partial response rates were 25% and 32%.

Patients in the thalidomide group reported significantly more overall toxicity of grade 3 or greater, compared with the lenalidomide group, 73% vs. 58% (P = .007) (Blood 2015 Sep 17. doi:10.1182/blood-2014-12-613927).

The E1a06 trial included 306 patients, median age 76 years, with newly diagnosed multiple myeloma. The median follow up was 41 months, and 139 patients received maintenance therapy, with similar proportions from each arm.

The researchers compared melphalan, prednisone and thalidomide (MPT) with melphalan, prednisone, and lenalidomide (MPR), but administered lower doses of melphalan, with the hope that it would be better tolerated with less myelosuppression. Emerging data suggest benefit in using thalidomide or lenalidomide continuously, and the drugs were incorporated as ongoing maintenance therapy in both arms, MPT-T and MPR-R.

The data are similar to the recent Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) trial, which had median participant age of 73 years. Although response rates were higher in the HOVON study, possibly due to higher doses of melphalan and lenalidomide, PFS was essentially identical.

For reasons unclear but possibly due in part to higher median age, outcomes in this trial were inferior to the MM-015 trial, which examined continuous lenalidomide therapy and included patients of median age 71 years. In the MM-015 trial MPR-R arm, median PFS and OS were much higher at 31 and 56 months, respectively.

The difference was most obvious in younger patients, who are able to tolerate higher melphalan doses and myelosuppression, according to Dr. Keith Stewart of the division of hematology, Mayo Clinic Arizona, Scottsdale, and colleagues.

“We assume this explains the wide difference in the MM-015 and E1a06 and suggests that a dose-intense approach in younger patients receiving MPR-R is advisable,” they wrote.

In the this study’s MPR-R arm, patients older than 75 years had shorter PFS by 5 months than did younger patients, but toxicity reports were similar across ages.

The majority of patients experienced at least grade 3 toxicity: 58% of MPR-R and 73% of MPT-T patients. Only hematologic toxicities of grade 4 or higher were recorded, so estimates of overall hematologic toxicity are incomplete. Patients in the MPR-R group reported better quality of life, mostly attributable to lower neuropathy rates.

Dr. Stewart disclosed ties with Celgene, maker of lenalidomide (Revlimid); Novartis, Bristol Meyers Squib, Sanofi Aventis, and Janssen.