Continuous therapy improved outcomes in multiple myeloma

Compared with fixed duration therapy for patients with multiple myeloma, continuous therapy significantly prolonged median progression by approximately 1 year and improved overall survival by about 10%, investigators reported online Aug. 17 in the Journal of Clinical Oncology.

The goal of continuous therapy is to maintain the results of first-line therapy by keeping the patient free of symptoms and preventing or delaying disease progression. There has been some concern, however, that patients who progress while on continuous therapy may become resistant to at least that particular regimen.

In the current study, Dr. Antonio Palumbo of the University of Torino (Italy) and his colleagues pooled the results of three randomized phase III trials to evaluate the impact of continuous therapy, compared with fixed duration of therapy on time-to-event endpoints. In addition to overall survival, they evaluated progression-free survival (PFS) at two different time points in the course of therapy.

PFS1 was defined as the time from random assignment until the first disease progression or death, while PFS2 was defined as the time randomization until the second disease progression or death. Using both of these endpoints more accurately estimated the impact of both first- and second-line therapies on patient outcomes, the investigators said.

The pooled analysis of the three trials included 604 patients who were randomly assigned to continuous therapy and 614 who were randomized to fixed duration therapy. The median follow-up was 52 months. In the intent-to-treat population, continuous therapy (n = 417), compared with fixed duration (n = 410) significantly improved PFS1 (median, 32 vs. 16 months, respectively; hazard ratio, 0.47; 95% confidence interval, 0.40-0.56; P less than .001), as well as PFS2 (median, 55 vs. 40 months, respectively; HR, 0.61; 95% CI, 0.50-0.75; P less than .001). Overall survival also was improved in the continuous therapy group (4-year overall survival, 69% vs. 60%, respectively; HR, 0.69; 95% CI, 0.54-0.88; P = .003) (J Clin Oncol. 2015 Aug. 17 doi: 10.1200/JCO.2014.60.2466).

“Our findings suggest that most of the PFS1 advantage associated with CT [continuous therapy] up front is maintained after first relapse and that CT does not induce a significant chemotherapy resistance,” Dr. Palumbo and his associates wrote. “The improvement in PFS2 suggests that most of the benefit observed during the first remission is not affected by a short second remission.”

The GIMEMA-MM-03-05 study was sponsored by Fondazione Neoplasie Sangue Onlus and supported by Janssen-Cilag and Celgene. The RV-MM-PI-209 study was sponsored by Fondazione Neoplasie Sangue Onlus and supported by Celgene. The CC-5013-MM-015 study was sponsored and supported by Celgene. Several of the coauthors reported financial relationships with industry, including Celgene and Janssen-Citag.

Compared with fixed duration therapy for patients with multiple myeloma, continuous therapy significantly prolonged median progression by approximately 1 year and improved overall survival by about 10%, investigators reported online Aug. 17 in the Journal of Clinical Oncology.

The goal of continuous therapy is to maintain the results of first-line therapy by keeping the patient free of symptoms and preventing or delaying disease progression. There has been some concern, however, that patients who progress while on continuous therapy may become resistant to at least that particular regimen.

In the current study, Dr. Antonio Palumbo of the University of Torino (Italy) and his colleagues pooled the results of three randomized phase III trials to evaluate the impact of continuous therapy, compared with fixed duration of therapy on time-to-event endpoints. In addition to overall survival, they evaluated progression-free survival (PFS) at two different time points in the course of therapy.

PFS1 was defined as the time from random assignment until the first disease progression or death, while PFS2 was defined as the time randomization until the second disease progression or death. Using both of these endpoints more accurately estimated the impact of both first- and second-line therapies on patient outcomes, the investigators said.

The pooled analysis of the three trials included 604 patients who were randomly assigned to continuous therapy and 614 who were randomized to fixed duration therapy. The median follow-up was 52 months. In the intent-to-treat population, continuous therapy (n = 417), compared with fixed duration (n = 410) significantly improved PFS1 (median, 32 vs. 16 months, respectively; hazard ratio, 0.47; 95% confidence interval, 0.40-0.56; P less than .001), as well as PFS2 (median, 55 vs. 40 months, respectively; HR, 0.61; 95% CI, 0.50-0.75; P less than .001). Overall survival also was improved in the continuous therapy group (4-year overall survival, 69% vs. 60%, respectively; HR, 0.69; 95% CI, 0.54-0.88; P = .003) (J Clin Oncol. 2015 Aug. 17 doi: 10.1200/JCO.2014.60.2466).

“Our findings suggest that most of the PFS1 advantage associated with CT [continuous therapy] up front is maintained after first relapse and that CT does not induce a significant chemotherapy resistance,” Dr. Palumbo and his associates wrote. “The improvement in PFS2 suggests that most of the benefit observed during the first remission is not affected by a short second remission.”

The GIMEMA-MM-03-05 study was sponsored by Fondazione Neoplasie Sangue Onlus and supported by Janssen-Cilag and Celgene. The RV-MM-PI-209 study was sponsored by Fondazione Neoplasie Sangue Onlus and supported by Celgene. The CC-5013-MM-015 study was sponsored and supported by Celgene. Several of the coauthors reported financial relationships with industry, including Celgene and Janssen-Citag.

Compared with fixed duration therapy for patients with multiple myeloma, continuous therapy significantly prolonged median progression by approximately 1 year and improved overall survival by about 10%, investigators reported online Aug. 17 in the Journal of Clinical Oncology.

The goal of continuous therapy is to maintain the results of first-line therapy by keeping the patient free of symptoms and preventing or delaying disease progression. There has been some concern, however, that patients who progress while on continuous therapy may become resistant to at least that particular regimen.

In the current study, Dr. Antonio Palumbo of the University of Torino (Italy) and his colleagues pooled the results of three randomized phase III trials to evaluate the impact of continuous therapy, compared with fixed duration of therapy on time-to-event endpoints. In addition to overall survival, they evaluated progression-free survival (PFS) at two different time points in the course of therapy.

PFS1 was defined as the time from random assignment until the first disease progression or death, while PFS2 was defined as the time randomization until the second disease progression or death. Using both of these endpoints more accurately estimated the impact of both first- and second-line therapies on patient outcomes, the investigators said.

The pooled analysis of the three trials included 604 patients who were randomly assigned to continuous therapy and 614 who were randomized to fixed duration therapy. The median follow-up was 52 months. In the intent-to-treat population, continuous therapy (n = 417), compared with fixed duration (n = 410) significantly improved PFS1 (median, 32 vs. 16 months, respectively; hazard ratio, 0.47; 95% confidence interval, 0.40-0.56; P less than .001), as well as PFS2 (median, 55 vs. 40 months, respectively; HR, 0.61; 95% CI, 0.50-0.75; P less than .001). Overall survival also was improved in the continuous therapy group (4-year overall survival, 69% vs. 60%, respectively; HR, 0.69; 95% CI, 0.54-0.88; P = .003) (J Clin Oncol. 2015 Aug. 17 doi: 10.1200/JCO.2014.60.2466).

“Our findings suggest that most of the PFS1 advantage associated with CT [continuous therapy] up front is maintained after first relapse and that CT does not induce a significant chemotherapy resistance,” Dr. Palumbo and his associates wrote. “The improvement in PFS2 suggests that most of the benefit observed during the first remission is not affected by a short second remission.”

The GIMEMA-MM-03-05 study was sponsored by Fondazione Neoplasie Sangue Onlus and supported by Janssen-Cilag and Celgene. The RV-MM-PI-209 study was sponsored by Fondazione Neoplasie Sangue Onlus and supported by Celgene. The CC-5013-MM-015 study was sponsored and supported by Celgene. Several of the coauthors reported financial relationships with industry, including Celgene and Janssen-Citag.