Regimen may lengthen survival in AL amyloidosis

Micrograph showing amyloidosis

High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.

The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.

Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.

“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.

Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).

They received full-dose melphalan at 200 mg/m² (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m² (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.

Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).

After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).

Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).

Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).

Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.

At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.

The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).

Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.

Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).

“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.

She and her colleagues also noted that this study included a “highly selected” group of new patients.

Micrograph showing amyloidosis

High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.

The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.

Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.

“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.

Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).

They received full-dose melphalan at 200 mg/m² (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m² (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.

Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).

After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).

Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).

Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).

Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.

At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.

The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).

Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.

Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).

“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.

She and her colleagues also noted that this study included a “highly selected” group of new patients.

Micrograph showing amyloidosis

High-dose melphalan and autologous stem cell transplant (HDM/SCT) may enable long-term survival in patients with light-chain (AL) amyloidosis, according to research published in Blood.

The study included more than 500 patients who were followed for a median of 8 years, and the median overall survival (OS) was 7.63 years.

Patients tended to live longer if they had a hematologic complete response (CR) to treatment and if they received the full dose of melphalan as opposed to a modified dose.

“While survival is strongly dependent upon achieving hematologic CR, the survival of patients who did not achieve a CR and of those who relapsed after CR is notable, suggesting a benefit of aggressive treatment,” said Vaishali Sanchorawala, MD, of Boston University School of Medicine in Massachusetts.

Dr Sanchorawala and her colleagues conducted this study by analyzing data from 629 patients with AL amyloidosis who received HDM/SCT between 1994 and 2014. The patients’ median age was 57 (range, 28 to 80).

They received full-dose melphalan at 200 mg/m² (n=350, 55.6%) or modified-dose melphalan at 100-140 mg/m² (n=279, 44.3%), based on their age and organ function. All patients received growth factor for stem cell mobilization.

Treatment-related mortality (TRM) was defined as death within 100 days of SCT. The rate of TRM was 7.4% (n=47). Eleven deaths occurred during stem cell mobilization and collection (before melphalan was given).

After 2005, there were no deaths during stem cell mobilization and collection, and TRM improved to 3.4% (n=10).

Overall, 543 patients (86.3%) were evaluable for response at 6 to 12 months after SCT. Of these patients, 40.3% (n=219) achieved a hematologic CR. However, 18.2% (n=40) of these patients later relapsed, at a median of 3.97 years (range, 1.89-12.45).

Hematologic CR was more likely among patients who received full-dose melphalan than those who received the modified dose, occurring in 44.9% and 33.7% of patients, respectively (P=0.0091).

Relapse was more likely among patients who received melphalan at the modified dose than the full dose, occurring in 60% and 40%, respectively.

At a median follow-up of 8 years, the median OS was 7.63 years. The median OS has not been reached among patients achieving a hematologic CR, but it was 6.3 years for patients who did not achieve a hematologic CR (P<0.0001). The median OS for patients who relapsed was 4.3 years.

The median OS was significantly longer for patients who received full-dose melphalan—10.47 years, compared to 5.15 years for patients who received the modified dose (P<0.0001).

Likewise, the estimated OS rates at 1, 5, 10, and 15 years were higher for patients with a hematologic CR than for those without one. The 1-year OS is 100% and 94%, respectively. The OS at 5 years is 88% and 60%, respectively. The 10-year OS is 72% and 34%, respectively. And the OS at 15 years is 57% and 18%, respectively.

Forty patients who achieved a hematologic CR died of a cause other than relapse, including sudden death (n=7), metastatic malignancy (n=6), heart failure (n=5), renal failure (n=5), therapy-related myelodysplastic syndrome/acute myeloid leukemia (n=4), sepsis (n=4), stroke (n=3), bleeding complications (n=2), and unknown cause (n=4).

“Strategies to better understand which patients may benefit the most from this treatment and reducing treatment-related mortality, as well as using combination therapies with novel agents to increase the CR rate, will likely improve outcomes in the future for patients who, just a few years ago, were considered to have a rapidly fatal diagnosis,” Dr Sanchorawala said.

She and her colleagues also noted that this study included a “highly selected” group of new patients.