Meeting News

Autologous HSCT effective, safe for older patients with multiple myeloma

Anita D'Souza, MD
Anita D'Souza

ORLANDO — Autologous hematopoietic stem cell transplantation appeared safe and effective for older patients with multiple myeloma, according to study results presented at ASH Annual Meeting and Exposition.

The study — the largest to examine autologous HSCT for older adults with multiple myeloma — showed patients aged 70 years and older achieved outcomes after transplant comparable to those of patients aged 60 to 69 years.

In addition, older patients achieved better outcomes when they received the conditioning chemotherapy drug melphalan at the standard 200 mg/m2 dose rather than the reduced dose of 140 mg/m2 that they often receive.

“The number of older individuals undergoing transplant has increased over time and, based on these results, I think we will continue to see even more transplants performed in this population,” Anita D’Souza, MD, assistant professor of medicine in the division of hematology/oncology at Medical College of Wisconsin, told Healio. “We are being more inclusive and not taking away an effective treatment just because of chronologic age. I think biologic age is much more important.”

Autologous HSCT helps patients with multiple myeloma achieve deep, durable remission. However, less than half of patients with myeloma receive this therapy.

The median age at myeloma diagnosis is 70 years, but older adults often are excluded from clinical trials that evaluate transplant due to other health issues. Consequently, physicians may avoid offering transplant to older patients due to fear that it is too risky.

D’Souza and colleagues used the Center for International Blood and Marrow Transplant Research database to identify adults aged 20 years or older who underwent upfront autologous HSCT for newly diagnosed multiple myeloma between 2013 and 2017.

Researchers assessed outcomes after transplant across age groups.

The analysis included 15,999 patients (median age, 62 years; range, 20-83; 57% men; 78% white) who received a single autologous HSCT with melphalan conditioning within 12 months of diagnosis.

The age breakdown was as follows: 20 to 39 years, 1.9% (n = 308); 40 to 49 years, 10% (n = 1,615); 50 to 59 years, 30.9% (n = 4,952); 60 to 69 years, 43.9% (n = 7,032); and 70 years or older, 13% (n = 2,092).

Patients aged 70 years or older accounted for a larger percentage of total transplants over time (11.1% in 2013 vs. 15.7% in 2017).

All age groups had comparable distribution of sex, race, ethnicity, Karnofsky performance score, comorbidity index and stage III disease.

Forty-five percent of patients had Karnofsky scores less than 90%, 54% had International Staging System/Durie-Salmon Staging stage III disease, and 27% had high-risk cytogenetics. High-risk cytogenetics were more prevalent among patients aged 70 years or older (30%) than those aged 49 to 49 years (24%) or 20 to 39 years (20%). The oldest age group comprised a higher percentage of white patients than the 20-to-39 age group (85% vs. 64%).

The majority (82%) of the overall study population received melphalan 200 mg/m2; however, more than half (58%) of the oldest age group received melphalan 140 mg/m2.

Investigators performed multivariate analysis to calculate nonrelapse mortality, relapse/progression, PFS and OS. Due to the large sample size, they established a P value less than .01 as the threshold for statistical significance.

Unadjusted analysis showed one case of 100-day nonrelapse mortality in the oldest age group but no cases among younger patients (P < .01).

Results showed no significant difference between age groups with regard to 2-year relapse or 2-year PFS. However, 2-year OS was significantly lower among those aged 70 or older (86%) compared with those 60 to 69 years (89%), 50 to 59 years (90%), 40 to 49 years (91%), and 20 to 39 years (94%; P < .01).

Researchers also conducted multivariate analyses adjusted for functional status, comorbidities, disease stage and other factors. The results, using patients aged 60 to 69 years as the reference group, showed those aged 70 years or older had comparable risks for nonrelapse mortality (HR = 1.3; 95% CI, 0.99-1.7), relapse (HR = 1.03; 95% CI, 0.93-1.13), PFS (HR = 1.05; 95% CI, 0.96-1.16) and OS (HR = 1.18; 95% CI, 1.02-1.38).

Primary disease was the leading cause of death across all age groups.

Among the oldest age group, reduced melphalan dose — 140 mg/m2 instead of 200 mg/m2 — predicted poorer outcomes, including nonrelapse mortality at 100 days (1% vs. 0%; P = .003), 2-year PFS (64% vs. 69%; P = .003) and 2-year OS (85% vs. 89%; P = .01).

Researchers could not determine whether patients who received the reduced melphalan dose had higher frailty prior to transplant, thereby contributing to the poorer outcomes.

However, the results show that clinicians should not administer the reduced melphalan dose simply because of a patient’s age, D’Souza said.

“This is a geriatric cancer, and we all have to do a better job performing geriatric assessments,” D’Souza said. “We need to use the tools from our geriatric oncology colleagues to risk-stratify patients better and, if they don’t have a high frailty index, maybe those are the patients to whom we can safely give the full melphalan dose.” – by Mark Leiser

Reference: Munshi PM, et al. Abstract 782. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando.

Disclosure: D’Souza reports research funding from Merck, Mundipharma EDO, Prothena, Sanofi and TeneoBio, a consultant role with Prothena; and board of directors or advisory roles with Akcea, Imbrium Therapeutics and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.

Anita D'Souza, MD
Anita D'Souza

ORLANDO — Autologous hematopoietic stem cell transplantation appeared safe and effective for older patients with multiple myeloma, according to study results presented at ASH Annual Meeting and Exposition.

The study — the largest to examine autologous HSCT for older adults with multiple myeloma — showed patients aged 70 years and older achieved outcomes after transplant comparable to those of patients aged 60 to 69 years.

In addition, older patients achieved better outcomes when they received the conditioning chemotherapy drug melphalan at the standard 200 mg/m2 dose rather than the reduced dose of 140 mg/m2 that they often receive.

“The number of older individuals undergoing transplant has increased over time and, based on these results, I think we will continue to see even more transplants performed in this population,” Anita D’Souza, MD, assistant professor of medicine in the division of hematology/oncology at Medical College of Wisconsin, told Healio. “We are being more inclusive and not taking away an effective treatment just because of chronologic age. I think biologic age is much more important.”

Autologous HSCT helps patients with multiple myeloma achieve deep, durable remission. However, less than half of patients with myeloma receive this therapy.

The median age at myeloma diagnosis is 70 years, but older adults often are excluded from clinical trials that evaluate transplant due to other health issues. Consequently, physicians may avoid offering transplant to older patients due to fear that it is too risky.

D’Souza and colleagues used the Center for International Blood and Marrow Transplant Research database to identify adults aged 20 years or older who underwent upfront autologous HSCT for newly diagnosed multiple myeloma between 2013 and 2017.

Researchers assessed outcomes after transplant across age groups.

The analysis included 15,999 patients (median age, 62 years; range, 20-83; 57% men; 78% white) who received a single autologous HSCT with melphalan conditioning within 12 months of diagnosis.

The age breakdown was as follows: 20 to 39 years, 1.9% (n = 308); 40 to 49 years, 10% (n = 1,615); 50 to 59 years, 30.9% (n = 4,952); 60 to 69 years, 43.9% (n = 7,032); and 70 years or older, 13% (n = 2,092).

Patients aged 70 years or older accounted for a larger percentage of total transplants over time (11.1% in 2013 vs. 15.7% in 2017).

All age groups had comparable distribution of sex, race, ethnicity, Karnofsky performance score, comorbidity index and stage III disease.

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Forty-five percent of patients had Karnofsky scores less than 90%, 54% had International Staging System/Durie-Salmon Staging stage III disease, and 27% had high-risk cytogenetics. High-risk cytogenetics were more prevalent among patients aged 70 years or older (30%) than those aged 49 to 49 years (24%) or 20 to 39 years (20%). The oldest age group comprised a higher percentage of white patients than the 20-to-39 age group (85% vs. 64%).

The majority (82%) of the overall study population received melphalan 200 mg/m2; however, more than half (58%) of the oldest age group received melphalan 140 mg/m2.

Investigators performed multivariate analysis to calculate nonrelapse mortality, relapse/progression, PFS and OS. Due to the large sample size, they established a P value less than .01 as the threshold for statistical significance.

Unadjusted analysis showed one case of 100-day nonrelapse mortality in the oldest age group but no cases among younger patients (P < .01).

Results showed no significant difference between age groups with regard to 2-year relapse or 2-year PFS. However, 2-year OS was significantly lower among those aged 70 or older (86%) compared with those 60 to 69 years (89%), 50 to 59 years (90%), 40 to 49 years (91%), and 20 to 39 years (94%; P < .01).

Researchers also conducted multivariate analyses adjusted for functional status, comorbidities, disease stage and other factors. The results, using patients aged 60 to 69 years as the reference group, showed those aged 70 years or older had comparable risks for nonrelapse mortality (HR = 1.3; 95% CI, 0.99-1.7), relapse (HR = 1.03; 95% CI, 0.93-1.13), PFS (HR = 1.05; 95% CI, 0.96-1.16) and OS (HR = 1.18; 95% CI, 1.02-1.38).

Primary disease was the leading cause of death across all age groups.

Among the oldest age group, reduced melphalan dose — 140 mg/m2 instead of 200 mg/m2 — predicted poorer outcomes, including nonrelapse mortality at 100 days (1% vs. 0%; P = .003), 2-year PFS (64% vs. 69%; P = .003) and 2-year OS (85% vs. 89%; P = .01).

Researchers could not determine whether patients who received the reduced melphalan dose had higher frailty prior to transplant, thereby contributing to the poorer outcomes.

However, the results show that clinicians should not administer the reduced melphalan dose simply because of a patient’s age, D’Souza said.

“This is a geriatric cancer, and we all have to do a better job performing geriatric assessments,” D’Souza said. “We need to use the tools from our geriatric oncology colleagues to risk-stratify patients better and, if they don’t have a high frailty index, maybe those are the patients to whom we can safely give the full melphalan dose.” – by Mark Leiser

Reference: Munshi PM, et al. Abstract 782. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2019; Orlando.

Disclosure: D’Souza reports research funding from Merck, Mundipharma EDO, Prothena, Sanofi and TeneoBio, a consultant role with Prothena; and board of directors or advisory roles with Akcea, Imbrium Therapeutics and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.

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