Autologous, allogeneic HSCT ‘highly efficacious’ for Waldenström macroglobulinemia
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ORLANDO — Autologous and allogeneic hematopoietic stem cell transplantation both conferred encouraging survival outcomes among patients with Waldenström macroglobulinemia, according to results of a systematic review and meta-analysis presented at TCT | Transplantation & Cellular Therapy Meetings.
Both approaches induced similar overall response rates. Allogeneic HSCT appeared associated with a twofold lower risk for relapse; however, the potential advantage of allografting was offset by increased likelihood of nonrelapse mortality, Ricardo D. Parrondo, MD, second-year hematology-oncology fellow at Mayo Clinic in Jacksonville, Florida, and colleagues concluded.
Waldenström macroglobulinemia is an incurable immunoglobulin M-producing lymphoproliferative disorder.
Although it is an indolent disease, patients with high-risk disease based on the International Prognostic Scoring System typically survive less than 4 years. In addition, approximately 15% of patients with low-risk disease who achieve remission after first-line therapy develop progressive disease, according to study background.
Autologous and allogeneic HSCT often are prescribed for treatment of patients with Waldenström macroglobulinemia despite a lack of randomized controlled studies.
“Most of the data related to stem cell transplantation — both autologous and allogeneic — for Waldenström macroglobulinemia are retrospective in nature, or they are from small single-center studies,” Parrondo told Healio. “Nobody has really ever pooled all of the data, so that’s what we decided to do.”
Parrondo and colleagues searched the PubMed, Medline and EMBASE databases for published data on OS, PFS, overall response rate, relapse rate and nonrelapse mortality associated with these two approaches.
Investigators included 15 studies — eight related to autologous HSCT (n = 291) and seven related to allogeneic HSCT (n = 311) — in their analysis.
Median age of patients in the autologous HSCT studies ranged from 49 to 60 years; 58% received melphalan conditioning and 41% received BEAM conditioning, which consists of carmustine, etoposide, cytarabine and melphalan.
Researchers calculated a pooled OS rate of 70% (95% CI, 51-87) with high heterogeneity (I2 = 87%) and a pooled PFS rate of 50% (95% CI, 38-61) with moderate heterogeneity (I2 = 59%). They calculated a pooled nonrelapse mortality rate of 4% (95% CI, 1-7) with low heterogeneity (I2 = 0%).
Median age of patients in the allogeneic HSCT studies ranged from 43 to 57 years. Slightly more than half (52%) received a reduced-intensity conditioning regimen.
Researchers calculated a pooled OS rate after allografting of 57% (95% CI, 50-65) with low heterogeneity (I2 = 19%). They calculated a pooled PFS of 49% (95% CI, 42-56) with low heterogeneity (I2 = 15%) and a pooled nonrelapse mortality rate of 29% (95% CI, 24-34) with low heterogeneity (I2 = 0%).
Results showed pooled ORRs of 90% (95% CI, 82-96) with autologous HSCT and 86% (95% CI, 76-95) after allogeneic HSCT, with moderate heterogeneity for both.
Relapse rates were 42% (95% CI, 30-55) after autologous HSCT and 23% (95% CI, 18-28) after allogeneic HSCT, with moderate heterogeneity for both (I2 = 68.3%).
“Both allogeneic and autologous transplants are highly efficacious for these patients, with high response rates and complete response rates of about 20%,” Parrondo told Healio. “It is rare to achieve that high of a complete response rate, even with novel agents. You achieve a higher PFS rate with allogeneic transplant but also greater nonrelapse mortality, so that balance has to be taken into account.”
Highly effective and well-tolerated agents — such as ibrutinib (Imbruvica; Pharmacyclics, Janssen), bortezomib or rituximab — provide long-term disease control for patients with Waldenström macroglobulinemia, so the role of HSCT going forward is in question, Parrondo said.
“Some may ask the question: Why would you transplant a patient with Waldenström macroglobulinemia given it is an indolent disorder and there are other effective novel agents,” Parrondo said. “However, transplant is an efficacious treatment with low toxicity. It affords about a 4-year PFS, and it’s one shot and you’re done, whereas some of the other treatments require prolonged therapy or — in some cases — indefinite therapy. For that reason, I think transplant is something to consider, particularly for patients who are chemorefractory or refractory to novel agents, or those who are not interested in continuous therapy.” – by Mark Leiser
Reference: Parrondo RD, et al. Abstract 363. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.
Disclosures: Parrondo reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.