Bone marrow transplant may extend survival in high-risk follicular lymphoma
Patients with high-risk follicular lymphoma demonstrated low nonrelapse mortality and promising OS rates after hematopoietic stem cell transplantation, according to published findings.
“Our data support HSCT as an appropriate and effective option for transplant-eligible follicular lymphoma patients with early treatment failure because of the noted long-term survival of 70% of patients undergoing either autologous HSCT or matched sibling donor allogeneic HSCT,” Sonali M. Smith, MD, professor in the section of hematology/oncology and director of the lymphoma program at The University of Chicago, and colleagues wrote.
One-third of patients with follicular lymphoma experience long-term survival, but one-fifth of patients die within a few years of diagnosis.
HSCT has been established as a viable option for patients with relapsed follicular lymphoma. However, efficacy of HSCT among patients who experience early treatment failure has not been evaluated, and the role of transplant has remained controversial due to the development of less toxic agents.
Smith and colleagues examined data from the Center for International Blood and Marrow Transplant Research database to compare autologous HSCT (n = 240) with either matched sibling donor (n = 105) or matched unrelated donor (n = 95) allogeneic HSCT as a first transplantation approach for patients with follicular lymphoma and early treatment failure.
Researchers defined early treatment failure as disease relapse or progression within 2 years of initiated rituximab (Rituxan, Genentech)-based chemotherapy treatment.
OS served as the primary endpoint. Secondary endpoints included PFS, relapse and nonrelapse mortality.
Median followup was 69 to 73 months.
The 5year adjusted probability of nonrelapse mortality was 5% for patients who underwent autologous HSCT compared with 17% of those who underwent matched sibling donor HSCT and 33% for matched unrelated donor HSCT (P<.0001).
Multivariate regression models indicated that matched sibling donor (RR = 5.46; 95% CI, 2.07-14.39) and matched unrelated donor HSCT (RR = 13.15; 95% CI, 5.34-32.38) appeared associated with higher risk for nonrelapse mortality within the first 21 months after transplant compared with autologous HSCT. Nonrelapse mortality did not appear significantly different between the approaches after 21 months.
Researchers reported higher 5year adjusted probability of relapse for patients who underwent autologous HSCT (58%) than for matched sibling donor allogenic HSCT (31%) and for matched unrelated donor allogenic HSCT (23%; P<.0001).
Multivariate regression models showed no difference in the risk for relapse or progression between the approaches within the first 7 months of transplant. However, researchers observed a lower risk for relapse or progression after 7 months in the matched sibling donor group (RR = 0.38; 95% CI, 0.22-0.64) and matched unrelated donor group (RR = 0.09; 95% CI, 0.03-0.3) compared with the autologous HSCT group.
Researchers reported 5-year adjusted probabilities of PFS of 38% for the autologous HSCT group, 52% for matched sibling donor allogeneic HSCT and 43% for matched unrelated donors allogeneic HSCT.
Multivariate regression models showed inferior PFS within the first 6 months after transplant in the matched unrelated donor group compared with patients who underwent autologous HSCT (RR = 2.6; 95% CI, 1.67-4.03).
After 6 months, patients who underwent allogenic HSCT from matched sibling donors (RR = 0.67; 95% CI, 0.45-0.99) and matched unrelated donors (RR = 0.67; 95% CI, 0.23-0.71) had superior PFS compared with the autologous HSCT group.
Adjusted probability of 5year OS appeared higher for patients who underwent autologous HSCT (70%) or matched sibling donor HSCT (73%) than matched unrelated donor HSCT (49%; P=.0008).
“Until better risk-stratification tools are available for follicular lymphoma, autologous HCT and matched sibling donor [allogeneic HSCT] should be considered as effective treatment options with excellent long-term survival for high-risk patients as defined by early treatment failure,” researchers wrote.
The study demonstrated that patients who experienced early treatment failure may have a long-term survival benefit from either autologous or allogenic transplant.
“Historical data ... found that only 50% of patients with early treatment failure were alive 5 years after the time of their diagnosis. The current study found that autologous HSCT and matched sibling-donor allogeneic HSCT were associated with a 5-year OS rate of up to 70% from the time of transplantation,” Ryan C. Lynch, MD, assistant professor of medicine at University of Washington, and Ajay K. Gopal, MD, associate professor of medicine at University of Washington and from the clinical research division at Fred Hutchinson Cancer Research Center, wrote in an accompanying editorial. “Although the aforementioned is not a matched historical control, it does show that a select group of patients may experience long-term survival in this setting.”
Still, the high rates of relapse and nonrelapse mortality should be noted.
“Appropriate counseling of patients with these caveats is critical because we do not have a way to directly compare these results with those for a similar population of patients who did not undergo HSCT,” Lynch and Gopal wrote. – by Melinda Stevens
Disclosures: One study author reports participation in speaker bureaus for Alexion Pharmaceutical, Incyte Corp. and Seattle Genetics. Gopal reports grants and nonfinancial support from Bristol-Myers Squibb, Effector, Merck, Takeda, Teva and TG Therapeutics; grants, personal fees and nonfinancial support from Gilead Sciences, Incyte Corp., Janssen, Pfizer, Seattle Genetics and Spectrum; and personal fees from Aptevo, BRIM bio and Sanofi outside of the study. Lynch reports no relevant financial disclosures.