Large Registry Analysis Confirms Autologous Hematopoietic Cell Transplantation Is Feasible in Older Patients

Older patients (≥65 years) with hematologic malignancies are often considered unsuitable for autologous hematopoietic cell transplantation (AHCT) because of the potential for higher risks of complications. As a result, they are often excluded from or under-represented in clinical trials studying transplantation. A large cohort study presented at the 2016 ASH Annual Meeting specifically examined overall survival (OS) rates for older patients undergoing AHCT, and provides some assurance that it is safe.

“Our data convincingly suggest that age, per se, should not be an exclusion criterion to consider AHCT in this [older] population,” the authors, led by Isabel Sánchez-Ortega, MD, PhD, from the Institut Català d’Oncologia, Hospital Durán i Reynals in Barcelona, Spain, wrote. The results also call into question whether the age limit on AHCT is valid (a topic ASH Clinical News covered in November 2016, “For Transplants, Is Age Just a Number?”), and highlight the need “to assess comorbidity and frailty beyond age in older AHCT candidates.”

Dr. Sánchez-Ortega and authors collected information on consecutive patients ≥65 years of age undergoing AHCT who had data reported to the European Society for Blood and Marrow Transplantation (EBMT) registry between 2000 and 2014. A total of 21,390 patients undergoing AHCTs were analyzed, including 3,514 with second or subsequent procedures, from 515 EBMT centers in 45 countries.

The median patient age was 67 years (range = 65-89 years); 17,531 patients were ages 65 to 69 years old (group 1) and 3,859 were ≥70 years old (group 2).

Most patients (61%) were male, and patients had the following diagnoses:

  • multiple myeloma (62%)
  • lymphoproliferative disorders (30.5%)
  • acute leukemia (3.4%)
  • other (3.3%)

Nearly all patients (99%) received peripheral blood stem cells, and 10.3 percent had reduced-dose preparative regimens for advanced age. The median time from diagnosis to AHCT was 8.9 months (range = 5.9-18.7 months), and this was significantly longer for those in group 2 (9.4 vs. 8.8 months; p<0.001).

Neutrophil and platelet engraftment were achieved after a median of 12 days (range = 10-13 days) and 17 days (range = 14-22 days), respectively, and 1.4 percent of patients experienced primary or secondary graft failure. The most common post-AHCT complication was mucositis (occurring in 67.5% of patients), and veno-occlusive disease occurred in 0.8 percent of patients. The incidence of complications did not differ between age groups.

OS was 87 percent (95% CI 86.5-87.5) at one year post-AHCT, and 66.7 percent (95% CI 66.8-68.5) at three years post-AHCT. OS was significantly lower for patients in group 2 compared with group 1, both at one year (87.7% [95% CI 87.2-88.3] vs. 83.4% [95% CI 82-84.7]; p<0.001) and three years post-AHCT (69.1% [95% CI 68.2-70] vs. 60.8% [95% CI 58.8-62.9]; p<0.001).

The median follow-up for survivors was 15.3 months (range = 4.2-41.7 months). Causes of death included relapse or disease progression (76%), transplant-related mortality (9.4%), secondary malignancies (4.2%), and other (10.3%).

Rates of non-relapse mortality (NRM) were 4.9 percent (95% CI 4.6-5.2) at one year post-AHCT and 8.3 percent (95% CI 7.8-8.7) at three years post-AHCT.

Patients ≥70 years old were at a significantly greater risk for NRM than patients between 65 and 69 years old at both time points:

  • 1 year post-AHCT: 5.9% (95% CI 5.1-6.8) vs. 4.6% (95% CI 4.3-5; p<0.001)
  • 3 years post-AHCT: 7.8% (95% CI 7.4-8.3) vs. 10.4% (95% CI 9.2-11.6; p<0.001)

Overall incidence of relapse was 21.6 percent (95% CI 21-22) at one year and 50 percent (95% CI 50-51.8) at three years; again, this was significantly higher for those in group 2 at both time points:

  • 1 year post-AHCT: 20.6% (95% CI 19.9-21.3) vs. 26.6% (95% CI 25-28.2; p<0.001)
  • 3 years post-AHCT: 50% (95% CI 49-51) vs. 55% (95% CI 53-57; p<0.001)

While these results “confirm the feasibility of AHCT in older patients, with acceptable NRM and OS at one and three years overall,” the authors wrote, patients in age group 2 experienced significantly poorer outcomes.

The authors determined that several factors were associated with greater post-AHCT NRM risk and lower OS, including a diagnosis of chronic leukemia and a longer time from diagnosis to AHCT. See TABLE for other variables that affected NRM and OS.

Between 2000 and 2014, the rate of AHCT performed in the older population increased from 3.4 percent (n=443/13,163) to 9.8 percent (n=2,444/23,883; p<0.001), suggesting that, in real-world practice, clinicians are becoming more comfortable with recommending transplant for these patients. Dr. Sánchez-Ortega and authors noted that the study is limited by its retrospective registry design.


Reference

Sánchez-Ortega I, Basak GW, Beohou E, et al. Autologous hematopoietic cell transplantation in elderly patients aged 65 and older: A retrospective analysis by the complications and quality of life working party of the EBMT. Abstract #678. Presented at the 2016 ASH Annual Meeting, December 5, 2016; San Diego, CA.

TABLE. Analysis of Factors Related to NRM and OS
Covariables Hazard Ratio 95% CI p Value
NRM
Age increment in 5-year intervals 1.31 1.19-1.43 <0.0001
Diagnosis (compared with MM)
    Acute leukemia 1.98 1.58-2.48 <0.0001
    Chronic leukemia 2.58 1.75-3.82 <0.0001
    Lymphoma 1.55 1.39-1.73 <0.0001
    Other plasma cell disorders 1.49 1.17-1.88 0.001
Time from diagnosis to AHCT >12 months 1.22 1.10-1.35 0.0001
OS
Age increment in 5-year intervals 1.29 1.23-1.35 <0.0001
Diagnosis (compared with MM)
    Acute leukemia 2.23 2.01-2.49 <0.0001
    Chronic leukemia 1.47 1.14-1.89 0.003
    Lymphoma 1.23 1.16-1.30 <0.0001
Time from diagnosis to AHCT >12 months 1.08 1.02-1.13 0.006
Year of AHCT 0.98 0.97-0.99 <0.0001
NRM = non-relapse mortality; OS = overall survival; MM = multiple myeloma; AHCT = autologous hematopoietic cell transplantation

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