Post-Transplant High-Dose Chemotherapy Increases Risk of Toxicities in Older Patients with Lymphoma

Most patients with lymphoma who are over age 60 experience cardiovascular toxicities with high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT), but these patients tend to have similar 100-day and one-year non-relapse mortality, compared with younger patients, according to a study published in Blood Advances.

High-dose chemotherapy after AHCT, either as frontline therapy or in the relapsed/refractory setting, is an established therapeutic strategy for patients with lymphoma. Despite its efficacy, some studies suggest this approach may increase the risk of non-relapse mortality in patients older than 60. In addition, few studies have been conducted to examine the risk-benefit ratio of post-AHCT high-dose chemotherapy in patients ≥70 years old.

In the study, led by Parastoo Dahi, MD, of Memorial Sloan Kettering Cancer Center (MSKCC), investigators retrospectively examined the toxicities associated with carmustine, etoposide, cytarabine, and melphalan (BEAM), and AHCT in 346 older patients with non-Hodgkin lymphoma (NHL). The patients were stratified by age:

  • 60 to 69 years (median age=64.8 years; n=279)
  • ≥70 years (median age=71.8 years; n=67)

Patients in this study underwent BEAM and AHCT between 2000 and 2018 at MSKCC. At the time of AHCT, a total of 136 patients had diffuse large B-cell lymphoma, 119 had mantle cell lymphoma, 21 had follicular lymphoma, 61 had T-cell NHL, and nine had other NHL subtypes.

The median age was 65.8 years, ranging from 60 to 77 years at the time of AHCT. Approximately 51.7% of patients (n=179) received upfront consolidative AHCT. More than half of the cohort (54.6%) received two or more lines of therapy before transplant. A total of 37 patients (10.5%) received radiation therapy prior to AHCT.

The majority of patients (n=302) received an induction regimen comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen. A combination of ifosfamide, carboplatin, and etoposide was the most common salvage therapy used in 109 patients.

Chemosensitive disease was reported in all patients. At baseline, both age groups had similar histology distribution, number of prior lines of therapy, remission status, hematopoietic cell transplantation comorbidity index, Karnofsky performance status, albumin level, and stem cell dose.

During the median follow-up period of 6.5 years, many patients developed severe toxicities. The median number of toxicities per patient in the older and younger groups were three and two, respectively.

Febrile neutropenia, gastrointestinal, infections, and cardiovascular toxicities were the most common severe toxicities reported in the overall population. Compared with the younger cohort, older patients had a significantly higher risk of grade ≥3 cardiovascular toxicities (hazard ratio [HR]=3.36; 95% CI 2.25-5.00; p<.001) and cutaneous toxicities (HR=2.45; 95% CI 1.08-5.54; p=0.032).

In patients age 70 and older, the non-relapse mortality rate at 100 days was 2.99% (95% CI 0.55-9.32), while the two-year non-relapse mortality rate in these patients was 6.2% (95% CI 1.97-13.95). The younger patients had 100-day and two-year respective non-relapse mortality rates of 1.79% (95% CI 0.68-3.92) and 2.91% (95% CI 1.37-5.42).

In an analysis adjusted for the number of grade 3 or higher toxicities within the first 100 days of transplant, patients age 70 and older had a 1.71-fold (95% CI 1.08-2.71) higher risk of disease progression or death compared with younger patients.

According to a univariable regression analysis in the older cohort, those in partial remission had no increased risk of mortality (HR=2.26; 95% CI 0.96-5.32), relapse (HR=2.21; 95% CI 0.94-5.22), or death or progression (HR=1.71; 95% CI 0.74-3.94) compared with patients in complete remission.

Limitations of this study include its retrospective design and the relatively small number of patients in the older cohort. Additionally, as only patients who proceeded to AHCT were included, these findings may not generalize to older patients with NHL who do not undergo transplant due to age, toxicity, comorbidity, or disease progression.

The authors report no relevant conflicts of interest.

Reference

Dahi PB, Lee J, Devlin SM, et al. Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma. Blood Adv. 2021;5:2608-2618.