The addition of etoposide to cyclophosphamide, doxorubicine, vincristine, and prednisone chemotherapy (CHOP) improved overall survival (OS) in patients with ALK+ anaplastic large T-cell lymphoma (ALCL) but not other disease subtypes, according to a study published in Blood. In other subtypes of peripheral T-cell lymphomas (PTCLs), consolidation with autologous hematopoietic cell transplant (AHCT) in the first line significantly increased OS.
PTCLs are a group of rare diseases that consist of many different subtypes, explained lead author Mirian Brink, MD, PhD, of Netherlands Comprehensive Cancer Organization.
“There is a paucity in evidence supporting treatment guidelines. Daily care treatment practices differ worldwide,” Dr. Brink said.
In the Netherlands, CHOP with the addition of etoposide (CHOEP) has been the standard of care for the past decade with consolidative AHCT in fit patients. However, prospective randomized trials regarding the effect of etoposide and AHCT are lacking.
“In general, the outcome of PTCL is poor,” Dr. Brink said. “Hence, there is an urgent medical need for more effective treatments. Most trials in PTCL are not properly powered to address the [effect of new] treatments among subtypes.”
To help improve this, Dr. Brink and colleagues conducted a nationwide, population-based study identifying all patients ages 18-64 with ALCL, angioimmunoblastic T-cell lymphoma (AITL), and peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) diagnosed between 1989 and 2018. Patients were grouped by two time periods: pre- and post-etoposide and AHCT. The study included 1,427 patients: 35% with ALCL, 21% with AITL, and 44% with PTCL-NOS.
The five-year OS increased from 39% in the pre-era to 49% in the post-era (p<0.02). For the entire cohort, the five-year OS was 43% and was superior in those patients treated with CHOEP compared with CHOP (64% vs. 44%; p<0.02).
“Our study showed that only patients with ALK+ ALCL actually benefit from the addition of etoposide to CHOP, whereas patients with other PTCL subtypes did not,” Dr. Brink said.
The complete response rate was 86% for patients with this subtype who received CHOEP compared with 61% for CHOP (p=0.03). Specifically, when adjusted for subtype, international prognostic index (IPI) score, and AHCT, the risk for mortality was 6.3 times higher in patients with ALK+ ALCL when treated with CHOP compared with CHOEP.
For ALK- ALCL, AITL, and PTCL-NOS, the complete remission rate in patients receiving CHOEP was also higher compared with CHOP but with borderline statistical significance (60% vs. 49%; p=0.06).
According to Dr. Brink, because patients with other PTCL subtypes did not see a similar benefit, they “should not be routinely treated with CHOEP.”
In a landmark analysis, the five-year OS for consolidation with AHCT was 78% compared with 45% for induction chemotherapy (p<0.01). Among patients who achieved complete remission, those consolidated with AHCT had a superior five-year OS of 82% compared with 47% for patients not receiving transplant (p<0.01), supporting the use of AHCT for fit patients younger than 65.
“Overall, this population-based study provides data to guide clinical decision-making [on] whether to implement etoposide and consolidative AHCT in first-line treatment of the three most prevalent subtypes of PTCL, thereby accounting for the subtype of PTCL a patient is diagnosed with,” Dr. Brink said. “Our data show that the positive effect of etoposide was beneficial only in ALK+ ALCL but not in ALK- ALCL, AITL, or PTCL. This should be taken into account for future studies.”
Study limitations relate to the lack of detailed information on first-line treatment from 1989 to 2013 and the lack of information on comorbidities, relapse, and subsequent therapy lines, as well as the potential misclassification of one subtype of PTCL to another. Further, standard of care in ALK+ ALCL has evolved with the availability of brentuximab vedotin, making it difficult to clarify optimal treatment.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Brink M, Meeuwes F, van der Poel M, et al. Impact of etoposide and ASCT on survival among patients <65 years with stage II-IV PTCL; a population-based cohort study. Blood. doi: 10.1182/blood.2021015114.