Adolescent and young adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia experienced varying outcomes when treated with pediatric-inspired protocols and adult chemotherapy regiments such as hyperCVAD/MA.
Adolescent and young adult (AYA) patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) experienced varying outcomes when treated with pediatric-inspired protocols (PIPs) and adult chemotherapy regiments such as hyperCVAD/MA (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with methotrexate and cytarabine), according to data presented at the Society of Hematologic Oncology 2023 Annual Meeting.
The two-year event-free survival (EFS, the time following treatment where a patient experiences no cancer-related complications) was 65.8% — 80.6% for patients who received PIP and 52.6% for patients treated with hyperCVAD.
Among the 103 total evaluable patients in the single-center retrospective review, the two-year recurrence-free survival (RFS, the time following treatment without any signs or symptoms of cancer) was 75.6%, in which 93.7% of patients received PIP and 59.6% of patients received hyperCVAD.
HyperCVAD/MA is a regimen used for the treatment of adult patients with Ph-negative ALL. Pediatric patients, however, receive modified treatments, most of which feature higher doses of asparaginase (a chemotherapy drug) and corticosteroids (an anti-inflammatory medication).In the analysis, investigators compared treatment outcomes of 57 patients treated with hyperCVAD with 56 patients treated with a PIP across the phase 2 CALGB 10403 trial and the phase 3 GRAALL-2005 trial.
Although overall survival (OS, the time a patient lives following treatment) outcomes were numerically improved among those who received a PIP vs. hyperCVAD, the difference was not statistically significant, explained Omar Shahin, who presented the data during the meeting. The two-year OS rate for all treated patients was 72.2%, with patients in the PIP group having a two-year OS rate of 80.3% vs. 65.7% for those in the hyperCVAD arm.
“Pediatric-based treatment protocols lead to better two-year EFS and RFS than hyperCVAD for AYA patients with Ph-negative ALL … (and) prospective trials comparing both adult treatment and PIPs are warranted,” Shahin, a medical oncologist at the King Hussein King Hussein Cancer Foundation and Center in Cairo, Jordan said. “Over the past decades, researchers have identified a distinct group known as AYAs with ages between 15 and 39 years. This group has higher survival rates than adults but lower rates than children (and) this (has) prompted many research groups to evaluate pediatric-inspired regimens in the treatment of AYA patients with ALL.”
Shahin showed that in an analysis of SEER data, the five-year survival rates of patients with ALL aged younger than 15 years was 92.1% compared with 77% among those aged 15 to 19 years, 66.8% among those aged 20 to 39 years and 43% among those aged 40 to 64 years.
The analysis evaluated outcomes from patients ages 18 to 39 years treated at King Hussein Cancer Center between 2010 and 2022. Shahin noted that baseline characteristics were well-balanced between the groups. Overall, most patients were men (77.9%), had T-cell ALL (63.8%) or B-cell ALL (36.2%), and cytogenetic risk factors as follows: diploid (51.3%), other (16.8%), failed (11.5%), unknown (20.4%). High-risk disease was reported in 4.4% of patients.
A notable difference was observed in age. Among those who were treated with a PIP, the median age was 23 years vs. 27 years for those who received hyperCVAD. This was deemed significant.
“Looking at secondary outcomes, almost 93% of all patients (92.8%) achieved complete remission (CR) at the end of induction with no difference between the groups and we had eight (patients with) refractory disease distributed evenly between the hyperCVAD group and the PIP (group),” Shahin said.
Other outcomes included 22.5% of patients having relapse, with 22 patients who received hyperCVAD (38.6%) experiencing disease relapse versus three patients in the PIP group (5.6%) for a statistically significant difference. Extramedullary (outside of the bone marrow) relapse occurred in the central nervous system in five patients, all of whom were in the hyperCVAD group. Other sites of extramedullary relapse included skin, lymph nodes, lungs and testicular sites and were reported in four patients in the hyperCVAD group (7%) and two patients in the PIP group (3.7%).
Overall, 23.9% of patients received allogeneic stem cell transplant, which included 16 patients in the hyperCVAD group and 11 patients in the PIP group. Among the 27 patients, the primary indications for proceeded to transplant were high-risk characteristics, refractory disease, relapse or unknown. None of these were statistically significant between the groups.
Outcomes at last follow-up deemed statistically significant included CR and relapse. In the hyperCVAD group, the CR rate at last follow-up was 71.9% compared with 89.1% in the PIP group. The relapse rate was 28.1% vs. 7.3% in the hyperCVAD and PIP groups, respectively.
“We had two unfortunate deaths during induction, and both of those occurred during induction with PIP, one (because of) liver failure and cerebral hemorrhage and one (because of) septic shock,” Shahin said. “We had 11 deaths during CR occurring during maintenance or consolidation distributed evenly between both the groups with no significant difference (and) most of these death(s) occurred (because) of neutropenic complications, with (others attributed to) COVID-19 and GVHD (graft-vs-host disease).”
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