Are Adolescents and Young Adults (AYA) with Acute Lymphoblastic Leukemia (ALL) Receiving Pediatric or Adult ALL Regimens: A Population-Based Statewide Evaluation of the Approach to AYA ALL across Pediatric and Adult Cancer Centers

Background:

Abundant evidence suggests that AYA with ALL have improved outcomes when treated following pediatric-inspired, as opposed to adult, ALL chemotherapy regimens. Given the complexity of pediatric ALL protocols, it is unclear whether this approach has been universally accepted by medical oncologists treating AYA ALL patients across the population.

Methods:

The population-based California Cancer Registry (CCR) was used to evaluate socio-demographics, location of ALL induction therapy (adult- vs pediatric-setting), and therapies administered to AYAs (15-39 years) with ALL newly diagnosed and treated in the state of California between 2004-2014. Specific ALL regimens were determined through abstraction of registry treatment text fields. Facility volume was defined as AYA ALL inductions per year and categorized by quartiles (≥7/year highest and <1/year lowest). Chi-square and student t-tests characterized differences by patient demographics, treating facilities, and treatment regimens. Multivariable logistic regression was performed to examine the association of the sociodemographic and clinical factors with receipt of pediatric-inspired ALL regimen at an adult cancer center, adjusted for clustering by induction facility. Results are presented as adjusted odds ratios (OR) and associated 95% confidence intervals (CI).

Results:

Of 1591 AYAs with ALL, 61% were treated in an adult oncology-setting and 28% were treated in a pediatric-setting. Treatment setting could not be determined in 11% (n=175) of patients who were excluded from additional analyses. 32% of patients were 15-18 years, 39% were 19-29 years, and 29% were 30-39 years. The majority of patients were males (64%), of Hispanic race/ethnicity (64%), and had public (46%) or private (44%) insurance. AYAs who were younger (P<0.001), diagnosed in more recent years (P=0.03), and those with public insurance (P= 0.01) were more likely to receive induction treatment in a pediatric-setting. 59% and 41% of AYAs treated in a pediatric- versus adult-setting, respectively, received induction therapy at an NCI-designated cancer center (P<0.001). Only 5% of AYAs treated in the pediatric-setting received care at low volume (<1 AYA ALL case per year) facilities, whereas 27% of AYAs treated in the adult setting received care at low volume facilities (P<0.001). ALL treatment regimen was evaluable in 1131 (79%) of patients and revealed that amongst AYAs treated in the adult-setting, 22% received pediatric-inspired and 78% received adult ALL regimens over the decade. Although pediatric-inspired regimens were administered more frequently by medical oncologists over-time, 62% of AYAs treated by medical oncologists from 2013-2014 received adult ALL regimens, with Hypercvad used most commonly (70%). Multivariable regression revealed that younger patient age (19-24 vs 35-39 years: OR 2.1, 95% CI 1.4-3.2), treatment at an NCI-designated cancer center (OR 5.3, 95% CI 2.5-11.3), and treatment at higher volume AYA ALL facility (mid quartile versus lowest quartile: OR 2.3, 95% CI 1.0-5.2; highest quartile versus lowest quartile: OR 7.4, 95% CI 2.7-20.4) were significantly associated with receipt of pediatric-inspired ALL regimens by medical oncologists; whereas, year of diagnosis, sex, race/ethnicity, and insurance had no significant association.

Conclusions:

Our population-level findings demonstrate that AYAs with ALL across the state of California are most commonly treated in adult oncology community settings where the volume of AYA ALL patients seen on a yearly basis is frequently very low. Strikingly, as recently as 2014, AYAs with ALL continue to be treated predominantly with adult ALL regimens. Receipt of pediatric-inspired ALL regimens is significantly more likely if AYAs with ALL receive treatment at NCI-designated cancer centers and/or centers that treat a higher yearly volume of AYA ALL patients.