Treatment of Relapsed or Refractory Acute Lymphoblastic Leukemia in Real-World US Practices

BACKGROUND

Acute Lymphoblastic Leukemia (ALL) in adults is a rare malignancy associated with high rates of relapse and poor outcomes. Despite the availability of multi-agent chemotherapies and the recently-approved novel targeted therapy blinatumomab (BLINA), most adults with relapsed or refractory (R/R) ALL are unlikely to achieve remission, undergo hematopoietic cell transplant (HCT), and experience long-term survival. The objective of this study was to determine current real-world standard of care, patient characteristics, healthcare resource utilization, and outcomes for adult R/R ALL after first relapse. Here we report patient characteristics, treatment patterns, and outcomes for this population.

METHODS

We conducted a retrospective study using Symphony Health Solutions' Integrated Dataverse, a longitudinal transactional database that includes prescription, medical and hospital claims across > 4,900 US payers. Eligible patients were >15 yr, and had at least 1 ICD-9 or ICD-10 diagnosis code for ALL between Jan 1, 2009 and Aug 31, 2016. Adolescent and young adults were defined as age 15-39, adults > 40, induction therapies, and salvage regimens were based on NCCN ALL guidelines Ver 2, 2016. To identify patients receiving their 1^st salvage regimen (S1), the following criteria were applied: patients had at least 1 medical or 1 hospital claim 12 months prior to first ALL diagnosis, and either one prior induction or an ALL diagnosis of relapse or remission on or before the start of first identified induction. Those with prescriptions for a tyrosine kinase inhibitor were excluded to focus analyses on Philadelphia chromosome negative ALL only. Index date was the start of S1. A minimum of 90 days follow-up to study end was required. Patients who died prior to the end of minimum follow up were also included. Baseline comorbidities and the Charlson Age-adjusted Comorbidity Index (CCI) were analyzed for up to 6 months prior to index date. We categorized the most frequently-used S1 regimens, with regimens representing <10% of the sample grouped as "other". Summary statistics were reported.

RESULTS

588 R/R ALL patients receiving a S1 regimen met the inclusion/exclusion criteria. Median duration of follow-up was 415 days (range 7-700). Median age was 37 (range 15-87), with 54% aged 15-39, 46% aged >40, and a slight male predominance (57% vs 43%). The 4 most commonly used S1 regimens were BLINA 33%, liposomal vincristine (LV 19%), nelarabine (NEL 12%), and hyper-CVAD (HCVAD 10%). BLINA was commonly used among patients >40 (41%; 113 patients/273 Total), although LV was most frequently used in patients > 65 (41%; 32 patients/78 Total). Patients receiving LV and BLINA were the oldest (median 49 and 47 yr, respectively). Patients on HCVAD were the youngest (median 30 yr).HCT use pre-S1 (23%) and post-S1 (22%) was highest in NEL patients. Overall, post-S1 HCT use was low (11%), and was lowest after BLINA (7%) (Table 1).

At baseline, CCI was highest (mean 4.5) for patients receiving LV (mean 3.9, 3.8, and 4.0 for BLINA, HCVAD, and NEL, respectively). As expected, most patients suffered from bone marrow insufficiency, including anemia, neutropenia, and thrombocytopenia, with patients on HCVAD having the highest prevalence. Corresponding constitutional and gastrointestinal (GI) problems were also prevalent, including fever, nausea, fatigue, headache, cough, pain (back, abdominal, extremities), constipation, diarrhea, dehydration, and infections (pneumonia, sepsis, bacteremia). Anxiety and depression were frequent. Comorbidities associated with advanced age, such as hypertension, diabetes, and congestive heart failure (CHF) were the lowest among patients on HCVAD and higher for patients on LV and NEL (Table 2).

CONCLUSIONS

The burden of illness for adults with R/R ALL is high. This real-world study suggests that age and comorbidities may be associated with choice of S1 therapy. Overall, BLINA was the most common S1 choice. Patients treated with HCVAD were younger, had higher hematological burden, and lower age-related comorbidities. Patients receiving LV were older, had lower hematological disease burden, but a higher overall CCI. HCT rates were low after all S1 therapies, with BLINA having the lowest rate despite being the newest, most commonly used option. It would be important to determine resource utilization, cost and outcomes of various treatment choices.

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