Need for Patient Reported Outcomes (PRO) in Adult Acute Lymphoblastic Leukemia (ALL)

Abstract

AbstractAbstract 4704 Background:Acute lymphoblastic leukemia (ALL) accounts for about 20% of adult leukemias and occurs with increasing frequency in adults after 50 years of age. Symptoms include bone and joint pain, increased bruising and bleeding, weakness or tiredness, fever, loss of appetite and weight loss, paleness, pain or feeling of fullness below the ribs, pinpoint red spots on the skin (petechiae), lymphadenopathy, and night sweats. For adult ALL, appropriate induction therapy can result in complete remission in 60–80% of patients, with between 35–40% of adult patients expected to survive 2 years. Aggressive induction combination chemotherapy requires effective supportive care to manage infection, bleeding, and other concomitant issues. These treatment-related symptoms, combined with the disease symptoms argue for measurement tools that provide a clear understanding of the impact on the patients’ health-related quality of life (HRQOL), record changes over time, and can demonstrate clinical benefit in trials. The objective of the study was to describe and assess the PRO instruments that can be used in adult ALL setting, summarize PRO’s in clinical trials, and evaluate the labeling potential when using these measures for patient self-report in adult ALL, particularly as it relates to selecting and implementing PROs and interpreting data. Methods:An in depth literature review was conducted. Elsevier and Medline databases were consulted using Embase platform. Studies were included if they were: published from 01/01–12/11, in English, and included terms related to leukemia disease and PROs. A thorough review of abstracts was performed using selection criteria including those where PRO instruments were used and/or psychometric validation was performed. References for selected articles were used to identify other relevant sources. Clinical trials.gov was also used to search for adult ALL trials from 2001–2011. Results:Very few studies were found specific to HRQOL and adult ALL, although the broader search for HRQOL in leukemia found 15 PRO instruments: 4 leukemia-specific, 5 on treatment-related impact, and 6 on general cancer HRQOL. (Table 1a). 1245 studies in clinicaltrials.gov were found using the search term adult acute lymphocytic leukemia. This was reduced to 11 studies when QOL was requested as an endpoint and age was restricted to 21 and above. Of those, there was 1 observational study and 10 intervention studies. HRQOL instruments were not identified in 8 of the studies. The QLQ-C30, EQ-5D, HADS, and NCCN distress thermometer were used in 1 phase 2 and 2 phase 3 studies (Table 1b). No specific labeling claims were found in labels made to date for adult ALL related compounds to FDA or EMA.Table 1aSummary of PRO instruments used in leukemiaPRO instruments# Items/QuestionsValidation (Yes/No)Leukemia specificMedical Research Council QLQ-Leu32NFACT-Leu44YLIP (Life Ingredient Profile)51YEORTC QLQ CLL 1616OngoingTreatment relatedQLQ Leu BMT32NFACT-BMT50YDBMT (Demands of BMT Recovery Inventory)59NFACT-BRM40YHADS14YCancer specificEORTC QLQ C3030YFACT-G27YFLIC22YCARES (CARES –SF)139 (59)YNCCN distress thermometerSingle item scaleYTable 1b:Summary of PRO instruments used in ongoing adult ALL clinical trialsPRO InstrumentsComparatorPopulation/PhaseHADS, NCCN distress thermometerKetamine HCl/PlaceboAdult ALL in remission, recurrent adult ALL with neuropathic pain/P3EORTC QLQ C30, EQ-5Dinotuzumab ozogamicin/FLAG (fludarabine, cytarabine, and G-CSF) or HIDAC (high dose cytarabine) or cytarabine and mitoxantroneRelapsed or Refractory CD22-Positive ALL/P3EORTC QLQ C30lenalidomide + dexamethasoneRefractory B-cell lineage ALL or Relapse after 2 lines of treatment/P2 Conclusions:Several instruments contain only general cancer related symptoms, but omit most ALL specific symptoms. While there are some leukemia specific measures, most ongoing adult ALL trials are using only cancer specific instruments. The lack of leukemia-specific measures in adults with ALL, argues for the need to understand the patient's burden of disease and impact of ALL treatment. A detailed evaluation of existing instruments and instrument development/modification is needed with a goal of influencing patient-centered outcomes and product differentiation. Disclosures:Mehta:Sanofi: Employment. Joulain:Sanofi: Employment, Equity Ownership. Hageman:Sanofi: contract employment Other. Trask:Sanofi: Employment.