PS1404 RELATIONSHIP BETWEEN COMORBIDITY AND ELIGIBILITY CRITERIA FOR CLINICAL TRIALS IN MULTIPLE MYELOMA. A CRITICAL APPRAISAL

• Published in: HemaSphere Vol. 3; no. S1; pp. 644 - 645
• Main Authors: Persona, E. Pérez, Ormategui, I. Oiartzabal, Viñaspre, A. Vega González, Cilaurren, A. Unamunzaga, López, A. Santamaría, Castro, D. Robles, Miguel Sánchez, C., Palomares, L. Cuevas, Jalón, M. Gabilondo, Navarro, G.A. Mendez, Salinas, I.M. Parra, Herrero, C. Pisón, Castro, J.M. Guinea
• Format: Journal Article
• Language: English
• Published: 01.06.2019
• ISSN: 2572-9241; 2572-9241
• DOI: 10.1097/01.HS9.0000563892.11907.79

Background: Approval of new standards of treatment in cancer is preceded by phase III clinical trials that provide information on safety and efficacy. Nevertheless, excessive rigidity eligibility criteria may compromise extrapolation of results to the target population (external validity). Klausen et al (Leukemia 18), report that over 60% of patients diagnosed of multiple myeloma (MM) would not fulfill eligibility criteria for clinical trials. So, safety and efficacy data may differ from clinical trials to real life. Aims: The aim of our study is to assess the correlation between patient comorbidities by Cumulative Illness rating score (CIRS) score and eligibility in clinical trials. Methods: Eligibility criteria of 3 commercial (VISTA, FIRST, ALCIONE) and 2 academic clinical trials (GEM05MAS65 and GEM10MAS65) were verified for all patients with newly diagnosed transplant‐ineligible multiple myeloma (TIMM) at Hospital Universitario de Araba (Spain). CIRS score was calculated for all de patients. Results: From February 2010 to December 2017, 143 MM patients were diagnosed. Of them, 92 patients (64%) were transplant‐ineligible and were treated with a bortezomib‐melphalan‐prednisone scheme. For TIMM patients median age was 77 years old, higher than published trials (median age VISTA: 71, FIRST: 73, ALCIONE: 71, GEM05: 73, GEM10: 75). CIRS score identify different prognostic groups in overall survival: CIRS <4: 52.3 months; CIRS 4 to 8: 57 months and CIRS> 8: 13.5 months (p: 0.017) (figure 1). Applying eligibility criteria, clinical trials result in high exclusion rates: VISTA: 75% FIRST: 70%; ALCIONE 75%; GEM05: 75%; GEM10: 77%. Considering only external validity criteria, exclusion rate was slightly lower: VISTA: 59%; FIRST: 46%; ALCIONE 59%; GEM05: 58%; GEM10: 62%. Regarding comorbidities, no correlation among CIRS score and possibility to be included in clinical trials was observed, although high exclusion was observed for patients with CIRS score >8 vs ≤8 (VISTA 77% vs. 54%; FIRST: 50% vs. 44%; ALCIONE 67% vs. 56%; GEM05: 72% vs. 54%; GEM10: 83% vs. 57%, respectively) (table 1). The presence of grade 3 or 4 comorbidities was not associated with higher exclusion rates. Summary/Conclusion: Eligibility criteria in multiple myeloma clinical trials are excessively restrictive, and do not reflect comorbidities of the patients. Safety and efficacy of recently approved drugs and combinations schemes for treatment of newly diagnosed TIMM in real life may differ from those reported on clinical trials. Selection criteria of clinical trials must be updated and adapted to reality.