Clinical Trials Underestimate Age of Chronic Myeloid Leukemia (CML) Patients: Epidemiological Study in a Representative Area in Germany.

Abstract

Epidemiological information on chronic myeloproliferative disorders (CMPD), notably Philadelphia (Ph) and/or bcr/abl positive chronic myeloid leukemia (CML), is rare. National cancer registries and clinical trials differ with regard to median age of CML patients by 10 to 20 years (Table). Therefore, an evaluation was conducted in a defined area in Germany between 1998 and 2000 to determine incidences and compare clinical characteristics of Ph and/or bcr/abl positive CML patients participating and not participating in trials. 68 (37.4%) hospitals and 241 specialty practices (16.4%) reported 893 newly diagnosed CMPD patients. CML patients represented 24.9% of all cases with CMPD. The crude incidence of CML cases (n=218) was 0.79, that of the 172 Ph and/or bcr/abl positive CML cases 0.62 and that of CMML (n=61) 0.22. The incidence of CML and CMML cases combined was 1.01. 110 (64.0%) of the 172 Ph and/or bcr/abl positive CML patients participated in clinical studies, mainly CML Studies III and IIIA of the German CML Study Group. Median age was significantly different between patients participating and not participating in clinical trials: (54.1 vs. 64.8 years, p=0.0001). The chance for a Ph and/or bcr/abl positive CML patient < 65 years to be enrolled in a clinical study was 3.8 times higher than for a CML patient ≥ 65 years (OR=3.8, CI: 1.9–7.3). Male patients had a slightly higher probability to be enrolled in a study than females (OR=1.5 (CI: 0.8–2.8)). Our data indicate that 36% of the Ph and/or bcr/abl positive CML patients registered in a defined area of Germany are not treated in clinical trials, that elderly patients have a lower probability to be included in trials than younger patients and that patients participating in trials are 10.7 years younger than those who do not.Age of CML Patients in Population based Registries and in Clinical TrialsA) RegistriesAge mean (years ± S.D.) /Thames Cancer Registry, U.K.65 (20–98)SEER Cancer Statistics Review, 1975–200468 (range not available)SEER cancer statistics review, 1973–199864 (range not available)B) TrialsThe Italian Cooperative Study Group on Chronic Myeloid Leukemia. N Engl J Med 199448 ± 14Hehlmann et al., Blood 199448 (17–85)Guilhot et al., N Engl J Med 199750 (7–70)Hasford et al., JNCI 199849 (10–85)The Benelux CML Study Group. Blood 199856 (20–83)Baccarani et al., Blood 200245 ± 13Hehlmann et al., Leukemia 200348 (10–83)O'Brien et al., N Engl J Med 200350 (18–70)Hehlmann et al., Blood 200749 (11–90)