Survival improvement of patients with chronic lymphocytic leukemia (CLL) in routine care 1995–2017

Figures & data

Table 1. Patient characteristics.

	TOTAL		Diagnosis 2001 or earlier		Diagnosis 2002–2008		Diagnosis 2009–2017
Age at diagnosis	N = 724		N = 258		N = 233		N = 233
median/range	67 years	35–92 years	65 years	35–86 years	68 years	39–92 years	70 years	41–92 years
Age groups	N	%	N	%	N	%	N	%
<65 years	286	39.5	122	47.3	84	36.1	80	34.3
65–69 years	131	18.1	48	18.6	51	21.9	32	13.7
70–75 years	129	17.8	50	19.4	39	16.7	40	17.2
>75 years	178	24.6	38	14.7	59	25.3	81	34.8
Sex	N = 724		N = 258		N = 233		N = 233
male	427	59.0	150	58.1	140	60.1	137	58.8
female	297	41.0	108	41.9	93	39.9	96	41.2
Stage at diagnosis	N = 724		N = 258		N = 233		N = 233
Binet A	556	76.8	197	76.4	184	79.0	175	75.1
Binet B	91	12.6	26	10.1	33	14.2	32	13.7
Binet C	36	5.0	13	5.0	9	3.9	14	6.0
not available	41	5.7	22	8.5	7	3.0	12	5.2
ECOG performance status at diagnosis	N = 442		N = 81		N = 157		N = 204
ECOG ≤1	395	89.4	72	88.9	143	91.1	180	88.2
ECOG ≥2	47	10.6	9	11.1	14	8.9	24	11.8
Age adjusted Charlson Comorbidity Index (aaCCI)	N = 683		N = 232		N = 225		N = 226
aaCCI 2–3	132	19.3	54	23.3	39	17.3	39	17.3
aaCCI 4	180	26.4	68	29.3	59	26.2	53	23.5
aaCCI 5	160	23.4	53	22.8	60	26.7	47	20.8
aaCCI 6–11	211	30.9	57	24.6	67	29.8	87	38.5

Table 2. 1st line, 2nd line and 3rd line therapies according to the period of CLL diagnosis.

	1st line								2nd line								3rd line
	TOTAL		Diagnosis 2001 or earlier		Diagnosis 2002–2008		Diagnosis 2009–2017		TOTAL		Diagnosis 2001 or earlier		Diagnosis 2002–2008		Diagnosis 2009–2017		TOTAL		Diagnosis 2001 or earlier		Diagnosis 2002–2008		Diagnosis 2009–2017
	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%
bendamustine	14	4.2	2	1.3	5	4.4	7	9.6	14	6.6	5	4.3	8	11.9	1	3.3	7	5.4	4	5.2	2	4.7	1	10.0
bendamustine + mitoxantrone (BM)	6	1.8	3	2.0	3	2.7	0	0.0	48	22.5	40	34.5	8	11.9	0	0.0	13	10.0	11	14.3	2	4.7	0	0.0
bendamustine + rituximab (BR)	51	15.2	6	4.0	25	22.1	20	27.4	22	10.3	7	6.0	12	17.9	3	10.0	11	8.5	4	5.2	5	11.6	2	20.0
bendamustine + mitoxantrone +  rituximab (BMR)	14	4.2	1	0.7	6	5.3	7	9.6	33	15.5	18	15.5	13	19.4	2	6.7	34	26.2	23	29.9	10	23.3	1	10.0
chlorambucil	149	44.5	114	76.5	34	30.1	1	1.4	8	3.8	2	1.7	4	6.0	2	6.7	5	3.8	4	5.2	1	2.3	0	0.0
chlorambucil + obinutuzumab	11	3.3	0	0.0	4	3.5	7	9.6	2	0.9	0	0.0	0	0.0	2	6.7	1	0.8	0	0.0	1	2.3	0	0.0
cyclophosphamide	0	0.0	0	0.0	0	0.0	0	0.0	3	1.4	1	0.9	2	3.0	0	0.0	2	1.5	2	2.6	0	0.0	0	0.0
cyclophosphamide + vincristine +  prednisone (COP)	3	0.9	2	1.3	1	0.9	0	0.0	5	2.3	5	4.3	0	0.0	0	0.0	2	1.5	2	2.6	0	0.0	0	0.0
CHOP	1	0.3	1	0.7	0	0.0	0	0.0	1	0.5	1	0.9	0	0.0	0	0.0	3	2.3	3	3.9	0	0.0	0	0.0
R-CHOP	5	1.5	1	0.7	0	0.0	4	5.5	4	1.9	1	0.9	2	3.0	1	3.3	0	0.0	0	0.0	0	0.0	0	0.0
fludarabine	7	2.1	5	3.4	2	1.8	0	0.0	20	9.4	20	17.2	0	0.0	0	0.0	4	3.1	3	3.9	0	0.0	1	10.0
fludarabine + cyclophosphamide (FC)	23	6.9	6	4.0	16	14.2	1	1.4	3	1.4	2	1.7	1	1.5	0	0.0	2	1.5	0	0.0	2	4.7	0	0.0
fludarabine + cyclophosphamide +  rituximab (FCR)	31	9.3	4	2.7	13	11.5	14	19.2	10	4.7	2	1.7	5	7.5	3	10.0	12	9.2	8	10.4	4	9.3	0	0.0
ibrutinib	4	1.2	0	0.0	0	0.0	4	5.5	5	2.3	1	0.9	4	6.0	0	0.0	4	3.1	2	2.6	1	2.3	1	10.0
idelalisib + rituximab	0	0.0	0	0.0	0	0.0	0	0.0	3	1.4	1	0.9	1	1.5	1	3.3	1	0.8	0	0.0	0	0.0	1	10.0
rituximab	4	1.2	0	0.0	1	0.9	3	4.1	11	5.2	1	0.9	2	3.0	8	26.7	20	15.4	9	11.7	9	20.9	2	20.0
alemtuzumab	2	0.6	1	0.7	0	0.0	1	1.4	1	0.5	0	0.0	0	0.0	1	3.3	2	1.5	0	0.0	1	2.3	1	10.0
prednison/prednisolone	1	0.3	0	0.0	0	0.0	1	1.4	2	0.9	1	0.9	1	1.5	0	0.0	1	0.8	0	0.0	1	2.3	0	0.0
others	9	2.7	3	2.0	3	2.7	3	4.1	18	8.5	8	6.9	4	6.0	6	20.0	6	4.6	2	2.6	4	9.3	0	0.0
SUM	335	100	149	100	113	100	73	100	213	100	116	100	67	100	30	100	130	100	77	100	43	100	10	100

Figure 1. Overall survival, defined as time between treatment start and death/last contact in years, for patients who had CLL treatment 2001 or earlier, between 2002 and 2008 or between 2009 and 2017.

Figure 2. Overall survival, defined as time between treatment start and death/last contact in years, for patients with chemoimmunotherapy with an anti-CD20 monoclonal antibody and for patients without chemoimmunotherapy.

Table 3. Output of the Cox regression model.

Variables	Estimates
	beta	standard error	p-value	hazard ratio	95% confidence interval
Age	0.052	0.015	0.001	1.054	1.023	1.086
Sex	0.201	0.198	0.309	1.223	0.830	1.802
Binet A			<0.001
Binet B	0.756	0.247	0.002	2.130	1.312	3.460
Binet C	1.320	0.352	<0.001	3.743	1.878	7.461
aaCCI	0.083	0.097	0.388	1.087	0.899	1.314
ECOG 0			<0.001
ECOG 1	0.152	0.220	0.490	1.164	0.756	1.793
ECOG 2-3	1.098	0.254	<0.001	2.998	1.822	4.932
No CLL therapy			0.040
CLL therapy without anti-CD20 antibody	0.686	0.285	0.016	1.986	1.137	3.469
CLL therapy including anti-CD20 antibody	0.438	0.229	0.056	1.550	0.990	2.428