Treatment of Diffuse Large B-Cell Lymphoma and Preexisting Congestive Heart Failure: A Retrospective Analysis from Moffitt Cancer Center TCC Database

Introduction: The treatment of choice for newly diagnosed patients with advanced diffuse large B-cell lymphoma (DLBCL) is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) [Feugier P, Van Hoof A, Sebban C et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 2005; 23: 4117-4126]. Anthracycline-based treatment is also superior to other drugs in controlling disease and prolonging survival in elderly patients [Hershman DL, McBride RB, Eisenberger A et al. Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma. J Clin Oncol 2008; 26: 3159-3165], however these individuals frequently have concomitant cardiac comorbidities such as congestive heart failure (CHF) that preclude the use of these agents. 

Methods: A search of the Moffitt Total Cancer Care™ database between January 1^st 2008 and December 31^st 2014 identified a cohort of 854 adult patients with a diagnosis of DLBCL. We performed a retrospective chart review of these patients and identified 40 individuals with documented CHF prior to the initiation of chemotherapy, due to either systolic (ejection fraction less than 50%) or diastolic dysfunction. The primary aim was to determine the chemotherapy regimens given to patients with DLBCL and CHF at Moffitt Cancer Center, and their related cardiovascular and oncologic outcomes. The study was approved by the University of South Florida Institutional Review Board.

Results: 3 out of the 40 patients did not receive any chemotherapy and were excluded from the analysis. The median age was 71 years (range 21-93) with a median follow-up time of 19 months. Baseline characteristics are represented on table 1.

	N	Percentage (%)
Sex	11	29.7
F
M	26	70.3
Race	3	8.1
African  American
Asian	1	2.7
White	33	89.2
ECOG PS	9	24.3
0
1	16	43.2
2	8	21.6
NA	4	10.8
Baseline Ejection  fraction	21	56.8
<50%
>=50%	16	43.2
Systolic Heart Failure	15	40.5
No
Yes	18	48.7
UNK	4	10.8
Diastolic Heart Failure	6	16.2
No
Yes	16	43.2
UNK	15	40.5
Ann Harbor Stage	6	16.2
I
II	5	13.5
III	9	24.3
IV	17	45.9

25 patients (67%) received R-CHOP or R-CHOP like (R-EPOCH) chemotherapy. The remaining patients received non R-CHOP regimens, being R-ICE (n=3), R-Hyper-CVAD (n=1), R-MTX (n=2), R-Bendamustine (n=2), R-CVP (n=2), R-CEOP (n=3). We observed an association between the type of treatment (R-CHOP vs non R-CHOP) and the type of heart failure, with diastolic CHF patients being more likely to receive a R-CHOP chemotherapy. (Table 2)

		R-CHOP		non R-CHOP		p-value	OR	95% CI
		N	Percentage (%)	N	Percentage (%)
Diastolic HF	Yes	15	88.2	1	20.0	0.005	30	(2.14, 421.12)
	No	2	11.8	4	80.0
Systolic HF	Yes	7	31.8	11	100	<0.001	0
	No	15	68.2	0	0

There was a trend toward better response to chemotherapy among patients with diastolic heart failure compared to systolic heart failure. We observed a larger number of cardiac events, defined as hospitalization for CHF, for cerebrovascular insult, for chest pain, for ischemic or non-ischemic cardiac events or cardiac-related deaths, in the group treated with R-CHOP, but this was not statistically significant, given low patients numbers. Although patients treated with a R-CHOP regimen demonstrated higher complete remission rates compared to non R-CHOP regimens (73.7% vs. 55.5% respectively), this result was not statistically significant (p=0.37), and there was no significant difference in overall survival or 2-year relapse free survival.

Conclusion: To our knowledge, this is the largest series evaluating DLBCL treatment regimens in elderly patients with baseline cardiac dysfunction. This study demonstrated that elderly patients with DLBCL and baseline systolic CHF were more likely to receive non R-CHOP based regimens compared to patients with diastolic dysfunction.  Non R-CHOP treatments seem to be better tolerated with fewer adverse cardiac events. The major limitations of this study are the small sample size from one center and the retrospective design. Future studies examining larger patient populations in a prospective fashion will provide more information about how to best treat DLBCL patients with heart failure.