Clinical Characteristics, Survival Outcomes, and Prognostic Factors in Lymphocyte-Depleted Hodgkin's Lymphoma: National Cancer Database Analysis (2004-2018)

Introduction lymphocyte-depleted Hodgkin's lymphoma (LDHL) is the least common type of classical Hodgkin lymphoma (cHL), it accounts for about 1% of cHL cases. The survival rate of this rare entity is significantly less compared to other types of cHL. The rarity of this entity made it difficult to have large-scale studies describing the natural history and evaluating the outcomes with different treatment modalities.

Materials and Methods The National Cancer Database (NCDB) was queried for patients diagnosed with LDHL between 2004 and 2018. All patients aged 18 years or older diagnosed with LDHL were included and excluded patients who lost to follow-up (unknown vital status of last contact). Kaplan-Meier and multivariate Cox regression were used in the analyses

Results 945 patients with LDHL were identified over 15 years in the NCDB. Of whom, 591 (62%) were males, 760 (80%) were Caucasian, and 151 (16%) were African American, 716 (75%) received chemotherapy and 112 (12%) received radiation. HIV test results were available in 599/945 (63%) patients with 103/599 (17%) were positive and 496/599 (83%) were negative. Of the 954 patients, 282 (30%) had confirmed early stage (stage I and II) disease and 523 (55%) had confirmed advanced stage (stage III and IV) disease. The median age at diagnosis was 54 (range 18-90) years and the median overall survival (OS) for the whole cohort was 109 months (95% CI 88.8-129.5). Compared to patients with advanced stage, patients with early stage LDHL had better OS (median OS was 143 vs. 88 months, P=0.006).

Compared to patients who received chemo, patients who did not receive chemo were older (median age 66 (range 19-90) vs. 51 years (range 18-90)), more likely to be female (45% vs. 36%, P=0.014), more likely to have early stage disease (60% vs. 40%, P<0.001), less likely to have B-symptoms (45% vs. 55%, P=0.008), more likely to have Charlson-Deyo score of 3 or more (8.9% vs. 4.9%, P=0.006). There was no statistically significant difference in median OS between HIV-negative and HIV-positive patients in both early and advanced stages (median OS was 143 months vs. not reached with P=0.790 and 79 vs. 103 months with P=0.865, respectively).

In patients with the early-stage disease, those who received combined modality therapy (CMT) with chemoradiation (N=49) had better median 5-year survival rate compared to patients who received chemotherapy alone (N=149) (90% vs. 64%). In the advanced stage, there was no statistically significant difference in the OS between patients who received chemoradiation therapy (N=31) and patients who received chemotherapy alone (N=394) (median OS 110 vs. 118 months, P=0.435).

In multivariate analysis, factors associated with worse OS were age (HR 1.042 95% CI 1.033-1.051; P<0.001), African American compared to Caucasian race (HR 1.401 95% CI 1.038-1.891; P=0.028) and Charlson-Deyo score of 3 or more (HR 2.681 95% CI 1.712-4.198; P<0.001). Whereas absence of B-symptoms was associated with better OS (HR 0.628 95% CI 0.493-0.800; P<0.001).

Conclusion LDHL is a very rare subtype of cHL with high incidence in HIV-infected patients. Age distribution is unimodal predominantly affecting the middle age group. In the early-stage disease, CMT is superior to chemotherapy alone whereas addition of radiation to chemotherapy did not result in survival improvement in the advanced-stage disease. HIV status has no significant impact on survival. Long-term OS is rather limited in advanced-stage disease. Further research is necessary to determine novel therapies for LDHL.

Tun:Gossamer Bio, Inc.: Consultancy, Research Funding.