Direct-Acting Antivirals: An Option for Patients With Hepatitis C Virus–Associated Lymphoma?

As is the case with Epstein-Barr virus, hepatitis C virus (HCV) infection has been linked to the development of B-cell lymphoproliferative disorders, and the prevalence of HCV is higher in patients with B-cell non-Hodgkin lymphoma (NHL) than in the general population, leading researchers to question whether treatments for HCV could induce a hematologic response in patients with B-cell lymphoproliferative disorders.

In a retrospective study published in Blood, Luca Arcaini, MD, of the Department of Molecular Medicine at the University of Pavia Medical School in Italy, and authors examined whether direct-acting antiviral (DAA) therapies for HCV (which have been shown to induce viral eradication in more than 90% of HCV patients and to be safer and more tolerable than interferon-based antiviral therapies) led to a hematologic overall response rate (ORR; based on response criteria from the Lugano Classification and the International Workshop on CLL) of 67 percent of patients co-infected with HCV and indolent lymphoproliferative disorders.

“[Based on these results], indolent lymphomas associated with HCV infection, especially of marginal zone origin, should be treated with DAAs if an immediate conventional treatment is not needed,” Dr. Arcaini told ASH Clinical News.

Patients were included in the study if they had B-cell NHL or chronic lymphocytic leukemia (CLL) and HCV (defined as HCV-RNA positivity) and were treated with DAAs. The median patient age was 59 years, and 61 percent were female. Three patients had CLL and 43 had NHL. The most frequent type of NHL was marginal zone lymphoma (MZL; n=37; 81%).

Of the 46 patients, 10 had received chemotherapy to treat their hematologic malignancy, and 12 patients had received an interferon-based antiviral regimen to treat HCV. The majority of patients were treated with a sofosbuvir-based DAA regimen (n=39). The median duration of treatment was 12 weeks (range = 6-24 weeks), with all but one patient receiving the entire course of DAA therapy.

Nearly all patients (98%) had a virologic response to DAA therapy (defined as undetectable HCV viral load of <15 IU/ml), Dr. Arcaini and colleagues wrote, and this high rate of response was associated with a hematologic ORR of 67 percent, including complete responses in 26 percent (n=12) of patients and partial responses in 41 percent (n=19). Patients with MZL appeared to have higher hematologic response rates than patients with other lymphoproliferative disorders. See TABLE for all hematologic outcomes.

The authors observed that none of the four patients with CLL/small lymphocytic lymphoma responded. Univariate analyses “found trends for a better lymphoma response in patients with extranodal disease (odds ratio [OR] = 0.1; 95% CI 0.1-1.1; p=0.059) and paraproteinemia (OR=0.1; 95% CI 0.1-1; p=0.048), features typically associated with HCV-associated NHLs.”

After a median follow-up of eight months of DAA therapy (range = 2-30 months), the median progression-free survival (PFS) was not reached, though the estimated one-year PFS was 75 percent (95% CI 51-88). The median overall survival (OS) was also not reached, and the estimated one-year OS was 98 percent (95% CI 86-100). Four patients had early progression that occurred during (n=1) or within three months (n=3) of completion of DAA therapy. In addition, two patients with splenic MZL progressed after more than three months following DAA therapy.

The toxicity of DAA treatment was “negligible,” the authors reported, with 13 patients experiencing grade 1/2 treatment-related adverse events (including 5 cases of anemia in those treated with ribavirin) and one patient experiencing a grade 3 event (asthenia).

“Our data strongly suggest that antiviral treatment should be used as the first option for HCV-associated MZL when cytoreductive treatment is not immediately necessary,” the authors concluded. “Because of DAA safety, rapidity, and efficacy to obtain virologic response as well as good tolerance profile, DAA therapy should be preferred to interferon-based antiviral treatment.”

The study is limited by its retrospective design, heterogeneity of antiviral treatments, and limited follow-up. “Ongoing prospective trials will be able to determine precisely the impact of DAA therapy in HCV-infected patients with B-cell NHL,” Dr. Arcaini told ASH Clinical News.


Reference

Arcaini L, Besson C, Frigeni M, et al. Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection. Blood. 2016 September 7. [Epub ahead of print]

TABLE. Hematologic Response Rates
  Complete response Partial response Stable disease
All patients (n=46) 12

(26%)

19

(41%)

11

(24%)

Marginal zone lymphomas (n=37) 11 16 6
     Splenic (n=17) 4 7 5
     Nodal (n=1) 1 0 0
     Extranodal (n=15) 5 7 0
     Leukemic (n=4) 1 2 1
Follicular lymphoma (n=2) 0 2 0
Lymphoplasmacytic lymphoma (n=2) 0 1 1
Low-grade B-cell NHL NOS (n=1) 1 0 0
CLL/SLL (n=4) 0 0 4
NHL = non-Hodgkin lymphoma; NOS = not otherwise specified; CLL = chronic lymphocytic leukemia; SLL = small lymphocytic lymphoma

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