DAAs Well Tolerated with Chemotherapy for Comorbid HCV, Non-Hodgkin's Lymphoma

FEBRUARY 07, 2018
Kenneth Bender, PharmD, MA
Marcello PersicoMarcello Persico, MD
Direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection was well tolerated and appeared synergistic with chemotherapy of comorbid non-Hodgkin's lymphoma (NHL).

The risk for NHL is increased with HCV infection, and successful treatment of HCV with pre-DAA era treatments has been associated with remission in HCV-related low-grade NHL, according to Marcello Persico, MD, part of the Internal Medicine and Hepatology Unit at San Giovanni di Dio University Hospital and Ruggi d'Aragona Salernitana Medical School at the University of Salerno, in Italy, and colleagues.

Although chemotherapy is the only viable option for more severe B-cell non-Hodgkin's lymphomas, Persico and colleagues sought to determine whether DAA treatment of HCV is tolerated and beneficial with concurrent chemotherapy of diffuse large B-cell lymphoma.

Considering the efficacy and ease of the DAA treatments compared to the older, PEGylated interferon-based regimens, Persico and colleagues commented, “This, in our mind...was a not-to-be-missed opportunity, especially for those neoplastic patients with a more aggressive form of lymphoma.”

The investigators recruited 20 consecutive HCV-positive genotype 1b-infected patients affected with diffuse large B-cell lymphoma (DLBCL; 13 male, 7 female) referred to 1 of 3 hepatology clinics for DAA treatment, from hematological treatment centers providing their chemotherapy.  A historical cohort of 101 HCV-positive patients with aggressive DLBCL NHL who had not received any antiviral treatment constituted an "untreated" control group against which to compare the adverse and therapeutic effects of the DAA treatment.

In an editorial accompanying the study, Michael Kriss, MD, and Matthew Burchill, PhD, of the Division of Gastroenterology and Hepatology at the University of Colorado School of Medicine in Aurora, welcomed this prospective assessment, pointing out that there have been only limited observations of DAA therapy in cancer patients, albeit generally indicating that the antivirals are efficacious, durable and with few drug-drug interactions.
Michael Kriss, MDMichael Kriss, MD

"Despite these observations, prospective data are limited, and with the exception of patients being considered for a bone marrow transplant, there are no current guidelines for the use of DAA therapy in HCV-infected cancer patients," Kriss and Burchill observed.

The cohort enrolled by Persico and colleagues were receiving chemotherapeutic regimens of cyclophosphamide, doxorubicin, vincristine, and prednisone, with (n = 14) or without (n = 6) rituximab. All were treated orally with sofosbuvir-ledipasvir (Harvoni, Gilead Sciences), 1 tablet orally daily for 12 weeks. The overall survival (OS) and disease-free survival (DFS) were evaluated through 52 weeks, with weekly evaluations for liver function, adverse events (AEs) and drug-drug interactions.

The investigators reported no statistically significant difference in OS or in adverse events between DAA and the untreated historical cohort, while there was a significantly higher DFS rate associated with DAA treatment.  Multivariate analysis determined that only the International Prognostic Index (IPI) scores and the antiviral treatment were independently correlated with a better DFS. 

"Taken together, the data reported here endorse the concept that eradication of the infection positively affects the outcome of NHL and confirm once more a pathogenic role for HCV in NHL," Persico and colleagues noted.

Kriss and Burchill concurred, remarking, "excitingly, DAA treatment was the single greatest predictor of DFS in multivariate analysis (hazard ratio 0.277).  This study highlights the potential for pre-emptive DAA treatment to directly impact oncologic outcomes in carefully identified patient populations."

The study, “The evaluation of  DAA treatment of HCV with chemotherapy for comorbid non-Hodgkin's lymphoma,” was published in Hepatology.

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