Antiviral Agent HARVONI® for the Treatment of HCV-associated Indolent B-Cell Lymphoma

• Status: Unknown status
• Trial end date: 2021-08-15
• Target enrollment: 0
• Participant gender: All

Summary

We and other investigators have revealed an association between Hepatitis C virus (HCV) seropositivity and an increased risk of developing marginal zone B-cell lymphoma (MZ), lymphoplasmacytic lymphoma (LPL, also known as Waldenström's macroglobulinemia), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). The sustained virologic response (SVR) to treatment with interferon or pegylated (Peg)IFN with ribavirin was closely associated with the regression of HCV-associated B-cell NHL (mainly MZL, and LPL).

Currently, the second-generation direct-acting antiviral agents (DAAs), such as sofosbuvir, have been shown to have a higher cure rate, less side effects, and a shorter duration of therapy for chronic HCV infection. After the approval of DAA for HCV therapy, several recent anecdotal case reports showed that indolent low-grade B-cell NHLs regressed after HCV clearance by DAAs. It is noted that the time to complete remission of these lymphomas was around 20 to 24 weeks after starting DAAs. These findings indicate that DAAs can eradicate the trigger of lymphomagenesis by curing chronic HCV infection.

Because DAAs are more potent and efficient than pegylated (Peg) interferon plus ribavirin and well-tolerated for the treatment of HCV infection, it is reasonable to use DAAs as the frontline treatment for HCV-positive patients with indolent B-cell NHL, such as MZL, LPL, and low-grade FL, who do not require immediate cytoreductive therapy. The aim of this proposal is to assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of these lymphomas..

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Taiwan University Hospital
• Treatments: Antiviral Agents; Ledipasvir; Ledipasvir, sofosbuvir drug combination; Sofosbuvir

Criteria

Inclusion Criteria:

1. Patients older than 18 years with histologically proven diagnoses of indolent B-cell NHLs and with positive genotype 1 or 2 HCV (non-cirrhotic status) were eligible.

2. Indolent B-cell NHLs includes:

• Low-grade marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type: known as MALT lymphoma.

• Splenic marginal zone lymphomas (SMZL)

• Waldenström's macroglobulinemia (WM, known as lymphoplasmacytic lymphoma) .

• Grade 1, 2 follicular lymphoma (FL). 3 Stage I to III (modified Ann Arbor stage), and non-life threatening IV lymphoma. 4 Patients had not previously been treated with chemotherapy or immunotherapy, were eligible. 5 Patients with clinical, echographical, or radiological suspicion of lymphoma lesions were eligible.

Exclusion Criteria:

1. Evidence of histologic transformation to a high-grade lymphoma (such as grade 3 and 4 follicular lymphoma, and high-grade MALT lymphoma).

2. Life-threatening disseminated lymphoma.

3. Primary gastric lesions were not eligible.

4. Prior diagnosis of neoplasm within 5 years, except cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer.

5. Evidence of clinically significant cardiac disease, as defined by history of symptomatic ventricular arrhythmias, congestive heart failure or myocardial infarction within 12 months before study entry.

6. Evidence of symptomatic central nervous system (CNS) disease.

7. Evidence of active opportunistic infections.

8. Liver cirrhosis B and C (Child-Pugh score)

9. Known HIV infection.

10. Pregnant or lactating status.