Chronic HCV Infection and Autologous Stem Cell Transplantation for Multiple Myeloma
Authors: Gruchet Cécile , Guidez Stephanie , Fouquet Guillemette , Azais Isabelle , Durand Geraldine , Javaugue Vincent , Brigaud Antoine , Plasse Florent , Diolez Jeremie , Sabirou Florence , Moya Niels , Bobin Arthur , Systchenko Thomas , Machet Antoine , Desmier Deborah , Levy Anthony , Dieval Celine , Primault Sylvain , Barrier Jocelyn , Corby Anne , Daras Claire , Princet Isabelle , Bauwens Delphine , Richez Valentine , Franques Paul , Gardeney Helene , Bouyer Sabrina , Dindinaud Elodie , Avet Loiseau Herve , Bridoux Franck , Christine Silvain , Leleu Xavier 
Published: October 2019

Abstract
Introduction. The pronostic of Chronic hepatitis C (Hep C) has transformed towards cure in recent years with the advent of the antiviral treatment by SOFOSBUZIR (400mg/j) and DACLATASVIR (60mg/j) during 11 weeks usually turning HepC into a complete response (undetectable HCV viral load) or with HARVONI (LEDIPASVIR 90mg and SOFOSBUVIR 400mg) during 12 weeks.
In parallel, Multiple Myeloma is a known hematological malignancy characterized with a very severe immuno deficiency status particularly of regards to hypogammaglobulinemia, but also recurrent short period of neutropenia, and often lymphopenia, induced by the various treatments available in the armamentarium of Myeloma. One treatment carries certainly the greatest risk of maximizing the global immunodepression of patients with Multiple Myeloma, that is the intensification using autologous transplantation conditionned with high dose melphalan (ASCT). Studies have demonstrated that the vaccination status of patients with Myeloma was severely impaired and that patients could develop infections particularly in the context of the autologous transplantation.
We sought to study whether cured Hep C might relapse in patients with Myeloma while treated with induction, autologous transplantation and post transplant treatment phases.
Method. We have reviewed 2 cases of MM plus Hep C homogeneously treated on a transplant eligible schema for MM and also treated using the most advanced cure for Hep C treatments. The 2 patients had a VTd- ASCT-VTd for MM treatment. The 2 patients were of genotype 4 Hep C, with the following viral loads, 1 966 055 UI/ml and 7 907 720/ml with normal hepatic enzymes.
Results. AGE, sex ratio male, ISS-R was 1 and 3 (b2m elevated plus elevated LDH) respectively. None of the patients was diagnosed with either plasmablastic features, adverse cytogenetic (t(4 ;14) or del17p), PCL or EMD. MM Response prior to ASCT at completion of Induction was CR and PR, respectively. The 2 patients had undetectable viral loads prior to undergo ASCT. Interestingly, we noticed a relapse for one patient 1 month after ASCT (viral load 471 680 UI/ml), the second patient being pending at this timepoint.
For the first patient in relapse for Hep C, a second Hep C treatment was started with VIEKIRAX and RIBAVIRINE during 12 weeks allowing the patient to enter again into complete response for Hep C. One year after this second treatment there is no relapse for HCV infection and for multiple myeloma.
Conclusion. Autologous stem cell transplantation induces a major immunosuppression increasing the risk for HCV cure treatment failure. We have looked a tour series of patients and already identified one case with such issue, and possibly a second case to come. This data question on the need to use the Hep C cure treatment PRIOR to ASCT in patients with MM given the risk the cost issue and the risk of failure. This data question also the ability of the Hep C cure treatment to be given post ASCT with possibly a greater chance of success. This data must be confirmed on a larger international effort.

Disclosures
Leleu: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.