No Improvement Of Overall Survival After Extended Follow-Up Of Donor Versus No Donor Analysis Of Newly Diagnosed Myeloma Patients Included In The HOVON 50/54 Study
Authors: Lokhorst Henk , Holt Bronno van der , Cornelissen Jan , Kersten Marie José , Van Oers Marinus H.J. , Raymakers Reinier , Minnema Monique C. , Zweegman Sonja , Janssen Jeroen JWM , Zijlmans Mark , Bos Gerard M.J. , Schaap Nicolaas PM , de Weerdt Okke , Wittebol Shulamiet , Ammerlaan Rianne , Sonneveld Pieter 
Published: October 2019

Abstract

Background
The value of Allo-SCT in myeloma is heavily disputed. In our previous Donor versus No Donor (DvND) comparison we found no survival benefit of Allo-RIC in newly diagnosed myeloma. (Lokhorst et al:Blood 2012119: 6219-6225). However, a recent update of the EBMT-NMA 2000 trial (Gahrton el al:Blood 2013121: 5055-506) suggested that extended follow-up (> 5 years) may be necessary for a correct interpretation of a potential survival benefit for Allo-RIC. Here we present the extended follow-up of our trial, in which the median follow-up of patients now exceeds over 7.5 years since the first autologous SCT.

Methods
Patients with an HLA–identical sibling donor included in the phase III HOVON-50 study, that was designed to assess the role of thalidomide in induction treatment and maintenance after high-dose therapy (HDM 200 mg/m2), could proceed to the Hovon 54 study in which an Allo-SCT was performed after conditioning with low dose TBI only, between 2-6 months after HDM. Among the 536 eligible patients randomized in the HOVON-50 trial, ultimately 260 patients were eligible to be included into the DvND analysis: 122 patients with a donor, of whom 99 patients received an Allo-RIC and 138 without a donor, of whom 115 patients started maintenance therapy with thalidomide. Groups were comparable with regard to age, myeloma stage, and prognostic factors including cytogenetics and ISS stage.

Results
93% of the patients in the no donor group achieved at least a PR (38% CR, 71% at least VGPR ), versus 96% of the patients in the donor group (43% CR, 73% at least VGPR). After a median follow-up of 91 months after HDM, PFS and OS were comparable between the two groups. In the intention to treat analysis median PFS was 29 months for the no donor group and 30 months the no donor group (P=0.25). Median OS was 76 for the donor group and 81 months for the no donor group (P=0.61). For the patients who actually received their allocated treatment (Allo-RIC or maintenance), PFS curves started to diverge after 3 years, however no statistical difference was observed (P=0.07). Allo-RIC improved the median overall survival from 73 to 94 months compared to patients receiving maintenance. However, due to frequent late mortality (> after 96 months) in the Allo-RIC group the benefit was not statistically significant (P=0.54). No subgroup including those achieving CR or those with high risk features (ISS, deletion of chromosome 13) did benefit from Allo-RIC.

Conclusion
This analysis failed to show improvement of tandem Auto Allo-RIC as part of first line therapy in myeloma as compared to Auto-SCT followed by maintenance therapy, even after extended follow-up.

Disclosures:
Lokhorst: Genmab A/S: Consultancy, Research Funding; Celgene: Honoraria; Johnson-Cilag: Honoraria; Mudipharma: Honoraria. Minnema:Janssen Cilag: Consultancy, Honoraria. Sonneveld:Janssen-Cilag: Honoraria; Celgene: Honoraria; Onyx: Honoraria; Janssen-Cilag: Research Funding; Millenium: Research Funding; Onyx: Research Funding; Celgene: Research Funding.