Outcomes in newly diagnosed young or high-risk myeloma patients receiving tandem autologous/allogeneic transplant followed by bortezomib maintenance: a phase II study

Despite novel drugs and autologous HCT, MM remains incurable, with short survival in patients with poor biological characteristics. Allo HCT may be curative in some patients but is hampered by high rates of toxicity and relapse. We hypothesized that bortezomib (BTZ), with its anti-myeloma and immunologic properties, could improve PFS and cGVHD after allo HCT in newly diagnosed MM patients. In this prospective phase II study, we included 39 young (<= 50 years) and high-risk patients who received a tandem auto-allo HCT followed by BTZ. Patients had prospective minimal residual disease (MRD) evaluations using Next-Generation Flow cytometry prior to allo HCT, prior BTZ and every 3 months for 2 years. With a median follow-up of 48 months, we report PFS and OS at 5 years of 41% and 80%, with a non-relapse mortality of 12%. Incidences of grade II-IV aGVHD at 12 months and moderate/severe cGVHD at 2 years were 26% and 57%. In a multivariate analysis model including cytogenetics, ISS and MRD status, MRD positivity prior to allo HCT (HR 3.75, p = 0.037), prior BTZ (HR 11.3, p = 0.018) and 3 months post-BTZ initiation (HR 9.7, p = 0.001) was highly predictive of progression. Peritransplant MRD assessment thus strongly predicts disease progression.

Automated summary

Despite novel drugs and autologous HCT, MM remains incurable and patients with poor biological characteristics have short survival. Allo HCT may cure some patients but is hindered by high toxicity and relapse. BTZ may improve PFS and cGVHD after allo HCT in newly diagnosed MM patients, with promising results in this prospective phase II study.