PF646 ASSOCIATION BETWEEN BORTEZOMIB CUMULATIVE DOSE AND TREATMENT‐FREE INTERVAL IN TRANSPLANT‐INELIGIBLE PATIENTS WITH PREVIOUSLY UNTREATED MULTIPLE MYELOMA
Authors: Paz‐Filho G. , Hu P. , Nemat S. , Appiani C. , Lam A. , Richarz U. , He J. 
Published: June 2019

Background:

The phase III VISTA study has demonstrated that bortezomib‐melphalan‐prednisone (VMP) leads to improved clinical outcomes, such as significant improvement of overall survival (OS) for patients with myeloma who are ineligible for stem cell transplantation, in comparison with melphalan‐prednisone (MP) (San Miguel et al, J Clin Oncol, 3:448–455, 2013). It was demonstrated a higher cumulative bortezomib dose is associated with improved OS (Mateos MV et al, Am J Hematol 90:314–319, 2015). Treatment‐free interval (TFI) is another important clinical outcome measure proposed by ASCO and ESMO Draft Value Frameworks for neoplastic drugs (Becker DJ et al, J Oncol Practice, 13:e753‐e665, 2017; Richardson P et al, Expert Review of Hematology 10:933–939, 2017). However, it is not known whether higher cumulative bortezomib doses are associated with a prolonged TFI.

Aims:

To determine whether a higher cumulative bortezomib dose (obtained by longer treatment duration, more intensive therapy or both) is associated with longer TFI, or lower cumulative incidence of subsequent therapy.

Methods:

This is a post hoc analysis of the patients treated with VMP in the VISTA randomized clinical trial with the data cut of 2008. Baseline characteristics and clinical outcome (TFI, defined as time from the last dose of study drug to the start of subsequent treatment) were analysed in two groups based on median cumulative bortezomib dose. For subjects who were not known to have died, survival time was censored at the date last known to be alive. Multivariate competing risks hazard ratios (HR), as well as estimates of cumulative incidence (CI) of subsequent therapy, were computed using the Fine and Gray proportional hazards (PH) model for sub‐distributions. HR <1 is in favour of higher bortezomib cumulative group.

Results:

The median cumulative dose of bortezomib was 39 mg/m2. The median follow‐up was 25.9 months. Patients in the higher cumulative bortezomib dose group (n = 170) were significant younger (70.8 ± 4.6 vs. 73.6 ± 6.2, P < 0.0001) than the lower group (n = 170). No major differences between groups are identified in respect of gender, ISS, type of myeloma, ECOG, cytogenetic risk, and baseline creatinine clearance. Only 44 (25.9%) and 24 (4.1%) patients in the lower and higher dose group had documented subsequent therapy, respectively. Overall, 39 (22.9 %) and 10 (5.9%) patients died in lower and higher dose group, respectively. TFI did not reach the median for either dose group, though it was significantly longer in the higher (≥39 mg/m2) versus lower (<39 mg/m2) cumulative bortezomib dose group, with HR as 0.48 (P = 0.004) and age‐adjusted HR as 0.49 (P = 0.009). The CI at month 12 for subsequent therapy was 0.134 for the higher dose group vs. 0.258 for the lower dose group (Figure 1).

Summary/Conclusion:

With relative short follow up in this study, higher cumulative bortezomib dose was associated with significantly delayed subsequent therapy. Further studies are warranted to understand the relationship between cumulative bortezomib dose and TFI, OS and other clinical outcomes.

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