Abstract
Background
Multiple myeloma (MM) is an incurable hematologic malignancy, which is now managed as a chronic disease. The general upfront treatment paradigm is induction therapy, followed by autologous stem cell transplant (ASCT) for those who are candidates, then maintenance for two years or until progression. The development of multiple novel drugs has extended median survival to over seven years. Patients who achieve a complete response (CR) or better following ASCT have improved outcomes. Likewise, minimal residual disease (MRD) negativity is associated with increased progression-free survival (PFS) and overall survival (OS), but its implications on practice patterns remain unclear. This raises the question of whether patients who achieve undetectable disease will benefit from maintenance therapy. Time off treatment may improve quality of life and decrease healthcare expenditure.
Methods
A retrospective chart review was performed on all adult patients who underwent ASCT for MM at the University of Virginia between January 2012 and December 2016. Tandem or salvage transplants were excluded from the analysis. Data were collected on patient characteristics (age, sex), disease characteristics (immunoglobulin and light chain restriction, ISS stage, cytogenetic abnormalities), lines of systemic treatment prior to ASCT, depth of response achieved pre- and post-ASCT, and post-ASCT maintenance therapy. For patients who achieved CR or better post- ASCT, time to relapse, time to death, and duration of follow-up were collected. Patients with t(4;14), t(14;16), deletion 17p (or p53 deletion) were categorized as poor risk.
Cox proportional hazard models were used to assess the relationship between the outcomes of interest and the different covariates of interest. In the univariate models, if the p -value was less than 0.1, then the covariate was considered in the final model. In the final model, covariates were removed if their p -values were greater than 0.1. For the final model, hazard ratios (HR) with confidence intervals (CI) are provided.
Results
Seventy-six patients were included in the analysis. Patient demographics and pre- and post-ASCT disease characteristics are described in Table 1. Median age at ASCT was 62 years. Sixty-three percent were male and 37% were female. Eighty-five percent of patients had poor-risk cytogenetics. Most patients proceeded to transplant after one (72%) or two (20%) lines of induction therapy. Thirteen percent achieved CR or better pre-ASCT versus 28% post-ASCT. Maintenance therapy was the only variable associated with time to relapse post-ASCT (p=0.005), as shown in Figure 1. Patients who did not receive post-ASCT maintenance were three times more likely to relapse (HR 3.0, 1.4-6.4 95% CI).
Twenty-one patients (28%) achieved CR or better post-ASCT. Median follow-up was 27.5 months. Median time to relapse and death for these patients was 19.3 and 25.6 months, respectively. Thirteen patients received maintenance with bortezomib or lenalidomide, while seven were observed off maintenance. Data were unavailable for one patient. Four of the 13 patients on maintenance relapsed, while six of seven patients off maintenance relapsed. There was no significant difference in time to relapse between those who received maintenance and those who did not (p=0.91; HR 1.1, 0.3-4.1 95% CI).
Discussion
Multiple myeloma is a chronic disease. New drug development and optimizing treatment combinations continue to extend time to next therapy and OS. Our findings of improved PFS with post-ASCT maintenance are consistent with prior large studies. The proportion of our patients who achieved CR or better post-ASCT is comparable to those in other prospective trials. Interestingly, maintenance did not seem to impact outcomes for our patients who achieved CR or better post-ASCT. Considering these findings, we question the additional benefit of maintenance therapy for patients with undetectable disease. It is possible these patients may remain off therapy for years and realize higher quality of life while sparing healthcare resources and expenditure. Our findings and conclusions are limited by the small population size and retrospective analysis. Larger, prospective studies are warranted.
Foster: Bristol Meyers-Squibb: Other: Clinical trial investigator.
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