Only about one-third of patients with multiple myeloma who experience a very good partial response to therapy following first relapse, according to a new study.
The study, published in the journal Cancers, suggests half of first-relapse patients are symptomatic, and 1 in 5 receive regimens containing newer agents. Three in 10 of those patients achieve a very good partial response (VGPR), the study found.
Corresponding author Allan Zhi Kai Goh, of Singapore General Hospital, and colleagues said they began their research because, despite great gains in the treatment of MM thanks to new therapies, most patients will ultimately relapse, and the scientific literature into the natural history of such patients is relatively thin.
The authors constructed a retrospective study of 300 patients whose first relapse occurred between the years 2004 and 2019. The patients were treated at one of two medical centers in Singapore, and they had an average time to first relapse of 22.7 months. The goal of the research was to calculate survival among these patients and identify prognostic factors.
Among the 300 patients, 94.7% had received initial therapy with a novel agent, and 41.3% subsequently underwent autologous stem-cell transplant (ASCT). Roughly half (48.6%) of patients achieved at least VGPR.
One hundred and forty-five patients later experienced clinical relapse; the remaining patients showed biochemical relapse, the authors said. Regimens including new agents were given to 57 patients (19%), and 17 patients (5.7%) underwent a second ASCT, but less than one-third achieved VGPR.
Rates of VGPR varied depending on treatment type. Patients who received newer agents in their salvage regimen had a VGPR rate of 45.6%. The VGPR rate was 27.4% in patients receiving novel agent-based regimens, and just 12.9% in patients receiving conventional therapy.
Overall, the patients had progression-free survival after first relapse of 12.0 months, and overall survival of 44.8 months.
The authors said a number of factors appeared to negatively affect survival. They include non-hyperdiploid karyotype at diagnosis and clinical relapse. The study also had notable data regarding treatment sequence.
“Although the current study is not designed to demonstrate the significance of a particular sequence, our result is consistent with the notion that at least one novel agent that the patient was never exposed to previously should be used, either by switching the therapeutic backbone or incorporating it directly, which is supported by the idea that initial treatment provides a selective pressure for resistant clones underlying disease relapse,” the authors wrote.
Goh and colleagues also said that factors that have prognostic value at diagnosis, such as ISS, LDH, and high-risk FISH, do not appear to have significant implications for post-first-relapse survival.
“They are always used as variables to define high-risk disease in the relapse setting,” the authors noted. “Our study suggests that there may be other more important factors in determining post-relapse survival.”
The investigators said their study should serve as a starting point in terms of better understanding how to treat patients with MM at first relapse, though they said many questions remain.
“Access to newer agents is likely to further improve the outcome of relapsed patients,” they said. “How to justify their use in the real-world practice with relatively limited resources needs to be addressed carefully in further studies.”
Reference
Wang C, Soekojo CY, Mel S, et al. Natural history and prognostic factors at first relapse in multiple myeloma. Cancers (Basel). Published online July 2, 2020. doi:10.3390/cancers12071759
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