Early-phase trial evidence for RRMM treatment highly heterogenous

While early-phase clinical trials may demonstrate substantial levels of overall response rates (ORRs) in patients with relapsed/refractory multiple myeloma (RRMM), high heterogeneity of evidence prevents the accurate assessment of clinical benefit before patient participation, reports a recent meta-analysis.

Drawing from the databases of PubMed, the Cochrane Library, and Embase, the researchers retrieved 61 phase I (n=1,835) and 37 phase II (n=2,644) trials which investigated the efficacy of experimental compounds, either alone or in combination with dexamethasone, against RRMM. ORR, the primary outcome, was defined as the best-reported partial response (PR) or better.

ORRs for investigational drugs were reported in all trials but one. Heterogeneity of evidence was high, such that 95 percent confidence intervals [CI] of estimated overall response ranged from 8.1 percent to 16.8 percent in phase I trials, and from 18.9 percent to 28.3 percent in phase II trials.

In turn, the prediction intervals for estimated overall responses likewise varied widely: from 0.8 percent to 67.6 percent in phase I trials, and from 6.9 percent to 55.2 percent in phase II trials. The researchers identified several potential sources of heterogeneity, including year of publication and drug class.

A similar pattern was reported for the clinical benefit rate, which was significantly heterogenous in both phase I (p<0.001) and II (p<0.01) trials. In phase I trials, for example, the 95 percent CIs ranged from 13.7 percent to 24.1 percent, while the prediction interval ranged from 3.0 percent to 62.4 percent. Corresponding ranges in phase II trials were 28.7 percent to 40.4 percent and 12.4 percent to 65.8 percent.

“We found that the ORR of early-phase clinical trials is highly variable but seems to have improved over the past decade without a concurrent rise in toxicities,” the researchers said.

“Our findings can be used to facilitate debate on the risks and benefits of participation in early-phase clinical trials in oncology in general and may be used by clinicians to guide assessment and communication on enrolment of RRMM patients in early-phase clinical trials,” they added.