What The Princess Bride Teaches Us About Outcomes in Multiple Myeloma

Abstract

outdated measures of efficacy that may stifle the innovation needed to ultimately cure this disease. We should celebrate the fact that a significant majority of our patients are able to receive effective therapies after first and second relapses and a patient can catch up even after a less effective earlier regimen.

Ensuring Ethical Postprogression Therapy for Patients in Randomized Trial Control Arms

“…There is often confusion about whether appropriate crossover constitutes confounding [30][31][32] -that is, whether receipt of the interventional therapy by patients in the control arm after progression inappropriately affects trial outcomes, particularly OS. But when a drug is known to have efficacy, this is not confounding, but rather the desired comparator arm of the study, both for the trial participants' sake and to ensure that the trial yields outcomes most helpful in informing clinical practice.…”

Perils of Ignoring Overall Survival in Interpreting the Myeloma Literature

“…In their editorial, D'Souza et al 2 quote The Princess Bride to highlight how recent treatment advances in multiple myeloma would have been considered inconceivable in the past.…”

“…As D'Souza et al 2 rightfully state, overall survival (OS) is indeed a function of access to postprotocol therapies. Although D'Souza et al 2 reference pivotal trials in Table 1 of their editorial, they do not highlight reporting of and access to postprotocol therapies in those trials and how that contextualizes to an OS benefit.…”

“…As D'Souza et al 2 rightfully state, overall survival (OS) is indeed a function of access to postprotocol therapies. Although D'Souza et al 2 reference pivotal trials in Table 1 of their editorial, they do not highlight reporting of and access to postprotocol therapies in those trials and how that contextualizes to an OS benefit. When summarizing recent trials for myeloma in the relapsed and/ or refractory landscape, the only trials that have demonstrated an OS advantage benefit are ASPIRE (carfilzomib-lenalidomide-dexamethasone) and ELOQUENT-2 (elotuzumab-lenalidomide-dexamethasone).…”

“…7 D'Souza et al 2 state that good salvage therapy does not eliminate the benefit of effective prolongation of progression-free survival (PFS) but can diminish the benefits as measured by OS, but does not reduce the value or benefit of PFS prolongation. 2 We thus beg the following question: What is the value of a PFS prolongation that does not translate into an OS prolongation? Is this a palpable benefit that a patient can feel, considering that PFS is defined by arbitrary changes in protein levels?…”