Dan T. Vogl, MD, Associate Professor of Medicine at the Hospital of the University of Pennsylvania and Director of the Abramson Cancer Center at the Perelman School of Medicine, Philadelphia, told The ASCO Post that the follow-up of the UK NCRI Myeloma XI trial confirms the importance of lenalidomide maintenance after autologous stem cell transplantation as part of a strategy for long-term control of myeloma and improvement of overall survival in newly diagnosed patients. What the study does not do, he said, is answer the question of the optimal duration of maintenance lenalidomide.

Dan T. Vogl, MD

“It’s important to keep in mind the trial was not designed to answer the question of when we can safely stop lenalidomide maintenance. It did not take patients who had completed 3 years of maintenance and then randomly assign them to continue or stop. It compared patients on lenalidomide maintenance without disease progression who continued on lenalidomide to those who had been randomly assigned to observation (no maintenance) and continued on observation. It would be a mistake to say the study showed a benefit at one time point but not in another, because it wasn’t designed to look at that,” he pointed out.

Dr. Vogl further noted that comparing patient populations at various time points is problematic, as the groups tend to dwindle in size and these comparisons lose statistical power.

The current analysis does, however, provide “preliminary guidance for designing future trials that will be able to address this important clinical question,” he said, noting that research scientists can now “pick through the data to glean where the most important questions might be.” 

Role of MRD Status

“I think the most important idea is to design a trial where we select a time point at which to stop vs to continue lenalidomide, maybe incorporating patient characteristics, such as MRD [measurable residual disease] status. Myeloma XI found a hint that, for MRD-negative patients, the benefit was concentrated in the first 3 years, with a little less evidence of ongoing benefit after this. In this group, therefore, it may make sense to examine stopping vs continuing after 3 years. For the MRD-positive population, maybe we should evaluate stopping later, or maybe we won’t study this approach at all.”

MRD status is already being used to guide the duration of maintenance in the current SWOG 1802 DRAMMATIC trial, which has overall survival as the primary endpoint. SWOG 1802 is comparing lenalidomide alone or with daratumumab as posttransplant maintenance, with a second randomization in MRD-negative patients to stop or to continue their assigned maintenance therapy after 2 years. “Dr. Pawlyn’s data should be used, as she suggested, as a guide to the construction of such trials,” Dr. Vogl reiterated, noting that studies of maintenance duration are ongoing for the transplant-ineligible population as well.

Clinical Implications

Meanwhile, can the findings be used to inform the care of the patient in the clinic, aside from the patient who is not tolerating lenalidomide (for whom discontinuation of therapy has always been acceptable)? “I don’t think so. The study, as designed, doesn’t provide good enough information to tell us when an individual patient may no longer be getting benefit,” he said.

“But for the patient sitting in front of you, we can flip the question around: we can ask whether there is evidence of ongoing benefit after completing 3 or 4 years of maintenance. The answer at this time is ‘no,’ because these studies have not yet been done. We don’t know if that patient really needs to continue lenalidomide.” 

DISCLOSURE: Dr. Vogl has served as a consultant for Karyopharm, CSL/Behring, Sanofi/Genzyme, GlaxoSmithKline, Genentech, Takeda, and Oncopeptides; and has received research funding from Takeda and Active Biotech.