Addressing the Challenges of Treatment Sequencing in Multiple Myeloma

As treatment options within the myeloma space continue to expand, a swell of sequencing challenges may be on the horizon, according to Sham Mailankody, MBBS.

“A big challenge in myeloma is how to sequence these different drugs. Much of the data focus on more advanced patient populations, including patients who have received more than 3 prior lines of treatment,” explained Mailankody, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City. “Sequencing the choices of different regimens for patients with relapsed/refractory myeloma boils down to toxicity profiles, prior treatments, and switching along classes of drugs. Toxicity profiles will inform treatment choices.”

However, he added, there are several different regimens for patients with relapsed/refractory myeloma. 

One trial, for example¾the OPTIMISMM study¾was deigned to examine a triplet of pomalidomide (Pomalyst), bortezomib (Velcade), and low-dose dexamethasone versus bortezomib/dexamethasone alone in patients with ≤3 prior lines of therapy, ≥2 having contained lenalidomide. Results showed an overall response rate of 82.2% with the triplet versus 50.0% with the doublet. Moreover, the progression-free survival (PFS) benefit was most significant in patients who had received 1 line of therapy (HR, 0.54; 95% CI, 0.36-0.82; P = .0027), but it was also shown in the intent-to-treat (HR, 0.61; 95% CI, 0.49-0.77; two-sided P<.0001) and lenalidomide-refractory populations (HR, 0.65; 95% CI, 0.50-0.84; P <.001).

Another trial, the ARROW study, evaluated 2 dosing schedules of carfilzomib (Kyprolis) in patients with relapsed/refractory multiple myeloma: 27 mg/m² administered twice weekly or 70 mg/m² given once a week. The higher dose a comparable safety profile and an improved PFS compared with twice-weekly carfilzomib dosing. “This has changed practice for those patients who are getting a doublet of carfilzomib and dexamethasone,” Mailankody said in an interview with OncLive^Ò, a sister publication of CancerNetwork^Ò.

Researchers are also evaluating the combination use of elotuzumab (Empliciti) with pomalidomide and dexamethasone in a phase II randomized study that shows improvements in response rate and PFS with a trend towards improved overall survival.

Of note, Mailankody said, these are only 3 of many trials evaluating drug regimens to treat this patient population. “There is another half dozen drugs and several more combinations that we currently have,” he added.

With so many options, the challenge of how to sequence certain treatments arises by the fact that head-to-head studies have not yet been conducted. 

“We have limited comparative effectiveness data for these different trials,” Mailankody said. “It boils down to prior treatments, toxicities, other options available in the specific setting in which these patients are seen, whether this is 1 to 3 prior lines [of therapy] or more than 3 prior lines. It's not uncommon for patients with multiple myeloma to have 5, 6, or 7 prior lines, which is a good problem to have. This is the challenge of sequencing these different treatments in the appropriate order.”

This article was adapted from an article that originally appeared on OncLive, titled “Sequencing Challenges Emerge in Myeloma After Recent Approvals.”