Updates in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma from ASH 2021 - Episode 1

Treatment Options for Patients With MM at First Relapse

Expert perspective on the management of multiple myeloma at first relapse in the context of recent clinical data from the ASH 2021 Annual Meeting.


Amrita Y. Krishnan, MD: For patients with first relapse in myeloma, there are multiple treatment options. A lot of it depends on the prior therapies for that patient and the toxicities and comorbidities. Many of us use daratumumab-pomalidomide, and dexamethasone based on the APOLLO study. It showed a benefit to daratumumab-pomalidomide plus dexamethasone compared with pomalidomide-dexamethasone alone in terms of progression-free survival. The other thing is that the advent of subcutaneous daratumumab has been also a tremendous step forward. Although the APOLLO study used intravenous daratumumab, in clinical practice, most of our patients are on subcutaneous daratumumab.

The APOLLO study was a very important study because it represents what we’re doing in clinical practice for patients with early relapse. In this trial, patients had to have at least 1 prior line of therapy, which included lenalidomide and a proteasome inhibitor. If they’ve had only 1 line of therapy, they had to be lenalidomide refractory. They were randomized to either daratumumab-pomalidomide and dexamethasone or pomalidomide and dexamethasone. The important part of this trial was that daratumumab was subcutaneous or IV [intravenous] on a traditional schedule.

What we found in the study was that the progression-free survival was significantly better for patients who received the daratumumab plus the pomalidomide-dexamethasone at 12.4 months vs only 6.3 months in patients who received pomalidomide-dexamethasone alone. The hazard ratio was 0.63. This trial was important because it cemented what we often do in clinical practice. Many of the patients we see are lenalidomide refractory because they’re progressing after lenalidomide maintenance. And the therapy that we choose at first relapse is often daratumumab plus pomalidomide and dexamethasone, especially with the advent of subcutaneous daratumumab.

One question that always comes up for us in that first-relapse setting—certainly, we use daratumumab quite a bit—is what’s the best partner for daratumumab? Would it be daratumumab, pomalidomide, and dexamethasone or daratumumab, bortezomib, and dexamethasone? Many of the patients that we’re seeing in that first relapse setting are lenalidomide refractory.

At the recent ASH [American Society of Hematology Annual Meeting], there was an abstract doing an indirect comparison of daratumumab-pomalidomide-dexamethasone with daratumumab-bortezomib-dexamethasone or bortezomib and dexamethasone in patients with relapsed/refractory myeloma. Of course, this is challenged by some of the issues with these indirect comparisons through patient databases. But they used the data for the daratumumab-pomalidomide-dexamethasone cohort from the APOLLO study and then data from the EQUULEUS study, which was a phase 1 study of daratumumab-pomalidomide-dexamethasone. For the daratumumab-bortezomib-dexamethasone arm, they used the data from the CASTOR trial, another open-label phase 3 study that compared daratumumab-bortezomib-dexamethasone with bortezomib-dexamethasone alone.

There were limitations when they were using some of these data sets. One of the biggest limitations was that they weren’t able to get ISS [International Staging System] data for a large number of patients and were also missing some data in terms of the myeloma type. You have to take that as a caveat because those may be important issues in terms of some of the responses, as we know in patients, especially ISS stage. But with these indirect treatment comparisons, what they did find was that there was a progression-free survival benefit for daratumumab, pomalidomide, and dexamethasone compared with daratumumab, bortezomib, and dexamethasone and bortezomib-dexamethasone alone. This isn’t particularly practice changing. It just reflects another reason to use our standard practice of daratumumab-pomalidomide-dexamethasone in that early relapse space.

With the advent and approval of subcutaneous daratumumab, there’s been a lot of question about its use vs IV daratumumab. For the majority of our patients, we use subcutaneous daratumumab, and that includes patients who’ve previously been treated with intravenous daratumumab; we’ve switched them over. Most have been quite happy with the switch, especially in terms of convenience, time in the chemotherapy room, and the lower degree of infusion reactions with that first dose. The use of subcutaneous has been a big step forward.

I’ve had a handful of patients I can count on 1 hand who requested to switch back to the IV formulation from the subcutaneous and not for any particular 1 adverse effect. One thought was that they had more neuropathy. Another was that they had some atypical joint pains with the subcutaneous formulation. As I said, a handful of patients requested the switch back to IV, but the majority of my patients are on subcutaneous daratumumab. Certainly, when we’re starting newly diagnosed patients or patients who are new to daratumumab, we always start with a subcutaneous route.

Transcript edited for clarity.