Options for Transplant Ineligible Patients in Multiple Myeloma

Thomas Martin, MD: What do you think about transplant-ineligible patients?

Yvonne Efebera, MD: There are so many treatment options. Again, a combination of 3 drugs is always better than 2 drugs. That has been shown in several trials. There are some patients who may not initially tolerate the 3 drugs, so you start them on 2: RVd (lenalidomide, bortezomib, dexamethasone) again, or RVd-lite with the weekly Velcade that has been shown; and you had mentioned earlier with the RVd-Lite, given weekly with Velcade for 3 weeks and 1 week off and still the dose of Revlimid. The MAIA study (NCT04307667) with DRd (daratumumab, lenalidomide, dexamethasone) is a blockbuster for me. In fact, I’m switching between RVd and DRd. Those are such good outcomes. That study that compared DRd was also a large study, more than 360 patients; the median follow-up was 28 months and showed that at 30 months, 70.6% of patients in the daratumumab arm were disease-free versus 55.6%. The CR (complete response) was also high in the daratumumab arm, 47.6%, versus 20%.

Then the DARA VMP (daratumumab plus bortezomib, melphalan, prednisone) was also published as the European study, where they did VMP (bortezomib, melphalan, prednisone) as the backbone versus DARA VMP. That also had about 350 patients in each, with a median follow-up of 40 months that showed the median progression-free survival for DARA VMP was 36.4 months compared with VMP, which was 19.3 months. All of those are good options.

RVd and DRd are really my first go-to, based on the trials. Again, in patients who have renal insufficiency where lenalidomide initially may not be an option—also, lenalidomide cannot be given inpatient unless you write the script—it takes a week. For patients who really need treatment right away, CyBorD—Cytoxan, bortezomib, dexamethasone—are good agents for patients with acute renal failure. Cytoxan/bortezomib is a great agent. KRd (carfilzomib, lenalidomide, dexamethasone) is another option, and carfilzomib/Cytoxan/dexamethasone. Those are other good options. What’s your favorite?

Thomas Martin, MD: I completely agree. I use CyBorD or VCd (bortezomib, cyclophosphamide, dexamethasone) for the people who have renal insufficiency, but most everybody else gets RVd. It’s a triplet, like you said. I’m starting to use more DRd as induction. It’s extremely well tolerated, so we’ll see how that evolves. The last thing I’ll say about transplant ineligibility is maintenance therapy. I think we’ve shown in multiple settings, in multiple studies—including the first study, and Dr Polombo did a randomized study of no maintenance versus maintenance 10 years ago or more using lenalidomide as maintenance—that continuous therapy always wins out. I usually give people somewhere between 8 and 12 cycles of induction therapy, and then I switch them to maintenance.

The same thing with transplant ineligibility, with the guidelines in my mind, is that most people get lenalidomide unless they’re not tolerating it, and then I go to bortezomib every other week. Give them bortezomib every other week and watch them for neuropathy. That goes well.

Yvonne Efebera, MD: That’s another area of contention: How long is maintenance? The Europeans do 1 year, maybe because of the medical insurance that they have. I did a debate at NCCN (National Comprehensive Cancer Network) last year in September, and they gave me the role of fixed duration of maintenance versus continuation, even though I do continuation of maintenance. That’s a debate area: how long should maintenance be? It’s really all over the place. The BMT CTN 1702 (NCT03904134) was the 3-arm study that looked at single autologous transplant followed by maintenance as the standard versus tandem autologous-autologous transplant followed by maintenance, or autologous transplant with consolidation VRd (bortezomib, lenalidomide, dexamethasone), followed by maintenance. The initial length of maintenance therapy was 3 years; I’m proud to say that my patient was the first patient on this study, and he’s doing well even 10 years out now, still on maintenance lenalidomide. After 3 years, we decided to do the long-term follow-up and give patients the option to either continue maintenance versus stopping. Some patients decided to stop.

At ASCO (American Society of Clinical Oncology annual meeting) this year, they presented the long-term follow-up of BMT CTN 1702, and it showed that patients who continued beyond 3 years had an improved PFS (progression-free survival) compared with those who stopped. They were in remission or the disease was stable, VGPR (very good partial response), or PR (partial response). When they stopped, the disease progressed earlier than those who continued maintenance. That’s the first study that has shown that, beyond 3 years, there is a benefit for lenalidomide maintenance. Patients, too, they read and see this. I’ve had patients who say, “I want to continue. I’m doing very well on it. I don’t want to stop.” You talk to them about the risk of second primary malignancies, which is about 7% to 8% compared with 4% in the placebo group, but with a 67% increased benefit, patients say, “Look, I’m going to continue and take my chances.”

Transcript edited for clarity.