Using IMiD-Based Strategies for Relapsed Myeloma

EP: 1.Overview of Newly Diagnosed Multiple Myeloma

EP: 2.Standard Induction for Newly Diagnosed Symptomatic Myeloma

EP: 3.High-Risk Multiple Myeloma: Selecting Initial Therapy

EP: 4.Improving Maintenance Therapy for Myeloma

EP: 5.Role of MRD Assessment in Myeloma

EP: 6.Approaching Treatment of Relapsed/Refractory Myeloma

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EP: 7.Using IMiD-Based Strategies for Relapsed Myeloma

EP: 8.CASSIOPEIA Trial of Dara-VTd in Transplant-Eligible Myeloma

EP: 9.PI-Based Combinations for Relapsed Myeloma

EP: 10.Treatment of Relapsed/Refractory Myeloma: Novel Agents

EP: 11.Role of BCMA-Targeted Agents in Myeloma

EP: 12.Using CAR T Therapy for Relapsed/Refractory Myeloma

EP: 13.CARTITUDE-1 and CARTITUDE-2 Trials in Multiple Myeloma

EP: 14.Investigational Agents for Relapsed/Refractory Myeloma

Keith Stewart, MD, ChB, MBA: Cristina, most of our patients who are relapsing have had Revlimid before, or are on it at the time of relapse. What is your strategy with those patients? Do you use pomalidomide?

Cristina Gasparetto, MD: Yes, of course. I use pomalidomide for first relapse a lot, and sometimes it depends on the type of myeloma or the rapidity of the progression. I may use different combinations in different situations, there are so many randomized, triplet regimens in the setting of the first relapse. But yes, pomalidomide is definitely a good drug for a first relapse, even when we don’t want to change the class.

Keith Stewart, MD, ChB, MBA: Let’s talk about some trials that we have. We have trials recently where selinexorhas been added to pomalidomide, where daratumumab has been added to pomalidomide, isatuximab has been added. Do you use pomalidomide alone, or do you use it in combination? If so, with what?

Cristina Gasparetto, MD: I definitely use it in combination, and yes, we do have a lot of studies with a pomalidomide backbone. Isatuximab combined with the pomalidomide, of course was tested in the ICARIA study, showing good and durable responses. It was similar to daratumumab, the APOLLO trial, sub-Q [subcutaneous] injection with pomalidomide, which also performs very well in that setting. We had another randomized study, the OPTIMISMM trial, where pomalidomide is combined with bortezomib and dexamethasone vs bortezomib and dexamethasone. Selinexor is also a part of the STOMP study. We don’t have phase 3 data yet, but we had an update of that combination arm of the STOMP study at ASCO [American Society of Clinical Oncology annual meeting], and we were able to achieve a conclusion on the recommended phase 2 dose for selinexor: given only once a week, very low dose, 60 mg, in combination with 4 mg of pomalidomide. It looks like an excellent oral combination. In particular, with the signal we have with selinexor and high-risk patients, I won’t have any objection to using it. I have a fair amount of experience with selinexor, so I think that at the right dosage and the right combination, it is an effective backbone.

Keith Stewart, MD, ChB, MBA: Cristina, would you use selinexor in early relapse or late relapse?

Cristina Gasparetto, MD: It depends on the situation. You saw the BOSTON study, which was recently approved. Selinexor, Velcade, dexamethasone versus Velcade and dex [dexamethasone] because of the superiority, deeper responses and longer PFS [progression-free survival] with a triplet combination. It’s a good combination. If I have a patient progressing after a long-sustained lenalidomide maintenance, even with a bit of compromised renal function, the elderly perform well, and the high-risk patients. I don’t have any objection to using that in first relapse.

Keith Stewart, MD, ChB, MBA: Joe, you’ve explored both monoclonal antibodies against CD38, both isatuximab and daratumumab. They’ve both been combined with pomalidomide. If you were to pick one to use, would you have a preference?

Joseph Mikhael, MD: It makes you ask the question, do you need to use pomalidomide there? We’ve done that for a long time, and I think pomalidomide can overcome lenalidomide resistance if someone’s on lenalidomide maintenance. But we have other options, which I know we’re going to explore in a moment. The issue between isatuximab and daratumumab is that they’re very similar. We have quite similar studies when they’re combined with carfilzomib, and similarly, we’re gaining more data from the phase 3 APOLLO study, with daratumumab, as we have with the ICARIA study. I think, in this situation, I’m not going to argue that one is superior to the other. I think a lot of it will ultimately depend on the dosing strategy. Daratumumab infusion is longer, but it can now be given subcutaneously. I think very often the pragmatic use of the drug is what may differentiate one choice over the other vs one being more potent than the other. Lastly, we probably wouldn’t want to sequence them one immediately after the other. We just published our study, at the Translational Genomics Research Institute of using isatuximab immediately after someone failed daratumumab, and it wasn’t that effective. I think we need a gap, as we’ve seen some studies showing, after the CD38 antigen may be regenerated after at least 6 months. Then we could potentially retreat or switch to a different CD38 antigen.

Keith Stewart, MD, ChB, MBA: You pre-empted my next question. I’m going to come back to that last point in a minute. Nina, if you were going to use pomalidomide in first relapse, what would you combine it with? There are lots of choices: carfilzomib, bortezomib, the monoclonal antibodies we just talked about. What would you combine it with?

Nina Shah, MD: I think, practically speaking, daratumumab is the most convenient to combine with pomalidomide. Ultimately patients have a chronic illness and they have chronic therapy. I think that’s probably my top choice. It’s very convenient to do this, with the subcutaneous formulation, and eventually, monthly. That’s the reason for that. I don’t think anyone’s going to do the daratumumab, pomalidomide, dexamethasone vs carfilzomib, pomalidomide, dexamethasone study, so we’ll never know what’s better. But I would say daratumumab is probably my top choice. And isatuximab, pomalidomide, dexamethasone is actually for the third line technically…. I think that would be a reasonable choice as well.

Keith Stewart, MD, ChB, MBA: Sagar, some people have concerns that if we use all these active drugs in the frontline setting, we may have less choices when it comes to relapse. So, if somebody has received daratumumab and lenalidomide at induction, not necessarily refractory but have received them, which is a lot of our patients, what would you use in first-line relapse?

Sagar Lonial, MD, FACP: I think if somebody’s had limited exposure to both daratumumab and/or lenalidomide, meaning they didn’t get lenalidomide for maintenance, or they maybe got a year of it but relapsed 5 years later, I would reconsider using both of those in the context of first relapse. One of the advantages of the way we’re considering using daratumumab as part of our frontline therapy, is that the patient gets RVd-dara [lenalidomide, bortezomib, dexamethasone plus daratumumab] for 4 cycles, and that’s it. We don’t give it to them in at consolidation or maintenance. I don’t have an issue using daratumumab again, in first relapse, in that situation.

Transcript Edited for Clarity