Multiple Myeloma: Navigating Treatment Options and Addressing Patient Needs

Amy Pierre:

I had the pleasure of attending the lecture entitled individualizing care for multiple myeloma and navigating patients' needs. It was amazing, because they discussed the latest published data on appropriate treatment regimens for patients with newly diagnosed myeloma, as well as relapsed/refractory myeloma based on current guidelines for evidence-based care in myeloma. They weaved in accounting for options based on risks and benefits and utilizing a patient-centric, individualized care approach that puts the patient in the forefront for shared decision-making.

The talk began with a case-based approach, discussing a very important patient population example: the non-transplant eligible, or frail or elderly population. And they reviewed incorporating the IMWG frailty score, which helps predict the risk of toxicity and mortality with treatment, and emphasized that as an AP, you do never want the treatment to be worse than the actual disease. Data was presented from the MYO trial, that's dara/rev/dex, and how this triple therapy shows clear benefit for the non-transplant eligible patients inclusive of a 56-month follow-up time, which is impressive data. And the subgroup analysis showed a survival benefit in high-risk myeloma patients.

It was great to hear how their practice approaches induction therapy in this patient population. So, that frail/elderly population, their approach is really using the MYO trial data with the dara/rev/dex for most patients. But if a patient has translocation (4;14), they utilize VRD light, as there's a benefit for patients utilizing a proteasome inhibitor who have that translocation. And if a patient has renal failure, they tend to use dara with bortezomib and dexamethasone.

Now, for our transplant-eligible patients, they reviewed several pivotal trial data inclusive of the ENDURANCE trial that was looking at VRD vs KRD, demonstrating pretty similar outcomes. So, choosing one therapy over the other should really be based on the individual patient and the side effect profile of those regimens. They also talked about the GRIFFIN trial that was dara with VRD, and how the Kaplan-Meier curves separate late, demonstrating that sustained MRD negativity with incorporation of daratumumab in induction, in consolidation, and maintenance. They also presented data from the isatuximab VRD trial, which is the other anti-CD38 on the market, which also demonstrated impressive CR response rates after induction. And also the MASTER trial, that's another quad regimen of daratumumab, carfilzomib, lenalidomide, and dexamethasone.

That is the first discontinuation study based on confirmed sustained MRD negativity in standard risk patients. Which as an AP, looking at the possibility of risk-adapted discontinuation therapy guidelines in myeloma is really exciting. And they did a quick comparison of the MASTER trial vs the GRIFFIN trial, which of course you're not really supposed to compare trials, but we all do it. And a quick comparison showed that they did have similar outcomes for patients who had high-risk disease. I also really enjoyed how they emphasized that MRD testing should be factored in when doing transplants, as there seems to be a transplant benefit for those who are MRD-positive based on the determination trial that had over a 70-month follow-up time.

And in terms of changes in practice, tandem transplant appears to be falling out of favor based on the StaMINA trial. We also saw that we may not need consolidation therapy either. For the young, fit transplant-eligible population, their approach is based on preexisting conditions of the patient. For example, if a patient has a history of peripheral neuropathy, they will choose an agent of KRD, but if no history of peripheral neuropathy, they'll choose VRD with a possibility of adding dara based on the GRIFFIN study. And if the patient has renal failure presentation, they use the quad regimen of daratumumab with bortezomib, cyclophosphamide, and dex, and they'll change to dara-VRd once the renal function improves.

Now, for our relapsed/refractory patients. They talked about the CANDOR study, which was looking at dara, carfilzomib, dex in 1-3 prior lines. The IKEMA study, which is looking at isatuximab, carfilzomib, and dex, and they had very similar high response rates in the 85% range. And the IKEMA study had very impressive MRD negativity rates as well. Data from the APOLLO study, which is dara/pom/dex, and the ICARIA study of isa/pom/dex, that was also presented, demonstrating similar and high response rates in the early relapse population.

Venetoclax, it was reviewed and it's of high value in patients who have translocation (11;14). One particular study, the CANOVA study, it didn't meet its primary endpoint, which is looking at ven/dex with pom/dex, but there's clear activity for our translocation (11;14) patients and we really look forward to what will be published in the future regarding this novel drug in myeloma. For later relapse, there are 5 BCMA-directed bispecifics in the pipeline with 2 currently approved, and they all have very similar response rates in the 60 to 70% range. Which is amazing, given we usually see response rates of 30% in this high-risk population.

We also currently have 2 CAR-T products approved, ide-cel and cilta-cel, and latest research shows that giving these agents in earlier lines after relapse, we see that response rates are better with CAR-T compared to standard of care. The way they approach early relapse patients is based on understanding what medications they are naive to, what they've relapsed on, or what they're refractory to, and they also believe that they should utilize venetoclax in earlier lines given its mechanism of action.

If I want to highlight some interesting factors that I learned, they talked about how the first remission is usually the longest, so you really want to use an approach in your induction regimen with the most efficacious regimen. Giving a BCMA-targeting bispecific before CAR T-cell therapy has demonstrated poor outcomes, so sequencing of these agents is important. We also see more neurotoxicity with the newer agent talquetamab vs the BCMA-directed bispecifics, teclistamab and elranatamab, and the most troublesome side effect with talquetamab is that taste changes and weight loss that's associated with that side effect.

And one pearl was reviewed, which is important for APs, is that these anti-CD38 antibodies are generally well-tolerated, but you need to be cognizant of infections in that patient population and utilizing IVIG for patients who are hypogammaglobulinemic. All in all, this lecture was a comprehensive and detailed evidence-based presentation on treatment of a variety of patients in myeloma, and how we as APs can continue to remain cognizant of the latest published guidelines and literature in a field of oncology that is rapidly evolving.