Newly Diagnosed MM: Optimizing Maintenance Therapy and Managing Toxicities

Ajay K. Nooka, MD, MPH, FACP, shares insight on strategies to optimally deliver maintenance therapy and manage toxicities in patients with multiple myeloma.


Ajay K. Nooka, MD, MPH, FACP: GRIFFIN [study] data has provided us a lot of information in terms of achieving those depths of responses, post-induction, post-transplant, post-consolidation. And with maintenance, you’re seeing the depth of responses.

What we don’t have in the long run is the safety of this combination, 6 or 7 years later, which we’ll be having down the line. But what we have in the United States is [the] advantage of the other studies that use the lenalidomide [Revlimid] maintenance as continuous therapy until progression.

We’ve seen that, as a single agent, these are very well tolerated, and these are able to sustain the responses. There are 2 ways of looking at it. Are you able to continue the maintenance with improving and sustaining that response? Or would we be losing that response in this same process?

All of what we are seeing was [that] continued maintenances led us to [the] improvement of these responses. And clearly, when you’ve achieved a mark of MRD [minimal residual disease] negativity, you’ve achieved a mark of a serological conventional response, like a deeper response, like a complete response. You are able to peel away 1 of those drugs, preferably daratumumab [Darzalex], because [of] your long-term safety data with lenalidomide in this maintenance setting, and we can continue this until progression.

And the side effects are much better in an aspect like this. Ideally, in a hypothetical world, every drug is paid [for] and the cost is never an issue. Continuing 2 drugs is absolutely the best way to go and the safety is much better as we had seen from all these trials.

But in the real world, that may not be applicable. In terms of resources, in terms of providing safety in the long run, it makes more sense for us to give the induction regimens using quadruplets, and then the maintenance using single-agent maintenance.

Daratumumab as a single agent is 1 of the most effective anti-myeloma agents with minimal side effects, yet even if there are minimal side effects every side effect needs to be addressed in the best possible way.

So what can you expect in the first cycles of daratumumab? Infusion-related reactions used to be a big deal, and management of infusion-related reactions to give the drug in the safest way used to be the practice with the IV version. With the transition to the subcutaneous version of daratumumab, which was approved 3 years ago, we have seen a significant mitigation of these adverse events.

And what was considered in the past to be a huge issue with the infusion-related reactions is no longer an issue. So, the first cycle, or the first dose and the second dose the patients need to be monitored very closely. In our practice, we typically keep the patients waiting for 4 hours or so after the first dose, which significantly declines as we go, starting the second dose [and] onwards.

So again, this is based on the median time [of] an infusion reaction based on the ... trials and the COLUMBA trial. Now, infusion reactions are not an issue. What are the specific issues that you can see with daratumumab?

Daratumumab is a good anti-myeloma agent, but it is used in a combination with lenalidomide or dexamethasone in the induction setting. So, the rates of neutropenia, anemia, [and] thrombocytopenia are slightly higher compared to what you see with the 3-drug regimen.

What else could you anticipate in the long run? There were infectious complications. This is an effective treatment. It not only affects the malignant plasma cells [but] the normal plasma cells are affected as well.

You can see hypogammaglobulinemia as an adverse event that you could see in the long run with [the] usage of daratumumab, and patients who have [a] higher risk of infection, who already have an infection as secondary prophylaxis would start IVIG [intravenous immune globulin] in these patients.

Daratumumab can also cause hepatitis reactivations. So anybody that has a positivity for the serologies, we certainly would like for them to be receiving antibody prophylaxis. These sufficient therapies really help to control the reactivations.

Transcript edited for clarity.

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