Three Specialists Offer Outlook on Employing Pomalidomide in Multiple Myeloma

Noopur Raje, MD

As therapy options for patients with relapsed or refractory multiple myeloma have expanded in recent years, so have clinical considerations about how best to incorporate new agents into the treatment paradigm.

Three experts in multiple myeloma tackled questions about integrating pomalidomide (Pomalyst) into the management of patients as part of an OncLive Insights video series program on multiple myeloma. Pomalidomide, which the FDA approved in 2013, is the third generation of the immunomodulatory drugs (IMiDs) that have long been employed in combination therapies for the malignancy.

Participating in the OncLive Insights program were Noopur Raje, MD, director of the Multiple Myeloma Program at Massachusetts General Hospital; Sagar Lonial, MD, vice chair of Clinical Affairs in the Department of Hematology and Medical Oncology at Emory University School of Medicine; and Ann McNeill, RN, MSN, an advance practice nurse specializing in multiple myeloma at John Theurer Cancer Center.

OncLive: When would you incorporate pomalidomide?

Noopur Raje: If you look at the pomalidomide label, you can use pomalidomide if you’ve seen lenalidomide and a proteasome inhibitor like bortezomib before. A lot of the trials had enriched for patients who were refractory to lenalidomide and still responded to pomalidomide. For example, if you look at MM-003, which actually got pomalidomide its approval in Europe, 75% of those patients were even refractory to bortezomib [Lancet Oncol. 2013;14(11):1055-1066].

So, certainly, in refractory patients, pomalidomide is a great drug. But, even so, if you’ve seen lenalidomide and bortezomib and have gotten maximal benefit out of that, I think going to pomalidomide is perfectly reasonable.

Pomalidomide in combination with dexamethasone is generally very well tolerated. And what we’ve learned with the IMiDs is that as we’ve gone from thalidomide to lenalidomide and now pomalidomide we’ve gotten better at managing the toxicities but also more so, I do think the toxicity profile has improved with the IMiDs.

When we first starting using thalidomide, we saw a lot of neuropathy. We saw a lot of constipation, and, at that time, we were using much higher doses. When we went to lenalidomide we saw a little bit of neuropathy, not a lot of constipation, and if you look at the doses we’re using, it goes to speak to the potency of these drugs. We started with 100 mg and 200 mg on thalidomide. Lenalidomide is 25 mg, and now with pomalidomide we’re using 4 mg, suggesting that we’re getting to more potent compounds which are a little more specific, and some of the toxicities that you see may in fact be off-target toxicities.

So coming to pomalidomide, it’s generally extremely well tolerated. The big toxicity that we encounter with the pomalidomide is myelosuppression. Even with skin rashes, which are a little more common with lenalidomide, about 20% to 25% of people will have the skin rashes associated with lenalidomide. You don’t see that same incidence with pomalidomide.

Neuropathy is seen, but, again, it’s much lower with pomalidomide. It’s very convenient because it’s oral and most of us start off using it at 4 mg, and depending n how patients are doing, you can always dose adjust.

How do you use pomalidomide? And it what line do you find it most effective?

Sagar Lonial: Pomalidomide is a drug that we’ve used a fair amount in the relapsed and refractory setting. Again, it tends to be in a lenalidomide-resistant patient population, and the advantage of pomalidomide is that it’s a pill. Patients can take it and come back and see you once a month or twice a month, depending upon their blood counts, and it’s a relatively straightforward regimen to use.

In the refractory setting, when do you incorporate an agent like pomalidomide or carfilzomib?

Ann McNeil: Those two drugs are the two newest agents that have been FDA approved for myeloma, and we use them in the relapsed/refractory setting. So both of these drugs are used in very specific indications, a very specific patient population.

These are patients who have had prior therapies. They have seen bortezomib in their past treatment history. They have seen an IMiD. For pomalidomide, they have had to have seen lenalidomide and they are refractory to their last treatment option. So they are either progressing right through that treatment or we stopped treatment for some reason, and within 60 days they have evidence of disease progression. They are considered refractory, and that’s when we would consider using either of those agents in that patient population.

What are some of the common toxicities a patient encounters on pomalidomide and how you handle those?

McNeil: Neutropenia I would say is the most common hematologic toxicity. It’s very manageable. We do see patients on a frequent basis when they start pomalidomide therapy.

Our policy in our cancer center is that for the first two months, we do see them at least every other week and most of the time we see them weekly. Patients with relapsed/refractory disease usually are not coming to us with very good blood counts, so we do want to keep an eye on their blood counts. It’s a very well tolerated drug. We do see fatigue. Fatigue seems to be something we can’t get away from for any of our patients regardless of the treatment option.

We also see constipation and diarrhea to a lesser degree than some of the other agents. We have seen some rare cases with confusion, but, again, we are always looking to rule out other etiologies for any kind of neurological symptom in this patient population before we attribute it to the drug. These patients are usually heavily pretreated. Some of them have preexisting neuropathy, so we are looking for any exacerbation of neuropathy in all of our patients, but, in general, pomalidomide is a very well tolerated agent in this setting.

Have you ever had to discontinue pomalidomide based on toxicity?

McNeil: We were involved in many of the clinical trials for pomalidomide so we did have to discontinue based on the guidelines as dictated in the clinical trial. We do discontinue pomalidomide, but for most of our patients the discontinuation is due to disease progression and not really intolerable toxicity.