Gomella Discusses Optimizing Sipuleucel-T in mCRPC

In an interview with OncLive, Leonard G. Gomella discusses the benefits, limitations, and considerations of sipuleucel-T for patients with prostate cancer.

Leonard G. Gomella, MD

In the nearly 5 years since the immunotherapeutic vaccine sipuleucel-T (Provenge) was approved, much has changed in the treatment of metastatic castration-resistant prostate cancer (mCRPC).

As more therapies are approved, additional data are presented, and treatment guidelines evolve, it can be complex to understand how and when sipuleucel-T is appropriate for use, says Leonard G. Gomella, professor and chairman of the Department of Urology at the Sidney Kimmel Cancer Center, Thomas Jefferson University, said at the 8th Annual Interdisciplinary Prostate Cancer Congress.

In an interview with OncLive at the Congress, Gomella took a second glance at the IMPACT trial, which was the basis of the FDA’s decision to approve sipuleucel-T in 2010. He also discussed the benefits, limitations, and considerations of sipuleucel-T for patients with prostate cancer.

OncLive: When is it appropriate to use sipuleucel-T?

Dr Gomella: You really have to use it in the earliest stages before patients become symptomatic. You can’t use it if they have liver metastasis, and you can’t use it with visceral metastasis; it really has to be used for bone-only mCRPC. Data show it’s better to use it in earlier stages.

There was some very interesting retrospective work done by Paul F. Schellhammer and associates examining the original IMPACT trial, which led to the approval of sipuleucel-T. In this data, if you looked at PSA and you broke it down in PSA ranges of less than 22, 22-50, 50-134, and above 134, there was almost a stair-step progression in the survival increases, with the earlier PSA levels being the lowest. In fact, the most pronounced survival averages, sometimes going over 42 to 44 months, were of patients who received sipuleucel-T with a PSA of less than 22.

This was a retrospective analysis and not part of the original study; however, it is very impressive. It just drives home the point that if you are going to use sipuleucel-T, use it early and before the PSA gets significantly elevated.

The other interesting thing about sipuleucel-T, which we currently have a paper under review for, is that we actually think sipuleucel-T works better than the IMPACT trial even suggested for one simple reason. Patients who progressed in the trial and were given the placebo were then eligible for a secondary treatment with sipuleucel-T. Therefore, a lot of patients in the control arm were ultimately treated with a modified form of sipuleucel-T based on frozen cells.

That paper is currently under review and will be presented at some upcoming conferences. This really enforces the fact that immunotherapy in prostate cancer is real, and it was really sipuleucel-T that sort of broke open the whole concept that prostate cancer could be treated with an immunotherapy approach.

How can oncologists manage some of the logistical challenges of treatment with sipuleucel-T?

When you use sipuleucel-T, there are some logistical challenges with it. It is an autologous immunotherapy, which means it has to be the patient’s own immune cells.

There are some challenges with actually setting it up. The patients have to undergo leukapheresis, their cells have to be packaged, sent to the processing plant, exposed to the PAP-GM-CSF, and then the actual activated dendritic cells are returned to the site of the patient and infused into them. That cycle is repeated about three times over a 1-month period.

There are logistical challenges, but the manufacturer has helped with this and has made much of the logistics easier for different sites. Right now, the challenge is getting an appropriate place for the leukapheresis that is convenient for both the provider and the patient. If you asked me right now what the biggest challenge was with sipuleucel-T, that is probably it. There are not as many sites around the United States as we’d like to see that can do a leukapheresis. However, the company which manufacturers the drug is good at setting up the logistics for the patient and the provider.

How do the patients react to this process?

There are many good teaching materials for patients to understand the logistics of sipuleucel-T and this new immunotherapy approach. They are well counseled about it, there are good videos online, and there are good support mechanisms made available to them, both by the provider and the manufacturer of sipuleucel-T. Patients understand that it is a little bit of a chore, but they also understand that it is an FDA approved drug and, when used appropriately, can give a significant advantage to patients.

What side effects patients should be aware of?

When you talk about sipuleucel-T therapy, the side effects are really very limited and almost all of them are associated with the infusion. To manage it we can use some diphenhydramine and some acetaminophen. We can also counsel patients who might feel a fever, chills, and a little nausea—it’s not too different than what patients sometimes get with immunizations, because it is an immunotherapy.

Again, it is the educated patient who really does the best with this. As long as the patient understands that they may feel yucky for 24 to 48 hours afterward, they are able to deal with it. Hospitalization is exceedingly rare; however, it can happen with patients who get dehydrated or feel bad enough that they can’t function, but that is extraordinarily rare.


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