MCD Clinical Trials and Treatment at an Expert Center

Corey Casper, MD, MPH:One of the most common questions that faces a patient and a provider after the diagnosis of Castleman’s disease is what are my chances? What happens next? What is the prognosis with this disease? The challenge in this is that many patients and providers will look at the Internet and will find studies that show very high mortality rates with multicentric Castleman’s disease, and that can be very alarming. Some studies you can find on the Internet show that less than 50% of patients are alive five years after diagnosis. I think all of the studies that exist to date, one has to be very understanding of the fact that the patients included in these series where they draw the nice survival curves are patients who are referred and are diagnosed at expert centers, so they’re the more severe cases. For your common patients who may not have the severe manifestations of the disease, they may not be included in these reviews.

But, a recent review, looking back at several hundred cases, found that for unicentric disease over five years, the survival rate was in excess of 95%. For multicentric disease, again, for patients who receive various treatments, the 5-year survival was in excess of 90%. In my own experience, in my clinic where we have several hundred patients with Castleman’s disease, those who are in treatment, and by that I mean even watchful waiting, but for those who are under observation and being managed aggressively, none of our patients have experienced mortality due to Castleman’s disease. I have seen cases of Castleman’s disease that have progressed to lymphoma, that have been missed, or cases of Castleman’s disease that were not treated aggressively upfront, and those cases have led to death. But, I would say the majority of our patients, over 90% even with multicentric CD, the 5-year survival is excellent. I tell my patients that they’re likely to enjoy a long and healthy life, especially if they manage to get the disease treated and respond well to treatment.

The only way that we can advance new therapies for rare diseases like Castleman’s, or even common diseases, is to do clinical trials. The only drug that’s been licensed, to date, for the treatment of Castleman’s disease came to be licensed through carefully designed clinical trials that took years to complete. But, [these trials] are so essential in informing how we deal with Castleman’s disease, and there are so many unanswered questions that remain. Unanswered questions remain about the frequency of administration and the duration of administration of therapy, the optimal sequencing of therapy for relapsed or refractory disease, and treatment of unicentric versus multicentric or idiopathic versus human herpesvirus-8—associated MCD. So, there are many, many questions that we don’t yet understand the answers to and only will gain the answers if patients participate in clinical trials.

Unfortunately, we know from national data that in the setting of cancer, even a severe disease, for which everyone wants new answers, only 3% of patients at most cancer centers actually participate in clinical trials. This is an enormous missed opportunity for patients. Enrolling in a clinical trial allows access to a therapy that can be really revolutionary. For the first several years that siltuximab was being tested, it was only available through a clinical trial and patients who had access to it had remarkable successes. So, I would say that it’s essential that we continue to design and deploy clinical trials, and that we continue to encourage our patients to enroll and participate in these to answer those remaining unanswered questions and help us to advance new and more effective therapies or use existing therapies more appropriately in a setting of this very rare disease.

A very important question in patients with Castleman’s disease is when to treat, what to treat with, how to treat, and how to monitor. And, these are all very complicated decisions. Although I’m biased, I would definitely say that for patients with a rare disease, it’s important to see specialists or providers who have seen other patients with that rare disease. And, unfortunately, for Castleman’s, because it is such a rare disease, there are very few centers where a critical mass of Castleman’s patients have come and where the experience with those patients is recognized by a small group of providers. I think just like anything else in life, the more often you do something, the better you become at it. It has nothing to do with brilliance or clinical prowess of providers who are at specialty centers, but I think it just is really attributable to seeing enough volume of patients with Castleman’s disease to understand when therapy isn’t going well or what the variations are in the disease that prompt you to choose one therapy or the other, or even the best way to monitor patients, or what might be subsequent clinical trials that offer options for patients that have little options, otherwise.

I do believe that a patient with Castleman’s disease may be best to visit a specialty referral center where there are a number of patients with Castleman’s disease. Oftentimes, that may just be a single visit to confirm the diagnosis to establish a treatment pattern, and then these patients can be referred back to referring providers that may not have as much experience. I think through that interaction, you can actually build the capacity to treat this rare disease in the community setting. For myself, we had a number of patients referred to our specialty center, actually by the same providers in the community, and now after referring a couple of patients and discussing and reviewing management plans, those providers feel very comfortable treating patients with Castleman’s disease. Certainly, the ease of administering some of the newer therapies like siltuximab makes treatment in the community, and not at specialty centers, a really viable option. Not everyone can get to a specialty center. It can be challenging or expensive, and so, I think that, over time, as this disease becomes more broadly understood, more treatment can be given outside the specialty centers. But, I think today there still is value for a patient being seen by a provider that has seen a large number of Castleman’s patients and has a lot of experience in the disease.

Corey Casper, MD, provides information on the diagnosis and treatment of patients with Castleman Disease (CD).

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