We will discuss about the clinical management of patients with plasma cell leukaemia, primary plasma cell leukaemia mainly. Our discussion, the one of my colleague and I, Dr van de Donk, will be to focus on what are the practical aspects. So we will start with two clinical cases to discuss how you diagnose these patients, how you make the diagnosis and then how you decide the treatment for the patient, the specific therapy, the chemotherapy, but also how you manage the several complications that you can have in these patients.
What treatments might you use for somebody with PCL?
There are two types of therapies: you can decide to treat the patient with the standard approach outside of a clinical trial. In this case the treatment of choice generally is a bortezomib based regimen in combination with chemo or with immunomodulatory agents, based also on what is available in the different countries. Then if the patient is eligible for high dose chemotherapy the suggestion is to perform a transplant because auto-transplant prolongs the survival of patients who are able to receive this procedure. Otherwise, if the patient is not eligible the treatment should potentially continue for a long time period to maintain the disease under control.
Since these patients are generally the patients with plasma cell leukaemia are patients with a far higher risk and with a very bad prognosis, we encourage also the enrolment of these patients into clinical trials so that we can treat them with newer agents that potentially have a high efficacy. So we will discuss also the clinical management of a patient that will be enrolled in a clinical trial.
Does the low incidence of PCL make recruiting for clinical trials difficult?
Because most of the patients at the time of disease presentation, because of the high tumour burden, they can have cytopenia. It’s quite common in patients with plasma cell leukaemia to have free light chains, high levels of free light chains, or Bence-Jones proteinuria also at a high level so renal failure is quite common. So we will briefly discuss also about this, about the potential occurrence of tumour lysis syndrome, because again these patients have generally high tumour burden. So if the chemo works the result is that potentially the patient can have a tumour lysis syndrome. Other complications that are very frequent in myeloma, but especially in plasma cell leukaemia, are also infections, especially at the beginning of treatment. So the point is that even with all these complications you have to treat the complication but also to treat the disease and to use the chemo otherwise there’s no way to solve the problem. So these are very complicated patients for these two reasons.
What are the common complications, and what are the treatments for those?
We have this trial that is with carfilzomib and lenalidomide so basically we are using a proteasome inhibitor and an immunomodulatory agent second generation which is a treatment that up front is not allowed, not yet, it’s not reimbursed yet at least in Europe. So this is a promising regimen that we are evaluating in a clinical trial together with Dr van de Donk and Dr Mutis in Italy. This is a promising option; we do not have yet data on this combo.
There is another agent that, to me, is very promising which is venetoclax because it works in patients with translocation (11;14) which is a quite common chromosomal abnormality in patients with plasma cell leukaemia but again we do not have data on the efficacy of this agent specifically in this subset of very high risk patients. These are drugs that are promising, there is a lot going on but we still don’t have results.
When will the data be available?
It will take us years, still years, because of the rarity of the disease. Because if you want to treat these patients in clinical trials, as you know clinical trials have inclusion criteria so since the disease is complicated not often the patient with this type of disease can enter into the trial. So the enrolment is not so easy. But we have to go on, to hold on and try to get good results.
Do you have any advice for clinicians?
Every clinician should try to be positive, even with this very aggressive disease, and to do his best to treat these patients. If the patient is very elderly and is frail it is difficult that you can solve the problem. But otherwise now we have many drugs that can work in these patients, it’s just to try to treat the patient and treat the complications and use the chemo and do your best.
