EHA 2021 | Real-world application of NCCN guidelines in CLL/SLL

Just to understand the idea of what we did with this registry. We started this registry for the informCLL registry to include patients that were treated in the community and also in academic centers in the United States. And these went over several years. We enrolled 1,462 patients with more of the 90% of the patients coming from community practices. So, this is real, like real-world data what’s being done in the United States.

58% of the patients were previously untreated and 42% of the patients had previously had relapsed or refractory disease. And so, the objectives of our study were to summarize how the treatment regimens received by the patients that participated in the registry compared or aligned with NCCN recommended regimens for CLL/SLL in the United States and in other countries outside of the United States. NCCN guidelines can only provide a backbone of where or what treatment regiments are suggested for patients depending on their characteristics, diagnosis, and comorbidities.

And so, in this particular study, what we found out was a large proportion of the patients were not tested for 17p deletion or TP53 mutation, and unfortunately, those are, to our knowledge, the most important prognostic biomarkers because they identify patients that should not be treated with chemoimmunotherapy, or should be prioritized for treatment with clinical trials or targeted agents. Now with targeted agents, as these patients do not respond well to chemoimmunotherapeutic regimens.

What we identified was that we applied and compared the NCCN guidelines compared to the patients that participated in the informCLL registry and for patients that had the TP53 mutation or 17p deletion, about two thirds of the patients received the recommended regimens. But one quarter of the patients still received non-recommended chemoimmunotherapy with bendamustine and rituximab, or FCR. And why is this important? SO, these patients were exposed to toxic chemoimmunotherapy regimens, and we know that these patients, even though they may respond, the response is very brief, and they will be have to salvage with targeted agents.

So, we still need to educate our patients and our community physicians and our academic physicians that TP53 mutation and 17p deletion should be tested on all patients. For most patients without the deletion 17p or TP53 mutation, they did receive the recommended regimens across age and comorbidity groups, even though there were some patients that did receive patients, and not recommended regimens. The most common treatment regimens amongst the patients that had the deletion 17p or TP53 mutation, we use for ibrutinib, chemoimmunotherapy, and anti-CD20 monoclonal antibody, such as rituximab or obinutuzumab.

Considerations about our study that were in real-world registries like this, the informCLL rely on side reported information. So, some data may be incomplete or missing, we identify the comorbidity index based on what had been input in the data, on the database. And so, as such, we felt that the comorbidity index in this particular study results was not as high as some other registries, and it might be because some of this information had not been input. The other thing that we felt was important to know these are the treatment guidelines continued to evolve, the treatment decisions may change to reflect the most current guideline recommendations.

This registry actually provides a unique opportunity to evaluate CLL treatment patterns in a real world clinical practice setting. And the important information that we identified was that most of the patients were treated with the appropriate regimens that were recommended by the NCCN guidelines, but one third of the patients in the registry had no data available for deletion 17p or TP53 mutation. And so, these patients may have received sub-optimal treatment with chemoimmunotherapy, because we just never identified that.

So, these results underscored the need to not only know the regimens that should be used for patients as per guidelines, but also to identify any particular prognostic marker prior to initiation of any therapy, whether it is at initial therapy or at relapse/refractory time therapy, because these may change the way that you select a treatment for the patients.

That’s more or less in a nutshell what we did and it was good to learn that we are as much as we have excellent drugs for our patients with deletion 17p or TP53 mutation, we’re still not doing the optimal treatment strategy for all of them, at least here in America. So, we still have some education to do, not only for physicians, but also for patients so that they are aware that this is very important once they have the diagnosis of CLL.