Exploring the CLL14 Trial in Untreated CLL After 4 Years of Follow-up

Othman Al-Sawaf, MD, a physician at the University Hospital of Cologne in Germany, discusses the use of venetoclax (Venclexta) plus obinutuzumab (Gazyva) in patients with untreated chronic lymphocytic leukemia (CLL) on the CLL14 study (NCT02242942).

This open-label, multinational trial was started several years ago and now has 4 years of follow-up. The data showed there was better progression-free survival (PFS) in patients who received venetoclax plus obinutuzumab. Al-Sawaf describes the design and patient population in this trial, as well as the clinical implications of the results.

Transcription:

0:08: CLL14 is a randomized phase 3 study that was started several years ago and that's aims to enroll patients with previously untreated CLL with coexisting conditions. The patients were randomized to either receiving 12 cycles of chlorambucil/obinutuzumab or 12 cycles of venetoclax/obinutuzumab. The primary end point of the study was PFS. The primary read out of the study showed that there is a significant advantage in terms of PFS by the novel BCL-2 targeting treatments of venetoclax plus obinutuzumab.

The main aim of these ongoing follow-ups now is to better understand the long-term outcome of this fixed duration approach and basically to better understand how and when the disease progressions eventually occur, as we don't expect that the treatment is curative for most of the patients. his is basically why we are at this year’s EHA (European Hematology Association) Meeting presenting new data from longer follow-up. All patients in the study have been off treatment now for more than 3 years. This allows us to understand the long-term toxicities, the long-term efficacy, and the durability of the remissions eventually in both arms.

1:32: The study population and CLL14 is relatively special in that all patients have coexisting conditions. This was the main inclusion criteria. This was assessed by the cumulative illustrating scale, where all patients had to have more than 6 points suggestive of clinically relevant burden of coexisting conditions. Additionally, also impaired renal function with creatine clearance below 70 mL/min as this is a good surrogate also for the fitness of the patients. We can see in the baseline characteristics of the patients, that the median age was 72 to 73 years of [age], so a fairly elderly patient population. Also the median [score was 8] points, also suggesting that we do have a patient population with relevant coexisting conditions.

I think this is important to bear in mind when looking at the long-term data because we do see now that we are able to control the disease quite well with our BCL-2–targeting treatments. Although we do have a strong competing risk in all our survival analysis by the coexisting conditions, and therefore I think it is important to bear in mind that our patient population is quite vulnerable and is at risk of having cardiac events and other sorts of complications of the coexisting conditions.

3:00: The data suggests that frontline approach with venetoclax plus obinutuzumab is very feasible and very effective for an elderly patient population. We are in an interesting situation because the treatments in Europe and the United States is approved for all patients with previously untreated CLL. Whereas in this study, we are very strict and only enrolled elderly and unfit patients. There are ongoing studies that also enroll fit patients and let compare this treatment to more intensive chemoimmunotherapies than chlorambucil. We expect the first readouts within this year or early next year. But nevertheless, the fact that we see such deep remissions and MRD [minimal residual disease] rates higher than 70% in this elderly patient population are highly suggestive of similar efficacy also in younger and fitter patients. Therefore, I think overall, we can recommend—and I think most of the treatment guidelines that exist at the moment also reflect that we can recommend the treatment for all patients with previously untreated CLL. We also looked at different subgroups and see overall that the treatment is better for all biological and clinical subgroups compared to chemoimmunotherapy and therefore we can recommend it for all patients with previously untreated CLL irrespective of low- or high-risk CLL.