Nakhle Saba, MD

Nakhle Saba, MD, associate professor of clinical medicine at Tulane University School of Medicine, discusses the significance of the key findings of the ELEVATE-TN trial (NCT02475681) of acalabrutinib (Calquence) with or without obinutuzumab (Gazyva) for patients with chronic lymphocytic leukemia (CLL).

The phase 3 multicenter trial randomized 535 patients with previously untreated CLL 1:1:1 to receive the Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib plus obinutuzumab, acalabrutinib alone, or chlorambucil plus obinutuzumab. BTKis have previously showed efficacy first-line versus chlorambucil such as ibrutinib (Imbruvica) in the RESONATE-2 trial (NCT01722487).

Median progression-free survival (PFS) was not reached for either acalabrutinib arm at a median follow-up of 46.9 months versus 27.8 months for chlorambucil plus obinutuzumab. The results suggested that acalabrutinib plus obinutuzumab had prolonged PFS versus acalabrutinib alone, but the study was not powered to compare the 2 experimental arms. Saba says this is not enough evidence to suggest the combination will benefit patients over acalabrutinib alone.

Acalabrutinib was approved by the FDA based on these results as well as those of the ASCEND (NCT02970318), which enrolled patients with relapsed/refractory CLL to receive acalabrutinib monotherapy. Saba says that based on current data, he would not add an anti-CD20 such as obinutuzumab when giving a BTKi in the frontline or relapsed setting.

 We know that BTKi is superior to chemotherapy and that was reproduced in the ELEVATE-TN trial. The other key is whether an anti-CD20, particularly with regard to obinutuzumab—does it add anything to acalabrutinib single agent or not? So we know both arms, acalabrutinib plus [obinutuzumab] are superior to the chemoimmunotherapy arm, but what does obinutuzumab add to acalabrutinib? This study was not powered to look at that difference, although the odds ratio favors the combination with obinutuzumab over acalabrutinib alone. But this study was not powered to look at that difference.

So, for me, that’s still not convincing evidence that anti-CD20 adds any value to BTK alone in this particular setting. Acalabrutinib [is] awaiting more data, if any, I will see. But as of now, I would still favor if I’m using BTKI, either frontline or into relapse, I would not add an anti-CD20 to the mix unless with some very rare exceptions. But overall, I would not add it.

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Nakhle Saba, MD, discusses the significance of the key findings of the ELEVATE-TN trial of acalabrutinib with or without obinutuzumab for patients with chronic lymphocytic leukemia.

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Interpreting the Results of the ELEVATE-TN Trial for Treatment-Naive CLL