ASH 2018 News : Episode 6

Video

Dr. Pagel Highlights the Top Abstracts From the 2018 ASH Annual Meeting

John M. Pagel, MD, PhD, chief of the hematologic malignancies program at Swedish Cancer Institute, highlights the top abstracts presented at the 2018 ASH Annual Meeting.

In chronic lymphocytic leukemia (CLL), BTK inhibitors have transformed the field. At the meeting, 2 randomized phase III trials comparing ibrutinib (Imbruvica)-based regimens with chemotherapy were presented. Both trials demonstrated superiority with the ibrutinib-based combinations, says Pagel.

In the first trial, patients under the age of 70 were randomized to receive either ibrutinib and rituximab (Rituxan) or standard fludarabine, cyclophosphamide, and prednisone. The primary endpoint of progression-free survival was met with a 65% reduction in the risk of relapse or death with the ibrutinib-based regimen. An overall survival benefit was also reported in those who received ibrutinib, although there was a trend toward improved survival with FCR for patients with IGHV mutations.

Another practice-changing phase III trial compared the use of bendamustine and rituximab (BR) with ibrutinib monotherapy and the combination of ibrutinib and rituximab in untreated older patients with CLL. Again, there was a 60% reduction in the risk of progression or death when patients received the ibrutinib-based regimen. However, there were more deaths in the ibrutinib-containing arms than in the BR arm. The benefit was observed irrespective of rituximab. These results suggest that ibrutinib may be better suited for patients over the age of 65.

Follow-up data from the ACE-CL-001 trial, which looked at the use of acalabrutinib (Calquence) in treatment-naïve patients with CLL, were also presented at the meeting, confirming the safety and efficacy of the monotherapy. Of the 99 patients treated, approximately 91% remained on treatment at a median follow-up of 33 months.

The phase III AUGMENT trial randomized patients with indolent non-Hodgkin lymphomas to receive either lenalidomide (Revlimid) and rituximab (R2) or rituximab alone. Results showed a 46% reduction in the risk of relapse or death with R2. In mantle cell lymphoma, 2-year follow-up on acalabrutinib (Calquence) reflected durable responses. No new adverse events were reported. The BTK inhibitor was also compared with BR but demonstrated added toxicity.

In the FLYER trial, patients with favorable-risk diffuse large B-cell lymphoma (DLBCL) under the age of 60 were randomized to receive 6 cycles of R-CHOP or 4 cycles of R-CHOP plus 2 cycles of rituximab. The experimental arm was found to be noninferior to the standard 6 cycles, suggesting that not as much chemotherapy is needed, explains Pagel.

Selinexor, an oral small molecule inhibitor, is also being tested in a phase II trial in patients with relapsed DLBCL. Although activity was reported at the meeting, gastrointestinal toxicities have prompted the question of where the drug should be placed in a patient’s treatment course.

In refractory acute myeloid leukemia, a phase III trial is randomizing patients to receive either transplant and a radiolabeled antibody or cytotoxic chemotherapy. If patients on the chemotherapy arm fail to achieve a complete response (CR) or relapse within 6 months of having achieved a CR, they are allowed to cross over. Although it is still too early to report on efficacy data, investigators learned that all patients in the experimental arm were engrafted on time without any significant increase in complications, veno-occlusive disease of the liver, or graft-versus-host disease, says Pagel.

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