It doesn't appear that ibruvica is active against the GCB subtype.
this could be a way to get an accelerated approval of breakthrought therapy for our little combination.
•Patients with the ABC subtype showed a preferential response to ibrutinib monotherapy compared to those with the GCB subtype (ORR = 41% vs 5%, respectively, p=0.007, Fisher's exact test).
•Median overall survival (OS) was 9.7 months for the ABC subtype, compared to 3.35 months for the GCB subtype.
•Safety data from 70 patients identified no new safety signals. Grade 3 or higher AEs were seen in greater than 3% of patients and included fatigue (9%), hyponatremia (9%), pneumonia (7%), dehydration (4%), and pleural effusion (4%).
Dr. Younes: One can consider the same agents [outlined above, as they are] also showing some activity in diffuse large B-cell lymphomas. Ibrutinib preferentially has activity in the non-GCB—[or] non–germinal center type—mainly the ABC subtype or the activated B-cell lymphoma subtype of diffuse large B-cell lymphoma.12
The PI3 kinase inhibitors as a class have not shown much activity in diffuse large B-cell lymphoma.3 Somehow, if you treat with mTOR inhibitors, which is [targeting] downstream of the PI3 kinase, there seem to be higher response rates compared with PI3 kinase inhibitors. So, for example, with everolimus or temsirolimus, one can achieve a 30% response rate range,13-16 compared with a less than 10% response rate for the PI3 kinase inhibitors. But this is a pathway of interest that is frequently activated in diffuse large B-cell lymphoma, and I think we'll see more trials targeting this pathway in the future.
In diffuse large B-cell lymphoma, there are data to suggest that lenalidomide has preferential activity also in the ABC subtype.17-20 And based on these data, there are two trials combining lenalidomide with R-CHOP concurrently or giving lenalidomide in maintenance or adjuvant setting after R-CHOP chemotherapy. Those trials are ongoing, and hopefully we'll get some information, again, in the next few years from now.
Narrator: Currently available data from the trials integrating lenalidomide in the R-CHOP regimen have shown an acceptable toxicity profile. The two-year overall survival was greater than 90%, and the two-year progression-free survival rate was 75% to 80%.19 A retrospective analysis also indicated that most of the benefit from adding lenalidomide to R-CHOP was limited to the patients with a non-GCB phenotype.20
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