H&O How much does high-dose cytarabine improve patient outcome?
PM I do not think that has been very well defined. Not all of these data have sufficient long-term follow-up to comment on overall survival outcomes. Historically, patients were given R-CHOP followed by ASCT. The MCL-2 trial, published by Geisler and colleagues, added high-dose cytarabine and rituximab, and found that the outcomes were far superior in terms of progression-free survival and overall survival. However, these outcomes may not be solely due to high-dose cytarabine. Other explanations include the addition of rituximab, other changes in supportive care, and better pathology. Cytarabine may be part of that story, but it may not be the whole story.
The better trial to evaluate the potential role of cytarabine is the MCL Younger Trial that I mentioned earlier, which is a phase 3 trial published by Hermine and colleagues that compared 6 cycles of R-CHOP vs the R-CHOP/R-DHAP regimen. In this trial, the addition of R-DHAP seemed to reduce the risk of disease progression by approximately 30%. The study also found that the R-CHOP/R-DHAP regimen prepared people for ASCT better than R-CHOP alone.
A transcript of the full interview can be read here.