New Biological Insights and Recent Therapeutic Advances in the Management of Acute and Chronic Leukemias and Myelodysplastic SyndromesComparison of adult and pediatric treatment regimens for ALL and the use of pediatric regimens in the adult population
5:00 minutes.
TRANSCRIPTION:
DR STOCK: There are 2 general approaches to treatment in adults with ALL and 1 approach in children with ALL. And the pediatric approach has focused on intensification over years of steroids, vincristine and asparaginase-based regimens with intensive intrathecal therapy and 6 to 7 months of intensive multiagent combinations, which are complicated but very noncross-resistant drugs and then prolonged maintenance therapy. The adult regimens, many in the United States in the adult cooperative groups, for the most part, have evolved from those regimens but have focused not so much on the intensification of those 3 groups of drugs that I mentioned, vincristine, asparaginase and steroid. And so that’s one school of thought. It’s also clear that the drugs that I just mentioned are more difficult to tolerate in older adults, the vincristine, the steroids and the asparaginase. And so it’s probably a combination of things, why those regimens evolved the way they had evolved. But the world is shifting and there’s a different approach to ALL, which Hagop can mention, because it was developed at the MD Anderson Cancer Center. And it’s a different approach that doesn’t focus so much on the intensification of asparaginase-related treatment, and it is the hyper-CVAD regimen, which many people are familiar with. And both approaches have been used in the United States in the adult population. What we did in our patient population in our cooperative group setting was we looked at our outcomes and we realized that young adults would benefit, potentially, from a pediatric-like regimen. And so over the last decade, we basically stole a pediatric regimen, a highly successful pediatric regimen, and we applied it exactly to that group of patients, young adults with ALL, in the cooperative group settings. DR KANTARJIAN: So historically what has happened is, in the United States, the adult ALL regimens have abandoned the principles of pediatric ALL. They shifted to shorter maintenance with pumps and to reliance on autologous and allogeneic stem cell transplant. And then guess what? We were surprised that the results using adult regimens in the adolescent young adults were worse. This is what Wendy started with, and then it was reproduced across several adult regimens used in adolescent young adults. The Germans stuck with the principles of the pediatric regimens, and they have as good results. And they do use asparaginase, although asparaginase is prohibitive once you get to age 40 or above. DR LOVE: Can I just ask why? DR KANTARJIAN: Because they get much more pancreatitis. The incidence of pancreatitis is 10% to 15%. They get thrombotic events. They get liver dysfunctions, which is severe but transient in about 30% of the patients, so that delays the therapies. Also, the reliance on high-dose continuous steroids and vincristine is toxic in people when you start talking about age 60 or older. We have used the hyper-CVAD regimen. People may not like it, because it’s myelosuppressive and is associated with the usual myelosuppressive complications. But because of the pressure as a result of the studies by Wendy and others demonstrating that pediatric regimens were better in the adolescent young adults, we applied the exact augmented BFM to people up to the age of 40. And what we found is, our results now, with about 130 patients, are identical with the R-hyper-CVAD. Surprisingly, there is a higher incidence of CNS relapses with the augmented BFM, even though we use 16 to 22 intrathecals compared to only 8 with the hyper-CVAD. And I think it’s because there’s no high-dose ara-C with the augmented BFM regimen. So now there are 2 regimens which could be used. One is pediatric asparaginase based. And this is where the cooperative groups are going with this kind of a regimen up to the age of 40 or 50. At MD Anderson, we get a lot of pushback from the leukemia doctors, because they are used to the R-hyper-CVAD and they know how to deal with the myelosuppressive complications, as opposed to the asparaginase. If you use the pegylated asparaginase, I think you have to be cautious. Once you start using it in over the age of 50, there are complications. And some people resort to a maximum flat dose of 3,750. So, it’s 2,000 mg/m2, but 3,750, which will be the ampule and maximum upper limits, flat dose. |