Treating Young Adult Patients With Philadelphia Chromosome-Negative ALL

Richard M. Stone, MD: Let us talk about our approach to treating these patients. Let us say there is a Philadelphia chromosome–positive patient who is 30 years old. I would like to go around and see how people would treat that, because there are going to be some huge differences.

Ryan D. Cassaday, MD: We would call in an old-school approach. The best long-term data I’ve seen from any prospective trial in treating adults with Ph-positive ALL [acute lymphoblastic leukemia] were those from SWOG 0805, where hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone] was given in combination with afatinib with a plan to proceed on to a myeloablative transplant in first remission. Outside the context of a clinical trial, that is typically how I will manage a young adult with Ph-positive ALL who was otherwise fit and wants to be aggressive. There are certainly some exceptions to that, but that would be the usual approach.

Bijal Shah, MD: We at the Moffitt Cancer Center, have adopted hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone]–ponatinib combination especially for young adults in large part because it seemed to equate to a higher rate of MRD [minimal residual disease] negativity and a lower rate of transplant. The hope is to avoid that if possible. As more data are collected, whether that is going to be successful will be discovered. But the early data from the University of Texas MD Anderson Cancer Center group suggest that that was a highly effective mechanism to engender MRD negativity by 3 months.

Richard M. Stone, MD: Jae, what do you think?

Jae Park, MD: This is a little controversial, but for the younger guys, like a 30-year-old, we can do a TKI [tyrosine kinase inhibitor] plus chemotherapy vs dasatinib—or ponatinib later, but dasatinib plus a blinatumomab induction. I struggle to know what the right approach is. These patients are sent to transplant, especially the 30-year-old. I do not know whether they need it. The longest data are with a consolidative bone marrow transplant, although MD Anderson 2011-0030 hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone] data have 73. There will be a longer follow-up soon without the transplants.

Because of this study, these patients are sent to transplant. Given the D-ALBA study that was recently published, dasatinib plus blinatumomab with high rates of molecular CR [complete response] rate, which is quite comparable to ponatinib plus hyper-CVAD rate. This spares chemotherapy altogether. The post-transplant outcome may be better in terms of the tolerability of the regimen and the fitness of the patient. Although these are younger patients, so it may not matter as much. These 2 approaches can be used leaning toward a blinatumomab-based approach. In some of these patients the trouble is whether they need a transplant. However, a blinatumomab-based approach is used even in younger patients.

Richard M. Stone, MD: The D-ALBA approach has been used with the full induction for 85 days (about 3 months) and then giving them blinatumomab, regardless of their MRD status, followed by a stem cell transplant. This was recently used with a Harvard medical student who’s about 24 years old. 

Ryan D. Cassaday, MD: There was a lot of excitement about that combination. When you get published in the New England Journal of Medicine, you are doing something right. The issue seen from that study was the relative lack of conversion from MRD negativity after the dasatinib and prednisone induction. Whether that is some immunosuppressive effect of the preceding therapy, consider what the German experience has been in chemorefractory MRD with high rates of conversion to MRD negativity. There may not be as much efficacy out of the blinatumomab on the back end of that regimen as maybe otherwise seen.

For patients, because the risk of serious toxicity from chemotherapy in younger patients is quite low, at least in the modern era, there is less worry. The follow-up on that study is short when you consider particularly younger patient population where we have historical paradigms of established ways to treat these patients with a high rate of cure. It is a good option for patients, but not all are ready to wholesale incorporate it to everybody.

Richard M. Stone, MD: ECOG [Eastern Cooperative Oncology Group] will be leading the trial…comparing TKI hyper-CVD to the Italian approach. If people enroll in that trial, someday we will answer that question.

Transcript Edited for Clarity