Is there any benefit to transplant patients with Ph+ ALL who have achieved MRD-negativity?

First, some semantics: Asking if there is a "benefit to transplant" may imply there are randomized controlled trials addressing this question, but none to my knowledge have been performed. The last "donor-no donor" trials done in adults with ALL in first remission largely occurred in the pre-TKI era and before the routine incorporation of MRD testing (e.g., UKALL12/ECOG 2993 [Goldstone et al., PMID 18048644]). Thus, any conclusion that transplant provides benefit in this situation must rely on extrapolation from cross-trial comparisons.

The group from MD Anderson Cancer Center has reported relatively good outcomes for adults with Ph+ ALL treated with hyperCVAD + TKI who achieve a complete molecular response (i.e., undetectable BCR::ABL1 RT-PCR) by 3 months (Short et al., PMID 27235138) without the use of allogeneic HCT in a retrospective analysis. They have also shown excellent results with hyperCVAD + ponatinib without HCT in a prospective trial (Jabbour et al., PMID 30501869). Based on data like these, one could conclude that these approaches could be used to avoid HCT in first remission and still achieve long-term remission. However, the single-center nature of these trials does raise concerns about potential bias. It is also unclear how easy it is to acquire ponatinib for someone with newly-diagnosed Ph+ ALL; in my practice, I often have to document failure of other TKIs or the presence of a T315I mutation in order to get insurance authorization for this drug.

Newer approaches using blinatumomab plus TKI have shown very impressive 1-2 year survival rates without the routine use of transplant (e.g., Foà et al., PMID 33085860). Follow-up from these approaches is still too short for me to consider as the new standard of care. Furthermore, similar issues with insurance authorization for blinatumomab could also arise with these approaches.

In my opinion, the best outcomes from a reasonably-sized multicenter prospective trial come from SWOG 0805, which used hyperCVAD + dasatinib and (when possible) myeloablative allogeneic HCT in first remission (Ravandi et al., PMID 29046900). This is a very intense approach that cannot be offered to all patients with this diagnosis. However, for someone who is relatively young, fit, and wants to be aggressive, this remains my preferred approach. Until we have longer follow-up from the blinatumomab-based approaches, and unless other studies can recapitulate the findings published from MD Anderson, I will generally only consider these other strategies in patients for whom transplant is not likely feasible (e.g., limited social support, medical comorbidities, etc.).