The key question is, when are cellular therapies best used for patients with del(17p), now that we have novel agents that work well but may have limited durability, especially in the relapse setting? The answer is that it depends on the patient. It is an individualized process, and we need to consider the treatment history for each patient. If he or she has del(17p) and is previously untreated, one would assume that the response is going to be much more durable than in a patient who had multiple lines of prior therapy. And then it is a stepwise approach; you would put the patient on a BTK inhibitor and see what gets the best response. A related question becomes, do you want to wait to refer the patient for cellular therapy until he or she develops clinically active, relapsed disease? Or do you want to catch that patient at the time of best response, or when he or she shows initial signs of emerging subclones that have a resistant phenotype, such as the BTK and PLCG2 mutations? Or do you wait until the patient develops increasing levels of residual disease, which we can monitor by minimal residual disease assessment?

These are complex and individualized discussions that we need to have with our patients, who are oftentimes fearful of transplant-related toxicity and morbidity. Such individuals may be difficult to motivate to move to transplant at a time when they are in remission and in good health, and are generally aware that venetoclax could be a very reasonable salvage option. Often the trend currently is to not transplant upon best response to a BTK inhibitor, but rather to put patients who have suboptimal responses or who progress on a BTK inhibitor on venetoclax next, and then to initiate the cellular therapy or transplant process. However, it should be noted that, ideally, contact with the transplant team should have already been established, and then the transplant would be planned for the time of best response to venetoclax.