Amit Patel, BSc, MBBS, PhD: Optimal patient selection and sequencing are important considerations for potential CAR[chimeric antigen receptor]T candidates. If we think about patient selection, its important to remember that autologous CAR T-celltherapy is not high-dose therapy, so it isnot the same asautologous stem cell transplantation and is also not the same as allogeneic stem cell transplantation. In other words, the lymphodepleting chemotherapy is not likely to cause significant organ impairment and is likely to be deliverable to patientswho are much older and more comorbid than those patients who would not be otherwise suitable for autologous allogeneic stem cell transplant.

When somebody has either been refractory orhasrelapsedafter first-line therapy, thats the time to think whether somebody is likely to be a candidate for CAR T therapy.If theyre not a candidate for autologous stem cell transplant,then they will have second-line therapy but invariably will relapse. By that point, that patientat the earliestopportunity shouldbe puton a CAR T treatment pathway.Arguably, thatpatient is already on a CAR T treatment pathway if theyhave relapsed or not responded to first-line therapy and are unable to be considered a candidate for autologous transplant.

For patients who have relapsed/refractory disease after first-line therapy who are potential autologous stem cell transplant candidates from a fitness perspective, those patients will go on to receive platinum-based salvage therapy. Unfortunately, half of patients will not respond to salvage and therefore will transition to an autologous CAR T therapy treatment pathway. For those patients who do respond, some patients will still end up not being able to go on to receive autologous stem cell transplant because either they cant have peripheral blood stem cell harvest undertaken or undertaken in a timely manner such that they have disease that hasnt relapsed within that time frame.Those patients will then end up moving to an autologous CAR T treatment pathway.You can see now thatthe majority ofpatients could be considered potential autologous CAR T patients in the relapsed and refractory setting for DLBCL[diffuse large B-cell lymphoma].

In terms of patient selection, there is no upper age limit for this therapy because its not high-dose therapy;its an immune effector cell therapy.The chemotherapy is not limiting,andreallyits the ability to tolerateadverse effects,including cytokine release syndrome and neurotoxicity. We also know that in terms of patient selection, lower thresholds can be applied for renal function.For example, the EBMT[European Society for Blood and Marrow Transplantation]recommendation is a creatinine clearance of 30mg/g. We also know that lower cardiac ejection fraction is tolerated, so the EBMT recommendation is also lower than what we would typicallyacceptfor autologous or allogeneic stem cell transplant.

Its important toremember that these potentially nontransplant-eligible patients, of which there are lots in the relapsed/refractory setting, are candidates for autologous CAR T therapy. The other way I would think about this is really anybody who has DLBCL who failed first-line therapy shouldbe consideredfor autologous CAR T therapy, and that consideration should be actively excluded if somebody is not suitable.


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EP. 4: Optimizing Patient Selection for CAR T-Cell Therapy - OncLive

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