ICML 2023 | Outcomes of autoSCT, alloSCT & CAR-T cell therapy in patients with TP53-altered MCL
Marcus Messmer, MD, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, discusses a retrospective study evaluating the outcomes of patients with TP53-altered mantle cell lymphoma (MCL) following autologous stem cell transplantation (autoSCT), allogeneic SCT (alloSCT), and CAR-T therapy. While there was an improvement in event-free survival (EFS) in the overall population following autoSCT, this was not observed in patients with TP53-mutated disease. Furthermore, there was no improvement in EFS in those receiving alloSCT or CAR-T therapy, suggesting the need for earlier incorporation of these approaches in this high-risk patient population. This interview took place at the 17th International Conference on Malignant Lymphoma (ICML), held in Lugano, Switzerland.
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Transcript (edited for clarity)
So we know from numerous prior studies that TP53 alteration and particularly TP53 mutation is associated with very poor prognosis in mantle cell lymphoma and attempts to overcome this with more aggressive chemotherapy, autologous transplant, have really not been very successful. So some of the attempts that investigators have looked into to try to achieve long-term remissions in this population include allogeneic transplant and CAR-T cell therapy...
So we know from numerous prior studies that TP53 alteration and particularly TP53 mutation is associated with very poor prognosis in mantle cell lymphoma and attempts to overcome this with more aggressive chemotherapy, autologous transplant, have really not been very successful. So some of the attempts that investigators have looked into to try to achieve long-term remissions in this population include allogeneic transplant and CAR-T cell therapy. And so we wanted to look specifically at this TP53 altered population across many institutions to see if we could get any insights about whether these more aggressive approaches could achieve long-term remission in this high-risk population. And so we looked at the overall TP53 mutated and deleted and overexpressed population with a total of 254 patients. And then we looked specifically at autologous transplant, allogeneic transplant and CAR-T cell therapy. In terms of autologous transplant, we did see an improvement in event-free survival for the overall population that was associated with autologous transplant. Although when we look specifically at the TP53 mutated population, we did not see a benefit and there was no overall survival benefit in either the total group or in the TP53 mutated group. And we know that the patients with TP53 mutation particularly are the highest risk. In terms of allogeneic transplant and CAR-T cell therapy, both of these had pretty short even-free survivals after treatment. So for allogeneic transplant, it was just 1.5 years. And for CAR-T cell therapy, it was just 0.9 years. I think that the caveat here is that these patients were pretty heavily pretreated. So it remains to be seen whether particularly with CAR-T early incorporation of this strategy may be more successful because I think that with TP53 mutation, you have a tendency to develop other mutations over time and have clonal evolution, particularly with chemotherapy. And so it’s possible with a non-chemotherapy approach upfront, followed by CAR-T cell therapy, that you may see better outcomes than what we saw in our study.
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