PracticeUpdate Conference Series ASH 2018

First Transplant Following CART-Cell Therapy Boosts Leukemia-Free Survival inALL But patients with a history of previous transplantation did not show similar benefits. P atients with acute lymphoblastic leukemia (ALL) who receive their first hematopoietic stem cell trans-

plantation (HSCT) after chimeric antigen receptor (CAR) T-cell therapy have improved leukemia-free survival. In the phase I/II PLAT-02 trial, research- ers analyzed 64 subjects with ALL who underwent CAR T-cell therapy in the form of infusions of SCRI-CAR19v1 in order to evaluate the benefits of consolidative HSCT. According to Corinne Summers, MD, of Seattle’s Children Hospital, who pre- sented results from the trial, while most ALL patients go into remission after CAR T-cell therapy, approximately one-half of patients recur. In the trial, 14 patients either died, relapsed, or did not respond to the CAR T-cell therapy. Of the remaining 50 evalu- able subjects, 34 had a history of at least one prior HSCT, while 16 had no history of HSCT. The 1-year leukemia-free survival for those subjects who were evaluated was 76%. Overall, there was a trend toward better rates of leukemia-free survival among patients who underwent HSCT following infusion with SCRI-CAR19v1, compared with those who did not (P = .076). However, Dr. Summers reported that she and her colleagues continued to see late relapses, including CD19+ relapses at 12 and 27 months, and CD19– relapses at 41 and 37 months after infusion with SCRI-CAR19v1. “Therefore, we aimed to evaluate the role of bone marrow transplant in maintaining leukemia-free survival and overall survival in subjects who gained leukemic remis- sion for more than 63 days after CD19 CAR T-cell therapy,” Dr. Summers said during her presentation. “And we com- pared leukemia-free survival and overall survival between subjects regarding the receipt of allogeneic HSCT following a sustained remission.” “Transplant appears to improve leu- kemia-free survival,” she reported, although she added that she and her colleagues found no difference in over- all survival between the two groups. “We hypothesized this was due to continued

response to therapy following post-CAR relapse,” she said. When evaluating the 16 patients without history of transplant, 13 underwent HSCT after CAR T-cell therapy, and only 1 of these patients relapsed. On the other hand, 2 of the 3 patients without a his- tory of transplant who did not undergo HSCT after CAR T-cell therapy relapsed. There was a trend toward improved leu- kemia-free survival with the use of a first HSCT (P = .057). “Though it’s a small number of subjects, the data suggest there is a leukemia-free survival benefit for those without a his- tory of transplant who pursue a transplant once in remission following CAR T-cell therapy,” Dr. Summers said. Previous studies have shown that patients with a short duration (≤63 days) of B cell aplasia are at an increased risk of relapse following infusion with SCRI-CAR19v1. HSCT was found to be particularly bene- ficial among patients with a short duration of B cell aplasia who attained a complete response and did not relapse prior to day 63. Of the 15 patients with a short duration of B cell aplasia, 6 did not undergo HSCT,

and all experienced recurrence. Among the 9 patients who did undergo HSCT, 1 died and 2 relapsed. The rate of leu- kemia-free survival was superior for those who underwent transplantation (P = .007). As for the 34 patients with a history of transplant prior to CAR T-cell therapy “there does not appear to be a clear benefit to pursue a transplant following CAR T cells,” Dr. Summers said. Of the 10 patients who underwent a second trans- plant, 1 died from transplant complications, while 4 others relapsed. And of the 24 who did not undergo a second procedure, 17 have relapsed. Thus, the role of transplant following CD19 CAR T-cell therapy for patients with a his- tory of transplant is unclear, Dr. Summers said, adding that larger studies are needed. “Despite initial remissions, late leukemic relapse remains a barrier to long-term efficacy following CAR T-cell therapy for B[-cell] ALL,” Dr. Summers said. “Patients without a history of HSCT who achieve a sustained [minimal residual disease]-neg- ative remission following CD19 CAR T-cell therapy may benefit from HSCT.”

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ASH 2018 • PRACTICEUPDATE CONFERENCE SERIES 11