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CAR T-cell therapy shows efficacy for extramedullary ALL
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SALT LAKE CITY — Activity of anti-CD22 chimeric antigen receptor T-cell therapy occurred among children and young adults with extramedullary acute lymphoblastic leukemia, despite delayed time to optimal response, according to study results presented at BMT Tandem Meetings.
Chimeric antigen receptor (CAR) T-cell therapy has shown activity among patients with relapsed/refractory ALL, with responses typically observed 1 month after treatment. However, data are lacking on the efficacy of CAR T-cell therapy among patients with extramedullary ALL and non-Hodgkin lymphoma.
“We see extramedullary relapse happen not that infrequently among patients who relapse after transplant,” study principal investigator Nirali N. Shah, MD, MHSc, associate research physician in the Pediatric Oncology Branch (POB) of the NCI, told HemOnc Today. “We don’t quite know the role of any of our CAR T therapies specifically for pediatric lymphomatous disease, so the extramedullary manifestation of ALL offers a little insight into what that might look like.”
Researchers evaluated data from a subset of 35 patients treated in a pediatric phase 1 study of anti-CD22 CAR T cells.
“The majority of patients treated were heavily pretreated,” lead study author Bonnie Yates, NP, nurse practitioner at the POB/NCI, said during her presentation. “Eighty percent had a least one prior bone marrow transplant, and 86% received prior CD19-directed therapy.”
Also, 63% were CD19-negative partial or dim at the time of enrollment.
“We found that our CD22 protocol is active in CD19-negative, -dim and -positive ALL, with a complete remission rate of 73%,” Yates said.
Of 35 treated patients, nine (median age, 18 years; range, 8-30; 78% male) had active extramedullary disease, eight of whom had ALL and one who had diffuse large B-cell lymphoma. Sites of extramedullary involvement included orbit, lacrimal gland, temporal bone, parotid gland, axilla, pericardial and pleural effusions, pleura, pancreas, kidney, iliopsoas muscle and liver.
Eighty-nine percent of these patients had received a prior transplant, and all patients had received prior CD19-directed therapy. Seventy-eight percent were CD19 negative, 67% had concurrent bone marrow disease, and 44% had multiple sites of extramedullary disease.
Antitumor activity — determined by swelling and erythema at disease sites — appeared most prominent at the time of peak CAR expansion. For example, one patient with an orbital tumor had minor swelling pretreatment. At day 5, which marked the onset of CAR T-cell expansion, researchers observed increased swelling in the area around the orbit. But, by day 30, the swelling appeared resolved. This patient also had axillary lymph node disease and developed lymphedema at the time of CAR T expansion.
Researchers also observed pulmonary trafficking of CAR T cells to pleural-based disease. One patient showed progressive disease after apheresis. He had pleural fluid with 86% blasts and received interval chemotherapy prior to CAR T-cell therapy and showed improvement in his pleural-based disease. Day 16, at the onset of CAR expansion, he showed diffuse infiltrates with no infection and developed an oxygen requirement with demonstrating of CAR trafficking into the bronchoalveolar fluid at a later time point. By 3 months postinfusion, he had full resolution of pulmonary disease.
Also, researchers detected evidence of CAR re-expansion among some patients with extramedullary disease.
Overall, five of the patients with ALL attained minimal residual disease-negative remission in bone marrow at 1 month. One patient had an ongoing response. The patient with non-Hodgkin lymphoma showed stable disease, with partial responses at some sites.
Of the nonresponders, two did not have CAR expansion and one was partially CD22 positive with CAR expansion but had limited response.
Researchers found the time to optimal response might be delayed among patients with extramedullary disease.
“For instance, we had one patient who took 6 months to full resolution of the lymphomatous disease,” Yates told HemOnc Today. “Response, on average, was 2.5 months for these patients, but ranged from 1 month to 6 months.”
Further expansion of the non-Hodgkin lymphoma cohort in this protocol is a focus of future research, Yates said.
Also, researchers are interested in “the persistence of CAR in patients with lymphomatous disease, and whether that differs from our leukemia patients,” Shah told HemOnc Today. – by Alexandra Todak
Reference:
Yates B, et al. Abstract 65. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.
Disclosures: The authors report no relevant financial disclosures.