A cikin Fabrairury 2023, a phase 1 trial at a single institution found that it was safe and possible for people with heavily pretreated large B-cell lymphoma (LBCL) to use CD22-directed chimeric antigen receptor (CAR) T-cell therapy after relapse on CD19-directed CAR T-cell far. In addition, patients exhibited high overall response rates (ORRs), and complete responses (CRs) in these patients were found to be durable.
A presentation by lead study author Matthew J. Frank, MD, PhD, assistant professor of medicine in the Division of Bone Marrow Transplant & Cellular Therapy at the Stanford Cancer Institute, said, “A single infusion of CAR22 produced high response rates in heavily pretreated large B-cell lymphoma patients who relapsed after CAR19.” Frank is the director of the study and an assistant professor of medicine.
CD19-directed CAR T-cell far has led to significant responses in patients with relapsed/refractory LBCL; however, if relapse occurs, patients have a very poor prognosis, and many exhibit CD19 loss or reduced expression.
Frank ya ce, "Akwai ƙarancin hanyoyin kwantar da hankali da ake gudanarwa bayan koma baya na yau da kullun." Idan aka yi la'akari da rashin fahimta mara kyau na marasa lafiya waɗanda suka sake komawa bayan sun karbi magungunan carnitine, akwai buƙatar gaggawa na gaggawa don hanyoyin kwantar da hankali.
CD22 is of interest as a target for CAR T-cell therapy as it can be found on the surface of malignant B cells in 95% of B-cell acute lymphoblastic leukaemias (ALLs) and LBCLs. CD22-directed CAR T-cell therapy has already demonstrated high response rates in patients with heavily pretreated ALL.
Adults with B-cell ALL and B-cell ba Hodgkin lymphoma were enrolled in the dose-escalation phase 1 study of CAR T-cell therapy directed at CD22. Frank presented at the Tandem Meetings the results of the LBCL cohort.
All patients in the cohort had relapsed/refractory LBCL, including diffuse LBCL not otherwise specified, transformed follicular lymphoma, marginal zone lymphoma, na kullum lymphocytic cutar sankarar bargo/small lymphocytic lymphoma, primary mediastinal B-cell lymphoma, and secondary central nervous system involvement. In addition, patients were resistant to CD19-directed CAR T-cell therapy or had CD19-negative disease in conjunction with any CD22 expression. Patients who had previously received CAR T-cell therapy had to have at least 30 days passed since their last infusion and less than 5% CAR-positive cells in their peripheral blood, according to flow cytometry.
Patients received either 1 x 106 (dose level 1) or 3 x 106 (dose level 2) of the CD22-targeted drug (dose level 2). Prior to infusion, patients received intravenous fludarabine (30 mg/m2) and cyclophosphamide (500 mg) to administer lymphodepleting chemotherapy.
The primary objectives of the study were manufacturing feasibility, the phase 2 dose recommendation, safety, and toxicity. The investigator-assessed ORR, duration of response, progression-free survival (PFS), overall survival (OS), CAR T associated toxicity, CD22 antigen expression, CAR-positive cell levels in the blood, and serum cytokine profiling were secondary endpoints.
Daga cikin marasa lafiya 41 da suka yi rajista, an sami nasarar kera samfurin T-cell na CAR don 38 (95%), saboda 2 ba su da isassun ƙwayoyin T don leukapheresis. Matsakaicin lokacin tsakanin leukapheresis da jiko shine kwanaki 18.
The median age of participants who received CAR T-cell therapy was 65 (range, 25-84), they had an ECOG performance status of 0 or 1, and they had received a median of 4 prior lines of therapy (range, 3-8). 74% of patients had diffuse LBCL, and 21% had transformed follicular linzoma. 39% of patients were diagnosed with non-germinal centre B-cell-like disease, and 18% had double-hit status. 97% of patients had previously received CD19-directed CAR T-cell therapy, and 18% had previously undergone autologous hematopoietic stem cell transplantation. 29 percent of patients did not achieve a CR to any prior therapy.
Matsakaicin lokacin bin duk marasa lafiya shine watanni 18.4 (kewaye: 1.5-38.6), a lokacin ORR shine 68% kuma ƙimar CR shine 53%. PFS na tsakiya shine watanni 2.9 (95% tazarar amincewa [CI], 1.7-NR) kuma OS na tsakiya shine watanni 22.5 (95% CI, 8.3-NR).
A matakin kashi 1 (n = 29), an bi marasa lafiya don tsaka-tsakin watanni 14.1 (kewaye, 1.5-38.6), yana nuna 66% ORR da 52% CR rate. Rayuwa ba tare da ci gaba ba na tsaka-tsaki shine watanni 3.0 (95% CI, 1.6-NR) kuma rayuwa gabaɗaya ita ce NR (95% CI, 8.3-NR).
A matakin kashi 2 (n = 9), matsakaicin matsakaici shine watanni 27.1 (kewaye: 24.7-33.5), ORR shine 78%, kuma ƙimar CR shine 55%. Matsakaicin PFS shine watanni 2.6 (95% tazarar amincewa: 1.3-NR) kuma OS na tsakiya shine watanni 22.5 (tazarar amincewa 95%: 5.5-NR).
1 kawai daga cikin marasa lafiya 20 da suka sami CR sun sake komawa kamar yadda aka yanke bayanan, yana nuna cewa CRs suna da dorewa. A wata na uku, duk marasa lafiya da suka sami ci gaba a kan jiyya sun yi haka.
In 95% of patients, cytokine saki ciwo was observed, with grade 1 events occurring in 37%, grade 2 in 55%, and grade 3 in 3%. 8% of patients experienced neurologic events of grade 1 severity, while 5% experienced events of grade 2 severity. 18% of patients also reported toxicity resembling hemophagocytic lymphohistiocytosis.
Ɗaya daga cikin majiyyaci a matakin kashi 2 ya mutu daga sepsis a ranar 40, kuma wani mai haƙuri ya ci gaba da maganin cutar sankarar jini na myelodysplasia / m myeloid cutar sankarar bargo ba tare da shaidar dawowar LBCL na watanni 11 ba bayan karbar maganin CD22.
Matsayin shawarar da aka ba da shawarar don lokaci na 2 an ƙaddara ya zama 1.
Bayanan da aka buga a baya sun yi cikakken bayani game da maganin marasa lafiya uku na farko.
Duk marasa lafiya biyu suna da halayen haɗari masu girma kuma sun karɓi aƙalla layin jiyya guda biyar, gami da CD19-directed CAR T-cell far. Ɗaya daga cikin majiyyatan ya rigaya ya karɓi magungunan CAR T-cell guda biyu, na biyun wanda ya yi niyya CD19 da CD20. Duk marasa lafiya guda uku sun sami CR, tare da masu haƙuri 3 suna samun CR a ranar 28. An ajiye CRs fiye da shekaru uku.
Frank ya kuma lura cewa "yaduwan CAR22 ya ninka sau goma kuma ya fi na CAR19."
To learn more about patients who have relapsed after CD19-directed CAR T-cell therapy, a planned multicenter phase 2 trial of this agent is being set up. The trial will likely begin this summer.
References
1. Frank MJ, Sahaf B, Baird J, et al. CD22 CAR T cell therapy induces durable remissions in patients with large B cell lymphoma who relapse after CD19 CAR T cell therapy. Presented at: 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 15-19, 2023; Orlando, FL. Abstract 2.
2. Baird JH, Frank MJ, Craig J, et al. CAR T-cell mai jagora CD22 yana haifar da cikakkiyar gafara a cikin CD19-directed CAR-refractory babban lymphoma B-cell. Jinin jini. 2021;137(17):2321-2325. doi:10.1182/blood.2020009432
