Long‐term outcomes of relapsed/refractory double‐hit lymphoma (r/r DHL) treated with CD19/22 CAR T‐cell cocktail therapy

Long-term outcomes of relapsed/refractory double-hit lymphoma (r/r DHL) treated with CD19/22 CAR T-cell cocktail therapyDear Editor, Previously, we reported the safety and efficacy of sequential infusion of CD19/22 chimeric antigen receptor (CAR) T-cells immunotherapy in treatment of relapsed/refractory (r/r) B-cell lymphoma at first time and suggested its potential role in certain subsets of patients who carried high-risk genetic or chromosome aberrations.1 However, the long-term outcomes of r/r double-hit lymphoma (DHL) being treated by this immunotherapy has not been fully elucidated.DHL with c-MYC and BCL2 or BCL6 gene rearrangements have been defined as a new separate subtype in 2016 revised WHO classification of lymphoid neoplasms.2 Currently, no consensus has been reached in the treatment of DHL.Patients have inferior outcomes treated with conventional or targeted chemotherapy 3 and no significant benefit can be obtained from further consolidative transplantation.4 If DHL patients have either refractory or relapsed diseases after initial treatments, the prognosis will not be improved by noncross-resistant second-line chemotherapy and subsequent autologous-stem cell transplantation (ASCT).5 One investigation reported 50% response rate in 19 primary refractory and/or relapsed double-hit lymphoma (r/r DHL) patients treated with tisagenlecleucel.6 In ZUMA-1 trial, seven patients with confirmed high-grade B-cell Lymphoma (HGBL) or DHL had 90% objective responses (OR) treated with axicabtagene ciloleucel.7 Long-term survival data, however, were not reported in these studies.Recently, one DHL case was reported to maintain complete response (CR) for more than 1 year by treating with axicabtagene ciloleucel, indicating the potential survival benefit with CAR T-cell immunotherapy.8 Although ASCT still plays a potentially curative role in treatment of most types of r/r B-cell lymphoma, treatment of r/r DHL patients who hadworse prognosis as a higher risk subtype need incorporate with more investigational strategies rather than standard ASCT alone.9 Whether ASCT follow-