Follicular lymphoma (FL), a common indolent B-cell lymphoma, has the potential to transform into an aggressive lymphoma, such as diffuse large B-cell lymphoma (DLBCL). The outcome of patients with transformed follicular lymphoma (tFL) is poor, especially in patients with transformed lymphoma after chemotherapy and patients with progression within 24 months (POD24). Chimeric antigen receptor (CAR) T-cell therapy combined with autologous stem cell transplantation (ASCT) has promising antitumor efficacy.
Here, we described a 39-year-old male patient who was initially diagnosed with FL that transformed into DLBCL with POD24, CD20 negativity, TP53 mutation, and a bulky mass after 3 lines of therapy, all of which were adverse prognostic factors. We applied a combination approach: CD19 CAR T-cell infusion following ASCT. Ibrutinib was administered continuously to enhance efficacy, DHAP was administered as a salvage chemotherapy, and ICE was administered as a bridging regimen. The patient underwent BEAM conditioning on days -7~ -1, a total of 3.8 × 106/kg CD34+ stem cells were infused on days 01~02, and a total of 108 CAR T cells (relmacabtagene autoleucel, relma-cel, JWCAR029) were infused on day 03. The patient experienced grade 2 cytokine release syndrome (CRS), manifesting as fever and hypotension according to institutional standards. There was no immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR T-cell infusion. Finally, the patient achieved CMR at +1 month, which has been maintained without any other adverse effects.
This case highlights the amazing efficacy of CD19 CAR T-cell therapy following ASCT for R/R tFL, thus providing new insight on therapeutic strategies for the future.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is an aggressive B-cell malignancy. The management of a relapsed Ph+ ALL patient is challenging. Currently, either allogeneic stem cell transplant (allo-SCT) or CD19-targeted chimeric antigen receptor T-cell (CAR T-cell) are usually employed as salvage modalities for a relapsed patient. However, there are few reports concerning cases that had both allo-SCT and multiple CAR T-cell therapies, and the optimal management of such patients is unclear. Here, we report a relapsed Ph+ ALL male who was first salvaged with autologous CAR T-cell therapy, followed by allo-SCT. Unfortunately, he had a second relapse even with complete molecular remission (CMR) response after the first CAR T and allo-SCT. This patient was then successfully salvaged by a second CAR T-cell product that is donor-derived. However, even with a CMR response once again following the second CAR T-cell therapy and prophylactic donor lymphocyte infusion, he experienced a molecular relapse; ponatinib was employed as the subsequent salvage treatment. He achieved a CMR response following ponatinib and was still in remission at the last follow-up. No ABL kinase mutation was detected during the whole course of the disease. This case indicated that a repeated CD19-targeted CAR T-cell treatment is feasible and may be effective in a relapsed Ph+ ALL patient that had previous CAR T-cell and allo-SCT, even though both CAR T-cell have the same construction. However, even with a deep response after each CAR T-cell therapy and allo-SCT, there is still a very small amount of undetectable leukemic cells. The optimal management of Ph+ ALL patients who have a deep response after a second CAR T-cell therapy deserves further exploration.

High response rates in B-cell malignancies have been achieved with chimeric antigen receptor (CAR) T-cell therapy. Emerging reports indicate a risk of active tuberculosis (TB) with novel immunotherapy for tumors. However, studies of TB in patients post CAR T-cell therapy are limited. In this case series study, we describe five patients with active TB post CD19/CD22 target CAR T-cell therapy alone or following autologous stem cell transplantation (ASCT). One of the patients developed active TB within the first 30 days post CAR T-cell therapy, and fever was the dominant presenting symptom; extrapulmonary manifestations of active TB were common in the other four patients and manifested after the first 30 days of CAR T-cell therapy. Four of the five patients improved with anti-TB treatment, but one patient with isoniazid resistance died of central nervous system TB infection. Our study provides the first series report of active TB following CD19/CD22 target CAR T-cell therapy.

Burkitt lymphoma or leukemia (BL) is a highly aggressive non-Hodgkin lymphoma. Older age (over 60 years old) and the presence of high-risk factors (such as abdominal mass, high levels of the serum lactic dehydrogenase, Ann Arbor stage II-IV and so on) usually predict a poorer outcome. Chimeric antigen receptor T cells (CART) have achieved remarkable success in the treatment of B-cell leukemia and lymphoma. Here, for the first time, we report a 61-year-old, high-risk BL patient with autologous stem cell transplantation (ASCT) bridging therapy prior to CART as consolidation therapy. Our findings demonstrate that the combination of ASCT and CART for BL is safe and feasible.

Patients with postransplant lymphoproliferative disease (PTLD) who are refractory to rituximab-based regimens have extremely poor prognosis. Data is lacking in the setting of solid organ transplantation (SOT)-related PTLD treated with chimeric antigen receptor T-cell (CAR-T) therapy. Moreover, limited information is available on the influence of concomitant immunosuppressive drugs on CAR-T function. Here, we describe the clinical outcome in one PTLD patient and propose a strategy for tailoring immunosuppressive treatment and organ monitoring in patients with kidney allografts after CAR-T infusion. This report also reviews the limited published data in the setting of SOT-related PTLD treated with CAR-T, which appears to be a feasible treatment in this clinical scenario, without severe toxicity and capable of inducing sustained responses. A noteworthy finding is that in most reported cases patients underwent complete or partial discontinuation of immunosuppressive drugs, with only one documented case of allograft rejection.

Extramedullary multiple myeloma (EMM) is an aggressive sub-entity of multiple myeloma (MM). Despite an excellent improvement in survival for most patients with MM over recent decades, the overall survival (OS) of patients with EMM was usually not longer than 3 years. Standard treatment for patients with EMM has not been established, and their management is particularly challenging. We presented a heavily pretreated young patient with relapsed EMM and refractoriness to a proteasome inhibitor (PI; bortezomib), a next-generation PI (ixazomib), immunomodulatory drugs (IMiDs; lenalidomide), autologous hematopoietic stem cell transplantation (ASCT), and monoclonal antibody (directed against CD38: daratumumab) and indicated that myeloablative haploidentical hematopoietic stem cell transplantation (haploidentical-HSCT) as a salvage treatment of relapse after a chimeric antigen receptor (CAR)-T cell therapy that targeted B-cell maturation antigen (BCMA) (NCT04650724) is feasible. Taken together of the contemporary literature, the promising results on the effect of anti-BCMA CAR-T cell therapy and allogeneic HSCT might present a proof-of-principle for patients with EMM, and therefore, patients with the disease need to be included in future studies.