2026-07-05 | Efficacy and safety of CD19 CAR T-cell therapy in relapsed/refractory follicular lymphoma: A systematic review and meta-analysis.
Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma characterized by frequent relapses despite initial responsiveness to chemoimmunotherapy. CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown promising efficacy in relapsed or refractory disease, though safety concerns such as cytokine release syndrome (CRS) and neurological events remain. This study aimed to evaluate the efficacy and safety of CD19 CAR T-cell therapy in relapsed or refractory FL. A comprehensive search using six databases, including PubMed, Scopus, and Embase, was performed to identify relevant studies. Data on overall response rate (ORR), complete response rate (CRR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and adverse events, including CRS and neurological events, were extracted. Pooled estimates were calculated using the quality effects model. This review was registered in PROSPERO (CRD420251133655). Out of 2303 records initially identified, 6 studies met the inclusion criteria. The pooled efficacy analysis demonstrated an ORR of 93.5% (95% CI: 86.3-98.3%) and a CRR of 84.5% (95% CI: 72.6-93.6%). Regarding safety outcomes, the pooled estimate for CRS of any grade was 61.4% (95% CI: 45.0-76.6%). For neurological events, it was 33.6% (95% CI: 13.4-57.1%). Subgroup analyses identified prior therapy lines and CAR construct design as sources of heterogeneity. In conclusion, CD19 CAR T-cell therapy demonstrates high efficacy with a generally acceptable safety in relapsed or refractory FL, supporting its consideration for patients with limited treatment options while highlighting the need for further research on long-term outcomes.
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2026-07-03 | Diagnostic challenge of occult ER-positive breast carcinoma within bone marrow indolent B-cell lymphoma and response to CDK4/6 inhibitor: a case report.
Bone marrow metastasis from hormone receptor-positive breast cancer can be challenging to detect, especially in patients with concurrent hematologic malignancies, where isolated epithelial cells may be hidden by a dominant lymphoid infiltrate. This situation requires careful histopathologic and immunophenotypic evaluation to prevent misdiagnosis. We report a 74-year-old White woman with Waldenström's macroglobulinemia carrying the MYD88 L265P mutation and bone marrow infiltration by indolent B-cell non-Hodgkin lymphoma. She was evaluated for suspected skeletal disease progression due to rising tumor markers and inconclusive PET findings. Bone marrow biopsy revealed small clusters of epithelial cells positive for estrogen receptor (ER), cytokeratin AE1/AE3, and GATA3, consistent with metastatic breast carcinoma within a lymphoid background. Notably, ER positivity was the only marker indicating epithelial origin. The patient had previously received empirical aromatase inhibitor therapy after the initial detection of scattered ER-positive epithelial cells in 2018. Following disease progression in December 2024, she was treated with palbociclib and fulvestrant, while the indolent lymphoma was managed with active surveillance. At 6-month follow-up, the patient showed clinical stability, a biochemical response, and radiologic evidence of stable disease. This case emphasizes the importance of maintaining a high level of clinical and pathological suspicion when assessing bone marrow infiltration, especially in patients with a history of malignancy. The presence of isolated ER-positive epithelial cells within a lymphoid marrow environment should raise suspicion of occult breast carcinoma metastasis. Due to the rarity of this coexistence, the underlying mechanisms and optimal management strategies are still unclear. To our knowledge, this is one of the few reported cases of occult ER-positive breast carcinoma presenting solely as bone marrow involvement in a patient with indolent B-cell lymphoma, with documented response to CDK4/6 inhibitor-based therapy. This case report was prepared in accordance with the CAse REport (CARE) guidelines.
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2026-07-02 | A novel dose-dense strategy for CD19-directed CAR T-cell therapy is associated with durable responses without increased toxicity in patients with B-cell non-Hodgkin lymphoma.
CD19-directed chimeric antigen receptor (CAR) T-cell therapy induces durable remissions in only 30-40% of patients with relapsed or refractory (R/R) B-cell non- Hodgkin lymphoma (B-NHL), highlighting a major need to improve outcomes. In dose-escalation studies, higher CAR T-cell doses improved tumor control but caused prohibitive toxicities. Having established the maximum tolerated JCAR014 dose in patients with B-NHL at 2 x 106 CAR+ cells/kg, we hypothesized that a second infusion at day 14 ("dose-dense") at the same dose and without repeat lymphodepletion, would be safe and enhance antitumor efficacy. We report outcomes from the pilot dose-dense cohort of a phase 1/2 trial (ClinicalTrials.gov identifier: NCT01865617) with 8-year follow-up. Two CAR T-cell products, each containing 2 x 106 CAR+ cells/kg, were manufactured for all 20 treated patients; 17 received both infusions. Any-grade cytokine release syndrome (CRS) and neurotoxicity (NT) occurred in 10 (59%) and 3 (18%) of dose-dense patients, respectively, and-except for one grade 2 CRS-events followed the first infusion only. Despite no additional lymphodepletion, CAR T-cell re-expansion after the second infusion occurred in 16 (94%) patients. By Lugano criteria, overall and complete response rates were 47% (8/17) and 41% (7/17), respectively. Among responders, the 8-year durationof- response rate was 63% (95% CI: 37-100), comparing favorably with the 26% (95% CI: 14-48) observed in patients treated with a single infusion. In conclusion, early redosing on day 14 was feasible, safe and led to durable responses in patients with R/R B-NHL.
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