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Lisocabtagene maraleucel (liso-cel) has shown promising efficacy in clinical trials for patients with relapsed/refractory large B-cell lymphoma (LBCL). We present health-related quality of life (HRQOL) results from the TRANSFORM study, the first comparative analysis of liso-cel vs standard of care (SOC) as second-line therapy in this population. Adults with LBCL refractory or relapsed ≤12 months after first-line therapy and eligible for autologous stem cell transplantation were randomized 1:1 to the liso-cel or SOC arms (3 cycles of immunochemotherapy in which responders proceeded to high-dose chemotherapy and autologous stem cell transplantation). HRQOL was assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – 30 items and the Functional Assessment of Cancer Therapy-Lymphoma subscale. Patients with baseline and ≥1 postbaseline assessment were analyzed (liso-cel, n = 47; SOC, n = 43). The proportion of patients with meaningful improvement in global health status/quality of life (QOL) was higher, whereas deterioration was lower in the liso-cel arm vs SOC arm from day 126 to month 6. Mean change scores showed meaningful worsening in global health status/QOL at month 6, fatigue at day 29 and month 6, and pain at month 6 with SOC; mean scores for other domains were maintained or improved in both arms. Time to confirmed deterioration favored the liso-cel arm vs SOC arm in global health status/QOL (median: not reached vs 19.0 weeks, respectively; hazard ratio, 0.47; 95% confidence interval, 0.24-0.94). HRQOL was either improved or maintained from baseline in patients with relapsed/refractory LBCL in the liso-cel arm vs SOC arm as second-line treatment. This study is registered at clinicaltrials.gov as #NCT0357531.

This global, phase 3 study compared lisocabtagene maraleucel (liso-cel) with standard of care (SOC) as second-line therapy for primary refractory or early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (ASCT) were randomized 1:1 to liso-cel (100×106 CAR+ T cells) or SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose chemotherapy and ASCT in responders). The primary end point was event-free survival (EFS) by independent review. A total of 184 patients were randomized. In this primary analysis with a median follow-up of 17.5 months, median EFS was not reached (NR) for liso-cel versus 2.4 months for SOC (hazard ratio [HR] = 0.356; 95% confidence interval [CI]: 0.243‒0.522). Complete response (CR) rate was 74% for liso-cel versus 43% for SOC (P.0001) and median progression-free survival (PFS) was NR for liso-cel versus 6.2 months for SOC (HR = 0.400; 95% CI: 0.261‒0.615; P.0001). Median overall survival was NR for liso-cel versus 29.9 months for SOC (HR = 0.724; 95% CI: 0.443‒1.183; P = .0987). When adjusted for crossover from SOC to liso-cel, median overall survival was NR for liso-cel and SOC (HR = 0.415; 95% CI: 0.251‒0.686). Grade 3 cytokine release syndrome and neurological events occurred in 1% and 4% of patients in the liso-cel arm, respectively (no grade 4/5 events). These data show significant improvements in EFS, CR rate, and PFS for liso-cel over SOC and support liso-cel as a preferred second-line treatment compared with SOC in patients with primary refractory or early relapsed LBCL. (ClinicalTrials.gov; NCT03575351.).

Background: Patients with large B-cell lymphoma (LBCL) primary refractory to or relapsed within 12 months of first-line therapy are at high risk for poor outcomes with current standard of care, platinum-based salvage immunochemotherapy and autologous haematopoietic stem cell transplantation (HSCT). Lisocabtagene maraleucel (liso-cel), an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has previously demonstrated efficacy and manageable safety in third-line or later LBCL. In this Article, we report a prespecified interim analysis of liso-cel versus standard of care as second-line treatment for primary refractory or early relapsed (within 12 months after response to initial therapy) LBCL. Methods: TRANSFORM is a global, phase 3 study, conducted in 47 sites in the USA, Europe, and Japan, comparing liso-cel with standard of care as second-line therapy in patients with primary refractory or early (≤12 months) relapsed LBCL. Adults aged 18–75 years, Eastern Cooperative Oncology Group performance status score of 1 or less, adequate organ function, PET–positive disease per Lugano 2014 criteria, and candidates for autologous HSCT were randomly assigned (1:1), by use of interactive response technology, to liso-cel (100 × 106 CAR+ T cells intravenously) or standard of care. Standard of care consisted of three cycles of salvage immunochemotherapy delivered intravenously—R-DHAP (rituximab 375 mg/m2 on day 1, dexamethasone 40 mg on days 1–4, two infusions of cytarabine 2000 mg/m2 on day 2, and cisplatin 100 mg/m2 on day 1), R-ICE (rituximab 375 mg/m2 on day 1, ifosfamide 5000 mg/m2 on day 2, etoposide 100 mg/m2 on days 1–3, and carboplatin area under the curve 5 [maximum dose of 800 mg] on day 2), or R-GDP (rituximab 375 mg/m2 on day 1, dexamethasone 40 mg on days 1–4, gemcitabine 1000 mg/m2 on days 1 and 8, and cisplatin 75 mg/m2 on day 1)—followed by high-dose chemotherapy and autologous HSCT in responders. Primary endpoint was event-free survival, with response assessments by an independent review committee per Lugano 2014 criteria. Efficacy was assessed per intention-to-treat (ie, all randomly assigned patients) and safety in patients who received any treatment. This trial is registered with ClinicalTrials.gov, NCT03575351, and is ongoing. Findings: Between Oct 23, 2018, and Dec 8, 2020, 232 patients were screened and 184 were assigned to the liso-cel (n=92) or standard of care (n=92) groups. At the data cutoff for this interim analysis, March 8, 2021, the median follow-up was 6·2 months (IQR 4·4–11·5). Median event-free survival was significantly improved in the liso-cel group (10·1 months [95% CI 6·1–not reached]) compared with the standard-of-care group (2·3 months [2·2–4·3]; stratified hazard ratio 0·35; 95% CI 0·23–0·53; stratified Cox proportional hazards model one-sided p

Intracranial malignancy should be ruled out in any patient with a non-resolving torticollis with no plausible explanation. A 4-year-old boy presented with an acute torticollis to the left that had occurred immediately following a fall 2 weeks before. The head tilt was absent during sleep, and he complained of neck stiffness while at rest. He was alert, and there was an evident head tilt to the left. Head and neck showed full active and passive range of motion without pain. Palpation of the neck muscles was painful, but no abnormalities were found. Further physical and neurological examination was unremarkable. The working diagnosis was minor cervical muscle trauma following a fall. Two weeks later he represented to the emergency department after a collapse. The torticollis had remained unchanged, but he had suddenly been unable to stand that morning, had complained of severe headache and started vomiting. A left facial nerve paralysis, an evident ataxia, and a bilateral Babinski reflex were now present. A CT scan showed a

Sir, Anti-glomerular basement membrane (GBM) nephritis is an autoimmune disease characterized by IgG antibodyformation against the α3 (IV)NCI non-collagenous region of type IV collagen resulting in rapid progressive glomerulonephritis and, ultimately, renal failure when left untreated [1]. Several novel agents have been used when conventional therapy fails to suppress antibody formation. We describe the case of a young woman with severe anti-GBM disease who had persistently high antibody titres despite conventional therapy, experiencing successful antibody suppression after rituximab was added to her therapeutic regimen. A 20-year-old woman presented at the emergency department with acute, oliguric renal failure due to glomerulonephritis. Creatinine level was 624 mmol/L, urea level was 16 mmol/L, and 24-h protein excretion was 6.2 g. Anti-GBM titre was positive with 270 units, while ANCA-P3/MPO and ANA were negative. The diagnosis of anti-GBM glomerulonephritis was made, and plasmapheresis was initiated while the patient was started on methylprednisolone 1 g i.v. for 3 days followed by 1 mg/kg and cyclophosphamide 2 mg/kg, both orally. At Day 21, after 17 sessions of plasmapheresis with 3 L plasma volumes, the anti-GBM titre remained elevated at 180 units, and proteinuria worsened to 40 g/day. Rituximab was initiated at a dose of 375 mg/m2 with a 2-week interval. Four days after first rituximab treatment, the anti-GBM titre dropped to 130 units, and 11 days later the titre had further decreased to 85 units. Four weeks after the first dose of rituximab and 2 months after the diagnosis was made, the anti-GBM titre had dropped to below reference level, while proteinuria declined to 2 g/24 h and creatinine clearance rose to 32 (Modification of Diet in Renal Disease formula). Phenotyping of peripheral lymphocytes showed B cells to be almost completely absent. The use of rituximab in anti-GBM nephritis has only been described in case studies, with mixed outcome, but its use has been successfully studied as adjuvant or salvage therapy in antibody-mediated autoimmune diseases such as autoimmune thrombocytopenic purpura, autoimmune haemolytic anaemia, systemic lupus erythematosus and rheumatoid arthritis. [2–4] The production of antibody depends on the antigenically driven clonal expansion of B cells into antibody-producing effector plasma cells. Plasma cells are short-lived cells, and survival of the populations depends on differentiation from their progenitor B cells [5]. B-cell ablation with rituximab could prevent further plasma cell and subsequent antibody formation, extinguishing the inflammatory anti-GBM response. In our case, the anti-GBM titre did not decrease below reference level even though 51 L of plasma volume had been exchanged, suggesting a high rate of antibody formation. The rapid decline of antibody titre and proteinuria could very well have been due to a late effect of simultaneous earlier therapy, but the theory behind the use of rituximab does not rule out that the rituximab might have had beneficial effect on antibody formation. Conflict of interest statement. None declared.