Blood Cancer Journal最新文献

We examined the clinical course and risk factors for late onset neurotoxicities, including nerve palsies (IEC-NP) and parkinsonism (IEC-PKS), in patients with relapsed/refractory multiple myeloma (RRMM) treated with ciltacabtagene autoleucel (cilta-cel) in standard-of-care practice (SOC). Among 235 RRMM patients who received cilta-cel, 15 (6.4%) developed IEC-NP and 9 (3.8%) developed IEC-PKS with one patient developing both. Pre-infusion, patients with age >75 years, bone marrow plasma cells ≥20%, or involved free light chain ≥20 mg/dL had increased odds of IEC-PKS. Post-infusion, patients who developed ICANS, received higher cumulative steroid doses or received >1 dose of tocilizumab also had increased odds of IEC-PKS. High peak absolute lymphocyte count (ALCpeak) was a statistically significant predictor on univariate and multivariate analysis for IEC-NP and IEC-PKS. ALC_peak ≥ 3 × 10⁹/L was identified as a meaningful threshold (AUC = 0.838) to predict for late onset neurotoxicity. An ALC_peak ≥ 3 × 10⁹/L conferred a positive predictive value for delayed neurotoxicity of 31% vs a negative predictive value of 98% in patients with ALC_peak < 3 × 10⁹/L. All IEC-NP patients received steroid +/- IVIG; 87% had complete resolution of their cranial neuropathies (median 57 days). Four patients with IEC-PKS received cyclophosphamide (1.5-2 g/m²) within 1-13 days of symptom onset and all had observable symptom improvement within 1-2 days.

There is currently no clear consensus on the standard of care for relapsed or refractory follicular lymphoma (FL) beyond third-line therapy, where both anti-CD19 CAR-T-cell therapy (CAR-T) and CD3×CD20 bispecific antibodies (BsAbs) have demonstrated efficacy. This study aimed to examine their efficacy and toxicity profiles. Relevant studies published between January 2010 and June 2025 were identified through major databases. Of 3960 records screened, 12 studies met the inclusion criteria-7 involving CAR-T and 5 involving BsAbs. The pooled overall response rate (ORR) and complete response rate (CRR) were 93% and 82% for CAR-T, compared with 82% and 67% for BsAbs (p = 0.0002 and p = 0.005, respectively). Among patients with POD24, the CRR was 75% for CAR-T and 69% for BsAbs (p = 0.56). This translated into improved progression-free survival (PFS) with CAR-T: 6-month, 1-year and 3-year PFS rates were 85%, 74% and 54%, respectively, compared with 74%, 62%, and 42% for BsAbs (p = 0.006, p = 0.002 and p = 0.009, respectively). A trend toward higher 3-year overall survival (OS) was observed with CAR-T (80%) versus BsAbs (73%) (p = 0.48). Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred more frequently with CAR-T (8% vs. 0%, p = 0.04), whereas grade ≥3 infections were numerically higher with BsAbs (17% vs. 9%, p = 0.31). One-year non-relapse mortality (NRM) was similar between groups at 3%. Overall, CAR-T demonstrated potentially higher efficacy in this non-comparative meta-analysis, while the two therapies exhibited noticeable differences in toxicity profiles.

In the Phase 2 IZALCO study, we evaluated efficacy, patient preference, safety and pharmacokinetics for isatuximab administered SC by an innovative on-body injector (OBI) or manual injection, plus carfilzomib-dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM) patients. In Part 1, isatuximab SC was injected manually (cycles 1-6). In Part 2, patients were randomized to isatuximab SC by manual injection (cycles 1-3) followed by OBI administration (cycles 4-6) or to isatuximab OBI (cycles 1-3) followed by manual injection (cycles 4-6). From cycle 7, all patients could choose either treatment method. Overall, 74 RRMM patients received isatuximab SC plus Kd: 8 in Part 1 and 66 in Part 2. The patients had a median age of 65.0 years (44-85) with a median of 1 prior treatment line (1-5). The study met its primary efficacy endpoint with a 79.7% overall response rate (N = 74), at a median follow-up of 10.1 months. 74.5% of patients preferred the OBI rather than manual injection, 17% preferred manual injection, 8.5% had no preference. No impact of the SC delivery method was observed on efficacy, safety, pharmacokinetics, and immunogenicity of isatuximab given SC plus Kd, supporting the feasibility of using the OBI as a convenient method for isatuximab SC administration. Clinical trial information: ClinicalTrials.gov NCT05704049.

Renal impairment (RI) is a serious complication in multiple myeloma (MM), linked to poor survival and early mortality. Rapid renal recovery improves outcomes, yet patients with RI have been excluded from most key trials in transplant-eligible newly diagnosed (TE-ND) MM. REMNANT is an ongoing, academic, multicenter phase 2/3 study in TE-NDMM patients aged 18-75, regardless of baseline renal function. Here, we report a subanalysis of the non-randomized phase 2 component. All patients received four 21-day cycles of induction with bortezomib, lenalidomide, and dexamethasone. Lenalidomide was dosed higher than the recommended standard of care: 25 mg/day for eGFR ≥30 mL/min/1.73 m² and 15 mg/day for eGFR <30. Between August 2020 and September 2024, 382 patients were enrolled; 81 (21%) had RI, including seven (2%) on dialysis during cycle 1. Renal response was achieved in 77%, with complete renal response in 57%. Five dialysis-dependent patients became dialysis-independent. Overall response rates were similar, and adverse events were comparable between RI and non-RI groups, except for higher rates of anemia and thrombocytopenia in the RI cohort. Four RI patients (5%) experienced worsening renal function; two cases were possibly related to lenalidomide, both reversible. These findings support the safety and efficacy of increased lenalidomide-dosing during induction in TE-NDMM patients with RI, including those with severe impairment.