Impact of detectable monoclonal protein at diagnosis on outcomes in marginal zone lymphoma: a multicenter cohort study.

Given the paucity of data surrounding the prognostic relevance of monoclonal paraprotein (M-protein) in marginal zone lymphoma (MZL), we sought to evaluate the impact of detecting M-protein at diagnosis on outcomes in patients with MZL in a large retrospective cohort. The study included 547 patients receiving first-line therapy for MZL. M-protein was detectable at diagnosis in 173 (32%) patients. There was no significant difference in the time from diagnosis to initiation of any therapy (systemic and local) between the M-protein and no M-protein groups. Patients with M-protein at diagnosis had significantly inferior progression-free survival (PFS) compared with those without M-protein at diagnosis. After adjusting for factors associated with inferior PFS in univariate models, presence of M-protein remained significantly associated with inferior PFS (hazard ratio, 1.74; 95% confidence interval, 1.20-2.54; P = .004). We observed no significant difference in the PFS based on the type or quantity of M-protein at diagnosis. There were differential outcomes in PFS based on the first-line therapy in patients with M-protein at diagnosis, in that, those receiving immunochemotherapy had better outcomes compared with those receiving rituximab monotherapy. The cumulative incidence of relapse in stage 1 disease among the recipients of local therapy was higher in the presence of M-protein; however, this did not reach statistical significance. We found that M-protein at diagnosis was associated with a higher risk of histologic transformation. Because the PFS difference related to presence of M-protein was not observed in patients receiving bendamustine and rituximab, immunochemotherapy may be a preferred approach over rituximab monotherapy in this group and needs to be explored further.

Impact of early relapse within 24 months after first-line systemic therapy (POD24) on outcomes in patients with marginal zone lymphoma: A US multisite study.

Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of POD24 and the assessment of cumulative incidence of histologic transformation (HT) in POD24 versus non-POD24 groups. The study included 524 patients with 143 (27%) in POD24 and 381 (73%) in non-POD24 groups. Patients with POD24 had inferior OS compared to those without POD24, regardless of the type of systemic therapy received (rituximab monotherapy or immunochemotherapy) at diagnosis. After adjusting for factors associated with inferior OS in the univariate Cox model, POD24 remained associated with significantly inferior OS (HR = 2.50, 95% CI = 1.53-4.09, p = 0.0003) in multivariable analysis. The presence of monoclonal protein at diagnosis and those who received first-line rituximab monotherapy had higher odds of POD24 on logistic regression analysis. Patients with POD24 had a significantly higher risk for HT compared to those without POD24. POD24 in MZL might be associated with adverse biology and could be used as an additional information point in clinical trials and investigated as a marker for worse prognosis.

Focal impulse and rotor modulation: Acute procedural observations and extended clinical follow-up.

BACKGROUND: Focal impulse and rotor modulation (FIRM) was based on the premise that atrial fibrillation (AF) is sustained by rotors that are sufficiently stable to be eliminated by targeted ablation. Early experience reported high success as compared to conventional strategies. OBJECTIVE: The purpose of this study was to report on a single-center experience with extended follow-up by using FIRM in a variety of patients with AF. METHODS: All FIRM-guided ablation procedures were included. During spontaneous or induced AF, FIRM software constructed phase maps to identify putative AF sources, then targeted for radiofrequency ablation, with adjunctive pulmonary vein isolation (PVI), if needed. All mapped rotors and/or sources were eliminated on the basis of repeated FIRM mapping. RESULTS: Of 47 patients, sustained AF was not present or induced in 4 patients who did not undergo FIRM ablation. Of the remaining 43 patients, prior AF was paroxysmal in 9 (21%) and 72% had a median of 1 prior PVI. Spontaneous AF (n = 22, 52%) and induced AF (n = 21, 49%) were mapped, and all patients had rotors identified (1.8 ± 0.8 per patient; 70% in the left atrium). AF termination occurred in 2 patients (5%) and none organized to atrial tachycardia. Touch-up redo PVI was also performed in 31 patients (72%). At 16.0 ± 10.7 months (range 1-34 months), only 9 patients (21%) were free of recurrent AF; and only 5 patients (12%) were free of AF and off antiarrhythmic drugs. CONCLUSION: Long-term clinical results after FIRM ablation in this diverse challenging cohort showed poor efficacy. Randomized clinical trials are needed to evaluate the efficacy and clinical utility of the FIRM ablation approach for treating AF.