7 research outputs found
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
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A Multicenter Study Analyzing Survival and Prognostic Factors in Patients with Leukemic Phase Follicular Lymphoma
Introduction Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma. Leukemic-phase FL (LP-FL) is a rare entity comprising 1-3% of FL patients (pts). Controversy exists about prognosis of LP-FL with some studies suggesting worse outcome. No clear cut-point of circulating cells has been used to define LP-FL; however, a level > 5x103^3 cells/uL is defined in GELF criteria for high burden disease. No unified treatment recommendation is present for these pts with some opting to treat as indolent FL and some choosing a more aggressive approach. Furthermore, limited case series (n=7 to 37) on LP-FL are available, hence we aimed to better understand prognosis and treatment strategies associated with better outcome in LP-FL. Methods Pts with a pathology proven diagnosis of FL in lymph node and/or bone marrow and a positive flow cytometry in peripheral blood for clonal B cells (CBs), at diagnosis or at relapse, were included in the study. Data was collected from 5 academic institution in the US. We report time-to-event outcomes including median progression-free survival (mPFS) and overall survival (mOS) estimated by Kaplan-Meier method (only pts who received therapy included) . Uni and multivariable analyses were performed using Cox regression. CBs were divided into 4 groups: (10) 10^3/uL. Pts treatment was grouped in 4 categories: anti-CD20 monoclonal antibody (CD20mAb), CD20mAb+Bendamustine, CD20mAb+ CHOP, and other. Pts with CD10 negative clones on flow cytometry were excluded as they might represent different lymphoma type. Results Sixty-one pts (period 1998 to 2022) were identified in participating institutions with LP-FL, 10 of which had CD10- flow cytometry and excluded from study. Of 51 remaining pts, median age was 56 years (y). Nine (17.6%) pts were Hispanic and 44 (86.2%) pts were white. Most pts (37%) presented asymptomatic lymphadenopathy, 22% with B symptoms, 14% with incidental elevated WBC, 12% with organ compromise and 12% due to other reasons. Overall, B symptoms were present in 20 (39%) pts. Hepato/splenomegaly was present in 22 (43%) pts, high tumor burden (GELF criteria) in 12 (23%) pts, and most pts (n=42; 82%) presented ECOG PS 0-1. We less frequently observed anemia (Hg 10 10^3/uL in 10 (20%) pts. Median absolute lymphocyte count was 3.0 x10^3/uL. Cytogenetic data was available in tissue biopsies in 13 (25%) pts and all carried t(14;18). Treatment was as follows: 24 (47%) pts with bendamustine + CD20mAb , 15 (29%) pts with CD20mAb + CHOP, 7 (14%) pts were treated with CD20mAb, 3 (6%) pts underwent active surveillance, and 2 (4%) with other treatments. Overall response rate (ORR) was 87%. Of those 31 (65%) pts had complete response (CR) and 11 (23%) pts had partial response (PR). With a median follow up of 5.5 y the mPFS was 3.6 y and mOS was 9.6 y (Figure 1). Relapse/ progression of disease occurred in 26 (54%) pts and CBc was detect in 12/13 pts in which flow cytometry was done. Transformation on relapse occurred in 7 pts. In pts experiencing disease relapse/progression, CAR T-cell was given to 6 pts with an ORR of 83.3% (CR: in 4 and PR in 1 pts); one pt died due to CAR-T grade 5 neurotoxicity. Death occurred in 13 pts with 6 (46% of all deaths) being lymphoma-related. Age≥60 and male sex were associated with worse PFS in univariable analysis (Table 1), with age only remaining significant in a multivariable analysis that also included sex and frontline therapy (HR 3.19, p=0.01 ). Notably, FLIPI score, CBs count category, and type of frontline therapy did not predict PFS. Progression of disease within 24 months (POD24) predicted OS in univariable analysis (HR= 3.93; p=0.029). Multivariable analysis for OS was not performed due to small number of deaths. Conclusion To our knowledge, this is the largest study of LP-FL. Median OS was around 10 years, a comparable outcome to historical nodal FL survival. Treatment type also did not predict PFS or OS. Circulating monoclonal cell levels did not impact survival . This is notable as the current GELF criteria includes circulating malignant cells ≥5 x10^3/uL as an indication for treatment while our date shows that no set cut-point may be needed. In addition, CAR T-cell appears to be an effective therapy with similar results as in nodal FL
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Brentuximab vedotin plus AVD for Hodgkin lymphoma: incidence and management of peripheral neuropathy in a multisite cohort.
Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is increasingly used for frontline treatment of stage III/IV classical Hodgkin lymphoma (cHL). Peripheral neuropathy (PN) was the most common and treatment-limiting side effect seen in clinical trials but has not been studied in a nontrial setting, in which clinicians may have different strategies for managing it. We conducted a multisite retrospective study to characterize PN in patients who received BV + AVD for newly diagnosed cHL. One hundred fifty-three patients from 10 US institutions were eligible. Thirty-four patients (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage, performance status, and comorbidities. PN was reported by 80% of patients during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of patients because of PN leading to BV discontinuation in 23%, dose reduction in 17%, and temporary hold in 4%. With a median follow-up of 24 months, PN resolution was documented in 36% and improvement in 33% at the last follow-up. Two-year progression-free survival (PFS) for the advanced-stage patients was 82.7% (95% confidence interval [CI], 0.76-0.90) and overall survival was 97.4% (95% CI, 0.94-1.00). Patients who discontinued BV because of PN did not have inferior PFS. In the nontrial setting, BV + AVD was associated with a high incidence of PN. In our cohort, which includes patients who would not have been eligible for the pivotal ECHELON-1 trial, BV discontinuation rates were higher than previously reported, but 2-year outcomes remain comparable