Fenske, Timothy S.

PURPOSE Systematic integration of tobacco cessation treatment within cancer centers is needed to improve smoking cessation outcomes among cancer patients and survivors. The current study characterizes baseline rates of tobacco use, use of cessation support, and changes in tobacco use over time among 756 participants diagnosed with cancer and enrolled in 9 ECOG-ACRIN Cancer Research Group trials. MATERIALS AND METHODS Participants completed surveys at trial enrollment and at 3- and 6-month follow-ups. Descriptive statistics were used to characterize patient characteristics and selected items from the Cancer Patient Tobacco Use Questionnaire (C-TUQ). Generalized estimating equations were used to examine the time point effect on tobacco product use. RESULTS At baseline, 11% of participants (n = 740) currently smoked cigarettes. Among participants with data available at all time points (n = 443), prevalence of current smoking was stable over time, with 7.2% of participants (n = 32) reporting current smoking at baseline, 7.0% (n = 31) at the 3-month follow-up assessment, and 6.8% (n = 30) at the 6-month follow-up assessment. Most participants (n = 77/104) who smoked cigarettes within the year prior to their cancer diagnosis continued smoking after their diagnosis, and during (n = 44/72) and following completion (n = 30/46) of their treatment. Sixty-two percent of participants (n = 81) who were currently smoking at baseline reported using smoking cessation medication and 32.1% reported use of nonpharmacologic smoking cessation support since their cancer diagnosis. In longitudinal analyses, the odds of using cigarettes since their cancer diagnosis, 3-month follow-up, and 6-month follow-up was higher than the odds of using cigarettes for the past 30 days at baseline (odds ratio [OR] = 1.97, OR = 1.62, and OR = 1.50, respectively; all p s < .01). CONCLUSION Smoking persists over time among patients with cancer enrolled in therapeutic cancer trials. Findings highlight the importance of increasing access to integrated and longitudinal smoking cessation support.

Abstract Introduction: Anti-CD19 chimeric antigen receptor T-cell (CART) therapy is feasible with an acceptable safety profile in older patients (pts) with relapsed/refractory (RR) large B-cell lymphoma (LBCL) (Tun et al, AJH 2024). However, immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent and challenging toxicity in older pts, and its characteristics and associated risk factors are not well defined. Methods: Seven centers participated in this retrospective study. Pts aged ≥65 years (yrs) with RR LBCL treated with a commercial CART product were included. Baseline characteristics, treatment, CART toxicity, and outcomes were collected. ICANS was graded by the ASTCT criteria in most pts. Cumulative incidences of ICANS were estimated using deaths/progressions as competing risks, and associations between incidences and variables were assessed by Gray's test. A 30-day landmark was set after infusion to reduce immortal time bias. Progression-free survival (PFS; time from the landmark to disease progression or death) and overall survival (OS; time from the landmark to death) were analyzed with the Kaplan-Meier method. Statistical analyses were done in JMP v18. Results: A total of 224 pts were included. Median age at infusion was 71 yrs (range 65–89; ≥80 yrs, 12%. 142 (63%) were male and 27 (13%) had an ECOG PS scale of ≥2. The median HCT CI was 1 (range 0–6). LDH was elevated in 110 (51%) pts, 23 (19%) had bulky disease ≥7 cm, 176 (82%) had advanced-stage, and 145 (71%) had extranodal disease. Median number of prior treatments was 2 (range 1–8), and 44 (20%) had prior bendamustine. Prior stem cell therapy was done in 47 (21%) pts (autologous stem cell transplant [SCT], n = 45; allogeneic SCT, n=2). Axicabtagene ciloleucel (axi-cel) was most frequently used (58%; n=131) followed by lisocabtagene maraleucel (liso-cel) (16%, n=36) and tisagenlecleucel (tisa-cel) (25%, n=57). Median duration of ICANS was 6 days (interquartile range [IQR] 3–11; range 1–303). Median time to ICANS onset was 6 days (IQR 3.8–8.0; range 0–24). The 30-day cumulative incidence of all grade ICANS was 50.9% (95% confidence interval [CI] 44.7–57.9) and grade ≥3 ICANS was 29.8% (95% CI 24.0–37.0). There was no significant difference in incidence of all grade (P=0.39) and grade ≥3 (P=0.49) ICANS as well as duration of ICANS (≥14 vs &lt;14 days; P=0.08) according to the age groups (≥65–69 vs ≥70–74 vs ≥75–79 vs ≥80–89). In contrast, pts with an ECOG PS scale of ≥2 were associated with a higher incidence of all grade (30-day estimate, 66.7% vs 47.0%; P=0.02) and grade ≥3 ICANS (30-day estimate, 53.8% vs 25.6%; P=0.002). In addition, pts with an elevated LDH level had a higher incidence of grade ≥3 ICANS than those without (30-day estimate, 37.5% vs 18.8%;P=0.004). The incidence of ICANS varied among various CART products, with 30-day estimates of 64.9% vs 33.3% vs 29.8% (P&lt;0.0001) for all grades and 40.1% vs 13.2% vs 18.0% (P=0.004) for grade ≥3 ICANS in pts treated with axi-cel vs tisa-cel vs liso-cel, respectively. A trend toward higher grade ≥3 ICANS was seen in pts treated with ≥3 prior lines than those treated with 2 or 1 (30-day estimate, 35.7% vs 28.1% vs 10.5%; P = 0.07). ICANS was managed with steroids in 47 (41%) pts, levetiracetam +/- other agents in 46 (40%) pts, biologic agents +/- other drugs in 15 (13%) pts, and supportive care in 6 (5%) pts. Median follow-up from the 30-day landmark post-infusion was 17.2 months (95% CI 14.2–22.4). Median PFS was 10.5 months (95% CI 5.7–18.2) and OS was 18.2 months (95% CI 13.3 vs 27.5). There was no difference in PFS and OS in pts who experienced ICANS vs no ICANS (median PFS 14.7 vs 10.1 months; P=0.65 and median OS 18.2 vs 24.7 months; P=0.49). However, there was a trend toward inferior PFS and OS in pts who experienced high-grade ICANS compared to those who had grade 0-2 ICANS (median PFS 9.2 vs 21.2; P=0.14 and median OS 11.7 =vs 22.9; P=0.39). Conclusions: This large study of older pts with RR LBCL demonstrated acceptable risks of ICANS, comparable to that in pivotal registration trials, with a relatively higher rate of grade ≥3 ICANS. The risks of ICANS were similar regardless of patient age, including those aged ≥80 yrs, but different among CART products. Similar to younger pts, high tumor burden disease and poor performance status at CART infusion were associated with higher risks of ICANS. A comprehensive neurologic and frailty assessment is warranted to identify suitable CART candidates.

Abstract Purpose: Polatuzumab vedotin (polatuzumab) was approved for up-front treatment of diffuse large B-cell lymphoma in combination with chemoimmunotherapy (Pola-R-CHP) based on the POLARIX trial. However, when stratified by cell of origin (COO), polatuzumab seems to have greater efficacy in activated B-cell than germinal center B-cell (GCB) subtype disease. Most studies of polatuzumab used RNA expression to assess COO, whereas in routine clinical practice, the immunohistochemistry-based Hans algorithm is used. Experimental Design: To assess the impact of COO by immunohistochemistry on polatuzumab efficacy, we conducted a multicenter real-world study of adults with large B-cell lymphoma (LBCL) receiving polatuzumab from 2015 to 2024, split by receipt of polatuzumab in first-line versus relapsed/refractory settings. The primary endpoint was overall response rate (ORR) to polatuzumab-based treatment in GCB versus non-GCB relapsed/refractory LBCL. Results: Of 740 patients, 305 received polatuzumab in the first-line setting and 435 in the relapsed/refractory setting. In the relapsed/refractory cohort, the ORR in non-GCB versus GCB LBCL was 59.7% versus 36.3% [OR, 2.6; 95% confidence interval (CI), 1.77–3.84; P &lt; 0.0001], with a complete response rate of 35.7% versus 17.7% (OR, 2.6; 95% CI, 1.66–4.02; P &lt; 0.0001). Progression-free survival was longer for patients with non-GCB versus GCB COO (HR, 0.64; 95% CI, 0.5–0.83; P = 0.0006). In the first-line cohort, ORR, complete response rate, and progression-free survival were similar in non-GCB versus GCB LBCL, as hypothesized based on outcomes in the Pola-R-CHP arm of POLARIX, suggesting that the addition of polatuzumab overcomes the adverse risk of non-GCB COO in patients receiving R-CHOP. Conclusions: Based on these data, COO classification by the Hans algorithm is a strong predictor of polatuzumab efficacy in LBCL, informing real-world treatment decisions.

Abstract Background: MCL is a B-cell non-Hodgkin lymphoma for which auto-HCT is often employed in first CR, based on non-randomized phase 2 trials, and a randomized trial (Dreyling et al, Blood 2005) conducted before the advent of more effective induction and maintenance regimens. The TRIANGLE trial (Dreyling et al, Lancet 2024) suggested that auto-HCT may not add benefit to more effective induction and maintenance regimens containing high-dose cytarabine, rituximab and BTK inhibitors. E4151 explored whether auto-HCT benefits pts achieving deep first remission, as measured by a highly sensitive immunoglobulin high throughput sequencing minimal residual disease (MRD) assay. Methods: EA4151 is a four arm trial conducted through the U.S. National Clinical Trials Network (NCTN) and Blood and Marrow Transplant Clinical Trials Network (BMT-CTN). Pts with MCL between the ages of 18 and 70 and in first remission were eligible. After induction, pts underwent PET/CT, bone marrow biopsy, and the clonoSEQ® MRD assay from peripheral blood. Pts in CR with uMRD at 1 in 10-6 sensitivity (uMRD6) were randomized 1:1 to Arm A (auto-HCT + 3 years of maintenance rituximab [MR]) or Arm B (3 years of MR alone), stratified by MIPI-c score and intensive vs non-intensive induction. Pts with either MRD-positive (MRD+) CR or MRD-indeterminate CR (Arm C and Arm D, respsectively) both received auto-HCT + 3 years of MR. Pts who were MRD+ pre-transplant had MRD repeated at day 100. Primary endpoint was to compare overall survival (OS) in Arms A and B, with secondary endpoints including progression-free survival (PFS). Primary analysis population included all randomized pts. As some pts refused their assigned treatment (N=65 [25.3%] for arm A and N=2 [0.8%] for arm B), a “treated as assigned” analysis was also performed. Stratified logrank test was used to compare survival distributions. P-values are two-sided. Results: From Aug 2017 to July 2024, 650 pts were assigned to a treatment arm with 257, 259, 49, and 85 pts enrolled on Arms A, B, C, and D, respectively. Pts were 79% male and 92% white race. Median age was 60 years (range 27-70). MIPI-c was low/low-intermediate (LI) in 63% and high/ high-intermediate (HI) in 37%. Induction was intensive (defined as high-dose cytarabine-containing) in 73% and non-intensive in 27%. A BTK inhibitor was given during induction in 7.2% of pts, and during maintenance in 0.3% of pts. The third pre-planned interim analysis was based on data as of 7/15/24, with median follow up of 2.7 years. The futility boundary was an OS hazard ratio (HR) of 0.984 for Arm A vs B. The estimated OS HR for Arm A vs B in all randomized (n=516) and pts treated as assigned (n=375) were 1.11 (CI 0.71-1.74, p=0.66) and 1.00 (CI 0.58-1.74, p=0.99), respectively and crossed the futility boundary. The 3 year (yr) OS for Arms A and B were 82.1% and 82.7% in all randomized pts, and 86.2% and 84.8% in pts treated as assigned. The estimated PFS HR for Arm A vs B in all randomized and pts treated as assigned were 1.05 (CI 0.71-1.56, p=0.79) and 0.95 (CI 0.59-1.54, p=0.84), respectively. The 3 yr PFS for Arms A and B were 76.6% and 77.4% in all randomized pts, and 81.5% and 80.4% in pts treated as assigned. For Arm C, 3 yr OS and PFS were 81.9% (CI 69.6-96.4%) and 76.9% (CI 64.4-91.7%), respectively. For Arm D, 3 yr OS and PFS were 85.1% (CI 76.0%-95.4%) and 73.4% (62.7-85.9%), respectively. For the MIPI-c low/LI group, 3 yr OS was 84.6% vs 85.7% for Arm A vs B (p=0.96), while in the MIPI-c high/HI group, 3 yr OS was 77.4% vs 77.6% for Arm A vs B (p=0.71). For the intensive induction group, 3 yr OS was 83.0% vs 86.2% for Arm A vs B (p=0.30), while in the non-intensive induction group, 3 yr OS was 79.5% vs 72.8% for Arm A vs B (p=0.48). Exploratory analysis of MRD+ pts (Arm C) showed that pts who converted to uMRD6 post auto-HCT (n=17) had 3 yr OS of 100% and PFS of 100%, whereas those who remained MRD+ (n=13) post auto-HCT had 3 yr OS of 63.6% and PFS of 48.8%. Causes of death (COD) in Arm A were 4.7% lymphoma, 5.1% COVID-19, and 5.0% other/unknown. COD in Arm B were 3.5% lymphoma, 6.6% COVID-19, and 4.6% other/unknown. In Sept 2024, the DSMC recommended termination of accrual and release of trial findings based on these results. Conclusion: In this interim analysis, in the era of highly effective induction and maintenance regimens, MCL pts in first CR with uMRD6 did not benefit from consolidative auto-HCT. Pts who remain MRD+ after induction may benefit from auto-HCT. Longer follow-up will be important to confirm these findings.

Introduction: Mantle cell lymphoma (MCL) is an uncommon B-cell non-Hodgkin lymphoma (NHL) Prognosis is highly variable due to underlying biological and molecular heterogeneity. The first-line (1L) treatment paradigm for MCL continues to evolve with increasing use of bruton tyrosine kinase inhibitors (BTKi) and decreasing use of autologous stem cell transplant (ASCT). TP53 alterations are associated with inferior outcomes in MCL. The aim of this retrospective study is to determine treatment strategies and clinical outcomes in MCL patients based on TP53 gene mutation status. Methods: Retrospective data were collected from 19 institutions in the United States from 1/1993 to 1/2024. We examined treatment patterns and outcomes among MCL patients &gt;18 years of age with known TP53 mutation status by sequencing. Patients who did not receive treatment were excluded. The analysis was stratified based on presence of TP53 mutations. Systemic therapies were categorized as chemo-immunotherapy (CIT), non-chemotherapy (including monoclonal antibodies, lenalidomide, venetoclax, and novel agents on clinical trial), and regimens containing BTKi. The primary outcome was overall survival (OS) and secondary outcomes were progression free survival (PFS) and time to next treatment (TTNT). OS and PFS were estimated with the Kaplan-Meier method and log-rank tests were used to compare groups. Results: 645 patients were included in the study, with 468 men (72.6%) and median age was 64 years (range 30-89). 230/645 patients (35.7%) had a TP53 mutation, of which 182 (79%) were identified prior to 1L. While the male/female distribution was the same between the mutated and unmutated groups, median age at diagnosis and MIPI risk score was higher in the TP53 mutated group (age 65.9 vs 63.1 yrs, p= 0.015; MIPI 6.4 vs 6.1, p&lt;0.001). TP53 unmutated patients had a median of 1 line of therapy vs. 2 for the mutated group (p&lt;0.001, range 1-8). Blastoid histology and higher ki67 were also associated with the TP53 mutated group (p=0.045, 0.01 respectively) The median OS was 14.2 years for TP53 unmutated and 8.3 years for TP53 mutated patients (p&lt;0.0001). PFS in 1L was 0.95 years in TP53 mutated compared to 2.02 years in TP53 unmutated group (p&lt;0.0001). Selection of 1L therapeutic strategy was not associated with presence of TP53 mutation (Χ2 p= 0.21) although more patients in the TP53 unmutated group underwent ASCT (119/415 vs 38/230; Χ2 p=0.0006) TP53 mutation was associated with inferior survival compared to TP53 unmutated patients for CIT in 1L but the difference did not reach statistical significance when non-chemotherapy regimens and regimens containing BTKi were used. For CIT in 1L, 5 year OS was 78% [71-84%] for unmutated compared to 58% [48-67%] for the mutated group (p=0.0001 ). For non-chemotherapy regimens, 5 year OS for unmutated patients was 73% [52- 86%] compared to 52% [25-73%] for the mutated group (p=0.09). For regimens containing BTKi, 5 year OS for unmutated was 93% [81-97%] compared to 57% [28-78%] for mutated (p=0.07). Within the TP53 mutated group, there were no differences in any clinical outcomes between those receiving CIT, non-chemotherapy, or BTKi in 1L. While median OS appeared numerically longer in the BTKi group (14.4 yrs vs 8.8 yrs for CIT and 6.8 yrs for non-chemotherapy), the difference did not reach statistical significance (p=0.58). In contrast,TP53 unmutated patients who received CIT in 1L had better TTNT (p=0.0039) compared to those in non-chemotherapy and BTKi groups. There was no improvement in PFS (p=0.79) or OS (p=0.47). Conclusions To our knowledge this is the largest retrospective real world dataset of MCL treatment outcomes stratified by TP53 mutation. As in prior studies, TP53 mutation portends a worse prognosis in MCL compared to TP53 unmutated patients, but outcomes are better than historically reported. CIT in 1L was not associated with improved OS in either group. Irrespective of TP53 mutation status, incorporation of BTKi in first line was not associated with improved clinical outcomes. The gap in OS between TP53 mutated and unmutated MCL may be narrowing as treatment paradigms shift away from intensive induction chemotherapy and ASCT, and due to an increasing number of effective therapies for relapsed patients. Clinical trials of novel agents are needed to further improve the OS of TP53 mutated MCL patients.

Background: Polatuzumab vedotin (Pola) is an antibody drug conjugate targeting CD79b that incorporates the microtubule disrupting monomethyl auristatin E payload. Pola was approved in 2023 for the upfront treatment of diffuse large B cell lymphoma (DLBCL) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (polaRCHP) based on the POLARIX trial. However, the activity of pola appears to vary based on DLBCL cell of origin (COO) subtype, with greater efficacy in activated B cell (ABC) DLBCL compared to germinal center B cell (GCB) DLBCL (Russler-Germain Blood 2023). When outcomes in POLARIX are stratified by COO, polaRCHP demonstrated progression free survival (PFS) and overall survival (OS) benefits over RCHOP in patients with ABC but not GCB subtype DLBCL (PFS HR 0.34 ABC vs 1.03 GCB, OS HR 0.27 ABC vs 1.64 GCB; Morschhauser ASH 2023 and FDA data). Most prospective studies of pola used gene expression to assess COO, which is not readily clinically available. This study aims to examine if COO subtype by Hans algorithm (based on CD10, BCL6, and MUM1 expression by immunohistochemistry) is predictive of pola responses and outcomes in patients with large B cell lymphoma (LBCL). Methods: We conducted a retrospective, multicenter observational study of adults with LBCL who received pola (monotherapy or in combination) from 2015-2024 with Hans algorithm COO data and response assessment available. Patients were stratified by receipt of pola in the frontline vs relapsed/refractory (R/R) setting. The primary endpoint was overall response rate (ORR) to pola-based treatment in GCB vs non-GCB subtypes. Secondary endpoints included complete response rate (CRR), PFS, and OS. For time to event endpoints, patients responding to pola who received CAR T or stem cell transplantation prior to progression were censored at time of cellular therapy. Demographics were summarized by descriptive statistics. Comparative and survival analyses used Chi squared/Fischer exact tests and Kaplan Meier analysis. Data cutoff was July 1, 2024. Results: 718 patients were included. Median follow-up was 15 months (interquartile range [IQR] 8-32). Median age at LBCL diagnosis was 66 years (IQR 56-74); 62% were men; 69 (10%) had double hit lymphoma (DHL); 129 (18%) had underlying low grade lymphoma. Pola was used in the frontline setting in 293 (41%) patients, of whom 139 (47%) had GCB vs 154 (53%) non-GCB COO. Of the 426 patients receiving pola for R/R LBCL (including one patient receiving pola retreatment), 224 (53%) had GCB vs 202 (47%) non-GCB COO. Among patients receiving pola-based regimens in the R/R setting (GCB vs non-GCB: pola monotherapy = 7% vs 4%, pola + R = 26% vs 26%, pola + BR = 55% vs 61%, pola + other = 12% vs 9%; p = 0.44), the ORR in GCB vs non-GCB LBCL was 36% vs 61% (p &lt; 0.001), while CRR in GCB vs non-GCB was 17% vs 36% (p &lt; 0.001). COO remained a significant component of logistic multivariate regression models of ORR (p &lt; 0.001) and CRR (p &lt; 0.001) when incorporating IPI at original LBCL diagnosis, histology, DHL status, and refractory status to frontline therapy. Despite this, no significant PFS or OS differences by COO were seen, potentially due to approximately 1/4 patients being censored due to receiving subsequent cellular therapy (e.g. CAR T) prior to progression. In patients receiving frontline pola-based regimens (of which 275 [94%] included an anthracycline), ORR and CRR were similar in GCB vs non-GCB (ORR 89% vs 88% p &gt; 0.5; CRR 76% vs 77% p &gt; 0.5). While PFS and OS were similar between COO groups in the frontline cohort, follow-up and cohort size were limited. Conclusion: Based on this real-world evidence, COO classification by Hans algorithm is a strong predictor of the activity of pola-containing therapy in R/R LBCL, with significantly higher ORR and CRR in patients with non-GCB compared to GCB COO LBCL. This aligns with the cumulative existing evidence. ORR and CRR to pola-containing therapy in the frontline setting did not differ significantly by COO subtype, but longer follow-up of larger cohorts is needed to clarify the predictive role of COO by Hans algorithm in this setting, especially considering the PFS advantage with polaRCHP in POLARIX was not associated with significant differences in ORR or CRR. Overall, clinicians should consider factoring COO subtype into treatment decisions regarding pola-containing regimens, and studies of pola-based therapies should stratify patients and report outcomes by COO subtype.

Abstract Chimeric antigen receptor T‐cell (CAR‐T) therapy, despite being a potentially curative therapy in relapsed or refractory (RR) large B‐cell lymphoma (LBCL), remains underutilized in older patients due to limited clinical data. We therefore studied the safety and efficacy of CAR‐T therapy in older patients with RR LBCL in the real‐world setting. Patients aged ≥65 years with RR LBCL, treated with anti‐CD19 CAR‐T therapy at 7 US institutions were included in this multicenter, retrospective, observational study. In total, 226 patients were included. Median age at infusion was 71 years (range 65–89). Best objective and complete response rates were 86% and 62%, respectively. Median follow‐up after infusion was 18.3 months. The median progression‐free survival (PFS) was 6.9 months, with 6‐ and 12‐month PFS estimates of 54% and 44%, respectively. The nonrelapse mortality (NRM) rate was 10.9% at day 180, primarily due to infections, and not impacted by the age groups. Grade ≥3 cytokine release syndrome and neurotoxicity occurred in 7% and 26%, respectively. In univariate analysis, no significant difference in PFS was seen regardless of the age groups or CAR‐T type, whereas ECOG PS ≥2, elevated LDH, bulky disease, advanced stage, extranodal involvement, the need for bridging therapy, and prior bendamustine exposure were associated with shorter PFS. These findings support the use of CAR‐T in older patients, including those aged ≥80 years. The age at CAR‐T therapy did not influence safety, survival, and NRM outcomes. Older patients should not be excluded from receiving CAR‐T therapy solely based on their chronological age.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In 2003, the Eastern Cooperative Oncology Group initiated a randomized phase III clinical trial (E4402) comparing two different rituximab dosing strategies for patients with previously untreated low–tumor burden follicular lymphoma. Rituximab-responsive patients (n = 299) were randomly assigned to either a retreatment rituximab (RR) strategy or a maintenance rituximab (MR) strategy. Each dosing strategy was continued until treatment failure. The primary end point of the study was time to treatment failure (TTF). In the original report, there was no difference in TTF between the two dosing strategies. Here, we report on the long-term outcomes for secondary end points of time to first cytotoxic therapy, duration of response, and overall survival (OS). At 7 years, 83% of MR patients had not required first chemotherapy compared with 63% of RR patients (hazard ratio, 2.37 [95% CI, 1.5 to 3.76]). At 7 years, 71% of MR remained in their first remission compared with 37% of RR patients. Despite the improved first remission length with MR, there was no difference in OS at 10 years (83% v 84%). With mature long-term data, we confirm that prolonged maintenance rituximab does not confer an OS advantage in low–tumor burden follicular lymphoma.