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Abstract Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes after thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor (CAR) T-cell therapy (CAR-T) delivered at relapse were compared after propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). Two-year PFS estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P = .005; and OS: HR, 0.62; P = .023) and CNS-isolated relapses (PFS: HR, 0.55; P = .002; and OS: HR, 0.39; P< .0001). ASCT (thiotepa or no thiotepa) also associated with improved survival in synchronous relapses (PFS: HR, 0.57; P = .023; and OS: HR, 0.48; P = .019). Higher survival with thiotepa-ASCT than CAR-T was observed after PSM (PFS: HR, 0.45; P = .005 and OS: HR, 0.41; P = .014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

Importance Molecular analyses of biospecimens collected from study participants are essential for identifying biomarkers that can tailor treatments to specific subsets of patients who are most likely to benefit. Sharing of data and biospecimens from clinical trials enables personalized, patient-centric use of cancer therapies and accelerates the development of new treatments. Objective To describe obstacles to sharing data and biospecimens and to propose strategies to enhance access and collaboration. Evidence Review This is a Special Communication authored by 53 academic investigators and patient representatives from the breast cancer community with extensive experience in conducting clinical and translational research. The article also evaluates the impact of biomarker research on specifying responsive subpopulations in the 29 registrational clinical trials that have led to approval of a new drug for treatment of breast cancer between 2017 and 2024. Findings Clinical trial participants are increasingly asked to provide tissue and/or body fluid biospecimens for biomarker research that is typically controlled by the sponsoring pharmaceutical company, but published biomarker studies are rare. Among 29 breast cancer registrational studies reported in the past 8 years, none resulted in biomarker research that restricted a drug’s approved indication. Herein, strategies to maximize the value of clinical data and biospecimens contributed by participants are proposed, thereby supporting the shared goals of the pharmaceutical industry and academia to improve patient care. These strategies include (1) establishing coleadership structures involving academia and patients in clinical trial design and conduct, (2) ensuring that informed consent forms state that data and biospecimens will be shared with academia for future research, (3) requiring the sharing of clinical data as a condition for regulatory approval, and (4) enabling access to biospecimens and translational research data for independent studies on biomarkers that may indicate drug efficacy and toxicity. Conclusions and Relevance Data and biospecimen sharing from registrational trials has been suboptimal. Improving clinical data, biospecimens, and biospecimens’ related data sharing requires concrete actions and a multidimensional stakeholder approach to accelerate the impact of clinical cancer research on the quality of patient care.

Abstract Introduction Introduction: Peyronie’s disease (PD) is a fibrosing condition of the tunica albuginea characterized by a palpable plaque with varying impacts on the patient’s erection: curvature, shortening, indentations, hinging, and narrowing. Stepwise intralesional injection of collagenase clostridium histolyticum (CCH) is the only FDA approved medical treatment for PD. We retrospectively reviewed Xiaflex® treated patients for satisfaction with therapy or pursuit of subsequent surgery. Objective Objective: To assess global satisfaction with intralesional Xiaflex based on whether patients subsequently elected surgery. Methods Methods: This is a retrospective review of patients presenting with PD to a single center and managed by a single provider from 2020-2024 with six-month follow-up post-treatment. Patient presentations were recorded in an Institutional Review Board approved database. Data storage and analytics were conducted using REDCap. Results Results: The cohort for this study was 159 men treated with intralesional Xiaflex. 18 of the 159 were excluded from analysis due to ongoing treatment. 48.9% of patients (69/141) were satisfied with CCH outcomes and sought no further therapy. 51.1% of patients (72/141) were not satisfied with their outcomes. Of the patients not satisfied with treatment, 48/72 (66.7%) elected subsequent surgical interventions: 18 penile plications, 8 incision and grafting and 22 inflatable penile prostheses. 51.7% (73/141) of patients completed (8) CCH treatments. Among the 73 men who had a complete set of CCH injections, 24.6% (18/73) elected subsequent surgery. Among the patients who had fewer than 8 treatments 46.9% (30/64) elected surgery following Xiaflex. Conclusions Conclusion: If successful medical management of Peyronie’s disease is defined by men who decline subsequent surgical interventions, Xiaflex® was highly successful 75% (55/73). Patients who have Peyronie’s disease are highly motivated and will pursue surgical interventions following a trial of CCH. Disclosure No

Abstract Introduction: Cilta-cel is a BCMA-directed CAR T-cell therapy that has shown remarkable efficacy in patients with RRMM. As real-world (RW) experience with cilta-cel continues to expand, and with the recent FDA guidance reducing the recommended proximity to the CAR T center from four to two weeks post-infusion, there is growing interest in identifying patients at low risk for severe early complications who may be safely managed in the outpatient setting and potentially ‘discharged’ home earlier. Methods Data were collected from 769 patients with RRMM treated with cilta-cel at 15 institutions in the U.S. via the Multiple Myeloma Immunotherapy Consortium.Logistic regression was used to identify predictors of patients who could be managed in the outpatient setting (low-risk group). Based on expert consensus within the Consortium, low-risk patients were defined as: grade ≤1 CRS, no ICANS, and no IEC-HS. The remaining patients were categorized as high-risk. We evaluated baseline characteristics with missingness < 20% as predictors, including age, sex, race, and ethnicity, ECOG performance status (PS) at time of lymphodepletion (LD), extramedullary disease, bone marrow plasma cell (BMPC) percentage, high-risk cytogenetics, bridging therapy including response, penta-refractory status, number of prior lines of therapy, prior anti-BCMA therapy, baseline C-reactive protein (CRP), and baseline ferritin. The cohort was restricted to patients with complete data on all predictors (n=455) and split into a training and testing cohort (80/20 split, n=364/91). Bidirectional stepwise regression was used to build the predictive model using variables with significance of p<0.15 selected for entry. The best model was selected based on the AIC (Akaike Information Criterion) and a significance level of p<0.05. Results Among the 455 patients with complete data included in the final model, 290 (64%) were categorized as low-risk and 165 (36%) as high-risk. Compared to the low-risk group, high-risk patients were more likely to have an ECOG PS ≥2 at time of LD (20% vs 9%, p<0.001), high-risk cytogenetics (47% vs 35%, p=0.009), and penta-refractory disease status (34% vs 24%, p=0.031). High-risk patients also had a higher median BMPC percentage (15% vs 5%, p<0.001), and higher baseline pre-LD CRP and ferritin. Overall response rates were high, at 95% vs 90% (p=0.047) for the low vs high risk groups, with complete response or better achieved in 73% vs 66% of patients, respectively (p=0.14). With a median follow-up of approximately 11 months, median progression-free survival was not reached (95% CI: 27-NA) in the low-risk group and 18.2 months (95% CI: 13.1-NA) in the high-risk group. In terms of safety, non-ICANS neurotoxicity (NINT) occurred less frequently in the low-risk group (6.6% vs 13%, p=0.015). Specifically, Parkinsonism was observed in 1.7% vs 6.1% (p=0.013), and cranial nerve palsy in 4.5% vs 5.5% (p=0.7), respectively. Non-relapse mortality (NRM) was lower in the low-risk group (4.2%) compared to the high-risk group (14%; p < 0.001). The most common causes of NRM in the low- and high-risk groups were acute toxicities (0% vs 36%, including CRS, IEC-HS, and ICANS), delayed toxicities (0% vs 8%, including colitis, NINT, and Parkinsonism), infections (50% vs 48%), and other unrelated causes (50% vs 8%). The best model to predict low-risk patients that could be managed in the outpatient settingincluded BMPC percentage and ECOG PS at LD. In the training cohort, patients with a higher pre-LD BMPC percentage and an ECOG PS ³2 were less likely to be in the low-risk group(OR per 1-unit change in BMPC percentage = 0.99, 95% CI=0.98-0.99, p<0.001 and OR for ECOG PS 2-4 = 0.38, 95% CI=0.20-0.72, p=0.003). The AUC for this model was 0.663 in the training cohort and 0.659 in the testing cohort. Conclusion In this large, multi-institutional cohort of patients with RRMM treated with cilta-cel, we identified clinical factors associated with lower risk for early severe toxicities, supporting outpatient administration and the potential for earlier discharge in selected patients, particularly those who are fit and have low disease burden. Our findings provide a practical framework to guide risk stratification and outpatient CAR T management strategies, particularly in light of evolving regulatory guidance and growing RW experience with cilta-cel.

Abstract Introduction: Older adults (OAs) with classic Hodgkin lymphoma (cHL) have inferior survival compared with younger patients (pts). NAVD has been widely adopted in clinical practice for frontline (1L) treatment of OAs with advanced stage cHL based on the subset analysis of S1826 study (Rutherford et al, JCO 2025) showing a 1-year progression-free survival (PFS) of 93% and 1-year overall survival (OS) of 95% after NAVD (n = 50) which remained durable on longer-term follow up. Another phase 2 study (Torka et al, JCO 2025) showed that NAVD is a highly effective and well-tolerated 1L regimen in OAs with cHL (n=40) across a wide range of geriatric impairments. Adverse events (AEs) and efficacy have not been reported in OAs treated with NAVD outside of a clinical trial. Hence, we sought to evaluate safety profile and efficacy outcomes of OAs with cHL treated with 1L NAVD in a real-world setting (RWS). Methods This is a multicenter retrospective cohort study of adults (≥18 years) with cHL treated with 1L NAVD between 2023 and 2025 at 20 US academic sites. Baseline characteristics and outcomes of pts ≥60 years were evaluated as a pre-planned subset analysis. The safety evaluable cohort received at least 1 cycle of NAVD and included pts who had not yet completed treatment. The efficacy evaluable cohort had completed 6 cycles of treatment including end of treatment (EOT) PET-CT and included pts who intended to complete treatment but died or discontinued due to progressive disease or AEs. The primary endpoint was EOT overall response rate (ORR). Secondary endpoints included EOT complete response rate (CRR), PFS and OS. PFS and OS were analyzed using the Kaplan Meier method. Results Among 311 pts, 81 were OAs (26%). Median age of the OA cohort was 70 (range 60-88) yrs, 65% male, 84% Caucasian, 71% nodular sclerosis subtype, 58% stage 4 disease, 59% B symptoms, 14% bulky disease (>7.5 cm), 69% extranodal sites, 41% EBV positive, 54% hypoalbuminemia, 49% IPS ≥ 4 and10% had an autoimmune disease. G-CSF was given in 81% pts. All 81 pts were evaluable for safety; 74% experienced a grade 3+ (≥G3) AE, 54% had ≥G3 hematological AE, 48% had ≥G3 neutropenia, 17% had febrile neutropenia. Infection rate was 28% with 10% ≥G3, neuropathy rate was 23% with 4% ≥G3. One infusion reaction was noted. Treatment related hospitalizations rate was 23% with median duration of 7 (range 1-16) days. There were 24 immune related AEs (IrAE) (30%) of which 5 were ≥G3. Most common IrAE was hypothyroidism (n=5), followed by inflammatory arthritis (n=4), pneumonitis (n=2, ≥G3, n=1), hepatitis (n=2, both ≥G3), adrenal insufficiency (n=2, ≥G3, n=1), colitis (n=2), and rash (n=2). One patient each had autoimmune neutropenia, sarcoidosis of lung/skin and myocarditis (≥G3). Overall, 15% pts required steroids with resolution of IrAEs in 56% cases, 30% (n=7) pts required continued therapy (levothyroxine in 4 pts, steroids in 3 pts, medical tx for heart failure in 1 pt). Treatment was interrupted in 22%, reduced in 22%, and discontinued in 23% pts. Nivolumab was discontinued in 14% pts. Among all pts (n=81), 81% had an interim PET-CT after 2-4 cycles. The ORR and CR rate at interim PET-CT were 100% and 81%, respectively. In the efficacy evaluable pts (n=52; 24 still on therapy), the EOT ORR and CRR were 93.2% and 84% in OAs compared to 96.8% and 91.7% in pts <60yrs, respectively. At a median follow up of 10.2 mo (range 0.27-28.52), the 1-yr PFS was 90.6% (95% CI: 82.7%-99.3%) in OAs and 95.5% (95% CI: 91.6%- 99.6%) in pts <60 yrs (p=0.044). 1-yr OS was 97.5% (95% CI: 94.1-100%) and not evaluable in pts <60yrs (p=0.017). None of the baseline features were predictive of response, additional analysis to understand impact on AEs and survival is ongoing. Among the 5 pts with progression/relapse, 4 were primary refractory. 4 pts received 2nd line (2L) therapy.79 pts are alive at data cut off, 2 deaths occurred- 1 infection-related and other unknown; both after the 1st cycle. Conclusions In this largest RWS cohort of OAs treated with NAVD we showed comparable response rates, AEs and 1-year survival outcomes to those in the pivotal S1826 trial. Notably, rates of ≥G3 AEs including infections, neuropathy and IrAEs remained low and manageable. Although survival significantly improved with NAVD compared to historical data, outcomes of OAs remained inferior compared to pts <60 yrs. Our data reinforces the use of NAVD as the preferred 1L option for OAs with advanced stage cHL.

Abstract Introduction: Ciltacabtagene autoleucel (cilta-cel) is a highly effective BCMA-redirected CAR T-cell therapy for RRMM. While the pivotal CARTITUDE-1 trial established a target dose of 0.75 x 10^6 CAR+ viable T-cells/kg, the approved cell dose is 0.5-1.0 x 10^6 and the optimal dosing strategy to balance efficacy and toxicity remains unclear. This question is of interest given that a dose-response association has been demonstrated for idecabtagene vicleucel (a related BCMA-directed CAR T product). It has also been hypothesized that lower doses of cilta-cel may be associated with reduced toxicity. This study aims to evaluate the association between cilta-cel dose and key efficacy and toxicity outcomes using a large, real-world dataset from the US Multiple Myeloma Immunotherapy Consortium. Methods: We conducted a multicenter, retrospective analysis of 751 RRMM patients treated with commercial cilta-cel across 15 US academic centers. The administered cilta-cel dose (million cells/kg) was categorized into four groups: low (<0.5), standard-low (0.5 to <0.6), standard (0.6 to <0.8), and standard-high (0.8 to 1.0). We compared incidence rates of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), delayed neurotoxicity (DNT), and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) across these dose categories using logistic regression. Best response rates and progression-free survival (PFS), estimated using the Kaplan-Meier method, were also compared, with differences assessed using the log-rank test for the latter. Results presented are derived from multivariable models adjusting for extramedullary disease, ECOG status, penta-refractory disease and receipt of bridging therapy. Results: Among 751 infused patients, the dose distribution was: <0.5 (n=33), 0.5 to <0.6 (n=131), 0.6 to <0.8 (n=550), and 0.8 to 1.0 (n=37). The four dose groups were well-balanced in terms of baseline patient and disease characteristics, including age, high-risk cytogenetics, and extramedullary disease, with the exception of t(14;16), which was more common in the standard-low and standard dose groups (p=0.006). There were no statistically significant differences in the rates of any grade CRS (p=0.11), any grade ICANS (p=0.84), grade ≥3 ICANS (p=0.36), duration of CRS (p=0.18) or ICANS (p=0.64), or IEC-HS (p=0.16) across the four dose categories. Time to onset of CRS was shorter for the standard-high dose compared to the low dose (6 days vs. 8 days; p=0.08). Importantly, there was no significant difference in the rate of DNT (3.0%, 9.2%, 8.8%, 5.4%; p=0.24). Similarly, there was no significant difference in overall response rates (97%, 96%, 96%, 88%; p=0.50) or complete response rates (75%, 65%, 75%, 66%; p=0.10) by dose. The median follow-up was 12.3 months (IQR: 6.9, 20.5). For patients who received a standard-low dose (0.5, 0.6), the median PFS was 17.5 (IQR: 13.5, NR) months. For the standard dose range of (0.6, 0.8), the median PFS was 28.7 (95% CI: 19.8, NR) months, while the median PFS for the standard-high dose (0.8, 1.0) was not reached. For the low dose range of <0.5, the median follow up was only 8.7 months, which did not allow reliable estimation of the median PFS. While the overall difference in PFS among the groups did not reach statistical significance by the log rank test, there was a clear trend toward improved PFS with higher cell doses in the multivariable model, with outcomes clearly ordered in the same direction as the cell dose categories. A similar trend was also evident in the rates of 12-month PFS which showed an improvement with increasing dose (62% ,67%, 73%, 80%). Conclusions: In this large, real-world cohort of RRMM patients treated with cilta-cel, a lower cell dose was not associated with reduced incidence or severity of CRS, ICANS, DNT, or IEC-HS. Conversely, a dose-response correlation with PFS was observed, with higher doses trending toward longer median and 12-month PFS. It remains unknown if a lower cell dose in the commercial setting reflects poor T cell quality, yet these findings suggest that dose reduction of cilta-cel may not be an effective strategy to mitigate toxicities and might be associated with a trend toward lower efficacy. Therefore, the standard target dose should be utilized to maximize patient outcomes and further prospective dose exploration is warranted.

Abstract Introduction: The GPRC5D-directed bispecific antibody (BsAb) Talquetamab (Talq) has shown promising results for patients (pts) with relapsed/refractory multiple myeloma (RRMM) in the MonumenTAL-1 clinical trial (Chari et al. NEJM 2022). However, there are limited data on the use of Talq in the real-world setting. Methods: All pts with RRMM who started Talq between 8/2023-3/2025 across 15 US academic centers were included. High-risk cytogenetic abnormalities (HRCA) were defined as del(17p), t(4;14), t(14;16) and/or gain/amplification 1q21. Time-to-event analyses were estimated using the Kaplan-Meier method. Toxicities including CRS and ICANS were graded using CTCAE v5.0 or ASTCT criteria. Results: A total of 484 pts were included, with a median age of 65 years (range 35-89), and 83 pts (17%) were aged ≥75 years. 20% of pts were black. 21% had baseline CrCl<40, 65% had HRCA and 29% had >1 HRCA (i.e Ultra high-risk MM). The median number of prior lines of therapy was 6 (IQR 4, 8). 50% were penta-refractory, 69% received at least one prior BCMA-directed therapy (46% CART; 32% BsAb). Prior to initiation of Talq, 11 pts (2%) had CNS MM, 29 (6%) had PCL and 126 (26%) had true extramedullary disease (EMD). 70% would have been ineligible for the MonumenTAL-1 trial. For most pts (n=405; 84%) the dosing strategy from Cycle 2 was 0.8 mg/kg every 2 weeks. and the 0.4 mg/Kg weekly dosing was used in 28 patients (6%). In 6% of pts, an additional drug was added to Talq, mostly pomalidomide (n=20) or daratumumab (n=10). 101 pts (21%) received Talq as bridging for CART. Median duration of Talq treatment was 102 days. 62% developed CRS (Grade ≥3, 2%; including one Grade 5 event). 15% developed ICANS (Grades 3-4, 4%). Steroids were used in 213 patients (44%), tocilizumab in 145 (30%) and anakinra in 9 (2%). 22 patients (5%) required ICU stay during the first cycle, for a median of 6 days (range 1-31). A total of 200 pts (41%) had infections (median 1 infection each, range 1-6), including 99 (20%) with bacterial infections, 113 (23%) viral infections and 21 (4%) fungal infections. IVIG was used in 261 pts (54%). 79% of patients (n=384) developed Talq-related oral toxicity, 55% (n=269) skin toxicity and 199 (41%) nail toxicity. 157 patients died after a median follow up of 11.5 months (mos), and the leading causes of death were MM progression (n=120) and infection (n=10). 8 pts (1.7%) developed invasive second primary malignancies. The ORR was 73%, including 46% ≥VGPR. The median PFS (mPFS) for the entire cohort was 7.8 mos (95% CI 6.9-9.4) and the 12 months PFS rate was 39%. The median OS had not been reached and the 12 months OS rate was 63%. For pts who would have been eligible for MonumenTAL-1, the mPFS was 12.2 mos (95% CI 9.7 – not reached (NR); for trial-ineligible pts, the mPFS was 6.9 mos (5.8 – 8.0; p=0.003). For BCMA-naive pts, the mPFS was 15.7 mos (11.8-NR); for BCMA-exposed pts, the mPFS was 6.8 mos (6.0-7.8; p=0.0002). For patients who received Talq as bridging prior to CART, the median PFS was NR (14.1 – NR); for those who did not receive Talq as bridging the mPFS was 6.5 mos (5.3-7.6; p<0.0001). In multivariable analyses, worse OS and PFS were associated with trial ineligibility [(HR 1.38, 95% CI 1.03-1.86; p=0.03) and (2.33, 1.31-4.14; p=0.004)], BMI<30 [(1.42,1.06-1.89; p=0.02) and (1.50, 1.01-2.22; p=0.045)] and true EMD at baseline [(1.95, 1.49-2.56; p<0.001) and (1.65, 1.16-2.36; p=0.005). On the other hand, use of Talq as bridging to CART was associated with better PFS (0.27, 0.17-0.43; p<0.001) and OS (0.13, 0.05-2.56; p<0.001). Ultra high-risk MM (1.40, 1.06-1.84; p=0.02) and baseline albumin <3 (1.68, 1.18-2.37; p=0.004) were associated with worse PFS; ECOG ≥2 (1.68, 1.18-2.40; p=0.004), and baseline Plt<50K (2.14, 1.48-3.10; p<0.0001) was associated with worse OS. Conclusions: In this large real-world analysis of 484 Talq recipients, the ORR was comparable to MonumenTAL-1 but the median PFS was shorter. This likely reflects differences in patient selection, with 70% of patients in our cohort being trial-ineligible. Patients who received Talq as pre-CAR-T bridging had superior survival outcomes. Rates of toxicities were similar to MonumenTAL-1, including >70% of patients developing dysgeusia.

Abstract Introduction: Elranatamab, a BCMA-CD3 bispecific antibody, has shown efficacy in relapsed multiple myeloma (MM), but real-world data on its safety and effectiveness are limited. Methods: We conducted a retrospective, multi-center study of patients (pts) treated with commercial elranatamab from 8/2023–3/2025 at 9 U.S. academic centers. Logistic and Cox regression were used for binary and time-to-event outcomes, respectively. Multivariable analysis (MVA) adjusted for prior lines of therapy (LOTs), baseline Hgb (per g/dL), and LDH (per 100 U/L) as continuous variables; and for BCMA exposure, extramedullary disease (EMD; extraosseous soft tissue lesions), and ECOG ≥2 as binary variables. Results: Of 130 pts, median age was 71 yrs (range 39–95); 57% were female, 82% white, 13% black, and 35% had ECOG ≥2 (11% ≥3). Median LOTs was 6; 91% were triple-class refractory, 49% penta-refractory, 49% BCMA-exposed (median 15.5 mo [IQR 11.8–20.5] since last exposure), and 49% had prior anti-BCMA CAR-T. Most recent BCMA exposures included: CAR-T (84%), TCE (9.4%), and ADC (6.3%). Only 22% met MagnetisMM-3 cohort A eligibility (which excluded BCMA-exposed pts). High-risk cytogenetics (del(17p), t(4;14), t(14;16), or amp(1q)) were present in 44% (25%, 13%, 6.3%, and 7.9%, respectively). EMD was seen in 22%. Median treatment duration was 4.0 mo (95% CI 2.93–6.3) overall and 7.9 mo (95% CI 5.83–NA) with ≥VGPR. Discontinuation due to toxicity or non-relapse mortality occurred in 12% but was significantly lower among those receiving IVIg (5% vs. 17%, p=0.031); IVIg was given in 47%. The overall response rate (ORR) was 65%, including ≥VGPR in 46% and ≥CR in 36%, consistent with MagnetisMM-3 (ORR 61%, ≥CR 35%; Lesokhin et al. Nat Med. 2023). After median follow-up of 7.5 mo, median PFS was 4.3 mo (95% CI 3.4–11.3), OS was 14.6 mo (95% CI 8.6–NA), and DOR was 12.2 mo (95% CI 6.1–NA). In contrast, MagnetisMM-3 (Prince et al., ASH 2024) reported median PFS and OS of 17.2 and 24.6 mo, respectively, with DOR not reached despite 28.4 mo of follow-up. In univariate analysis, ECOG ≥2 was associated with lower ORR (45% vs. 71%; OR 0.34, 95% CI 0.16–0.73, p=0.006), shorter OS (4.3 mo vs. NA; HR 2.41, 95% CI 1.33–4.35, p=0.004), and shorter PFS (1.7 vs. 6.5 mo; HR 1.77, 95% CI 1.09–2.87, p=0.020). Prior BCMA-directed therapy was linked to reduced odds of ≥VGPR (OR 0.38, 95% CI 0.19–0.77, p=0.008) and ≥CR (OR 0.43, 95% CI 0.20–0.89, p=0.025). Higher baseline LDH was linked to shorter OS (HR 1.37, 95% CI 1.23–1.53, p<0.001) and PFS (HR 1.31, 95% CI 1.18–1.44, p<0.001). Higher baseline Hgb was associated with higher ORR (OR 1.46, 95% CI 1.20–1.81, p<0.001) and ≥CR (OR 1.54, 95% CI 1.26–1.92, p<0.001). Among BCMA-exposed pts, recent exposure (<1 [n=15] vs. ≥1 yr [n=32]) was associated with shorter OS (4.1 mo vs. NA; HR 3.66, 95% CI 1.26–10.6, p=0.017). In MVA, higher baseline LDH remained independently associated with shorter OS (aHR 1.36, 95% CI 1.19–1.54, p<0.001) and PFS (aHR 1.27, 95% CI 1.13–1.43, p<0.001); higher Hgb with greater odds of ≥CR (aOR 1.44, 95% CI 1.14–1.85, p=0.003) and longer PFS (aHR 0.84, 95% CI 0.72–0.99, p=0.034); and BCMA exposure with lower odds of ≥CR (aOR 0.32, 95% CI 0.10–0.91, p=0.037). CRS occurred in 40% (grade ≥2 in 12.3%, grade 3 in 2.3%), and ICANS in 17% (grade ≥2 in 7.7%). These rates contrast with MagnetisMM-3 (no grade ≥3 CRS, 3.4% ICANS). ICANS risk was lower in BCMA-exposed pts (9.4% vs. 24%; OR 0.32, 95% CI 0.11–0.85, p=0.029), and decreased with more LOTs (OR 0.73, 95% CI 0.55–0.92, p=0.016) and higher Hgb (OR 0.71, 95% CI 0.52–0.94, p=0.023). Tocilizumab and steroids were used in 36% (treatment 28%, prophylaxis 9.2%) and 23%, respectively. Steroid use was less common in BCMA-exposed pts (11% vs. 34%; OR 0.23, 95% CI 0.08–0.60, p=0.004) and declined with more LOTs (OR 0.68, 95% CI 0.52–0.85, p=0.002). Infections occurred in 40% of the cohort, more common in pts with CrCl <40 mL/min (59% vs. 36%; HR 2.58, 95% CI 1.02–6.80, p=0.049). IVIg was linked to improved infection-free survival (HR 0.59, 95% CI 0.37–0.93, p=0.023). Conclusions: Elranatamab demonstrated meaningful activity in real-world relapsed MM, though PFS and OS were shorter than in MagnetisMM-3, likely reflecting an older, frailer population with higher disease burden. ICANS was more frequent than in MagnetisMM-3. Baseline anemia and elevated LDH, markers of poor marrow reserve and higher disease burden, were strongly linked to worse outcomes.

Abstract Use of Direct oral anticoagulants (DOAC) has increased exponentially since their introduction in 2010. Over the years they have been used without any systematic oversight, there have been ongoing concerns related to inappropriate or incorrect dosing, incorrect duration, and non-adherence to the drugs leading to adverse patient outcomes. Several factors have been attributed to DOAC non-adherence such as presence or fear of adverse effects, affordability, lack of perceived benefit, or concerns for reversibility. These barriers impact both primary (first time prescription) and secondary adherence (longer term prescription). Poor adherence can lead to adverse outcomes such as stroke, death, and higher medical resource utilization hence increased cost to the patient and payors. This study was conducted as a quality improvement (QI) initiative to improve the adherence to the prescription DOACS. We included patients 18 years old, a diagnosis of Atrial fibrillation and flutter who had a primary care provider writing the prescription for chronic DOAC therapy. Patients with venous thrombosis, pregnancy or who were institutionalized were excluded. The charts were reviewed for primary and secondary adherence using Surescripts functionality which can provide baseline information about prescription fills from the participating pharmacies. In the preimplementation phase we identified 1030 patients meeting inclusion criteria associated with the pilot sites within Mayo Clinic practice in preceding 6 months. For this population, Surescripts data found that the rates of primary and secondary adherence to be 84% and 86% respectively. We then implemented a 6-month pilot where we created workflow for a pharmacy led DOAC management unit. Herein, once a DOAC prescription was made for patients meeting inclusion criteria, they would enter a registry where the pharmacy team would review the charts for primary adherence by utilizing Surescripts data. If adherent these patients would be marked for follow up in the secondary adherence phase. However, if non adherent, the team would initiate intervention including engagement with patient online services which was further escalated to phone calls by the pharmacy team. Once the barriers were identified several remediation approaches were incorporated in the process, these included education about DOACS, medicare education, social work assistance to even switching to warfarin if necessary. The same process was followed for secondary adherence management. In the intervention cohort, we had 411 patients during the pilot, for primary adherence 87.1% of patients were adherent at baseline and an additional 3.4% became adherent with interventions, while 9.5% remain nonadherent. The primary causes of nonadherence, amongst 9.5%, were cost (86%) while 1% were concerned about side effects and 3% were concerned about lack of perceived benefit. The inverntions lead to impoved adherence in most patients and very few patients were transitioned to warfarin. For secondary adherence 92% of the patients were adherent without any intervention, an additional 4% of patients benefited with the interventions of the DOAC management unit with approaches to address cost considerations, while another 4% remained nonadherent where cost remained the primary reason for nonadherence, other reasons being lack of perceived benefit and side effect concerns. In summary, with active intervention, in our patient population we were able to improve the primary adherence from 84% to 91% and secondary adherence from 86% to 96% . Cost remained the biggest barrier for adherence followed by concern for side effects and lack of perceived benefit. Our engaged team of pharmacy staff was able to manage those concerns with the education and cost mitigation strategies leading to improved adherence. Based on previously published literature even a 5% difference in adherence to DOACS can make a huge difference in population-based outcomes. Our work was able to demonstrate a positive impact of the intervention, highlighting the need for a well-managed DOAC unit especially for complex care populations.

Abstract Background: IEC-HS is a potentially life-threatening complication following CAR-T therapy in RRMM. Reliable diagnostic biomarkers are needed to help expeditiously identify cases to initiate prompt treatment and supportive care. Serum ferritin, a routinely available laboratory parameter, is commonly elevated in IEC-HS and has been used to identify cases. However, ferritin can also be elevated in cytokine release syndrome (CRS) or secondary to baseline tumor-related inflammation. The optimal diagnostic threshold for post-CAR-T ferritin in IEC-HS in RRMM has not been previously established. Methods: This study used data from 15 centers within the US Multiple Myeloma Immunotherapy Consortium to identify the optimal post-CAR-T ferritin threshold to distinguish RRMM patients (pts) with and without a diagnosis of IEC-HS. Receiver operating characteristic (ROC) analysis was used to determine the optimal threshold based on Youden's Index. The performance of the threshold was evaluated overall and stratified by CAR-T product (cilta-cel, ide-cel). Additional analyses included the temporal relationship of peak ferritin and IEC-HS diagnosis, the evaluation of IEC-HS criteria according to ferritin levels, comparison of IEC-HS criteria co-occurrence, and comprehensive baseline characteristic comparisons across ferritin strata. Results: Of 1502 RRMM CAR-T recipients (ide-cel, n=712; cilta-cel, n=790), 74 patients (4.9%) had a provider-determined diagnosis of IEC-HS. A post-CAR-T ferritin threshold of 7470 ng/mL was identified as optimal for distinguishing pts with and without IEC-HS (AUC 0.938). Sensitivity (0.904) and specificity (0.934) were both very high, indicating high discriminatory ability. Stratified ROC analyses showed near-identical optimal thresholds for cilta-cel (7450 ng/mL; sensitivity 0.885, specificity 0.936, AUC 0.94) and ide-cel (7470 ng/mL; sensitivity 0.952, specificity 0.933, AUC 0.95), indicating minimal impact of CAR-T product on ferritin's prognostic utility. Baseline pt characteristics (N=1,413) differed significantly by ferritin threshold. Pts above the ferritin threshold of 7470 (N=154) were younger (median 64 vs 67 years; p=0.004), more frequently male (65% vs 56%; p=0.043), had higher baseline ferritin (1,300 vs 187; p<0.001), higher ECOG at apheresis (p=0.001), more likely penta-refractory (p=0.016), had higher baseline bone marrow plasma cell burden (p<0.001), and had higher R-ISS scores (p<0.001). Evaluation of IEC-HS criteria (Hines et al, TCT 2023) demonstrated significantly higher rates of laboratory and clinical criteria, including hepatic transaminase elevation (43% vs 15%), hypofibrinogenemia (53% vs 0%), cytopenias (95% vs 81%), hypertriglyceridemia (43% vs 8%), ICANS (52% vs 23%), renal insufficiency (20% vs 0%), and soluble IL-2 receptor elevations (47% vs 4%), in pts with ferritin >7500 ng/mL compared to those with lower ferritin. Heatmap visualization revealed distinct patterns of co-occurring criteria in high- and low-ferritin groups. Assessment of the timing of peak ferritin and IEC-HS diagnosis among IEC-HS cases revealed a median difference of 0 days (IQR: -1, 0), suggesting simultaneous occurrence. Median time to max ferritin was 9 days (IQR 8,12) in IEC-HS pts compared to 8 days (IQR 5,10) in non-IEC-HS pts (Wilcoxon p<0.05). Conclusions: In this analysis of over 1500 patients, a post-CAR-T ferritin level of 7500 ng/mL robustly identifies RRMM pts with IEC-HS following either cilta-cel or ide-cel. Pts exceeding this threshold demonstrate marked enrichment in IEC-HS diagnostic criteria and significant differences in baseline characteristics, warranting further study of the role of ferritin in IEC-HS diagnosis and early intervention.