Chavez, Julio C

Background: A diagnosis of cancer creates a stressful situation owing to the uncertainties related to the thought of possible suffering from complications associated with treatment toxicities, the fear of not responding to the prescribed treatment, or death. The prevalence of mental health disorders is relatively higher in cancer patients vis-à-vis the general population. Methods: We performed a retrospective cohort study to evaluate the impact of mental health disorders on outcomes of relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor T-cell (CAR T-cell) therapy using data from the TriNetX research network. Results: A total of 1587 patients met the inclusion criteria (858 with a mental health diagnosis and 729 without). After propensity score matching for age and gender, 1320 patients were included in the analysis (660 in each group). The 1-year OS was higher in patients without a mental health disorder (76.0% versus 69.4%, P = 0.004). Patients with mental health disorders had a higher incidence of cytokine release syndrome (all grades) compared with those without (35.5% versus 27.6%, P < 0.001) and immune effector cell-associated neurotoxicity syndrome (all grades) (16.8% versus 10.1%, P < 0.001). Conclusions: These findings emphasize the importance of thorough psychiatric evaluation and management in patients receiving CAR T-cell therapy. Patients with mental health disorders may need significant assistance with coordinating medical services to better adhere to required care management. Future studies are needed to help determine whether preventive and real-time mental health interventions can favorably impact outcomes of these patients.

e19046 Background: While outcomes in pts with R/R FL have improved with current SOC treatments (Tx), there remains a need for safe, efficacious, and convenient Tx options. GOLCA is a potential, first-in-class, oral CELMoD designed for Tx of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA induces rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing and immunomodulatory activity. GOLCA + R was well tolerated and effective in heavily pretreated pts in the two-part Ph 1/2 study, CC-99282-NHL-001. Here, we provide longer f/u in pts with R/R FL from Part B of the study. Methods: Pts with R/R FL with ≥2 prior lines of Tx (≥1 if prior anti-CD20 Tx) received GOLCA orally, once daily at 0.2 mg (n=22) or 0.4 mg (n=38) ± R for up to 2 y or until progressive disease (PD)/unacceptable toxicity. Primary endpoints included safety and RP2D determination; secondary endpoints are preliminary efficacy and PK. Results: As of September 15, 2025, 60 pts were enrolled. In 0.2 and 0.4 mg groups, median prior Tx lines were 3 and 3, 32% and 32% had prior lenalidomide (LEN), 27% and 29% had prior T-cell–redirecting Tx (CAR T and/or bispecific antibody) and 32% and 32% were refractory to last regimen. Tx is ongoing in 6 (27%) and 17 (45%) pts at 0.2 and 0.4 mg, respectively; discontinuations (d/c) were mostly due to PD. Neutropenia, an on-target side effect of GOLCA, was the most common grade 3/4 Tx-emergent adverse event (TEAE) occurring in 59% and 68% of pts at 0.2 and 0.4 mg, followed by anemia (9% and 16%) and febrile neutropenia (9% and 8%). Median time to resolution of neutropenia was 8 days. Dose reductions occurred in 14% and 37% of pts at 0.2 and 0.4 mg, most commonly due to neutropenia (5% and 21%) and febrile neutropenia (5% and 5%). No d/c or deaths were from GOLCA-related TEAEs. Non-hematologic TEAEs were infrequent and mostly low grade. In efficacy-evaluable pts (GOLCA 0.2 and 0.4 mg + R, n=22 and n=36), median f/u was 14.03 months (mo), overall response rate (ORR) was 77% (complete response rate [CRR], 41%) at 0.2 mg, and 97% (CRR, 78%) at 0.4 mg. In the 0.4 mg group, responses were consistent in high-risk subsets including pts with prior LEN (ORR, 100%; CRR, 75%) and/or T-cell–redirecting Tx (ORR, 91%; CRR, 64%). GOLCA 0.4 mg + R demonstrated durable responses (median DOR, 9.17 mo; 91% of pts who achieved a CR remained in CR at cutoff). Conclusions: With longer f/u, GOLCA + R demonstrated promising efficacy with durable responses and no new safety signals. The 0.4 mg group had higher ORR and CRR than 0.2 mg, including in pts with prior LEN-based and/or T-cell–redirecting Tx, with a manageable safety profile at both doses. The results support the development of GOLCA + R as a fixed-duration, chemotherapy-free outpatient Tx in the Ph 3 GOLSEEK-4 study in 2L+ FL (NCT06911502). Clinical trial information: NCT03930953 .

ABSTRACT Disease Overview Plasmablastic lymphoma (PBL) is a rare CD20‐negative aggressive lymphoma with poor prognosis when treated with standard treatment options. Although PBL is associated with HIV infection and other immunosuppressed states, it can also affect immunocompetent individuals. Diagnosis The diagnosis of PBL requires a high clinical suspicion and pathological confirmation. EBV‐encoded RNA (EBER) expression and MYC gene rearrangements are frequently detected in the malignant cells. The differential diagnosis includes EBV+ diffuse large B‐cell lymphoma (DLBCL), extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B‐cell lymphoma, among others. Risk Stratification Age ≥ 60 years, advanced clinical stage, and high International Prognostic Index scores are associated with worse survival. Management Combination chemotherapy regimens, such as infusional EPOCH, are recommended. The addition of bortezomib or daratumumab might improve outcomes. B‐cell maturation antigen‐targeted therapies have shown early efficacy. The participation of patients with PBL in prospective clinical trials is warranted.

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&lt; .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.

Abstract Introduction While outcomes in patients with R/R FL have improved with T-cell–redirecting treatments (e.g. CAR T-cell therapy, bispecific antibodies), there remains an unmet need for safe, efficacious, and more convenient chemotherapy-free treatment options (Caridà et al, Eur J Haematol. 2025). GOLCA is a potential, first-in-class, oral CELMoD agent designed for the treatment of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA drives the closed, active conformation of cereblon to induce rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing (agnostic of cell of origin) and immunomodulatory activity. In the two-part, multicenter, first-in-human Phase 1/2 study (CC-99282-NHL-001; NCT03930953), GOLCA was well tolerated and effective in patients with R/R FL (Cordoba et al, ICML 2025, #441). Here, we provide longer follow-up in patients with R/R FL from Part B of the study. Methods Patients with R/R FL with ≥ 2 prior lines of therapy (≥ 1 in Part B if prior anti-CD20 therapy) were included in the study. Patients received GOLCA monotherapy orally, once daily at different dosing schedules in Part A. In Part B, GOLCA was dosed at 0.2 or 0.4 mg (14 days on/14 days off) ± R. Total GOLCA treatment duration was up to 2 years or until progressive disease (PD)/unacceptable toxicity. Primary objectives included safety and recommended Phase 2 dose determination. Results As of April 3, 2025, a total of 72 patients with R/R FL were enrolled: 12 in Part A (GOLCA monotherapy) and 60 in Part B Cohort D (22 received GOLCA 0.2 mg + R; 38 received GOLCA 0.4 mg + R). Patients were heavily pre-treated. Median number of prior treatments was 4.5 (range, 2–6) in Part A and 3 (range, 1–12) in Part B Cohort D. Approximately one-third of the treated patients were exposed to prior T-cell–redirecting therapy, approximately one-third had prior lenalidomide (len) exposure, and approximately one-third were refractory to the last regimen received. At the time of data cutoff, in Part A, 4 patients completed 2 years of GOLCA, remaining in remission at last follow-up; 8 discontinued due to PD. In Part B Cohort D, 41% of patients treated with 0.2 mg and 63% with 0.4 mg were ongoing. PD was the most common reason for discontinuation. In the safety evaluable population (n = 60; GOLCA 0.2 or 0.4 mg + R), neutropenia, an on-target side effect of GOLCA, was the most common grade 3/4 treatment-emergent adverse event (TEAE) and occurred in 65% of patients, followed by anemia (13%) and febrile neutropenia (8%). Serious AEs related to GOLCA occurred in 22% of patients, most commonly infections (17%) and febrile neutropenia (7%); pulmonary embolism occurred in 1 patient with 0.2 mg. The most common causes of GOLCA interruption in the overall safety population were infections (32%) and neutropenia (18%). Dose reductions were mostly due to neutropenia (10%) and febrile neutropenia (5%). No discontinuations or deaths occurred from GOLCA-related TEAEs. Non-hematologic TEAEs were infrequent and mostly low grade, with the most common being gastrointestinal disorders (7%). In the efficacy evaluable patients (n = 56; GOLCA 0.2 or 0.4 mg + R) at a median follow-up of 10.8 months, the overall response rate (ORR) was 89% (complete response rate [CRR], 61%). With 0.2 mg, ORR was 81% (CRR, 43%) and with 0.4 mg, ORR was 94% (CRR, 71%). In the 0.4-mg group, responses were consistent in high-risk subsets, including patients with prior len (ORR, 100%; CRR, 73%) and/or T-cell–redirecting therapy (ORR, 91%; CRR, 64%). With GOLCA 0.4 mg, 10 patients had response lasting &gt; 12 months, including 5 with prior T-cell–redirecting therapy and 6 with prior len. Conclusions With additional follow-up, GOLCA + R continued to show promising efficacy with durable responses and no new safety signals. A higher ORR/CRR and similar tolerability were observed with GOLCA 0.4 mg + R vs GOLCA 0.2 mg + R, including in patients with prior len-based and/or T-cell–redirecting treatment. These data support continued development of GOLCA 0.4 mg + R as a fixed-duration, chemotherapy-free, outpatient option in the ongoing Phase 3 GOLSEEK-4 study in 2L+ FL (NCT06911502).