7001 Background: Human immunodeficiency virus (HIV)-related diffuse large B-cell lymphomas (DLBCL) are heterogeneous in nature, clinically, & molecularly. R-da-EPOCH is accepted as a standard of care in HIV+DLBCL. Classifying tumors with respect to immunophenotype & genomic features may facilitate personalized therapy to improve outcomes in this diverse disease. The Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (ibr), also inhibits inducible T cell kinase (ITK). As HIV hijacks host ITK during replication, ibr may have additional clinical benefits in HIV+DLBCL. This trial added ibr to R-da-EPOCH in HIV+DLBCL, with an attempt to enrich for non-germinal center B-cell (non-GCB) subtype, to evaluate safety, feasibility & activity, impact on T cells, & correlate lymphoma cell of origin (COO) with response. Methods: This multi-center study included a 3+3 dose de-escalation cohort followed by dose-expansion at recommended phase 2 dose (RP2D). Participants (pts) age 18-64 years (y) with stage II-IV HIV-DLBCL were untreated or received 1 cycle (cy) R-da-EPOCH/CHOP off-study. CD4 <100 & asymptomatic leptomeningeal disease were allowed. Ibr was dosed daily days 1-21 & R-da-EPOCH administered as previously published (PMID 32430507) for 6 total cy. Moderate/strong CYP3A4 inhibitors were excluded, due to effects on ibr and chemotherapy. Results: 43 pts were evaluable for toxicity & 37 evaluable for response. 41/43 (95%) pts tolerated ≥2 cy; median cy of study therapy (tx) received = 5. At baseline median age was 52y (24-64) & CD4 count 204 (21-757); 9 pts had CD4 <100. 81% were male, 42% White & 49% Black. 86% were stage III/IV, 40% non-GCB, & 88% had ECOG 0-1. Ibr RP2D was 560mg daily. Noting PET was optional, overall response rate was 100% with 57% (21/37) complete (CR) & 43% (16/37) partial responses (PR). Relapse/progression occurred in 16% (6/37; 1CR, 5PR) during a median follow-up of 4.2y (95%CI = 2.3 to 4.87); median duration of response = 2.8y. 3y event-free (EFS) & overall survival (OS) were 83 & 81% respectively (GCB: 88 & 87%, non-GCB: 76 & 63%). Among 679 treatment-related adverse events (TRAE), the most frequent were (total, % grade (gr) 3+) anemia (105, 50%), thrombocytopenia (81, 41%), neutropenia (60, 88%) & lymphopenia (60, 68%). Non-hematologic AEs (total TRAE, # max gr) included diarrhea (22, 2 gr3), nausea (21, 1 g3), hypokalemia (20, 4 gr3), fatigue (17, 17 gr1), & sepsis (1 gr4). Reasons for tx discontinuation: 1 progression, 4 withdrawal, 4 TRAE, 1 lost to follow up. Conclusions: Incorporating ibrutinib 560mg daily with R-da-EPOCH in HIV-related DLBCL treatment resulted in manageable toxicities typical of R-da-EPOCH. Although lower confirmed CR, 3y EFS & OS are comparable or higher than prior studies of HIV+DLBCL R-da-EPOCH. Ongoing studies to be updated at the meeting include impact on T cell subsets, & correlations of response & survival with circulating tumor DNA & lymphoma features (EBV, MYC, BCL2, BCL6 & genomic determinations of COO). Clinical trial information: NCI-2017-01240 .

Background: Plasmablastic lymphoma (PBL) is commonly associated with HIV, immunosuppression, old age, and autoimmune disorders, but can be seen in immunocompetence. Intensive regimens, including EPOCH, have a complete response (CR) rate of 40% to 65% and median overall survival 9-15 months. Patients (pts) with refractory or relapsed disease have a dismal prognosis. PBL has morphologic and immunophenotypic characteristics overlapping high-grade B-cell lymphoma and multiple myeloma (MM). It is CD20 negative, MYC + in 50% of cases and expresses plasma cell markers, including CD38, CD138, and MUM-1/IRF-4, with a proliferation index typically > 90%. Daratumumab (DARA) is a human IgG1k anti-CD38 monoclonal antibody (mAb) highly active and FDA approved in MM and active in pre-clinical lymphoma models. We hypothesized adding DARA to DA-EPOCH would be safe and feasible and may improve outcomes. We present the feasibility and early efficacy results of the first clinical trial dedicated entirely to PBL. The primary aim was to determine the percentage of newly diagnosed PBL pts completing ≥ 3 cycles of DARA with DA-EPOCH irrespective of HIV status. Given 85% of pts completed ≥ 5 cycles of DA-EPOCH alone in CALGB 50303 study (Bartlett JCO. 2019) and allowing for a lower proportion completing with the addition of DARA, we hypothesized> 75% of pts would complete ≥ 3 cycles of protocol treatment. One prior cycle of anthracycline-containing chemotherapy pre-enrollment was allowed. Planned enrollment 15 pts. Up to 3 replaced if they did not complete cycle 1 for reasons unrelated to DARA toxicity. Study Design and Methods: This is a non-randomized, multicenter study (NCT04139304) conducted by the AIDS Malignancy Consortium. Both HIV negative and HIV positive PBL pts ≥ 18 years old with Stage II to IV PBL or Stage I with elevated LDH and/or bulky tumor, with measurable disease and adequate organ function were eligible. HIV positive pts had a CD4 ≥ 100 cells/μL and were on concurrent combination antiretroviral therapy (cART) or agreed to start. Key exclusion criteria included receiving ≥ 1 prior cycle of combination chemotherapy, active hepatitis B seropositivity, and active CNS involvement. DARA was given in conjunction with 21 day cycles of DA-EPOCH for 6 cycles. DARA 16 mg/kg was be administered intravenously weekly for the first 3 cycles on days 1, 8, and 15, then on day 1 for cycles 4-6. DARA was held on day 8 and 15 for ANC <500 or platelets <25K.Results: 18 pts were enrolled with 3 pts inevaluable having only received 1 dose of DARA, removed from study unrelated to DARA toxicity and replaced as pre-specified. 1 had a non-infusion related atrial fibrillation and pulmonary embolus 7 days after the first dose of DARA and discontinued all further DARA at the investigator's discretion. 2 refused any further lymphoma therapy within days of first treatment. 15 evaluable pts, baseline: male 10. Stage IV 14, LDH elevated 10. HIV+ 7 with median CD4 203 (range=118-790) and HIV viral load median 1330 (range=20-70K, upper quartile 1600). Pathology: Ki-67 80-100%: 10 EBER +: 9. extra-nodal: 6. MYC +: 5/5 by immunohistochemistry (IHC); 3/4 by FISH one of whom also + by IHC. As of June 30th, 2025, the following is the disposition: 13/18 enrolled (69%) and 13/15 (87%) evaluable achieved the primary endpoint: feasibility of receiving ≥3 cycles of therapy with DARA. DARA dose density was 81% including a dose missed for a hurricane. With all 18 pts assessed for toxicity, a total of 48 SAEs occurred. Grade 4 heme toxicity is the expectation of DA-EPOCH which targets an ANC <500 at least once in each treatment cycle. Grade 4 neutropenia was noted in 10 pts, grade 4 thrombocytopenia in 5, grade 4 lymphopenia in 3. The remainder of the SAEs were typical of EPOCH . 11/15 (73%) evaluable for response achieved a CR with 2 relapses. 4 MYC + by IHC achieved a CR far. With a median follow up of 21.3 months (95%CI= 14 to 28.5), the 1-yr PFS: 71.5% (95%CI=40.4 to 88.3) and 1-yr OS: 78.8% (95%CI=47.3 to 92.7) and 2-yr OS: 70 (95%CI=37.9 to 87.8)Conclusions: It is feasible to add DARA to EPOCH for the treatment of plasmablastic lymphoma. Preliminary outcomes are promising. A non-randomized phase II is activated to determine the efficacy of this approach. Correlations with clinical outcomes will include predictive biomarkers including MYC over-expression and circulating tumor DNA. (Funding: UM1 CA121947 P30 CA008748)

Background: Despite a decreasing incidence, NHL remains the leading cause of cancer-attributable deaths in PWH (Horner MJ, et al. Clin Infect Dis 2021). Nevertheless, PWH were excluded based on their HIV status alone from trials leading to the FDA approval of the currently available CD19-directed CAR-T cell (CART19) products for relapsed or refractory B-cell lymphomas. Thus, information on safety and effectiveness of this potentially curative treatment has been largely limited to few published case reports. In this collaborative effort between the AMC and the CIBMTR, we determined outcomes of PWH who received CART19 therapy and compared them with a matched cohort of people without HIV. Methods: We prospectively collected data on 35 patients (pts) diagnosed with HIV who received CART19 therapy between 8/30/2017 and 11/05/2024 for B-cell lymphoid malignancies. Data on patient, HIV, and disease characteristics, treatment, treatment-related outcomes and toxicities were collected. We next created a matched cohort of 135 pts without HIV (HIV-) who underwent CART19 therapy during the same period matched on key clinical factors (age, performance score, NHL subtype, CART19 product, and disease status pre-CART). Outcomes compared included Cytokine Release Syndrome (CRS), Neurologic Toxicity Associated with Immune Effector Cells (ICANS), disease response, hematologic recovery, progression-free survival (PFS), and overall survival (OS). To account for matching, a marginal univariable Cox model (OS, PFS) and a marginal univariable Fine-Gray model (CRS, ICANS, hematological recovery, complete and overall response) were used for calculating and comparing survival probabilities and cumulative incidences, respectively, between both cohorts. Results: A total of 170 pts were included in this analysis (35 HIV+, 135 HIV-). The cohorts were matched for age (median age: HIV+ 56 years (y) (range 29-69); HIV- 57y (24-73)); disease subtype (DLBCL: 91%; FL: 6%; and MCL: 3%, each); CART19 product (axi-cel 97%; brexu-cel 3%, each); and response prior to CART19 (CR 3% each; PR 14% each; relapse/resistant 62.9% vs 60.7%; relapse untreated 2.9% vs 4.4%; relapse chemosensitive 8.6% vs 13.3%; relapse sensitivity unknown 8.6% vs 4.4%). The HIV+ cohort included more men (88.6% vs. 55.6%, p<0.01), more Blacks (25.7% vs 8.1%, p<0.01), and more people seropositive for HepB (17.1% vs 0%, p<0.01) or HepC (8.6% vs 0%, p<0.01). In addition, there were differences that did not achieve statistical significance: bendamustine lymphodepletion (17.1% vs 8.9%, p=0.22) and bridging therapy (62.9% vs 48.1%, p=0.15) were more common in the HIV+ cohort. For PWH, the median time from HIV diagnosis to CART19 was 132 months (1.6-490.0). Median pre-CART19 CD4 count was 191 cells/mm3 (0-252) and median pre-CART HIV viral load (VL) 20 copies/ml (0-10x106); only 11.4% had a HIV VL >400 copies/ml. CRS occurred less commonly in the HIV+ cohort (any grade 68.6% vs 82.2%, p=0.04). ICANS was comparable (any grade 22.9% vs 44.4%, p=0.17). Bacterial infections at 100 days were more common in PWH (28.6% vs. 10.4%, p<0.01). Median follow-up for survivors was 14.5 mo for the entire cohort. At 100 days, neutrophil recovery was similar (91.7% vs 94.8%; p=0.33) with delayed platelet recovery in PWH (71.1% vs 80.4% p=0.06). Cumulative incidence at 6 months of overall response (42.6% vs. 65.8%, p=0.013) and complete response (34.6% vs. 57.4%, p=0.021) was lower in PWH. PFS was not significantly different between cohorts (1-and 2-year PFS: 36.1%/28.3% (HIV+) vs 51.1%/43.6% (HIV-); p=0.103), but OS was lower in PWH (1- and 2-year OS 45.7%/37.3% (HIV+) vs 65.9%/59.7% (HIV-); p=0.016). There was no difference in treatment-related mortality (TRM; p=0.197). The primary cause of death was PD (94.7% (HIV+) vs 73.9% (HIV-) followed by infections (5.3% vs 6.5%) in both cohorts.Conclusion: CART19therapywas safely administered in this large prospective cohort of PWH with 28.3% alive and in remission at 2 years from therapy. Compared to a matched HIV- cohort, toxicities were mostly similar except for more infections in PWH. The lower OS and responses for PWH was driven by lymphoma-related features rather than TRM. Notably, the HIV+ cohort contained a larger proportion of Black patients who are commonly underrepresented in clinical trials and may represent a clinically distinct entity with worse outcomes (Lee MJ, et al. Cancer 2020). AMC-112 is currently enrolling onto a prospective CART19 study.

BACKGROUND:With the adoption of safer outpatient cancer care practices, much of cancer care has transitioned to outpatient settings, decreasing the need for inpatient systemic therapy (IST), which is associated with poorer end-of-life outcomes. We evaluated reasons for IST use, palliative care (PC) utilization, and outcomes among IST recipients to inform guidelines on appropriate IST use. MATERIALS AND METHODS:We conducted a retrospective chart review of all IST admissions at an academic center from January 2016 to December 2017. Patients were stratified by solid tumor (ST) vs hematological malignancies (HM). We recorded IST urgency, response, mortality, and other variables. Descriptive statistics and odds ratios were estimated from logistic regression models with mixed effects to account for multiple admissions per patient. RESULTS:We analyzed 893 admissions (19% ST) among 620 patients. HM patients required frequent elective IST admissions than ST (P < .0001). ST patients more often received IST for non-urgent indications (P = .0032) during non-cancer-related admissions. ST patients had fewer responses to IST compared to HM (36% vs 70%; P < .0001). PC services were more likely utilized for ST vs HM patients (48% vs 14%; P < .0001) and were associated with increased rates of health care proxy assignment, code status change, and hospice discharge. Early 60-day mortality was higher for ST vs HM patients (17.3% vs 5.8%; P < .001), and most patients (55%) died inpatient during the index admission. CONCLUSION:IST was overutilized in ST patients with poor response rates and significant early mortality. PC service utilization rates remain low but improved end-of-life transition planning.