Yoshikazu Ikoma

Polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) is a vincristine-free regimen recently approved for untreated diffuse large B-cell lymphoma (DLBCL). However, its safety in the early postoperative setting remains unclear. We report a case of primary intestinal DLBCL with suspected perforation managed with surgical resection followed by staged introduction of Pola-R-CHP. Rituximab was started on postoperative day 11, followed by CHP on day 15 as the first cycle of R-CHP. Pola was added from cycle 2. The patient showed an initial tumor reduction without serious gastrointestinal (GI) toxicity. This case suggests that staged introduction of Pola-R-CHP may minimize postoperative GI risk while maintaining safety.

Background: Bulky cervical diffuse large B‐cell lymphoma (DLBCL) with impending airway compromise presents an urgent management dilemma, particularly when diagnostic confirmation and timely initiation of definitive therapy must be balanced against the risk of abrupt airway deterioration. Evidence guiding airway‐first management before polatuzumab vedotin–containing frontline therapy remains limited. Case Presentation: We describe two older men with bulky cervical DLBCL who presented with progressive airway‐related symptoms and marked upper airway narrowing on endoscopic and radiologic evaluations. In both cases, semiurgent tracheostomy was prioritized over emergent radiotherapy or immediate systemic therapy, allowing pathological confirmation and treatment planning under controlled conditions. After DLBCL was pathologically confirmed, full‐dose polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola‐R‐CHP) were initiated 15 and 10 days after tracheostomy, respectively, and delivered without dose reduction or treatment delay. No perioperative or tracheostomy‐site complications occurred. Both patients completed six cycles of Pola‐R‐CHP followed by two cycles of rituximab. One patient achieved a partial metabolic response; after receiving salvage chemoimmunotherapy followed by CD19‐directed chimeric antigen receptor T‐cell therapy, he achieved a complete metabolic response. In the other patient, residual fluorodeoxyglucose uptake without corresponding structural lesions was managed with close surveillance after negative follow‐up evaluations, including laryngoscopy and thyroid fine‐needle aspiration. Conclusions: Although limited to two patients, these cases suggest that proactive airway stabilization can create a controlled window for diagnosis and treatment planning and may facilitate safe delivery of full‐dose Pola‐R‐CHP in selected patients with airway‐threatening cervical DLBCL.

Introduction: People living with HIV (PLWH) remain at increased risk of diffuse large B‐cell lymphoma (DLBCL). Polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola‐R‐CHP) has emerged as a standard first‐line option for DLBCL in the general population, but the pivotal POLARIX trial excluded PLWH, leaving limited evidence on feasibility with contemporary antiretroviral therapy (ART). Case Presentation: A 61‐year‐old man presented with progressive anorexia and weight loss. With durable virologic suppression (plasma HIV‐1 RNA below 20 copies/mL) and immune reconstitution (CD4+ T‐cell count approximately 300 cells/µL) on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), he was diagnosed with nongerminal center B‐cell DLBCL (Lugano stage II; International Prognostic Index score 2). Pola‐R‐CHP was administered every 21 days for six cycles (Cycle 1: inpatient and Cycles 2–6: outpatient), followed by two additional rituximab cycles, without ART modification. No grade 3–4 nonhematologic toxicity, febrile neutropenia, or serious infections occurred. HIV‐1 RNA remained below 20 copies/mL throughout treatment, and CD4+ T‐cell counts showed no clinically meaningful decline. End‐of‐treatment fluorodeoxyglucose positron emission tomography/computed tomography (FDG‐PET–CT) demonstrated a partial metabolic response with two small residual FDG‐avid foci (∼1 cm; SUVmax ∼4‐5). At the last follow‐up, the patient had no clinical or radiologic evidence of progression. Conclusion: Outpatient‐delivered Pola‐R‐CHP appeared feasible in PLWH with virologic suppression and immune reconstitution receiving BIC/FTC/TAF, without virologic breakthrough or unexpected toxicity. Prospective inclusion of PLWH in polatuzumab‐containing frontline studies is warranted.

The optimal second‐line chemotherapy regimen for relapsed or refractory diffuse large B‐cell lymphoma (R/R DLBCL) remains uncertain. We retrospectively compared efficacy and safety between gemcitabine, carboplatin, dexamethasone, and rituximab (GCD‐R) and cyclophosphamide, high‐dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER) as second‐line treatments for R/R DLBCL. We evaluated 68 R/R DLBCL patients receiving either GCD‐R ( n = 42) or CHASER ( n = 26) as second‐line treatment between 2004 and 2020. The primary endpoint was the complete response rate (CRR). Secondary endpoints included overall response rate (ORR), overall survival (OS), progression‐free survival (PFS), and adverse events. CRR (43% vs. 42%; p = 1.00) and ORR (60% vs. 50%; p = 0.46) were comparable between GCD‐R and CHASER groups. Median OS (GCD‐R 18.6 months, CHASER 11.2 months; p = 0.93) and median PFS (GCD‐R 10.0 months, CHASER 4.6 months; p = 0.47) showed no significant differences between groups. Further, among patients who subsequently underwent autologous stem cell transplantation, OS was also comparable between groups ( p = 0.44). However, febrile neutropenia was significantly less frequent with GCD‐R (33%) than with CHASER (92%; p < 0.001). As GCD‐R predominantly uses peripheral intravenous catheters, whereas CHASER frequently requires central venous access, catheter management was significantly simpler with GCD‐R ( p < 0.001). GCD‐R demonstrated equivalent efficacy to CHASER with significantly reduced toxicity and improved patient management, supporting its use as an effective and well‐tolerated salvage therapy for R/R DLBCL. GCD‐R represents a feasible treatment option not only for elderly patients, but also for patients eligible for subsequent stem cell transplantation.

Background: Epcoritamab, a bispecific CD3×CD20 antibody, offers a promising treatment for relapsed diffuse large B‐cell lymphoma (DLBCL). Its efficacy and safety after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remain unclear. Case Report: In a 64‐year‐old man with relapsed DLBCL, epcoritamab showed limited efficacy, achieving stable disease prior to allo‐HSCT; nevertheless, re‐administration after donor T‐cell engraftment resulted in a complete response without severe graft‐versus‐host disease or cytokine release syndrome. Conclusions: This observation suggests that donor‐derived T‐cell redirection with epcoritamab may enhance antitumor efficacy while maintaining safety in the post‐transplant setting, supporting its potential as a salvage therapy for relapsed DLBCL post‐allo‐HSCT.

Background/Objectives: The objective of this retrospective, multicenter cohort study was to compare the incidence of viral load blips between two-drug and three-drug antiretroviral therapy regimens in human immunodeficiency virus (HIV) patients. Methods: A total of 121 patients were included, with 44 receiving two-drug regimens (e.g., dolutegravir/lamivudine) and 77 receiving three-drug regimens (e.g., bictegravir/tenofovir alafenamide/emtricitabine) at the time of analysis. The primary outcome was the occurrence of viral blips, defined as transient HIV-RNA elevations ≥ 50 copies/mL; a sensitivity analysis used ≥20 copies/mL. Results: Generalized estimating equation models adjusted for clinical covariates showed no significant difference in the odds of blip occurrence comparing three-drug with two-drug regimens, both for blips ≥ 50 (odds ratio [OR]: 2.64; 95% confidence interval [CI]: 0.91–7.70; p = 0.075) and ≥20 (OR: 1.76; 95% CI: 0.76–4.08; p = 0.190). In the two- and three-drug groups, the predicted probabilities of blips were 1.4% and 3.7% (p = 0.075) for blips ≥ 50, and 6.9% and 11.5% (p = 0.190) for ≥20, respectively. No virologic failure was observed. Conclusions: These findings suggest that two-drug regimens provide virologic control comparable to three-drug regimens and may be a viable clinical option due to fewer drug interactions, lower toxicity, and reduced cost.

Venetoclax plus azacitidine (VEN + AZA) is widely used in acute myeloid leukemia (AML). This study explored the role of static and dynamic profiles of mutational clonal burden to predict outcomes by analyzing marrow samples from 228 VEN + AZA treated AML cases at “Pre-treatment” (n = 228), “Best-response” (n = 105), and “Relapse” (n = 27) phases using targeted-capture sequencing. In a multivariate model, older age, prior AZA, TP53 mutation with variant allele frequency ≥0.10, and RAS-pathway mutations predicted shorter overall survival (OS), while BCORL1 mutation predicted longer OS. Notably, myelodysplasia-related gene mutations, which constitute adverse factors in ELN 2022, predicted favorable survival. Achieving composite complete remission (CRc) significantly predicted longer OS (P < 0.001) but showed residual mutations in 76.2% of the cases. Among CRc cases, relapse-free survival was stratified by molecular clearance of mutations other than DNMT3A, ASXL1, and TET2 (P = 0.04). In addition, 37% of relapsed cases showed a change of major clones, with 40% having potential targets of molecular-targeting treatment. This study revealed the novel prognostic role of myelodysplasia-related gene mutations and established the importance of molecular response assessment in CRc phase.

This study investigated the prognostic impact of vitamin D deficiency and reduced skeletal muscle mass in diffuse large B-cell lymphoma (DLBCL) patients. A retrospective analysis of 186 newly diagnosed DLBCL patients from 2012 to 2022 was conducted, measuring serum 25-hydroxyvitamin D [25(OH)D] levels and the skeletal muscle index (SMI). Decreased vitamin D levels were linked to more severe DLBCL disease, with a median 25(OH)D concentration of 13 (4.0–27) ng/mL. Males in the group with a low SMI had a considerably lower 25(OH)D concentration. The optimal threshold of 25(OH)D levels for overall survival (OS) was 9.6 ng/mL, with lower values associated with a higher likelihood of recurrence and mortality. Multivariable analysis showed hazard ratios for OS of 1.4 [95% CI 0.77–2.5] for a low SMI and 3.2 [95% CI 1.8–5.8] for low 25(OH)D concentration. The combination of a low SMI and low vitamin D concentration resulted in the worst prognosis. Thus, low levels of vitamin D associated with disease progression significantly impact DLBCL prognosis, which can be further stratified by the SMI, providing valuable insights for patient management and potential therapeutic interventions.

This study evaluated the efficacy and safety of salvage chemotherapy with gemcitabine, carboplatin, dexamethasone, and rituximab (GCD ± R) for Japanese patients with relapsed or refractory non‐Hodgkin lymphoma (NHL). A multicenter, phase II trial of GCD ± R administered every 3 weeks for up to 6 cycles was conducted. Rituximab was administered as a therapeutic strategy for CD20‐positive lymphoma. The primary endpoint was the complete response (CR) rate. Secondary endpoints included the overall response (OR) rate, overall survival (OS), progression‐free survival (PFS), toxicity, and success rate of peripheral blood stem cell collection for eligible transplant patients. A total of 25 patients (median age 66 years) were evaluated, with a median follow‐up period of 66.7 months. CR and OR rates were 28% and 52%, respectively. Median PFS and OS were 8.7 and 32.2 months, respectively. The major toxicity was myelosuppression, but the regimen was generally well‐tolerated, with a low incidence of febrile neutropenia (20%) and no treatment‐related deaths. Of the 6 patients who were eligible for autologous stem cell transplantation and underwent peripheral blood stem cell mobilization, the required number of CD34‐positive cells was collected in 5 (83%). All 6 proceeded to transplantation and achieved successful engraftment without recurrence. The present results suggest that GCD ± R may be effective and well‐tolerated in Japanese patients with relapsed or refractory NHL. However, further investigation is needed to confirm these results.