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Objectives: Hematological malignancy (HM) patients treated with anti‐CD20 monoclonal antibodies are at higher risk for severe COVID‐19. A previous single‐center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. Methods: We included HM patients from 15 centers, from five countries treated with anti‐CD20, comparing those treated with obinutuzumab (O‐G) to rituximab (R‐G) between December 2021 and June 2022, when Omicron lineage was dominant. Results: We collected data on 1048 patients. Within the R‐G (n = 762, 73%), 191 (25%) contracted COVID‐19 compared to 103 (36%) in the O‐G. COVID‐19 patients in the O‐G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID‐19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe‐critical COVID‐19 occurred in 31.1% of patients in the O‐G and 22.5% in the R‐G. In multivariable analysis, O‐G had a 2.08‐fold increased risk for severe‐critical COVID‐19 compared to R‐G (95% CI 1.13–3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T‐C) prophylaxis. Further analysis comparing O‐G to R‐G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID‐19‐related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). Conclusions: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID‐19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk–benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks. [ABSTRACT FROM AUTHOR]

Background: Elderly patients account for nearly 70% of all primary central nervous system lymphoma (PCNSL) cases. They cannot tolerate aggressive treatment and have poor prognosis with a median overall survival (OS) of less than 2 years and progression‐free survival (PFS) of 6–16 months. Ibrutinib penetrates the blood–brain barrier and has shown activity in PCNSL. Methods: This prospective study investigated whether ibrutinib maintenance is feasible, and whether it can benefit elderly PCNSL patients in terms of expected 2‐year PFS. It is an open label, phase 2 study in newly diagnosed PCNSL patients 60–85 years old who responded to first‐line high‐dose methotrexate (HDMTX)‐based treatment with partial or complete response. Ibrutinib maintenance (560 mg/d) was continued until disease progression or intolerable toxicity. Results: Twenty patients were enrolled, with a median age of 72 years (range, 61–80). Median time on ibrutinib maintenance was 12.5 (range, 2–46) months. Twelve patients stopped treatment: five due to central nervous system relapse and seven due to adverse events that were mainly grade 2. Five patients died (25%) all due to relapse. The 1‐ and 2‐year PFS are 90% and 72.6%, respectively, and the 2‐year OS is 89%. Conclusions: The study reached its primary end points and also showed that ibrutinib maintenance is tolerated reasonably well by the elderly. Therefore, this study supports the concept that ibrutinib maintenance should be further evaluated as an optional consolidation measure in the elderly. Ibrutinib maintenance following first‐line high dose methotrexate‐based chemotherapy in elderly patients with primary central nervous system lymphoma is feasible and probably also effective. [ABSTRACT FROM AUTHOR]

In chronic lymphocytic leukemia (CLL), the immune system is skewed towards a suppressive milieu. Levels of thrombopoietin (TPO), promoting cellular immune regulatory activity in immune thrombocytopenic purpura, were shown to be elevated in CLL patients. This study explored TPO as a potential immunomodulator, supporting CLL progression. We evaluated CLL cell‐induced expression of TPO receptor (TPO‐R) on T‐cells and effects of its activation on T‐cell responses. CLL cell involvement in TPO generation was also assessed. Baseline TPO‐R expression on CD4 + T‐cells was found to be higher in CLL patients than in healthy controls (HC). Exposure of HC‐T‐cells to B‐cells, especially to CLL‐B‐cells stimulated with B‐cell activating molecules, resulted in enhanced TPO‐R expression on T‐cells. CLL‐T‐cell stimulation with TPO reduced their proliferation and expanded the regulatory T‐cell (Treg) population. At baseline, phosphorylation of STAT5, known to impact the Treg phenotype, was elevated in CLL‐T‐cells relative to those of HC. Exposure to TPO further enhanced STAT5 phosphorylation in CLL‐T‐cells, possibly driving the observed Treg expansion. The CLL immune milieu is involved in promotion of inhibitory features in T‐cells through increased TPO‐R levels and TPO‐induced intracellular signaling. TPO and its signaling pathway could potentially support immunosuppression in CLL, and may emerge as novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the role of additional chemotherapy before autologous hematopoietic cell transplantation (HCT) in patients with relapse/refractory diffuse large B‐cell lymphoma (DLBCL) who achieve partial remission following first salvage therapy. Methods: We conducted a multicenter retrospective study of all adult patients with DLBCL who underwent HCT between 2008 and 2020 and achieved partial response (PR) after the first salvage and were either referred directly to HCT (n = 47) or received additional salvage therapy before HCT (n = 22). Results: Post‐HCT CR rate and progression‐free survival were comparable between the two groups (66% vs. 68%, p =.86 and median not reached vs. 10.2 months [95% confidence interval, CI 7.1–12.3], p =.27, respectively). Median overall survival (OS) and estimated 3‐year OS favored patients who were directly referred to HCT (105.8 [95% CI 63–148] months vs. 14.5 [95% CI 0–44] months, p =.035, and 65% [95% CI 51%–75%] vs. 40% [95% CI 21%–53%], p =.035, respectively). In Cox regression model, while International Prognostic Index and primary refractory versus relapse disease did not impact OS, allocation to a second salvage regimen and older age were both associated with inferior survival (hazard ratio [HR] = 2.57 95% CI 1.1–5.8, p =.023 and HR = 1.04 95% CI 0.99–1.2, p =.064, respectively). Conclusions: Referring patients with chemotherapy‐sensitive disease in PR directly to HCT is associated with better OS compared to those receiving additional lines of treatment. [ABSTRACT FROM AUTHOR]

Summary: Belantamab mafodotin, an immuno‐conjugate targeting B‐cell maturation antigen, showed single‐agent activity in phase 1 and 2 studies, and was recently approved for heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients. Real‐world data and long‐term follow‐up are scarce. We conducted a multisite retrospective study aimed to assess safety and efficacy of belantamab mafodotin monotherapy administered via the GSK expanded access compassionate care programme. One‐hundred and six RRMM patients were treated with belantamab mafodotin between July 2019 and March 2021. The median age was 69.4 years. Patients were heavily pretreated with a median of six (range 2–11) prior therapy lines. Major adverse effects included ocular toxicity (keratopathy 68.4%, grade ≥3: 40.5%; blurred vision 36.8%, grade ≥3: 6.3%), thrombocytopenia (27.4%, grade ≥3: 17.9%) and infections (11.3%, grade ≥3: 7.5%). Median follow‐up time was 11.9 [95% confidence interval (CI) 10.0–13.8] months. Overall response rate was 45.5%. Median progression‐free survival was 4.7 (95% CI 3.5–5.9) months in the entire cohort and 8.8 (95% CI 6.6–10.9) months among responders. Median overall survival was 14.5 (95% CI 9.5–19.6) months, and not reached for responders. To conclude, in a real‐world setting, belantamab mafodotin monotherapy showed efficacy comparable with the prospective clinical trials, with a tolerable toxicity profile. [ABSTRACT FROM AUTHOR]

Purpose: Primary mediastinal B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL). Despite its aggressive course, PMBCL is considered curable. While in recent years dose-adjusted (DA) EPOCH-R (rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) has become widely endorsed as first-line therapy for newly-diagnosed PMBCL, the optimal treatment for this disease and the role of radiotherapy (RT) remains unclear. DA-EPOCH-R provides good clinical outcomes, albeit is associated with short-and long-term toxicity. To address this issue, the current retrospective bi-icenter analysis compared efficacy and toxicity of DA-EPOCH-R and a less toxic R-CHOP/R-ICE regimen used for the treatment of newly-diagnosed PMBCL. Patients and Methods: The study included all patients with a histologically confirmed PMBCL diagnosis treated with DA-EPOCH-R or R-CHOP/R-ICE between 01/2013-12/2020 at two tertiary medical centers. Patient demographic and clinical data were derived from institutional electronic medical records. The analysis included 56 patients: 31 received DA-EPOCH-R and 25 -R- CHOP/R-ICE. Results: At a median follow-up of 1.9 years (IQR 3.1 years), similar progression-free survival (2.1 versus 2.4 years; p = 0.7667), overall survival (2.5 versus 2.7 years; p = 0.8047) and complete response (80%) were observed in both groups. However, DA-EPOCH-R was associated with significantly longer hospitalization required for its administration (p < 0.001) and a trend for higher frequency of infections, stomatitis, thrombotic complications and febrile neutropenia-related hospitalizations. Conclusion: DA-EPOCH-R and R-CHOP/R-ICE provide similarly encouraging outcomes in newly-diagnosed PMBCL patients. R-CHOP/R-ICE is associated with lower toxicity and significantly reduced hospitalization. Our findings suggest that this regimen may be considered as an alternative to DA-EPOCH-R in this patient population. [ABSTRACT FROM AUTHOR]

Romidepsin is a class I selective histone deacetylase (HDAC) inhibitor approved by the Food and Drug Administration (FDA) for relapsed/refractory (R/R) cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL), treated with at least one prior systemic therapy. Currently, there is paucity of real-life data on the efficacy and safety of romidepsin in R/R T-cell lymphoma. This national, multicenter study presents real-life data on the efficacy and safety of romidepsin in R/R T-cell lymphoma. Patients diagnosed and treated with romidepsin for R/R CTCL or PTCL between 2013 and 2018 were retrospectively reviewed. Outcomes included overall survival (OS), event-free survival (EFS), overall response rate (ORR), complete response (CR), and adverse events. Fifty-three patients with R/R PTCL (n = 42) or CTCL (n = 11) were included. Among CTCL patients, median OS was not reached, ORR was 25%, and none achieved CR. Among PTCL patients, median OS was 7.1 months, EFS was 1.9 months, ORR rate was 33%, and 12.5% achieved CR. In a univariate analysis, predictors for longer EFS include any response to therapy, number of previous lines, and PTCL subclass (with better results for angioimmunobalstic T-cell lymphoma). In a univariate and multivariate analysis for OS, treatment response was the only factor predicting OS (OR 4.48; CI 95%, 1.57-12.79; P = .005). Most grade 3 and 4 adverse events were hematological (35%). Infections were reported in 34% of patients. This real-life experience with romidepsin confirms the results of the pivotal phase II trials. PTCL subtype and the number of previous lines of therapy have an impact on EFS. In addition, patients who had good response to romidepsin benefited most in terms of both EFS and OS. Efforts should be done to identify those patients. [ABSTRACT FROM AUTHOR]

This multicentre study evaluated 5-year progression-free ( PFS) and overall survival ( OS) in early and advanced Hodgkin lymphoma ( HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles ( PET-2). Between September 2006 and August 2013, 359 patients aged 18-60 years, were recruited in nine Israeli centres. Early- HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy ( ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced- HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET-2-negative patients further received ABVD ×4; PET-2-positive patients received EB ×4 and ISRT to residual masses. With a median follow-up of 55 (13-119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early- HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced- HL, the PFS was 81% and 68%, respectively ( P = 0·08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early- HL, even with additional ABVD and ISRT. Advanced- HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients. [ABSTRACT FROM AUTHOR]

The article discusses a study that describes alterations of bortezomib-induced peripheral neuropathy (BIPN) in patients with multiple myeloma (MM). It shows that reduced soluble brain-derived neurotrophic factor (sBDNF) levels in the plasma concomitant with elevated BDNF content in platelets of MM patients that developed BIPN. It unveils that the patients who developed BIPN had undetectable subclinical disease-related neuropathy before starting treatment.

This multicentre study evaluated 5-year progression-free (PFS) and overall survival (OS) in early and advanced Hodgkin lymphoma (HL), where therapy was individualized based on initial prognostic factors and positron emission tomography-computed tomography performed after two cycles (PET-2). Between September 2006 and August 2013, 359 patients aged 18-60 years, were recruited in nine Israeli centres. Early-HL patients initially received ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) ×2. Depending on initial unfavourable prognostic features, PET-2-positive patients received additional ABVD followed by involved-site radiotherapy (ISRT). Patients with negative PET-2 and favourable disease received ISRT or ABVD ×2; those with unfavourable disease received ABVD ×2 with ISRT or, alternatively, ABVD ×4. Advanced-HL patients initially received ABVD ×2 or escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone; EB) ×2 based on their international prognostic score (≤2 or ≥3). PET-2-negative patients further received ABVD ×4; PET-2-positive patients received EB ×4 and ISRT to residual masses. With a median follow-up of 55 (13-119) months, 5-year PFS was 91% and 69% for PET-2-negative and positive early-HL, respectively; 5-year OS was 100% and 95%, respectively. For advanced-HL, the PFS was 81% and 68%, respectively (P = 0·08); 5-year OS was 98% and 91%, respectively. PET-2 positivity is associated with inferior prognosis in early-HL, even with additional ABVD and ISRT. Advanced-HL patients benefit from therapy escalation following positive PET-2. EB can be safely de-escalated to ABVD in PET-2-negative patients., (© 2017 John Wiley & Sons Ltd.)