Ofatumumab with iphosphamide, etoposide and cytarabine for patients with transplantation-ineligible relapsed and refractory diffuse large B-cell lymphoma.

The efficacy of salvage treatment of diffuse large B-cell lymphoma (DLBCL) patients who relapse or progress (rrDLBCL) after initial therapy is limited. Efficacy and safety of ofatumumab with iphosphamide, etoposide and cytarabine (O-IVAC) was evaluated in a single-arm study. Dosing was modified for elderly patients. Patients received up to six cycles of treatment. The primary end-point was the overall response rate (ORR). Patients were evaluated every two cycles and then six and 12 months after treatment. Other end-points included progression-free survival (PFS), event-free survival (EFS), overall survival (OS) and safety. Seventy-seven patients received salvage treatment with O-IVAC. The average age was 56.8 years; 39% had an Eastern Cooperative Oncology Group (ECOG) performance status of at least 3; 78% had disease of Ann Arbor stage 3 or 4; 58% received one or more prior salvage therapies. The ORR for O-IVAC was 54.5%. The median duration of study follow-up was 70 months. The median PFS and EFS were 16.3 months each. The median OS was 22.7 months. Age, ECOG performance status and the number of prior therapy lines were independent predictors of survival. Treatment-related mortality was 15.5%. O-IVAC showed a high response rate in a difficult-to-treat population and is an attractive treatment to bridge to potentially curative therapies.

Outcomes of treatment with dose-adjusted EPOCH-R or R-CHOP in primary mediastinal large B-cell lymphoma.

BACKGROUND: The standard first-line treatment for primary mediastinal B-cell lymphoma (PMBCL) patients is rituximab-based immunochemotherapy; however, this is not due to the result of randomized clinical trials. AIMS: We retrospectively investigated 53 PMBCL patient outcomes treated either with R-CHOP-21 or DA-EPOCH-R-28. The primary endpoint was overall survival (OS). Secondary endpoints were complete remission (CR), overall response rate (ORR), progression-free survival (PFS), and treatment-related complications. RESULTS: Treatment with R-CHOP-21 resulted in a 92.0% ORR (60% CR), while DA-EPOCH-R yielded a 92.6% ORR (70.4% CR). There were no differences in the occurrence of grade 3-4 hematological adverse events, but grade 1-2 cardiologic complications (P = .003) were observed more frequently in the DA-EPOCH-R arm. Median PFS and OS were not achieved. The differences in estimated 12-month PFS in R-CHOP and DA-EPOCH-R group (87% vs 73.9%) and OS (100% vs 92%) were insignificant. Patients treated with R-CHOP-21 and autologous hematopoietic stem cell transplantation (auto-HSCT) had an improved OS (P = .03) but not PFS (P = .43) compared to those treated solely with R-CHOP-21. No differences in PFS or OS were observed between patients treated with R-CHOP-21/auto-HSCT and DA-EPOCH-R. CONCLUSION: The results of this study suggest that R-CHOP-21 may be an alternative to DA-EPOCH-R treatment for PMBCL patients.

Immune-Related Thyroid Adverse Events Predict Response to PD-1 Blockade in Patients with Melanoma.

Antibodies against programmed cell death protein-1 or its ligand (PD-(L)1) are a standard of care in melanoma; however, this treatment may cause immune-related adverse events. The aim of this study was to evaluate the immune-related thyroid adverse events (irTAEs) during anti-PD-1 therapy and analyze their influence on the overall survival rates in melanoma. We included 249 patients with metastatic melanoma treated in our institution between 2014 and 2021; the median age was 62 years (range: 17-90); 58% were males, and 37% of patients had the BRAF mutation. We included patients with a normal TSH at baseline and followed up with measurement of TSH levels during immunotherapy. In our group, 95 patients had a TSH outside the normal range: 63 not clinically significant and 32 with clinical symptoms of hypothyroidism. The 3-year overall survival rate was related to the irTAEs of clinical hypothyroidism, abnormal clinically not significant TSH, and euthyreosis at 56%, 43%, and 32%, respectively (p = 0.002). After adjusting the Cox model for potential confounding variables, clinically significant hypothyroidism was an independent prognostic factor with HR 0.51 (95% CI 0.29-0.87). In conclusion, the patients who developed clinically significant hypothyroidism requiring replacement therapy with L-thyroxin were the group who benefitted most from anti-PD-1 treatment.