Pinto, Antonio

Abstract Outcomes in classic Hodgkin lymphoma (cHL) have steadily improved; however, additional therapies are needed for patients who relapse or do not respond to novel agents. Here, we report the efficacy and safety of camidanlumab tesirine (Cami), an anti-CD25 antibody-drug conjugate, in patients with relapsed/refractory cHL after brentuximab vedotin/programmed cell death protein 1 inhibitor therapies from the phase 2 ADCT-301-201 study. Eligible patients were adults with cHL who had received ≥3 previous lines of systemic therapy (or ≥2 if ineligible for hematopoietic stem cell transplant). Patients received 45 μg/kg Cami (IV, once every 3 weeks) in cycles 1 to 2, followed by 30 μg/kg IV once every 3 weeks for ≤1 year. The primary end point was overall response rate (ORR) per 2014 Lugano classification. Secondary end points included complete response rate (CRR), progression-free survival (PFS), and overall survival (OS). In total, 117 patients were enrolled with a median age of 37.0 years (range, 19-87). The ORR was 70.1% (95% confidence interval [CI], 60.9-78.2), with a CRR of 33.3% (95% CI, 24.9-42.6). The median PFS was 9.13 months (95% CI, 5.3-15.0); median OS was not reached. Thirty-three (28.2%) patients discontinued treatment because of treatment-emergent adverse events; the most common reasons were skin and subcutaneous tissue disorders (n = 10 [8.5%] patients), infections and infestations (n = 5 [4.3%]), and nervous systems disorders (n = 5 [4.3%]). Guillain-Barré–type or polyradiculopathy-type events occurred in 8 (6.8%) patients. Cami was efficacious in this heavily pretreated population; however, the efficacy was overshadowed by substantial issues with the safety profile. This trial was registered at www.clinicaltrials.gov as #NCT04052997.

Abstract Nivolumab, an anti–programmed death-1 (PD-1) monoclonal antibody, showed promising activity in relapsed or refractory (R/R) follicular lymphoma (FL) in a phase 1 study. We conducted a phase 2 trial to further evaluate its efficacy and safety in patients with R/R FL and to explore biomarkers of response. Patients with R/R FL and at least 2 prior lines of therapy, each containing a CD20 antibody or an alkylating agent, were treated with nivolumab 3 mg/kg every 2 weeks. The primary end point was objective response rate (ORR) assessed by an independent radiologic review committee. Biomarker analyses included gene expression profiling and multiplex immunofluorescence studies of pretreatment tumor samples. A total of 92 patients were treated. After a minimum follow-up of 12 months, ORR was 4% (4 of 92 patients). Median progression-free survival (PFS) was 2.2 months (95% confidence interval [CI], 1.9-3.6 months). Median duration of response was 11 months (95% CI, 8-14 months). Exploratory analyses suggested that responders had significantly higher proportion of CD3+ T cells in the tumor microenvironment than nonresponders, but no significant differences in PD-1 or programmed death-ligand 1 expression were observed. High expression of a set of tumor-associated macrophage genes was associated with reduced PFS (hazard ratio, 3.28; 95% CI, 1.76-6.11; P = .001). The safety profile was consistent with previous reports of nivolumab. In conclusion, nivolumab monotherapy was associated with very limited activity in patients with R/R FL. Better understanding of the immune biology of this disease may facilitate the development of effective checkpoint-based strategies. This trial was registered at www.clinicaltrials.gov as #NCT02038946.

PURPOSEPatients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab.METHODSA phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review.RESULTSA total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively.CONCLUSIONLenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile.

Key Points Rd continuous significantly extended OS compared with MPT and resulted in comparable OS to that with Rd18 in patients with multiple myeloma. Patients achieving complete or very good partial response with Rd benefited greatly from continuous vs fixed treatment in terms of PFS.