Tina Nielsen

Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large b-cell lymphoma

Purpose Rituximab (R) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy is the standard of care in previously untreated diffuse large B-cell lymphoma (DLBCL). Obinutuzumab (G) is a glycoengineered, type II, anti-CD20 monoclonal antibody. GOYA was a randomized phase III study that compared G-CHOP with R-CHOP in patients with previously untreated advanced-stage DLBCL. Methods Patients (N = 1,418) were randomly assigned to receive eight 21-day cycles of G (n = 706) or R (n = 712), plus six or eight cycles of CHOP. Primary end point was investigator-assessed progression-free survival (PFS). Results After median observation of 29 months, the number of investigator-assessed PFS events was similar between G (201; 28.5%) and R (215; 30.2%), stratified hazard ratio was 0.92 (95% CI, 0.76 to 1.11; P = .39), and 3-year PFS rates were 70% and 67%, respectively. Secondary end points of independently reviewed PFS, other time-to-event end points, and tumor response rates were similar between arms. In exploratory subgroup analyses, patients with germinal-center B cell-like subtype had a better PFS than did patients with activated B cell-like subtype, irrespective of treatment. Frequencies of grade 3 to 5 adverse events (AEs; 73.7% v 64.7%, respectively) and serious AEs (42.6% v 37.6%, respectively) were higher with G-CHOP compared with R-CHOP. Fatal AE frequencies were 5.8% for G-CHOP and 4.3% for R-CHOP. The most common AEs were neutropenia (G-CHOP, 48.3%; R-CHOP, 40.7%), infusion-related reactions (G-CHOP, 36.1%; R-CHOP, 23.5%), nausea (G-CHOP, 29.4%; R-CHOP, 28.3%), and constipation (G-CHOP, 23.4%; R-CHOP, 24.5%). Conclusion G-CHOP did not improve PFS compared with R-CHOP in patients with previously untreated DLBCL. AEs reported with G were consistent with the known safety profile. Biomarker analyses may help define a future role for G in DLBCL.

Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy

Risk of hepatitis B virus (HBV) reactivation was assessed in B-cell non-Hodgkin lymphoma (NHL) patients with resolved HBV infection (hepatitis B surface antigen negative, hepatitis B core antibody positive) who received obinutuzumab- or rituximab-containing immunochemotherapy in the phase 3 GOYA and GALLIUM studies. HBV DNA monitoring was undertaken monthly to 1 year after the last dose of study drug. In case of HBV reactivation (confirmed, HBV DNA ≥29 IU/mL), immunochemotherapy was withheld and nucleos(t)ide analog treatment (preemptive NAT) started. Immunochemotherapy was restarted if HBV DNA became undetectable or reactivation was not confirmed, and discontinued if HBV DNA exceeded 100 IU/mL on NAT. Prophylactic NAT was allowed by investigator discretion. Among 326 patients with resolved HBV infection, 27 (8.2%) had HBV reactivation, occurring a median of 125 days (interquartile range, 85-331 days) after the first dose. In 232 patients without prophylactic NAT, 25 (10.8%) had HBV reactivation; all received preemptive NAT. Ninety-four patients received prophylactic NAT; 2 (2.1%) had HBV reactivation. No patients developed HBV-related hepatitis. On multivariate Cox analysis, detectable HBV DNA at baseline was strongly associated with an increased risk of reactivation (adjusted hazard ratio [HR], 18.22; 95% confidence interval [CI], 6.04-54.93; P < .0001). Prophylactic NAT was strongly associated with a reduced risk (adjusted HR, 0.09; 95% CI, 0.02-0.41; P = .0018). HBV DNA monitoring-guided preemptive NAT was effective in preventing HBV-related hepatitis during anti-CD20-containing immunochemotherapy in B-cell NHL patients with resolved HBV infection. Antiviral prophylaxis was also effective and may be appropriate for high-risk patients. These trials were registered at www.clinicaltrials.gov as NCT01287741 (GOYA) and NCT01332968 (GALLIUM).

END OF TREATMENT PET-CT PREDICTS PROGRESSION-FREE SURVIVAL IN DLBCL AFTER FIRST-LINE TREATMENT: RESULTS FROM THE PHASE III GOYA STUDY

increase the CRR compared to historical data. The null hypothesis (p0) has been set equal 0.60 on the basis of what reported by Peyrade et al (Lancet Oncol, 2011), and the alternative hypothesis (p1) was set at 0.75, with a type I and II error of 10% and 90%. A total of 71 patients were required with at least 48 CR to conclude for the efficacy of treatment. An interim analysis was planned after 34 patients, and at least 22 CR were required to proceed with enrollment. Analysis was by intention to treat. We here report the results of the stage 1. Results: Thirty‐four patients were enrolled from August 2015 to June 2016 by 15 Italian centers. One patient was subsequently excluded due to violation of inclusion criteria. Median age was 82 years (68‐ 89), 18 were males, and IPI was 3‐5 in 21 cases. Overall, 228 cycles were delivered, and 27 patients completed all 6 planned courses. Treatment was interrupted in 4 patients due to adverse events (AE) and in 2 due to lack of response. Final response was reported as CR in 14 patients (42%) and partial in 8 (24%); 10 patients had stable or progressive disease (30%), and 1 patient (3%) was not assessed. AEs were reported in 28 cases: hematological grade 3‐4 AEs included neutropenia (13 cases, 39%) and thrombocytopenia (1 case, 3%); grade 3‐4 non‐hematological AEs occurring in more than one case included skeletal muscle (2 cases, 6%) and metabolic disorders (3 cases, 9%). With the observed CR rate, the study has failed the planned interim analysis, and enrollment has been interrupted. Conclusions: GA101‐miniCHOP is active and well tolerated for the treatment of elderly unfit patients affected by DLBCL. Based on initial study assumptions and on the observed CRR, at the interim analysis, we will not be able to demonstrate the initial study hypothesis that GA101‐miniCHOP could improve results of historical data obtained with R‐miniCHOP in this setting of patients.

CLINICAL CHARACTERISTICS AND TREATMENT OUTCOMES FOR YOUNG PATIENTS WITH FIRST-LINE FOLLICULAR LYMPHOMA: A POOLED ANALYSIS OF 4249 PATIENTS FROM THE FLASH DATABASE.

grade B‐cell non‐Hodgkin lymphomas (NHL) is rare and has only been reported as case series. The distribution, demographics and outcomes of patients with low grade CNS NHLs have not been well characterized. Methods: The National Cancer Database (NCDB) represents ~70% of cancer cases in the United States. Using the 2004–2013 NCDB extranodal NHL database, we identified all CNS B‐cell NHLs based on ICD‐O‐3 site and histology codes. Primary or secondary CNS involvement could not be determined. Results: Out of 9435 CNS NHL cases, 475 [5.03%] had low grade histologies. In this group, the median age at diagnosis was 58 years [range 19–89]. Majority of the cases were female [56%], White, non‐Hispanic [72%], privately insured [53%], with no comorbidities [74%] and treated in academic/research programs [38%]. Site of CNS disease was not specified in 22%. HIV status was known in 318 cases (6.3% positive). The brain [44%] was the most common site of involvement followed by spinal cord [19%] and meninges [15%]. Follicular lymphoma (FL) [48%] was the most common histology overall followed by marginal zone (MZL) [37%], small lymphocytic (SLL) [8%] and lymphoplasmacytic lymphomas (LPL) [7%]. MZL was the most common histology in the brain [44%] and meninges [61%] while FL was most common in the spinal cord [77%] and nervous system, NOS, [69%]. Cranial nerves and eye (retina/optic nerve) involvement was very rare [2 and 1 case each—both MZL].The overall survival (OS) of CNS B‐cell NHL was significantly better if histology was low grade vs other [5‐year OS 74% vs 32%, P < 0.0001]. Among CNS low grade B‐cell NHLs, 5‐year OS was significantly affected by histology [MZL 83%, FL 75%, LPL 56% and SLL 50%, P = 0.0003] and site of disease [spinal cord 89%, meninges 78% and brain 63%, P = 0.03] in addition to age at diagnosis and co‐morbidities on both uni‐ and multivariate analysis. Survival was not influenced by sex, race, insurance, year of diagnosis, facility type or location. Conclusions: CNS involvement with low grade B‐cell NHL is rare but has a relatively good outcome with most patients surviving beyond 5 years. FL and MZL are the more common low grade histologies. Both histology and disease site are important factors affecting survival.