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MOSUNETUZUMAB DEMONSTRATES DURABLE RESPONSES IN PATIENTS WITH RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA AND >=2 PRIOR THERAPIES: UPDATED ANALYSIS OF A PIVOTAL PHASE II STUDY B Introduction: b Mosunetuzumab (Mosun) is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. B Conclusion: b Fixed-duration Mosun monotherapy demonstrated a high CR rate at EOT in pts with I R i / I R i FL, with many pts remaining event-free 2 years after EOT. [Extracted from the article]

B Introduction: b The antibody-like fusion protein RO7227166 simultaneously targets CD19 on B-cells and 4-1BB (CD137) on T cells. RO7227166 doses ranging from 360 ug up to 75 mg were assessed and the maximum tolerated dose was not reached. COMBINING CD19-4-1BBL (RO7227166) WITH GLOFITAMAB IS SAFE AND SHOWS EARLY EFFICACY IN PATIENTS SUFFERING FROM RELAPSED OR REFRACTORY B-CELL NON-HODGKIN LYMPHOMA. [Extracted from the article]

Rates (any gr) of febrile neutropenia (5.6% N vs. 6.4% BV), pneumonitis (2.0% N vs. 3.2% BV), ALT elevation (30.7% N vs. 39.8% BV), and colitis (1% N vs. 1.3% BV) were similar. B Background: b The addition of BV to initial chemotherapy improves outcomes in adult and pediatric patients (pts) with AS HL. NIVOLUMAB(N)-AVD IMPROVES PROGRESSION-FREE SURVIVAL COMPARED TO BRENTUXIMAB VEDOTIN(BV)-AVD IN ADVANCED STAGE (AS) CLASSIC HODGKIN LYMPHOMA (HL): RESULTS OF SWOG S1826. [Extracted from the article]

B Conclusions: b Our study suggests that radiomics features complementary to TMTV derived from baseline 18F-FDG PET/CT scans can improve outcome prediction for follicular lymphoma patients. A total of 7437 PET and CT features were calculated, including tumor radiomics from segmented lesions and host radiomics from segmented organs and correlated to PFS and OS. [Extracted from the article]

B Introduction: b Patients (pts) with diffuse large B cell lymphoma (DLBCL) refractory or relapsed (r/r) after initial therapy have poor survival. The overall response (OR) rate to platinum-based second line therapy is approximately 50% with complete response (CR) rate of 30%. Venetoclax combined with R-ICE (VICER) for second line treatment of diffuse large B cell lymphoma refractory or relapsed after initial chemoimmunotherapy. [Extracted from the article]

BACKGROUND Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin's lymphoma, including in preliminary studies involving previously untreated patients. METHODS We conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin's lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause. RESULTS Of994 patients who underwent randomization, 970 were included in the intention-totreat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P=0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation. CONCLUSIONS N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin's lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.). [ABSTRACT FROM AUTHOR]

Background: In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.Methods: In this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments.Results: Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response.Conclusions: In this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .). [ABSTRACT FROM AUTHOR]

Background: Ibrutinib has been approved by the Food and Drug Administration for the treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but has not been compared with chemoimmunotherapy. We conducted a phase 3 trial to evaluate the efficacy of ibrutinib, either alone or in combination with rituximab, relative to chemoimmunotherapy.Methods: Patients 65 years of age or older who had untreated CLL were randomly assigned to receive bendamustine plus rituximab, ibrutinib, or ibrutinib plus rituximab. The primary end point was progression-free survival. The Alliance Data and Safety Monitoring Board made the decision to release the data after the protocol-specified efficacy threshold had been met.Results: A total of 183 patients were assigned to receive bendamustine plus rituximab, 182 to receive ibrutinib, and 182 to receive ibrutinib plus rituximab. Median progression-free survival was reached only with bendamustine plus rituximab. The estimated percentage of patients with progression-free survival at 2 years was 74% with bendamustine plus rituximab and was higher with ibrutinib alone (87%; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.26 to 0.58; P<0.001) and with ibrutinib plus rituximab (88%; hazard ratio, 0.38; 95% CI, 0.25 to 0.59; P<0.001). There was no significant difference between the ibrutinib-plus-rituximab group and the ibrutinib group with regard to progression-free survival (hazard ratio, 1.00; 95% CI, 0.62 to 1.62; P=0.49). With a median follow-up of 38 months, there was no significant difference among the three treatment groups with regard to overall survival. The rate of grade 3, 4, or 5 hematologic adverse events was higher with bendamustine plus rituximab (61%) than with ibrutinib or ibrutinib plus rituximab (41% and 39%, respectively), whereas the rate of grade 3, 4, or 5 nonhematologic adverse events was lower with bendamustine plus rituximab (63%) than with the ibrutinib-containing regimens (74% with each regimen).Conclusions: Among older patients with untreated CLL, treatment with ibrutinib was superior to treatment with bendamustine plus rituximab with regard to progression-free survival. There was no significant difference between ibrutinib and ibrutinib plus rituximab with regard to progression-free survival. (Funded by the National Cancer Institute and Pharmacyclics; ClinicalTrials.gov number, NCT01886872 .). [ABSTRACT FROM AUTHOR]

BACKGROUND Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma.METHODS We conducted this multicenter, international, phase 3 superiority trial to evaluaterituximab plus lenalidomide, as compared with rituximab plus chemotherapy, inpatients with previously untreated follicular lymphoma. Patients were randomlyassigned to receive one of the two regimens, followed by maintenance monotherapywith rituximab. Treatment with rituximab plus lenalidomide consisted of 18 cyclesof the two drugs, followed by rituximab maintenance therapy every 8 weeks for 12cycles (six additional doses). Treatment with rituximab plus chemotherapy consistedof the investigator's choice of one of three rituximab-based regimens, followed bymaintenance monotherapy with rituximab every 8 weeks for 12 cycles. The primaryend points were complete response (confirmed or unconfirmed) at 120 weeks andprogression-free survival.RESULTSA total of 1030 patients were randomly assigned to receive rituximab plus lenalidomide(513 patients) or rituximab plus chemotherapy (517 patients). The rate of confirmedor unconfirmed complete response at 120 weeks was similar in the two groups:48% (95% confidence interval [CI], 44 to 53) in the rituximab–lenalidomide groupand 53% (95% CI, 49 to 57) in the rituximab–chemotherapy group (P=0.13). Theinterim 3-year rate of progression-free survival was 77% (95% CI, 72 to 80) and 78%(95% CI, 74 to 82), respectively. A higher percentage of patients in the rituximab–chemotherapy group had grade 3 or 4 neutropenia (32% vs. 50%) and febrileneutropenia of any grade (2% vs. 7%), and a higher percentage of patients in therituximab–lenalidomide group had grade 3 or 4 cutaneous reactions (7% vs. 1%).CONCLUSIONSAmong patients with previously untreated follicular lymphoma, efficacy results weresimilar with rituximab plus lenalidomide and rituximab plus chemotherapy (withboth regimens followed by rituximab maintenance therapy). The safety profile differedin the two groups. [ABSTRACT FROM AUTHOR]

BACKGROUND Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma. METHODS We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarba- zine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival. RESULTS At a median follow-up of 24.9 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [Cl], 78.7 to 85.0) and 77.2% (95% Cl, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% Cl, 0.60 to 0.98; P=0.03). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.72 [95% Cl, 0.44 to 1.17]; P=0.19). All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity. CONCLUSIONS A+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin's lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and use of subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals and Seattle Genetics; ECHELON-1 Clinical- Trials.gov number, NCT01712490; EudraCT number, 2011-005450-60.) [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma.Methods: We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee.Results: The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib.Conclusions: Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables. (Funded by Pharmacyclics and others; RESONATE-2 ClinicalTrials.gov number, NCT01722487.). [ABSTRACT FROM AUTHOR]

Discusses the cases of four patients with intravascular lymphoma who had laboratory or radiologic abnormalities that initially suggested a primary endocrine disorder complication. Patient characteristics; Immunohistochemistry; Biopsy findings; Autopsy findings.